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Best Pract Res Clin Obstet Gynaecol. 2006 Apr;20(2):227-51.
The effect of lifestyle factors on gynaecological cancer.
Rieck G, Fiander A.
Department of Obstetrics and Gynaecology, Wales College of Medicine, Cardiff University, Heath Park,Cardiff CF14 4XN, UK.

Several lifestyle factors affect a woman's risk of gynaecological cancer and-potentially-can be modified to reduce risk. This chapter summarises the evidence for the effect of lifestyle factors on the incidence of gynaecological malignancy. The incidence of obesity is increasing in the developed world such that it now contributes as much as smoking to overall cancer deaths. Women with a body mass index (BMI) >40 have a 60% higher risk of dying from all cancers than women of normal weight. They are also at increased risk from gynaecological cancer. Dietary factors significantly influence the risk of gynaecological cancer: fruit, vegetables and antioxidants reduce risk whereas high animal fat and energy intakes increase risk. Alcohol intake adversely affects breast cancer risk, possibly accounting for 4% of all breast cancers. Physical activity protects against ovarian, endometrial and postmenopausal breast cancer, independently of BMI. The oral contraceptive pill has a substantial and long-lasting effect on the prevention of ovarian and endometrial cancer and is one of the best examples of large-scale chemoprevention in the developed world. Childbearing is protective against ovarian, endometrial and breast cancer but increases the risk of cervical cancer. Smoking acts as a cofactor in cervical carcinogenesis and increases the risk of ovarian cancer, particularly mucinous tumours.

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J Minim Invasive Gynecol. 2006 Mar-Apr;13(2):114-20.
Laparoscopic-assisted vaginal hysterectomy versus total laparoscopic hysterectomy for the management of endometrial cancer: a randomized clinical trial.
Ghezzi F, Cromi A, Bergamini V, Uccella S, Beretta P, Franchi M, Bolis P.
Department of Obstetrics and Gynecology, University of Insubria, Del Ponte Hospital Varese, Verona, Italy. fabio.ghezzi@uninsubria.it

STUDY OBJECTIVE: To compare laparoscopic-assisted vaginal hysterectomy (LAVH) and total laparoscopic hysterectomy (TLH) for the treatment of endometrial cancer. DESIGN: Randomized, controlled trial. DESIGN CLASSIFICATION: Randomized controlled trial (Canadian Task Force classification I). SETTING: Two gynecologic oncologic units of university hospitals. PATIENTS: Seventy-two women with endometrial cancer randomized to undergo either LAVH or TLH. INTERVENTIONS: Total laparoscopic hysterectomy or laparoscopic-assisted vaginal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washing, and systematic pelvic lymphadenectomy. MEASUREMENTS AND MAIN RESULTS: Parameters of technical feasibility (operating time of hysterectomy phase, estimated blood loss, perioperative complications) were considered as major statistical endpoints. Thirty-seven women were allocated to the LAVH arm, and 35 were allocated to the TLH arm. Mean total operating time was significantly shorter in the TLH than in the LAVH group (184.0 +/- 46.0 vs 213.2 +/- 39.4 minutes, p = .003). The hysterectomy phase was longer in the LAVH than in the TLH group only in overweight (77.9 +/- 9.8 vs 68.1 +/- 9.3 min, p = .005) and obese patients (87.7+/- 13.1 vs. 62.1+/- 9.9 min, p < .0001). The median estimated blood loss during hysterectomy was similar between groups. Intraoperative complications occurred in three (8.1%) patients in the LAVH group and in one patient (2.8%) in the TLH group (p = .61). No difference was found in the postoperative complication rate between women undergoing LAVH and those who had TLH (24.3% vs 17.1%, p = .56). Within a median follow-up period of 10 months (range 3-17 months), 2 patients in the LAVH group developed recurrent disease. No port site metastasis and no vaginal cuff recurrence were detected in either group. CONCLUSION: Both LAVH and TLH can be performed successfully to manage endometrial cancer, with similar surgical outcomes. Obese patients benefit more from TLH than from LAVH in terms of shorter operating time.

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Eur J Surg Oncol. 2006 Mar 17; [Epub ahead of print]
Routine pelvic lymphadenectomy in apparently early stage endometrial cancer.
Zuurendonk LD, Smit RA, Mol BW, Feijen HW, de Graaff J, Sykora D, de Winter KA, Vd Wurff A, Snijders MP, Kruitwagen RF.
Department of Obstetrics and Gynaecology, St Elisabeth Hospital Tilburg, Tilburg, The Netherlands.

AIMS: Controversial issues with respect to the treatment of patients with endometrial cancer include indications for lymphadenectomy and adjuvant radiotherapy. PATIENT AND METHODS: Between 1998 and 2004 all women with endometrial cancer stage I were included (n=335). They all underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Two hundred and thirty-seven women also had a pelvic lymphadenectomy. When pelvic lymphadenectomy was performed, radiotherapy was administered only to patients with lymph-node metastases. Otherwise, adjuvant radiotherapy was based on the presence of risk factors. RESULTS: Eleven patients had lymph-node metastases. The overall absolute and relative survival-estimate at 5 years was 85.0 and 93.7%, respectively. Loco-regional recurrence was 8.5%. In the group with pelvic lymphadenectomy and negative lymph nodes these rates were 88.2, 93.9 and 5.6%, respectively. In 58 patients without any of the risk factors tumour grade III, deep myometrial invasion, or age >/=60 years, no lymph-node metastases were found. CONCLUSION: In patients with endometrial cancer FIGO stage I without risk-factors, a phenomenon which occurs in about 25% of patients with clinical stage I endometrial cancer, a lymphadenectomy can be omitted. In other patients, the debate regarding the optimal treatment will remain.

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Arch Gynecol Obstet. 2006 Mar 4; [Epub ahead of print]
Pelvic lymphadenectomy as alternative to postoperative radiotherapy in high risk early stage endometrial cancer.
Papanikolaou A, Kalogiannidis I, Goutzioulis M, Misailidou D, Makedos A, Vergote I, Makedos G.
4th Department of Obstetrics and Gynecology, Aristotles University of Thessaloniki, 38 Mavromichali str, 54248, Thessaloniki, Greece, kalogiannidis@mailbox.gr.

Objective: The purpose of the study is to evaluate whether surgery followed by radiotherapy in high-risk patients of early stage endometrial cancer can be replaced by formal surgical staging. Cancer-related survival and recurrence-free survival (RFS) were the endpoints of the analysis. Study design: One hundred and eighteen patients with endometrioid endometrial adenocarcinoma between 1996-2003 were reviewed. Patients with incomplete follow-up and extrauterine spread excluded, leaving 78 women in the final analysis. Low-risk patients (n=37) (Grade 1, myometrial infiltration <1/2 or Grade2, <1/3), treated by standard surgical procedure including total abdominal hysterectomy, bilateral salpingo-oophorectomy and peritoneal washing, while staging lymphadenectomy (n=24) or postoperative irradiation (n=17) was added in the high-risk group (Grade 1, >1/2 or Grade 2, >1/3 or Grade3). Results: The median age of patients was 65 years (range, 35-80 years) and the median follow-up 38 months (range, 9-98 months). The recurrence rate in low-risk patients was 2.7%, the cancer-related survival 97.5% and RFS 97%, while in the high-risk patients 12%, 93% and 88%, respectively. Comparing the therapeutic modalities (staging lymphadenectomy vs. postoperative irradiation) in the high-risk group the cancer-related survival and RFS was not differed (P=0.70, P=0.90, respectively). The high grade of the tumor was significantly correlated with RFS, while age, stage and myometrial infiltration were not. No moderate or severe complications developed after lymphadenectomy, while two moderate gastrointestinal complications occurred after adjuvant radiotherapy. Conclusion: According our results the low-risk patients of early stage endometrial adenocarcinoma had excellent survival with minimal intervention. The cancer-related survival and RFS in high-risk patients concerning the therapeutic modalities were comparable. Poor tumor differentiation was the most unfavorable prognostic factor related with RFS. Moderate complications developed only after postoperative radiotherapy.

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Gynecol Oncol. 2006 Mar 14; [Epub ahead of print]
The impact of age on long-term outcome in patients with endometrial cancer treated with postoperative radiation.
Jolly S, Vargas CE, Kumar T, Weiner SA, Brabbins DS, Chen PY, Floyd W, Martinez AA.
Department of Radiation Oncology, William Beaumont Hospital, 3601 West Thirteen Mile Road, Royal Oak, MI 48073, USA.

PURPOSE.: Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. Age has been associated with worse outcome in univariate analysis. However, the patterns of failure and associated risk factors in older patients remain unclear. We reviewed our institution's experience to assess the effect of age in a population of endometrial cancer patients treated with surgery and adjuvant radiation therapy. METHODS.: From 1992-2002, 243 endometrial cancer patients underwent a total abdominal hysterectomy and adjuvant radiation. Forty-nine patients with stage I-II (occult) endometrial adenocarcinoma (no clear cell or serous papillary) were treated postoperatively with vaginal intracavitary high-dose rate (HDR) brachytherapy alone using Iridium-192 (median dose 30 Gy) to a median length of 4 cm. Forty-eight patients with stage I-III endometrial adenocarcinoma (no clear cell or papillary serous) were treated with postoperative pelvic RT (median dose 45 Gy) and intracavitary HDR brachytherapy (median dose 20 Gy). One hundred forty-six patients underwent postoperative whole abdomino-pelvic irradiation (WAPI) secondary to unfavorable histology (clear cell or serous papillary) or two of the following: deep myometrial invasion, grade 3, or FIGO stage III. Age was analyzed as a continuous and a categorical variable. The age of 63 year split the age group using various statistical analyses. RESULTS.: Median follow-up of all patients was 4.2 years. Patients grouped by age of </=63 years or older had similar FIGO stage (P = 0.5), grade (P = 0.09), treatment modality (P = 0.7), and lymphovascular space invasion (LVSI) (P = 0.6). Twenty-five percent (60/243) of patients developed recurrence. Of these failures, 15% (15/102) were age </=63 years and 32% (45/141) were age >63 years at diagnosis (P = 0.02). For all patients, the 5-year event-free survival (EFS), cause specific survival (CSS), and overall survival (OS) were 64%, 82%, and 72%, respectively. Five-year EFS for patients age </=63 years and >63 years was 76% vs. 55% (P < 0.001). Five-year OS for age </=63 years and >63 years was 85% vs. 63% (P < 0.001). Five-year CSS for age </=63 years and >63 years was 91% vs. 75% (P = 0.003). Various factors were analyzed to determine an association with age. Older patients with stage III-IVA had significantly more failures than patients less than age 63 (P = 0.002). Older patients (>63 years) were found to have serous papillary histology (28%) more often than younger patients (15%) (P = 0.02). Greater depth of invasion was associated with older age (P = 0.01). On univariate analysis, older age (P = 0.003), LVSI (P = 0.002), FIGO stage (P < 0.001), grade (P < 0.001), and depth of invasion (P = 0.03) predicted for failure. On Cox multivariate analysis, older age (P = 0.006, HR 2.83), higher FIGO stage (P = 0.001, HR 1.96), and higher grade (P = 0.002, HR 2.66) were significant prognostic factors for recurrence. No difference was seen between the two age groups from date of surgery and start of radiation. The duration of therapy was not different between the two groups. CONCLUSIONS.: Older endometrial cancer (age >63 years) patients have a significantly decreased overall survival, cause-specific survival, and greater risk of recurrence following postoperative RT independent of other prognostic factors and/or treatment technique. The impact of treatment-related variables did not alter the age-related outcome.

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Gynecol Oncol. 2006 Mar 15; [Epub ahead of print]
Final analysis of RTOG 9708: Adjuvant postoperative irradiation combined with cisplatin/paclitaxel chemotherapy following surgery for patients with high-risk endometrial cancer.
Greven K, Winter K, Underhill K, Fontenesci J, Cooper J, Burke T.
Department of Radiation Oncology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.

PURPOSE.: A phase II study was completed by the RTOG to assess the feasibility, safety, toxicity, and patterns of recurrence and survival when chemotherapy was combined with adjuvant radiation for patients with high-risk endometrial cancer. MATERIALS AND METHODS.: Pathologic requirements included grade 2 or 3 endometrial adenocarcinoma with either >50% myometrial invasion, cervical stromal invasion, or pelvic-confined extrauterine disease. Radiation included 45 Gy in 25 fractions to the pelvis along with cisplatin (50 mg/m(2)) on days 1 and 28. Vaginal brachytherapy was performed after the external beam radiation. Four courses of cisplatin (50 mg/m(2)) and paclitaxel (175 mg/m(2)) were given at 4-week intervals following completion of radiotherapy. RESULTS.: Forty-six patients were entered between 10/97 and 4/99. Follow-up times range from 6.8 to 72 months with a median of 4.3 years. Maximum late toxicity was grade 1 in 16%, grade 2 in 41%, grade 3 in 16%, and grade 4 in 5%. At 4 years pelvic, regional and distant recurrence rates are 2%, 2%, and 19%, respectively. Overall survival and disease-free survival (DFS) rates at 4 years are 85% and 81%, respectively. Four-year rates for survival and DFS for Stage III patients are 77% and 72%, respectively. There have been no recurrences for patients with stage IC, IIA, or IIB. CONCLUSION.: Local-regional control is excellent following combined modality treatment in all patients suggesting additive effects of chemotherapy and radiation. Distant metastases continue to occur in more advanced staged patients. This regimen appears reasonable to be tested for efficacy in randomized studies.

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Gynecol Oncol. 2006 Feb 27; [Epub ahead of print]
Efficacy of systematic lymphadenectomy and adjuvant radiotherapy in node-positive endometrial cancer patients.
Mariani A, Dowdy SC, Cliby WA, Haddock MG, Keeney GL, Lesnick TG, Podratz KC.
Division of Gynecologic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

OBJECTIVE.: To assess the efficacy of systematic lymphadenectomy and adjuvant radiotherapy in minimizing pelvic sidewall and para-aortic failures. METHODS.: Between January 1984 and December 2001, a total of 146 patients with stage III and IV endometrial cancer and lymph node metastases were treated at our institution. Adequate pelvic lymphadenectomy was defined as the removal of more than 10 pelvic lymph nodes, and adequate para-aortic lymphadenectomy was defined as removal of 5 or more para-aortic lymph nodes. The 24 patients who received adjuvant chemotherapy were excluded. We assessed the ability of adequate pelvic and para-aortic lymphadenectomy, together with radiotherapy, to prevent pelvic and para-aortic recurrences. RESULTS.: Of the 122 patients studied, 94 (77%) had adequate pelvic lymphadenectomy and 47 (39%) had adequate para-aortic lymphadenectomy. Pelvic radiotherapy was administered to 78% and para-aortic radiotherapy to 29% of patients. Median follow-up of censored patients was 56 months. Twenty-five percent of patients had pelvic sidewall failure at 5 years. Pelvic sidewall failures at 5 years occurred in 57% of patients who had inadequate node dissection and/or no radiotherapy, compared with 10% for those having both adequate lymphadenectomy and radiotherapy (P < 0.001). After risk factor assessment in a regression model, only treatment with adequate lymphadenectomy and radiotherapy was a significant independent predictor of pelvic control (P = 0.03). The performance of definitive pelvic lymphadenectomy may have increased treatment-related morbidity in the subgroup of patients who had postoperative radiotherapy. For the 41 patients with positive para-aortic lymph nodes, the 5-year para-aortic failure rate was 34% after adequate lymphadenectomy but without adjuvant para-aortic radiotherapy. Likewise, 69% failed in the para-aortic area when adjuvant para-aortic radiotherapy was administered to patients not having adequate para-aortic lymphadenectomy; however, none of the 11 patients failed in the para-aortic area after adequate lymphadenectomy and para-aortic radiotherapy (P = 0.08). CONCLUSIONS.: Adequate (pelvic and para-aortic) lymphadenectomy and adjuvant radiotherapy appear complementary in reducing failures in both the pelvis and para-aortic areas in patients with node-positive endometrial cancer.

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Gynecol Oncol. 2006 Feb 18; [Epub ahead of print]
Surgical resection of recurrent endometrial carcinoma.
Awtrey CS, Cadungog MG, Leitao MM, Alektiar KM, Aghajanian C, Hummer AJ, Barakat RR, Chi DS.
Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, MRI-1026, New York, NY 10021, USA.

OBJECTIVE: Chances of survival after the diagnosis of recurrent endometrial cancer are poor. Although total pelvic exenteration has been described as a treatment for a select subset of patients with recurrent endometrial cancer, the use of other surgical procedures in this setting has not been well described. The objective of this study was to review our experience with non-exenterative surgery for recurrent endometrial cancer. METHODS: We reviewed the medical records of all patients who underwent non-exenterative surgery for recurrent endometrial cancer between 1/91 and 1/03. Survival was determined from the time of surgery for recurrence to last follow-up. Survival was estimated using Kaplan-Meier methods. Differences in survival were analyzed using the log-rank test. The Fisher's exact test was used to compare optimal versus suboptimal cytoreduction against possible predictive factors. RESULTS: Twenty-seven patients were identified. Fifteen patients (56%) had disease limited to the retroperitoneum, 10 patients (37%) had intraperitoneal disease, and 2 patients (7%) had both intra- and retroperitoneal disease. Cytoreduction to </=2 cm of residual disease was achieved in 18 patients (67%), while 9 patients (33%) had cytoreduction to residual disease >2 cm. There were no major perioperative complications or mortalities. The median hospital stay was 7 days (range, 1-18 days). Additional therapies included intraoperative radiation therapy in 9 patients (33%), radiation therapy in 12 patients (44%), and chemotherapy in 10 patients (37%). The median follow-up for the entire cohort was 24 months (range, 5-84 months). The median progression-free survival was 14 months (95% CI, 6-23), and the median disease-specific survival was 35 months (95% CI, 24-not reached). Size of residual disease was the only significant predictor for both progression-free and disease-specific survival. Patients with residual disease </=2 cm had a median disease-specific survival of 43 months (95% CI, 35-not reached) compared with 10 months (95% CI, 7-29) for those with >2 cm residual (P = 0.01). CONCLUSIONS: Surgical resection for recurrent endometrial cancer may provide an opportunity for long-term survival in a select patient population. The only factor associated with improved long-term outcome was the size of residual disease remaining at the end of surgical resection.

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Expert Rev Anticancer Ther. 2006 Jan;6(1):33-41.
An overview of uterine cancer and its management.
Carter J, Pather S.
Royal Prince Alfred Hospital, Sydney Cancer Centre, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW 2050, Australia. jocarter@mail.usyd.edu.au , Royal Prince Alfred Hospital, Sydney Cancer Centre, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW 2050, Australia.

Endometrial cancer is increasingly common in affluent Western countries, largely owing to the growing obesity of those populations. There are two recognized types of endometrial cancer: Type I is more common and is associated with obese postmenopausal women and comprises approximately 80% of all endometrial cancers; Type II describes a woman who is often younger and thinner with a more aggressive histologic type that is nonestrogen dependent, of either serous or clear cell histology, and consists of a more aggressive clinical course and results in poorer prognosis. As the majority of patients with endometrial cancer present with symptoms and have early disease, screening is unlikely to be cost effective or reduce the mortality rate. However, surveillance of high-risk populations is a different proposition. Patients who may benefit from routine surveillance include those with a family history of endometrial cancer, a history of hormone replacement therapy with less than 12-14 days of progestogens, long-term use of tamoxifen, hereditary nonpolyposis colorectal cancer family syndrome, Cowden's syndrome, Peutz-Jeghers syndrome, a history of breast cancer and obesity. Most patients with endometrial cancer are offered surgery as first-line therapy. The standard surgical procedure should be an extrafascial total hysterectomy with bilateral salpingo-oophorectomy. Adnexal removal is also recommended, even if the adnexa appear normal, as they may contain micrometastases. The safety of a laparoscopic approach in the surgical management of uterine cancer has not yet been demonstrated in prospective randomized trials, therefore, the field awaits the Gynaecologic Oncology Group's prospective Lap-2 study. While post-treatment follow-up guidelines vary between institutions and countries, in general, patients at high risk of recurrence are followed closely every 3-4 months for the first year or two, then every 6 months to complete 5 years of follow-up.

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Eur J Cancer. 2005 Dec 20; [Epub ahead of print]
Randomized evidence on chemotherapy and hormonal therapy regimens for advanced endometrial cancer: An overview of survival data.
Polyzos NP, Pavlidis N, Paraskevaidis E, Ioannidis JP.
Department of Hygiene and Epidemiology, University of Ioannina, School of Medicine, Ioannina 45110, Greece; Department Obstetrics and Gynaecology, University of Ioannina, School of Medicine, Ioannina 45110, Greece.

Several chemotherapy and hormonal therapy regimens have been used in advanced endometrial cancer. In this review we have systematically evaluated the available data from randomized trials on survival. We searched MEDLINE, EMBASE and the Cochrane Library (last search April 2005) for randomized controlled trials evaluating various chemotherapy or hormonal therapy regimens in locally advanced or metastatic endometrial cancer. We focused on survival outcomes and examined trial characteristics pertaining to quality and potential biases. Across 17 eligible trials (2964 patients randomized), only 4 regimens were involved in more than one trial, and only two trials had used the same comparison of regimens. A statistically significant effect in survival was seen only in one recent trial, but it was borderline (P=0.032) and amounted to only 3 months difference in median survival. Three more trials reported some survival benefits, but these were seen only after specific adjustments, and the difference was against the experimental arm in one of these three trials. Only four trials (24%) apparently analyzed all randomized patients and none of the trials were blinded. Median survival was seemingly longer in more recent compared with older trials, but this effect was driven by the inclusion of significantly fewer patients with poor performance status in more recent trials (P<0.001). Overall, randomized evidence on systemic treatment in advanced endometrial cancer is fragmented and survival benefits for specific regimens are questionable.

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Gynecol Oncol. 2005 Nov 28; [Epub ahead of print]
Radical pelvic resection and intraoperative radiation therapy for recurrent endometrial cancer: Technique and analysis of outcomes.
Dowdy SC, Mariani A, Cliby WA, Haddock MG, Petersen IA, Sim FH, Podratz KC.
Division of Gynecologic Surgery, 200 1st St. NW, Rochester, MN 55905, USA.

OBJECTIVE.: To describe the technique and assess outcomes and morbidity following radical resection combined with intraoperative electron radiation therapy (IOERT) in patients with recurrent endometrial cancer. METHODS.: From 1986 to 2002, 25 patients received treatment including radical resection and IOERT for recurrent endometrioid, endometrial cancer. Relevant clinical information was extracted through retrospective chart review. RESULTS.: Treatment prior to referral included radiation in 56% and either a secondary surgery or chemotherapy in 48%. External radiation (EBRT) was administered in addition to IOERT in 84%. Radical procedures performed at the time of IOERT included resection of the pelvic sidewall en bloc with the obturator nerve, external iliac vein, psoas, iliacus, or obturator internus muscles, ureter, or boney ileum. Seven patients required exenteration in combination with resection of the pelvic sidewall. The median IOERT dose was 1500 cGy (range 1000-2500 cGy). Overall five-year survival was 47% vs. 71% for those with a gross total resection but close margins. Two patients with recurrences limited to the para-aortic area are alive without evidence of disease at 54 and 71 months. Proportional hazards modeling showed concurrent EBRT, tumor size after resection, grade, and age to be associated with improved survival. The most common complications were peripheral neuropathy, functional ureteral obstruction, and fistula formation. CONCLUSIONS.: With an aggressive treatment approach including radical resection combined with IOERT, long-term survival is possible in a significant number of patients with localized recurrent endometrial cancer. Preoperative radiation paired with complete surgical resection utilizing extended procedures is paramount to achieving optimal outcomes.

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Am J Obstet Gynecol. 2005 Oct;193(4):1344-52.
A prospective randomized comparison between laparoscopic and laparotomic approaches in women with early stage endometrial cancer: a focus on the quality of life.
Zullo F, Palomba S, Russo T, Falbo A, Costantino M, Tolino A, Zupi E, Tagliaferri P, Venuta S.
Department of Obstetrics and Gynecology, University Magna Graecia of Catanzaro, Catanzaro, Italy.

OBJECTIVE: This study was undertaken to compare the quality of life (QoL) in women with early stage endometrial cancer treated with 2 different surgical approaches. STUDY DESIGN: Eighty-four women with clinical stage I endometrial cancer were enrolled in a prospective randomized controlled trial design and treated with laparoscopic or laparotomic approach. Another 40 women matched for demographic characteristics were studied as controls. In patients, before and after surgery, and in their matched controls, QoL was evaluated by using the Short-Form Healthy Survey (SF-36) and the climacteric symptoms using the Kupperman Index (KI). RESULTS: After randomization, no difference was detected in data recorded between the groups. At entry, QoL was similar in both treatment groups but significantly (P < .05) worse in comparison with controls. Throughout the study, QoL was significantly (P < .05) higher in laparoscopic group versus laparotomic group. After KI adjustment our data did not change. CONCLUSION: In early stage endometrial cancer, the laparoscopic approach provides significant benefits compared with laparotomy in terms of QoL.

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Br J Cancer. 2005 Oct 31;93(9):999-1004.
Phase II trial of docetaxel in advanced or metastatic endometrial cancer: a Japanese Cooperative Study.
Katsumata N, Noda K, Nozawa S, Kitagawa R, Nishimura R, Yamaguchi S, Aoki D, Susumu N, Kuramoto H, Jobo T, Ueki K, Ueki M, Kohno I, Fujiwara K, Sohda Y, Eguchi F.
Department of Medical Oncology, National Cancer Center Hospital, 104-0045 Tokyo, Japan. nkatsuma@ncc.go.jp

The purpose of this study was to determine whether docetaxel has antitumour activity in patients with advanced or recurrent endometrial carcinoma. Chemotherapy-naive or previously treated patients (one regimen) with histopathologically documented endometrial carcinoma and Eastern Cooperative Oncology Group performance status </=2 entered the study. Docetaxel 70 mg m(-2) was administered intravenously on day 1 of a 3-week cycle up to a maximum of six cycles. If patients responded well to docetaxel, additional cycles were administered until progressive disease or unacceptable toxicity occurred. Of 33 patients with a median age of 59 years (range, 39-74 years) who entered the study, 14 patients (42%) had received one prior chemotherapy regimen. In all, 32 patients were evaluable for efficacy, yielding an overall response rate of 31% (95% confidence interval, 16.1-50.0%); complete response and partial response (PR) were 3 and 28%, respectively. Of 13 pretreated patients, three (23%) had a PR. The median duration of response was 1.8 months. The median time to progression was 3.9 months. The predominant toxicity was grade 3-4 neutropenia, occurring in 94% of the patients, although febrile neutropenia arose in 9% of the patients. Oedema was mild and infrequent. Docetaxel has antitumour activity in patients with advanced or recurrent endometrial carcinoma, including those previously treated with chemotherapy; however, the effect was transient and accompanied by pronounced neutropenia in most patients.

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Obstet Gynecol Surv. 2005 Oct;60(10):648-649.
Whole Abdominal Radiotherapy in the Adjuvant Treatment of Patients With Stage III and IV Endometrial Cancer: A Gynecology Oncology Group Study.
Sutton G, Axelrod JH, Bundy BN, Roy T, Homesley HD, Malfetano JH, Mychalczak BR, King ME.
Division of Gynecologic Oncology, St. Vincent's Hospital and Health Services, Indianapolis, Indiana; Gynecologic Oncology, Western Pennsylvania Hospital, Pittsburgh, Pennsylvania; Statistics, Gynecologic Oncology Group, Roswell Park Cancer Institute, Buffalo, New York; Department of Radiation Oncology, St. Louis University Health Science Center, St. Louis, Missouri; Wake Forest School of Medicine, Brookview Research, Inc., Winston-Salem, North Carolina; Gynecologic Oncology, Albany Medical College, Albany, New York; Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY; and Clinical Pathology, Columbia University, New York, NY.

This study from the Gynecology Oncology Group investigated the use of postoperative whole abdominal radiation therapy in women with stage III and IV endometrial cancer. In the period between December 1986 and February 1994, 180 patients who met study criteria were enrolled in the study. Seventy-seven patients (mean age 63 years) had typical endometrial carcinoma (adenocarcinoma, endometrioid, glassy cell, mixed epithelial, adenosquamous, villoglandular, or undifferentiated) and 103 had papillary serous (median age 68.5 years) or clear cell carcinoma (median age 71 years) (P < .001 for age difference between typical and higher-risk tumors). Papillary serous tumors were more common in black women (78%) than in white women (53%), and grade 3 disease was more common in women with papillary serous/clear cell tumors (66%) than in those with typical endometrial cancer (44%).All patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic washings, and selective paraaortic and pelvic lymph node sampling. Radiation therapy was begun within 8 weeks of surgery and consisted of daily doses of 150 cGy to the whole abdomen for 20 days (total 3000 cGy) followed by 180 cGy per day to the pelvis for 11 treatments (total 1980 cGy). Women with positive paraaortic lymph nodes received a paraaortic boost totaling 1500 cGy.The frequency of gross disease and the extent and pattern of spread were similar in both groups except that metastases to the diaphragm were seen more frequently in women with papillary serous/clear cell disease (7.8%) than in those with typical disease (1.3%) (P = .05). Pelvic nodes and paraaortic nodes were positive in 45% and 39%, respectively, of patients with typical endometrial cancer and 51% and 31%, respectively, of patients with high-risk tumors.In this study, 22 patients (21%) had grade 3 or 4 hematologic toxicity associated with treatment. Nearly half of the participants (n = 78, 45%) had at least grade 2, and 11% (n = 20) had grade 3 gastrointestinal toxicity. Seven women developed severe gastrointestinal toxicity (grade 4), including 3 patients with no evidence of disease who died from complications of bowel obstruction. Two patients died from severe hemorrhages, one with a gastrointestinal bleeding 5 months after radiation and one who hemorrhaged after anticoagulation for deep venous thrombosis 60 days after surgery. Grade 3 or 4 hepatic toxicity was seen in 4 women (3%). Twelve patients (7%) experienced serious (grade 3 or 4) cardiovascular complications, including 4 pulmonary emboli and 2 instances of congestive heart failure.Sixty-five percent of patients with typical endometrial cancer and 67% of those with papillary serous/clear cell cancer had a recurrence of disease. Women with typical disease had recurrent disease diagnosed at various locations, but pelvis, abdomen, and lung were the most common (n = 7, 9, and 9, respectively). In the high-risk group, 21 of 69 recurrences were in the abdomen and 15 were in the lung.Among the 77 women with typical endometrial cancers, 58 had stage III disease and 19 had stage IV disease. Three-year survival rates for these patients were 34.5% and 21.1%, respectively. Seventy-five of the 103 participants with papillary serous/clear cell tumors were stage III and 28 were stage IV. Their 3-year survival rates were 48.1% and 10.7%, respectively.Overall survival rates were 31% for patients with typical endometrial cancers and 35% for patients with high-risk tumors. At 3 years, the disease-free survival rates for these groups were 29% and 27%, respectively.

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Int J Radiat Oncol Biol Phys. 2005 Oct 1;63(2):500-4.
Definitive radiotherapy in the management of isolated vaginal recurrences of endometrial cancer.
Lin LL, Grigsby PW, Powell MA, Mutch DG.
Department of Radiation Oncology, Washington University Medical School, St. Louis, MO.

Purpose: The aim of our study was to assess prognostic factors and overall survival after salvage radiotherapy for patients who had endometrial carcinoma and who experienced an isolated vaginal recurrence. Methods and Materials: We reviewed the records of 50 patients treated at our institution between 1967 and 2003 for an isolated vaginal recurrence of endometrial carcinoma. Initial treatment for endometrial carcinoma was definitive surgery in 49 patients and definitive radiotherapy in 1 patient. The median time from initial diagnosis of endometrial carcinoma to recurrence was 25 months (range, 4-179 months). Three patients (6%) received external-beam radiotherapy alone, 8 patients (16%) received brachytherapy only, and 39 patients (78%) received combined external-beam radiation therapy and brachytherapy. Median dose of radiation to the recurrence was 60 Gy (range, 16-85 Gy). Overall survival was calculated by the Kaplan-Meier method. Endpoints were measured from the date of diagnosis of the vaginal recurrence. Median follow-up of survivors after recurrence was 53 months (range, 8-159 months). Results: The 5-year and 10-year disease-free and overall survivals were 68% and 55%, and 53% and 40%, respectively. On multivariate analysis, age (p = 0.0242), Grade 1 or 2 vs. Grade 3 tumor (p = 0.002), and size of recurrence (p < 0.001) were significant predictors of overall survival. All patients who had Grade 3 disease were dead by 3.6 years from the time of recurrence. Five patients experienced a Grade 3 or 4 complication. Conclusions: Patients treated with radiotherapy for an isolated vaginal recurrence can be cured in over 50% the cases. Radiotherapy is well tolerated, with a low risk of complications. Factors predictive of overall survival include tumor grade, patient age at recurrence, and tumor size.

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Curr Opin Oncol. 2005 Sep;17(5):500-4.
What's new in systemic therapy for endometrial cancer.
Kieser K, Oza AM.
aDepartment of Gynaecologic Oncology and bDepartment of Medicine, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada.

PURPOSE OF REVIEW: Endometrial cancer is one of the most common gynecologic cancers. Most women present with early disease that is curable. In women with poor prognostic factors or advanced disease, survival is greatly diminished. Recently there have been several trials of adjuvant treatment and treatment for advanced and recurrent endometrial cancer. These trials of systemic therapy will be reviewed. RECENT FINDINGS: Several areas have been the focus of recent literature on systemic therapy for endometrial cancer. These include large phase III trials of multi-agent chemotherapy regimens for advanced and recurrent endometrial cancer, combined chemotherapy and radiotherapy treatments, and novel targeted agents. SUMMARY: New approaches to combining the traditional adjuvant modalities for high-risk endometrial cancer as well as combining new novel agents with traditional chemotherapeutics will improve patient outcomes.

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Oncologist. 2005 Sep;10(8):623-31.
Adjuvant radiotherapy in endometrial carcinoma.
Shaeffer DT, Randall ME.
Therapeutic Radiologists, Inc., 6600 Winchester, Suite 230, Kansas City, MO 64133, USA. dshaeffer@sbcglobal.net.

Endometrial cancer is a common female malignancy, affecting approximately 40,000 women per year. Despite the publication of several prospective randomized trials, there continues to be controversy regarding the use of adjuvant radiation therapy in endometrial cancer management. It is clear that most women with early-stage, low-risk disease will do well without adjuvant therapy. Intermediate-risk patients are at risk for local-regional relapse, and radiotherapy has been shown to effectively reduce this risk without significantly impacting overall survival. The absence of a clear impact on survival has resulted in a lack of consensus regarding the use of radiotherapy in intermediate-risk patients. At the same time, the patterns of failure in intermediate-risk patients have resulted in differing recommendations regarding appropriate radiotherapy targets. High-risk patients are at risk for both local and distant failure, and chemotherapy has been shown to improve outcome in these patients. High-risk patients are also at risk for local failure, and targeted radiotherapy may be appropriate. In this article, we discuss the controversies surrounding the use of adjuvant radiotherapy in endometrial cancer using an evidence-based approach.

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Gynecol Oncol. 2005 Aug 26; [Epub ahead of print]
Resection of lymph node metastases influences survival in stage IIIC endometrial cancer.
Havrilesky LJ, Cragun JM, Calingaert B, Synan I, Secord AA, Soper JT, Clarke-Pearson DL, Berchuck A.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Box 3079, Durham, NC 27710, USA.

OBJECTIVE.: Surgical staging of endometrial cancer identifies those patients with microscopic metastatic disease most likely to benefit from adjuvant therapy and may also confer therapeutic benefit. Our objective was to compare survival of patients who underwent resection of grossly positive lymph nodes (LN) to those with microscopically positive LN. METHODS.: Patients had stage IIIC endometrial cancer with pelvic and/or aortic LN metastases and underwent surgery between 1973 and 2002. Exclusion criteria included pre-surgical radiation and second primary cancer. Survival was analyzed using Kaplan-Meier method and Cox proportional hazards model. RESULTS.: Mean age of 96 patients with stage IIIC endometrial cancer was 64. There were 45 cases with microscopic LN involvement and 51 with grossly enlarged LN. Overall, 41% had disease in aortic LN, which in 18% represented isolated aortic LN metastasis. Adjuvant therapies were given to 92% of patients (85% radiotherapy, 10% chemotherapy, 10% progestins). Among those with grossly involved LN, 86% were completely resected. Five-year disease-specific survival (DSS) was 63% in 45 patients with microscopic metastatic disease compared to 50% in 44 patients with grossly positive LN completely resected and 43% in 7 with residual macroscopic disease. In multivariable analyses, gross nodal disease not debulked (HR = 6.85, P = 0.009), serosal/adnexal involvement (HR = 2.24, P = 0.036), diagnosis prior to 1989 (HR = 4.33, P < 0.001), older age (HR = 1.09, P < 0.001), and >2 positive lymph nodes (HR = 3.12, P = 0.007) were associated with lower DSS. CONCLUSION.: Grossly involved LN can often be completely resected in patients with stage IIIC endometrial cancer. These retrospective data provide evidence suggestive of a therapeutic benefit for lymphadenectomy in endometrial cancer.

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Gan To Kagaku Ryoho. 2005 Aug;32(8):1110-5.
[Endometrial cancer]
[Article in Japanese]
Kuzuya K, Nakanishi T.
Dept. of Gynecology, Aichi Cancer Center Hospital.

The current treatment of choice for endometrial cancer is reported to be primary surgery including a total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal cytologic sampling, and exploration, palpation, and biopsy of any suspicious lymph nodes or lesions. This allows determination of the extent of the disease, the stage of malignancy and the risk of recurrence. Adjuvant radiation therapy is administered to the pelvis for intermediate-risk patients, and a systemic chemotherapy is considered for high-risk ones, while no treatment is added for low-risk patients. But for patients with the malignancy, many Japanese gynecologists have performed extended hysterectomy instead of total hysterectomy to reduce the incidence of vaginal recurrence, achieved the pelvic and para-aortic lymphadenectomy as a substitute for biopsy sampling to avoid recurrence in lymph nodes, and given cytotoxic chemotherapy in place of irradiation to prevent radiation morbidity and recurrence at a distant site. Although differences in treatments for advanced disease have disappeared, further efforts are recommended to find useful prognostic factors for distinguishing patients with poorer prognoses, and to establish a standard treatment for endometrial cancer all over the world.

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Int J Radiat Oncol Biol Phys. 2005 Aug 16; [Epub ahead of print]
American Brachytherapy Society survey regarding practice patterns of postoperative irradiation for endometrial cancer: Current status of vaginal brachytherapy.
Small W Jr, Erickson B, Kwakwa F.
Division of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL.

PURPOSE: To survey the current postoperative recommendations for radiotherapy (RT) in patients with endometrial cancer, with an emphasis on vaginal brachytherapy (VBT). METHODS AND MATERIALS: In August 2003, a 32-item questionnaire was mailed to a random sample of 2396 members of the American Society for Therapeutic Radiology and Oncology and the American Brachytherapy Society. The sample excluded members-in-training, physicists, and non-U.S. members. A follow-up mailing was conducted in November 2003. Those who had not treated any patient in the previous year for endometrial carcinoma were instructed to indicate so at the beginning of the questionnaire and return it without responding to any other item. Responses were tabulated to determine the relative frequency distribution. RESULTS: Of the 2396 surveys sent out, 757 were returned, for a response rate of 31.6%. Of those who responded, 551 (72.8%) had performed postoperative irradiation for endometrial cancer and were included in this study. Of the 551 respondents, 99.8% had delivered external beam RT to some endometrial cancer patients. An increasing trend was found toward referrals for VBT; 91.5% of those who treated endometrial cancer performed VBT. The vaginal target most often irradiated was the upper vagina in 40.7%, upper 4-5 cm in 54.5%, and the entire vagina in 4.9%; 21.3% placed clips at the vaginal apex for applicator verification. The maximal dose to the bladder and rectum was recorded in 78.3% and 80.2% of patients, respectively. Of the respondents, 40% did not use low-dose-rate (LDR) VBT. The two most common LDR applicators were Delclos cylinders (29.7%) and Fletcher colpostats (29.3%). The mean boost dose delivered with LDR VBT when prescribed to the surface was 29.9 Gy and when prescribed to 0.5 cm was 23.8 Gy. When LDR therapy was used without external beam RT, the mean dose when prescribed to the surface was 56.8 Gy and when prescribed to 0.5 cm was 47.9 Gy. In 2002, 69.1% of respondents treated patients with high-dose-rate (HDR) VBT. Of the respondents, 90.6% used a single-channel vaginal cylinder, and 83.3% of cylinder users followed the curve of the cylinder to optimize dose, 67.9% adjusted the applicator position based on localization films, and 47% adjusted the applicator to be horizontal. The most common fractionation scheme when using HDR VBT as a boost was 5 Gy in three fractions prescribed to 0.5 cm (42.9%). The most common fractionation scheme used with HDR without external beam RT was 7 Gy in three fractions prescribed to 0.5 cm (41.8%). CONCLUSION: VBT is a common recommendation for postoperative adjuvant therapy for endometrial cancer. HDR appears to be the most popular approach, with a wide variety of dose fractionation schemes reported. Additional study is warranted to help define the ideal use of VBT.

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Eur J Obstet Gynecol Reprod Biol. 2005 Aug 8; [Epub ahead of print]
Laparoscopic treatment of endometrial cancer: Feasibility and results.
Volpi E, Ferrero A, Jacomuzzi ME, Carus AP, Fuso L, Martra F, Sismondi P.
Department of Gynecologic Oncology, University of Turin, Mauriziano Umberto I degrees Hospital, Turin and Institute for Cancer Research and Treatment Candiolo, Italy.

OBJECTIVE:: The aim of this study was to compare laparoscopic and abdominal approach in the treatment of endometrial cancer in our department. STUDY DESIGN:: From January 1999 to November 2002, 77 patients underwent surgery for stages I-III endometrial cancer. The first group of 36 patients had abdominal hysterectomy as well as salpingo-oophorectomy, with or without lymphadenectomy. The remaining 41 patients received laparoscopic assisted vaginal hysterectomy as well as salpingo-oophorectomy, with or without lymphadenectomy. In this retrospective study, we have compared the surgical results, the short- and long-term morbidity and the outcome of the two patient groups. RESULTS:: Body mass index (BMI) was significantly higher in the laparoscopic group (27.3 versus 24.6; p=0.009). The average time for surgery was significantly longer for the laparoscopic group (143.6min versus 109.7min; p=0.0001), but lymphadenectomy was performed in more patients (63.4% versus 25%; p=0.001). Postoperative hospital stay was significantly longer in patients undergoing the abdominal approach (4.59 days versus 3.18 days; p<0.0001). No blood transfusions were performed and the rates of complications were similar in the two groups. No differences were found in recurrence and survival rate. CONCLUSIONS:: In our experience, laparoscopic and abdominal surgery can achieve similar results in the treatment of endometrial cancer. In our series, even with the BMI and the number of lymphadenectomies being higher in the laparoscopic group, the rates of complications were similar in the two groups.

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Lancet. 2005 Aug 6-12;366(9484):491-505.
Endometrial cancer.
Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I.
Department of Obstetrics and Gynaecology, Division of Gynaecological Oncology, UZ Gasthuisberg, Katholieke Universiteit, Leuven, Belgium.

Each year, endometrial cancer develops in about 142,000 women worldwide, and an estimated 42,000 women die from this cancer. The typical age-incidence curve for endometrial cancer shows that most cases are diagnosed after the menopause, with the highest incidence around the seventh decade of life. The appearance of symptoms early in the course explains why most women with endometrial cancer have early-stage disease at presentation. For all stages taken together, the overall 5-year survival is around 80%. There is a substantial prognostic difference between the histological types of endometrial cancers. The most common lesions (type 1) are typically hormone sensitive and low stage and have an excellent prognosis, whereas tumours of type 2 are high grade with a tendency to recur, even in early stage. The cornerstone of treatment for endometrial cancer is surgery, which not only is important for staging purposes but also enables appropriate tailoring of adjuvant treatment modalities that benefit high-risk patients only. We review current concepts about epidemiology, pathology, pathogenesis, risk factors and prevention, diagnosis, staging, prognostic factors, treatment, and follow-up of endometrial cancer.

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Int J Radiat Oncol Biol Phys. 2005 Aug 1;62(5):1379-84.
Vaginal brachytherapy alone is sufficient adjuvant treatment of surgical stage I endometrial cancer.
Solhjem MC, Petersen IA, Haddock MG.
Division of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

PURPOSE: To determine the efficacy and complications of adjuvant vaginal high-dose-rate brachytherapy alone for patients with Stage I endometrial cancer in whom complete surgical staging had been performed. METHODS AND MATERIALS: Between April 1998 and March 2004, 100 patients with Stage I endometrial cancer underwent surgical staging (total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic +/- paraaortic nodal sampling) and postoperative vaginal high-dose-rate brachytherapy at our institution. The total dose was 2100 cGy in three fractions. RESULTS: With a median follow-up of 23 months (range 2-62), no pelvic or vaginal recurrences developed. All patients underwent pelvic dissection, and 42% underwent paraaortic nodal dissection. A median of 29.5 pelvic nodes (range 1-67) was removed (84% had >10 pelvic nodes removed). Most patients (73%) had endometrioid (or unspecified) adenocarcinoma, 16% had papillary serous carcinoma, and 11% had other histologic types. The International Federation of Gynecology and Obstetrics stage and grade was Stage IA, grade III in 5; Stage IB, grade I, II, or III in 6, 27, or 20, respectively; and Stage IC, grade I, II, or III in 13, 17, or 10, respectively. The Common Toxicity Criteria (version 2.0) complications were mild (Grade 1-2) and consisted primarily of vaginal mucosal changes, temporary urinary irritation, and temporary diarrhea. CONCLUSION: Adjuvant vaginal high-dose-rate brachytherapy alone may be a safe and effective alternative to pelvic external beam radiotherapy for surgical Stage I endometrial cancer.

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Curr Opin Obstet Gynecol. 2005 Aug;17(4):343-6.
Outcomes of laparoscopic treatment for endometrial cancer.
Magrina JF.
Department of Obstetrics and Gynecology, Mayo Clinic in Scottsdale, Scottsdale, Arizona, USA.

PURPOSE OF REVIEW: Laparoscopy has become the standard approach for the surgical management of a variety of benign gynecological conditions. Numerous studies have reported their findings on the laparoscopic approach for the treatment of patients with endometrial cancer. It is timely and relevant to provide a review of these findings. RECENT FINDINGS: Comparison analysis of recurrence and survival rates for patients treated by laparoscopy and laparotomy have found similar results. A similar or reduced cost is noted for the laparoscopic approach. Numerous patient advantages are indicated for the laparoscopic approach. This information is detailed in this review. SUMMARY: The open abdominal approach is an alternative to laparoscopy for the surgical treatment of patients with early endometrial cancer.

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Gynecol Oncol. 2005 Jun 24; [Epub ahead of print]
Laparoscopic-assisted vaginal hysterectomy versus abdominal hysterectomy in stages I and II endometrial cancer. Operating data, follow up and survival.
Zapico A, Fuentes P, Grassa A, Arnanz F, Otazua J, Cortes-Prieto J.
Department of Obstetrics and Gynaecology, "Principe de Asturias" Hospital, School of Medicine, Alcala University, Alcala de Henares, 28805 Madrid, Spain.

OBJECTIVE.: To assess the feasibility of laparoscopy in the treatment of early stage endometrial carcinoma and follow up outcomes compared to classic laparotomy. METHODS.: A retrospective review of 90 consecutive patients with endometrial cancer managed between January 1997 and December 2003. Two groups were defined whether they had been treated by laparoscopy (N = 38; LPS group) or by laparotomy (N = 37; LPM group). Nine patients treated by vaginal hysterectomy and 6 cases with stages III-IV were excluded from the study. RESULTS.: Both groups were comparable in mean age and mean BMI. Mean operating time was longer for LPS group, 164.91 +/- 5.60 (77-240) vs. 129.97 +/- 5.08 (60-180) min (P < 0.05). Intraoperative complications were seen in 7 patients (18.9%) from LPM and in 5 cases (13.2%) in the laparoscopic group. Two patients (5.2%) initially evaluated by laparoscopy were converted into laparotomy due to an increasing and uncontrollable hypercapnia. There were more post-operative complications in patients managed by laparotomy (14 cases; 38.8%), than by laparoscopy (7 cases; 18.4%) (P < 0.05). Blood transfusion was necessary in 4 patients (10.8%) in LPM group while none was required in LPS group (P < 0.01). Hospital readmission was only recorded in 3 patients treated by laparotomy (6.7%) (P < 0.05). Hospital stay was longer in LPM group 7.06 +/- 0.58 (4-21) vs. LPS 5.04 +/- 0.73 (2-17) days (P < 0.05). With a median follow up of 53.21 +/- 4.32 months for LPM (5-90) and 36.31 +/- 2.75 months for LPS (9-65) there was no significant difference in disease recurrence between the two groups. CONCLUSION.: Laparoscopic staging combined with vaginal hysterectomy appears to be a feasible alternative to classical surgical approach in patients with early stage I or II endometrial carcinoma.

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Gynecol Oncol. 2005 Jun;97(3):755-63.
Whole abdominal radiotherapy in the adjuvant treatment of patients with stage III and IV endometrial cancer: A gynecologic oncology group study.
Sutton G, Axelrod JH, Bundy BN, Roy T, Homesley HD, Malfetano JH, Mychalczak BR, King ME.
Division of Gynecologic Oncology, St. Vincent's Hospital and Health Services, 2001 W. 86th Street, Indianapolis, IN 46260, USA.

OBJECTIVE: To evaluate toxicity, survival, and recurrence-free interval in women with loco-regionally advanced endometrial carcinoma treated with postoperative whole abdominal radiation therapy. METHODS: Whole abdominal irradiation with pelvic plus or minus para-aortic boost was initiated within 8 weeks of total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic washings, and selective pelvic and para-aortic node sampling in eligible, consenting patients. RESULTS: Of 180 evaluable patients entered on the study with surgically staged III and IV endometrial carcinoma maximally debulked to less than 2 cm, 77 had typical endometrial adenocarcinoma and 103 had high-risk histology, either papillary serous or clear cell carcinoma. Patients with typical endometrial adenocarcinoma were significantly younger and had significantly fewer poorly differentiated cancers. Proportionally, there were twice as many non-Whites with high-risk histologies as non-Whites with typical endometrial adenocarcinoma. Forty-five percent of patients with typical endometrial adenocarcinomas had positive pelvic nodes compared to 51% of those with high-risk histologies. Both histologic groups had similar distribution for performance status, para-aortic node positivity, site and extent of disease, and International Federation of Gynecology and Obstetrics (FIGO) stage. The frequency of severe or life-threatening adverse effects among 174 patients evaluable for radiation toxicity included 12.6% with bone marrow depression, 15% GI, and 2.2% hepatic toxicity. The recurrence-free survival rates were 29% and 27% (at 3 years) for the typical endometrial adenocarcinoma and high-risk histologies, respectively. The survival rates were 31% and 35%, respectively. No patient with gross residual disease survived. CONCLUSION: Whole abdominal irradiation in maximally resected advanced endometrial carcinoma has tolerable toxicity, and it is suggested that the outcome may be improved by this adjunctive treatment in patients with completely resected disease.

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J Cancer Res Clin Oncol. 2005 Jun 16; [Epub ahead of print]
Carboplatin plus paclitaxel in the treatment of advanced or recurrent endometrial carcinoma.
Michener CM, Peterson G, Kulp B, Webster KD, Markman M.
Departments of Obstetrics/Gynecology and Hematology/Medical Oncology, The Cleveland Clinic Foundation, 9500, Euclid Avenue, Desk A81, Cleveland, OH, 44195, USA, michenc@ccf.org.

Purpose To evaluate the efficacy and safety of the combination of carboplatin plus paclitaxel in patients with advanced, metastatic and recurrent endometrial cancer. Methods Medical records were retrospectively reviewed to identify endometrial cancer patients treated in the Gynecologic Cancer Program of the Cleveland Clinic with carboplatin/paclitaxel who had both a histologic diagnosis of endometrial adenocarcinoma and either measurable (CT scan, physical examination) or evaluable (CA-125 criteria) disease. Results From 1994 to 2003, 22 individuals (median age 65 years) meeting the above noted criteria received a total of 23 courses of carboplatin (AUC 4-6)/paclitaxel (135-175 mg/m2) administered on a 21-day schedule (median six cycles/patient). The overall response rate was 87% (20/23). The most common toxicity was hematologic. Five patients required dose reductions due to excessive toxicity (three hematologic, one gastrointestinal, one fatigue). There were no treatment related deaths. With a median follow-up of 42 months, 13 patients have died of progressive cancer, while four currently have no evidence of disease at the time of last follow-up. Conclusions The combination of carboplatin plus paclitaxel demonstrates substantial biological activity in endometrial adenocarcinoma. The safety and efficacy of this regimen makes it an attractive option for first-line chemotherapy in patients with advanced or recurrent endometrial carcinoma.

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Int J Radiat Oncol Biol Phys. 2005 May 28; [Epub ahead of print]
Postoperative radiotherapy for stage 1 endometrial carcinoma: Long-term outcome of the randomized portec trial with
central pathology review.
Scholten AN, van Putten WL, Beerman H, Smit VT, Koper PC, Lybeert ML, Jobsen JJ, Warlam-Rodenhuis CC, De Winter KA, Lutgens LC, van Lent M, Creutzberg CL; PORTEC Study Group.
department of Radiation Oncology, Leiden University Medical Center, Leiden, Netherlands.

PURPOSE: In 2000, the results of the multicenter Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial were published. This trial included 714 Stage I endometrial carcinoma patients randomly assigned to postoperative pelvic radiotherapy (RT) or no further treatment, excluding those with Stage IC, Grade 3, or Stage IB, Grade 1 lesions. Radiotherapy significantly decreased the risk of locoregional recurrence (4% vs. 14%), without affecting overall survival. In this report the long-term outcome and results with central pathology review are presented. METHODS AND MATERIALS: The slides of 569 patients (80%) could be obtained for pathology review. Median follow-up for patients alive was 97 months. Analysis was done according to the intention-to-treat principle. The primary study endpoints were locoregional recurrence and death. RESULTS: Ten-year locoregional relapse rates were 5% (RT) and 14% (controls; p < 0.0001), and 10-year overall survival was 66% and 73%, respectively (p = 0.09). Endometrial cancer related death rates were 11% (RT) and 9% (controls; p = 0.47). Pathology review showed a substantial shift from Grade 2 to Grade 1, but no significant difference for Grade 3. When cases diagnosed at review as Grade 1 with superficial myometrial invasion were excluded from the analysis, the results remained essentially the same, with 10-year locoregional recurrence rates of 5% (RT) and 17% (controls; p < 0.0001). CONCLUSIONS: In view of the significant locoregional control benefit, radiotherapy remains indicated in Stage I endometrial carcinoma patients with high-risk features for locoregional relapse.

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Int J Radiat Oncol Biol Phys. 2005 May 1;62(1):111-7.
Intravaginal brachytherapy alone for intermediate-risk endometrial cancer.
Alektiar KM, Venkatraman E, Chi DS, Barakat RR.
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. alektiak@mskcc.org

PURPOSE: Despite the results of the Gynecologic Oncology Group trial No. 99 (GOG#99), some unanswered questions still remain about the role of adjuvant radiotherapy (RT) for intermediate-risk endometrial cancer. First, can intravaginal brachytherapy (IVRT) alone substitute for external beam RT but without added morbidity? Second, is the high-risk (HR) definition from GOG#99 a useful tool to predict pelvic recurrence specifically? The purpose of this study was to try to answer these questions in a group of patients with Stage IB-IIB endometrial carcinoma treated with high-dose-rate (HDR) IVRT alone. METHODS AND MATERIALS: Between November 1987 and December 2002, 382 patients with Stage IB-IIB endometrial carcinoma were treated with simple hysterectomy followed by HDR-IVRT alone at our institution. Comprehensive surgical staging (CSS), defined as pelvic washings and pelvic/paraaortic lymph node sampling, was performed in 20% of patients. The mean age was 60 years (range, 29-92 years). Lymphovascular invasion (LVI) was present in 14% of patients. The median HDR-IVRT dose was 21 Gy (range, 6-21 Gy), given in three fractions. Complications were assessed in terms of late Radiation Therapy Oncology Group (Grade 3 or worse) toxicity of the GI tract, genitourinary GU tract, and vagina. RESULTS: With a median follow-up of 48 months, the 5-year vaginal/pelvic control rate was 95% (95% confidence interval [CI], 93-98%). On multivariate analysis, a poor vaginal/pelvic control rate correlated with age > or =60 years old (relative risk [RR], 3, 95% CI, 1-12; p = 0.01), International Federation of Gynecology and Obstetrics (FIGO) Grade 3 (RR, 9, 95% CI, 2-35; p = 0.03), and LVI (RR, 4, 95% CI, 1-13; p = 0.051). The depth of myometrial invasion and CSS, however, were not significant. With regard to pelvic control specifically, the presence of GOG#99 HR features did not affect the pelvic control rate. The 5-year rate for HR patients was 96% (95% CI, 90-100%) vs. 96% (95% CI, 94-99%) for those without HR disease (p = 0.48). Even when the CSS effect was taken into account, the influence of HR features on pelvic control was still not significant (p = 0.51). In contrast, pelvic control was significantly influenced when patients were grouped according to CSS and stage/grade substages. For those with Stage IB Grade 3-IIB and no CSS, the 5-year pelvic control rate was 86% compared with 97% for those with Stage IB Grade 3-IIB and CSS, 97% for Stage IB, Grade 1-2 without CSS, and 100% for those with Stage IB, Grade 1-2 and CSS (p = 0.027). The 5-year disease-free survival rate was 93% (95% CI, 90-96%). On multivariate analysis, poor disease-free survival correlated with age > or =60 years (RR, 5; 95% CI, 1-18; p = 0.002), FIGO Grade 3 (RR 5, 95% CI 2-17; p = 0.013), and LVI (RR 3, 95% CI 1-8; p = 0.054). Unlike pelvic control, disease-free survival was significantly affected by GOG#99 HR features, with a 5-year rate of 87% (95% CI, 76-99%) vs. 94% (95% CI, 91-97%) for those without HR features (p = 0.027). The 5-year overall and disease-specific survival rate was 93% and 97%, respectively. The overall 5-year actuarial rate of Grade 3 or worse complications was 1% (95% CI, 0-2%). CONCLUSION: Tumor grade, depth of invasion, and the use of CSS were better predictors of pelvic control than the GOG#99 HR factors. IVRT alone seemed to provide adequate tumor control with very low morbidity. Therefore, it seems prudent to consider it for intermediate-risk patients because of its superior therapeutic ratio compared with that for surgery alone or pelvic RT. Additional follow-up, however, with a larger number of patients is needed, especially for those with LVI.

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Obstet Gynecol Surv. 2005 May;60(5):302-3.
Vaginal hysterectomy and abdominal hysterectomy for treatment of endometrial cancer in the elderly.
Susini T, Massi G, Amuni G, Carriero C, Marchionni M, Taddei G, Scarselli G.
Department of Gynecology, Perinatology and Human Reproduction, and the Department of Human Pathology and Oncology, University of Florence, Florence, Italy.

This study presents the results of a retrospective review of all women (n = 171) older than 70 years of age who underwent surgery for treatment of endocervical cancer between 1980 and 1999 at the University of Florence. Women who were obese, or who were otherwise considered poor surgical risks, had a vaginal hysterectomy, always with bilateral salpingo-oophorectomy and removal of a short vaginal cuff (1-2 cm). Healthy women, or those with a large uterus or coexistent adnexal mass, underwent abdominal hysterectomy and bilateral salpingo-oophorectomy. Pelvic lymphadenectomy was done at the surgeon's discretion. Patients with poorly differentiated disease or deep myometrial invasion received postoperative adjuvant whole-pelvis irradiation. Follow up was at 3- month intervals for 2 years, every 6 months until 5 years, and once a year thereafter. The median follow-up period was 67 months. Patients who died of other causes were considered to have survived until the time of their death.The mean age of patients was 74 years. Vaginal hysterectomy with bilateral salpingo-oophorectomy was performed in 128 women (75%), 11 of whom also had extraperitoneal pelvic lymphadenectomy. Most of these patients (85%) had spinal anesthesia. Forty-three patients (25%) had abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy in 27 patients.There was no significant difference in the 2 groups in rates of disease recurrence or death from disease. Seventeen of 128 patients (13.3%) in the vaginal hysterectomy group and 8 of 43 patients (18.6%) in the abdominal group died of disease. Only 1 patient, who had undergone a vaginal procedure, of 26 with disease recurrence did not die of disease. There was no significant difference between the groups in the pattern of disease recurrence. Recurrence was local in 44.4% and 50% of the vaginal and abdominal hysterectomy groups, respectively. Distant metastases were seen in 33.3% and 25%, and distant and local in 22.2% and 25%, respectively.No significant differences in survival were seen. Overall 5-year and 10-year survival rates were 84% and 80%, respectively, in the vaginal group and 78% each in the hysterectomy group.The 38 patients who underwent pelvic lymphadenectomy, only 3 of whom (7.9%) had positive nodes, had 5- and 10-year survival rates (82% each) that were similar to overall survival rates.Five percent of the women in the vaginal hysterectomy group and 7% of those in the abdominal group had serious complications associated with surgery (cerebral vascular accident, wound dehiscence, ureteral stricture, bowel obstruction, or myocardial failure). One patient in the abdominal group died from myocardial infarction.Fewer patients who had a vaginal procedure had general anesthesia (15% vs. 100% in the abdominal group; P <.001), median operative time was shorter (46 minutes vs. 115 minutes; P = .01), median blood loss was less (210 mL vs. 400 mL; P = .01), and hospital stays were shorter (median 6 days vs. 10 days; P = .05) compared with the abdominal hysterectomy group. Requirements for blood transfusion were not significantly different.

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Am J Clin Oncol. 2005 Apr;28(2):157-64.
The effects of age and comorbidity on treatment and outcomes in women with endometrial cancer.
Truong PT, Kader HA, Lacy B, Lesperance M, MacNeil MV, Berthelet E, McMurtrie E, Alexander S.
Radiation Therapy Program, British Columbia Cancer Agency, Vancouver Island Centre, Victoria, British Columbia, Canada. ptruong@bccancer.bc.ca

BACKGROUND: Although the incidence of endometrial cancer increases with age, the effect of patient age on treatment selection and outcomes is unclear. In addition, although aging is associated with increased prevalence of comorbid conditions, the extent to which comorbidities influence endometrial cancer management is not well documented. METHODS: This population-based analysis evaluates the effect of age and comorbidity on endometrial cancer treatment and outcome in a cohort of 401 patients referred to the Vancouver Island Centre, British Columbia Cancer Agency from 1989 to 1996. Treatment and 5-year actuarial overall survival (OS) and disease-free survival (DFS) were compared by age at diagnosis (<65, 65-74, and > or =75 years) and comorbidity index (Charlson score 0-1 and > or =2). RESULTS: Median follow-up time was 7.8 years. In this cohort, 148 (37%), 152 (38%), and 101 (25%) were aged <65, 65-74, and > or =75 years, respectively. Charlson comorbidity scores > or =2 were found in 18% of patients. Distributions of disease stage, tumor characteristics, and surgical therapy were similar across age and comorbidity subgroups. Standard surgery in this cohort comprised hysterectomy without routine lymphadenectomy. In stage Ic disease, the use of postoperative RT declined with advanced age (96%, 97%, and 74% in patients aged <65, 65-74, and > or =75 years, respectively, P = 0.05) and with increased comorbidities (91% and 79% in patients with Charlson score 0-1 and > or =2, respectively, P = 0.07). Among stage Ic patients aged > or =75 years, pelvic/vaginal relapse occurred in 2 of 6 patients treated with hysterectomy alone compared with 0 of 20 patients treated with postoperative radiotherapy (P = 0.006). On multivariable Cox modeling, age at diagnosis, performance status, stage, grade, lymphovascular invasion, surgery, and radiotherapy use, but not Charlson comorbidity score, were significant predictors for overall survival. CONCLUSIONS: Although surgical therapy for endometrial cancer was not influenced by age or comorbidities, reduced use of postoperative radiotherapy in stage Ic disease was observed among women with advanced age and high comorbidity index. The associated pelvic/vaginal relapse rates were higher in elderly patients not treated with radiotherapy. Chronologic age alone should not preclude patients from consideration of optimal local therapy.

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J Br Menopause Soc. 2005 Mar;11(1):18-22.
Advances in the treatment of endometrial cancer.
Oehler MK, Fung A, Jobling TW.
Department of Gynaecological Oncology, Monash Medical Centre, Melbourne, Australia.

Endometrial cancer (EC) most commonly affects postmenopausal women. It is curable if treated early, but tumours with adverse histopathological features or at an advanced stage are associated with a high mortality rate. These cancers require a complex therapeutic approach, consisting of surgery, radiotherapy, chemotherapy and/or hormonal therapy. As one of the leading causes of death from malignancy in women, EC has been subject to intense clinical investigation. This article examines recent advances in the surgical treatment of the disease, such as sentinel lymph node sampling and total laparo scopic hysterectomy, as well as topics such as conservative treatment of EC for fertility preservation. Furthermore, new agents for EC treatment are presented, for example inhibitors of the mTOR pathway and the angiogenesisinhibitor VEGF-trap.

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J Natl Cancer Inst Monogr. 2005;(34):43-7.
Fertility-sparing surgery for malignancies in women.
Gershenson DM.
Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center-Unit 1362, P.O. Box 301439, Houston, TX 77230-1439. dgershen@mdanderson.org.

Never before have women with newly diagnosed gynecologic malignancies had more options for preservation of fertility. Girls or women of childbearing age with several ovarian cancer subtypes have a high probability of unilateral ovarian involvement, and, thus, may be candidates for fertility-sparing surgery with preservation of a contralateral normal ovary and uterus. These subtypes include ovarian tumors of low malignant potential, malignant ovarian germ cell tumors, and ovarian sex cord-stromal tumors. For women with invasive epithelial ovarian cancer who have early-stage disease, fertility-sparing surgery may be an option. In some cases, fertility-sparing surgery may be followed by postoperative chemotherapy. For women with invasive cervical cancer, fertility-sparing surgery may be possible. Options include conization alone for stage IA(1) or IA(2) disease, radical trachelectomy with stage IA(2) or IB disease, or ovarian transposition for women undergoing chemoradiation. Non-operative options, such as hormonal therapy, may be considered for women with early-stage, low-grade endometrial cancer. For all women of childbearing age with gynecologic malignancies, in vitro fertilization techniques or cryopreservation of ovarian tissue may be an option prior to definitive treatment.

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Gynecol Oncol. 2005 Mar;96(3):610-5.
Paclitaxel and carboplatin with amifostine in advanced, recurrent, or refractory endometrial adenocarcinoma: a phase II study of the Southwest Oncology Group.
Scudder SA, Liu PY, Wilczynski SP, Smith HO, Jiang C, Hallum AV 3rd, Smith GB, Hannigan EV, Markman M, Alberts DS; Southwest Oncology Group.
University of California Davis Medical Center, Sacramento, CA 95817, USA.

OBJECTIVES: To evaluate the response rate and progression free and overall survival of patients with advanced endometrial cancer treated with paclitaxel, carboplatin and amifostine. To evaluate the toxicity of amifostine when used in combination with carboplatin and paclitaxel. METHODS: Forty-seven eligible patients (median age: 66; range 45-82) with bidimensionally measurable advanced, recurrent, or refractory endometrial cancer were treated with carboplatin (AUC = 6), paclitaxel (175 mg/M2) and amifostine (740 mg/M2) every 4 weeks for 6 cycles or until disease progression or unacceptable toxicity. RESULTS: There were 4 CRs (8%) (2 confirmed, 2 unconfirmed) and 15 PRs (32%) (9 confirmed, 6 unconfirmed) for a total response rate of 40% (95% confidence interval [CI], 26% to 56%). The median progression-free survival (PFS) was 7 months (95% CI, 6-9 months) and a 6-month PFS rate of 64% (95% CI, 50% to 78%). The median overall survival was 14 months (95% CI, 12 to 17 months). Toxicity was tolerable. While 79% of patients developed Grade 3/4 neutropenia (30% Grade 3, 49% Grade 4), there were no episodes of Grade 4 febrile neutropenia and one episode of infection with grades 3-4 neutropenia. CONCLUSION: The combination of paclitaxel and carboplatin with amifostine was well reasonably tolerated in this cohort. The regimen demonstrated significant activity in endometrial cancer, comparable to other multi-agent chemotherapy programs in terms of response rate and survival, and with a favorable toxicity profile.

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J Clin Oncol. 2005 Feb 28; [Epub ahead of print]
Retrospective Analysis of Selective Lymphadenectomy in Apparent Early-Stage Endometrial Cancer.
Cragun JM, Havrilesky LJ, Calingaert B, Synan I, Secord AA, Soper JT, Clarke-Pearson DL, Berchuck A.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cancer Prevention, Detection, and Control Research Program, Duke University Medical Center, Durham, NC.

PURPOSE: Selective lymphadenectomy is widely accepted in the management of endometrial cancer. Purported benefits are individualization of adjuvant therapy based on extent of disease and resection of occult metastases. Our goal was to assess effects of the extent of selective lymphadenectomy on outcomes in women with apparent stage I endometrial cancer at laparotomy. PATIENTS AND METHODS: Patients with endometrial cancer who received primary surgical treatment between 1973 and 2002 were identified through an institutional tumor registry. Inclusion criteria were clinical stage I/IIA disease and procedure including hysterectomy and selective lymphadenectomy (pelvic or pelvic + aortic). Exclusion criteria included presurgical radiation, grossly positive lymph nodes, or extrauterine metastases at laparotomy. Recurrence and survival were analyzed using Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: Among 509 patients, the median number of lymph nodes removed was 15 (median pelvic, 11; median aortic, three). Pelvic and aortic node metastases were found in 24 (5%) of 509 patients and 11 (3%) of 373 patients, respectively. Patients with poorly differentiated cancers having more than 11 pelvic nodes removed had improved overall survival (hazard ratio [HR], 0.25; P < .0001) and progression-free survival (HR, 0.26; P < .0001) compared with patients having poorly differentiated cancers with 11 or fewer nodes removed. Number of nodes removed was not predictive of survival among patients with cancers of grade 1 to 2. Performance of aortic selective lymphadenectomy was not associated with survival. Three (27%) of 11 patients with microscopic aortic nodal metastasis are alive without recurrence. CONCLUSION: These data add to the literature documenting the possible therapeutic benefit of selective lymphadenectomy in management of patients with apparent early-stage endometrial cancer.

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Curr Opin Obstet Gynecol. 2005 Feb;17(1):77-82.
Update on the role of laparoscopy in the treatment of gynaecological malignancy.
Rouzier R, Pomel C.
Department of Gynaecologic Oncology Surgery, Gustave Roussy Institute, Villejuif, France.

PURPOSE OF REVIEW: To update the available information and to report on how the recent literature has better defined the role of laparoscopy for the management of gynaecological malignancies. RECENT FINDINGS: When compared with laparotomy, laparoscopy provides a similar outcome with a shorter hospitalization, an earlier recovery, and an improved quality of life for the treatment of endometrial cancer. Recent reports in the literature on cervical cancer management now include follow-up data; however, only one study included a control group. These studies confirm the feasibility of radical hysterectomy by laparoscopy. The 2-year disease-free and overall survivals were similar in patients treated by laparoscopy and laparotomy in the study that included a control group. The role of laparoscopy for early ovarian cancer is limited by the absence of available data on upstaging. For advanced ovarian carcinoma, new applications of laparoscopy, such as laparoscopic fluorescence detection after intraperitoneal application of 5-aminolevulinic acid, have been reported but the real utility needs further investigation. One of the challenges for the development of laparoscopic surgery is the difficulty for physicians of acquiring advanced laparoscopic surgical skills. SUMMARY: The feasibility and safety of laparoscopy for most of the surgical procedures that are used for gynaecological malignancies are now established from cohort or case-control analytical studies. The absence of large phase III studies needs to be balanced by the relatively low incidence of cervical and ovarian cancer.

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Gynecol Oncol. 2005 Feb;96(2):362-7.
Vaginal hysterectomy and abdominal hysterectomy for treatment of endometrial cancer in the elderly.
Susini T, Massi G, Amunni G, Carriero C, Marchionni M, Taddei G, Scarselli G.
Department of Gynecology, Perinatology and Human Reproduction, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. tommaso.susini@unifi.it

OBJECTIVE: The purpose of this study was to analyze the outcome of vaginal and abdominal hysterectomy for treatment of endometrial cancer in elderly patients. METHODS: In a retrospective series of 171 patients with age > or =70 years and at stages I-III, we evaluated operative and hospitalization data, as well as morbidity, mortality, and long-term survival associated with vaginal and abdominal hysterectomy. A total of 128 patients were operated on with vaginal hysterectomy and 43 cases underwent abdominal hysterectomy. RESULTS: Medically compromised patients were significantly more frequent in the vaginal surgery group (P = 0.01). Overall, the 10-year disease-specific survival rates after vaginal and abdominal hysterectomy were 80% and 78%, respectively (P = n.s.). Limiting the analysis to stage I (130 patients), 10-year disease-specific survival was 83% in 95 women operated on by the vaginal route and 84% in 35 patients operated by the abdominal approach (P = n.s.). Patients in the vaginal surgery group had a significantly shorter operative time (P = 0.01), less blood loss (P < 0.05), and were discharged earlier (P < 0.05). Severe complications occurred in 5.4% of the vaginal and in 7.0% of the abdominal procedures. Perioperative mortality was zero after vaginal hysterectomy and 2.3% after abdominal hysterectomy, respectively. CONCLUSIONS: Vaginal hysterectomy showed a high cure rate, shorter operative time, less blood loss, reduced morbidity, and no mortality and therefore may be considered the elective approach for treatment of elderly patients with endometrial cancer.

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Semin Oncol. 2004 Dec;31(6 Suppl 14):17-24.
Recent updates in the clinical use of platinum compounds for the treatment of gynecologic cancers.
Muggia FM.
New York University Cancer Institute, New York University School of Medicine, New York, NY 10016, USA. muggif01@gcrc.med.nyu.edu <muggif01@gcrc.med.nyu.edu>

Platinum compounds have long played a role in the treatment of gynecologic cancers. Single-agent cisplatin and carboplatin have shown activity in endometrial cancer, and more recent studies have begun to investigate a variety of new platinum-based combinations. In cervical cancer, chemotherapy is used primarily to treat advanced or recurrent disease. Agents with proven single-agent activity in this setting include cisplatin, ifosfamide, and doxorubicin, and a number of cisplatin-based combination therapies are under clinical investigation. A variety of cisplatin-based combinations have also been used in ovarian cancer chemotherapy, with more recent studies investigating the substitution of carboplatin or oxaliplatin for cisplatin and the addition of paclitaxel. This review will examine recent clinical data on the use of platinum-based chemotherapies for the treatment of these gynecologic cancers.

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Zentralbl Gynakol. 2004 Oct;126(5):306-11.
[Treatment strategies for endometrial cancer.]
[Article in German]
Deppe G, Baumann P.
Division of Gynecologic Oncology, Wayne State University/Detroit Medical Center.

This paper focuses on the controversies surrounding management of endometrial cancer, the most common carcinoma of the female genital tract. We discuss current management strategies, especially the importance of surgical staging and briefly describe ongoing prospective randomized trials. Actual treatment suggestions are attached as tables. Adenocarcinomas represent the majority of endometrial cancers. In contrast, papillary-serous and clear cell carcinomas comprise 1-10 % of endometrial cancers. While adenocarcinomas may well be treated by surgery and radiation therapy, identifying appropriate treatment modalities for patients with papillary-serous and clear cell carcinoma and poor prognosis is of critical importance. Data on radiation therapy or chemotherapy, to date, are of limited value secondary to small sample sizes and the heterogeneous treatment modalities that many times were applied. Individualized treatment strategies have to take into account accompanying co-morbidities, more importantly, though, whether the patient underwent surgical staging. Co-operative, prospective randomized trials across borders are needed more than ever to answer remaining questions.

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Gynecol Oncol. 2004 Oct;95(1):235-41.
Weekly topotecan for recurrent endometrial cancer: a case series and review of the literature.
Traina TA, Sabbatini P, Aghajanian C, Dupont J.
Developmental Chemotherapy Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

OBJECTIVE.: Topotecan, a topoisomerase 1 inhibitor, has demonstrated antitumor activity in ovarian and endometrial cancers when administered daily for 5 days every 3 weeks. Recently, topotecan has been studied on a weekly dosing schedule for the treatment of ovarian cancer and found to have efficacy with reduced toxicity. The aim of this study is to review the Memorial Sloan-Kettering Cancer Center (MSKCC) experience with weekly topotecan dosing in women with recurrent endometrial cancer. We have included a review of the literature of weekly topotecan in the treatment of patients with gynecologic cancer. METHODS.: After Institutional Review Board (IRB) approval, we identified all women with recurrent endometrial cancer treated with topotecan at MSKCC from May 1996 to February 2004. Patients treated on a weekly schedule were assessed for toxicity and response. A review of the literature pertaining to weekly topotecan in the treatment of endometrial cancer was also performed. RESULTS.: Eleven patients were treated with weekly topotecan during the study period, with doses ranging from 2.5-4.0 mg/m(2) on a 2- or 3-week schedule with 1 week off. The median age of the patients was 60 years old (range, 47-76 years), and the median Karnofsky performance status was 80%. Six of the 11 patients were previously treated with more than three chemotherapy regimens and eight had received prior pelvic radiation. Ninety-seven percent of treatment doses were delivered as scheduled, and only two patients required dose reductions. One patient achieved a prolonged partial response for 54 weeks, and two patients had stabilization of disease for 15 weeks each. CONCLUSIONS.: Weekly topotecan has antitumor activity and is well tolerated in patients with recurrent endometrial cancer, including those patients with multiple prior treatments. Topotecan on a weekly bolus schedule should be evaluated in prospective trials to better establish its role in the treatment of recurrent endometrial cancer.

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Gynecol Oncol. 2004 Oct;95(1):133-8.
Hormonal therapy for the management of grade 1 endometrial adenocarcinoma: a literature review.
Ramirez PT, Frumovitz M, Bodurka DC, Sun CC, Levenback C.
Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, United States.

OBJECTIVE: We reviewed reported cases of grade 1 endometrial adenocarcinoma that were conservatively managed with hormonal therapy in an effort to identify the most effective treatment regimen. METHODS: We searched MEDLINE and other databases for English-language articles describing patients with grade 1 endometrial adenocarcinoma who were treated with hormonal therapy. The search included articles published between January 1966 and December 2003. The following key words were used: endometrial cancer, uterine cancer, adenocarcinoma, hormones, progesterone, medroxyprogesterone acetate, megestrol acetate, conservative therapy, fertility, and female. A total of 79 articles were found. Studies were excluded for the following reasons: advanced stage, metastatic or recurrent disease, progestin use after radiation, chemotherapy, or surgery, concurrent with radiation therapy or chemotherapy, administration of progestin other than orally or intramuscularly, tumor confined to a polyp, grade 2 or 3 disease, undocumented grade, nonendometrioid histology, progestin use in conjunction with ovarian wedge resection or other hormones, and hyperplasia. Our study ultimately included 81 patients in 27 articles. RESULTS: Sixty-two patients (76%) responded to treatment. The median time to response was 12 weeks (range, 4-60 weeks). Fifteen patients (24%) who initially responded to treatment recurred. The median time to recurrence was 19 months (range, 6-44 months). Ten (67%) of the patients with recurrence ultimately underwent total abdominal hysterectomy. Residual endometrial carcinoma was found in six patients (60%). Nineteen patients never responded. Twenty patients were able to become pregnant at least once after completing treatment. The median follow-up was 36 weeks (range, 0 weeks-30 years). No patients died of their disease. CONCLUSION: The majority of patients reported with well-differentiated endometrial adenocarcinoma who undergo conservative treatment with a progestational agent respond to treatment. When an initial response is not achieved or when disease recurs, carcinoma extending beyond the uterus is rare.

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Gynecol Oncol. 2004 Oct;95(1):95-100.
Feasibility study of concurrent weekly cisplatin and whole abdominopelvic irradiation followed by doxorubicin/cisplatin chemotherapy for advanced stage endometrial carcinoma: a Gynecologic Oncology Group trial.
Soper JT, Reisinger SA, Ashbury R, Jones E, Clarke-Pearson DL.
Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC 27710, United States.

PURPOSE: A prospective Phase I study to determine toxicity of concurrent weekly intravenous cisplatin/whole abdominopelvic radiation therapy followed by four cycles of intravenous doxorubicin/cisplatin chemotherapy. MATERIALS AND METHODS: Ten patients with advanced endometrial cancer confined to the abdominal cavity and/or paraaortic lymph nodes with small residual disease were treated postoperatively with 3000 cGy whole abdominopelvic irradiation combined with 1500 cGy boost to the pelvis or pelvic and aortic fields. Cisplatin 15 mg/m(2) was given every week during irradiation. After completing radiotherapy, patients were to receive doxorubicin 50 mg/m(2) and cisplatin 50 mg/m(2) every 3 weeks for four cycles. Graduated dose reduction and acceleration of the doxorubicin dose were specified depending upon hematologic toxicity. Toxicities were monitored with weekly laboratory studies during treatment and frequent examinations. RESULTS: Five patients with Stage IIIC (paraaortic node involvement) and five with Stage IVB disease were treated on this study. Acute toxicity during chemoirradiation included one patient with grade 4 neutropenia and one patient with persistent grade 1 thrombocytopenia. Seven patients received chemotherapy after completing radiation therapy, two progressed before chemotherapy, and one had thrombocytopenia. Toxicity during chemotherapy included grade 4 neutropenia in all patients with four having five episodes of febrile neutropenia. Despite doxorubicin dose reductions for hematologic toxicity, three patients exhibited grade 4 neutropenia after both the second and third cycles. One patient developed a small bowel obstruction from radiation therapy that required surgery. There were no treatment-related deaths. Overall median survival was 14 months, with only one long-term survivor free of disease at 58 months. CONCLUSIONS: Without cytokine support, whole abdominopelvic irradiation and concurrent weekly cisplatin followed by doxorubicin/cisplatin chemotherapy without cytokine support has prohibitive hematologic toxicity.

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Int J Clin Oncol. 2004 Aug;9(4):317-21.
Postoperative adjuvant chemotherapy with cisplatin, cyclophosphamide, and anthracycline (doxorubicin, epirubicin, pirarubicin) for endometrial cancer.
Yahata H, Hirakawa T, Fujita T, Ariyoshi K, Sonoda K, Amada S, Kobayashi H, Nakano H.
Department of Obstetrics and Gynecology, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan.

BACKGROUND: Doxorubicin and cisplatin are the most commonly used chemotherapeutic agents in the treatment of endometrial cancer, but their clinical efficacy is still controversial. The aim of this study was to retrospectively assess the efficacy and toxicity of combination chemotherapy using cisplatin, cyclophosphamide, and anthracy-clines in patients with stage III/IV adenocarcinoma of the endometrium. METHODS: Forty patients with advanced endometrial cancer received postoperative adjuvant combination chemotherapy, using cisplatin (50 or 70 mg/m2), cyclophosphamide (500 mg/m2), and one of three anthracyclines (10 patients with doxorubicin [50 mg/m2], 18 with epirubicin [50 mg/m2], and 12 with pirarubicin [40 mg/m2]), from 1987 to 1999. All patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, with pelvic lymph node dissection in 36 patients and paraaortic lymph node biopsy in 38 patients. Patients were considered eligible if they had adnexal metastasis, paraaortic lymph node metastasis, positive peritoneal cytology, or distant metastasis. The patients were divided into two groups: patients with no measurable lesion (group 1; n = 27), and those with residual measurable lesion (group 2; n = 13) after surgery. The response rate and progression-free survival rate were evaluated in group 2. RESULTS: In group 1, 7 patients (26%) had recurrence, and all of them died of the disease. No patients in stage IIIa (n = 10), however, had recurrence. In group 2, 6 of the 13 (46%) showed response to chemotherapy (complete response [CR], 31%; partial response [PR], 15%). Toxicity was moderate: 10 patients had grade 4 neutropenia; and dose reductions were mandated in 12 patients. CONCLUSION: In group 1, the survival of patients receiving chemotherapy was considered favorable, but patients with recurrent lesions had poor prognosis. On the other hand, in group 2, the efficacy of the chemotherapy was almost equal to that reported in the literature; however, this regimen did not contribute to an improvement in the survival rate. In conclusion, a new effective regimen of postoperative adjuvant therapy is highly desirable in patients with measurable residual lesions.

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Gynecol Oncol. 2004 Aug;94(2):383-6.
High-dose rate brachytherapy for Stage I/II papillary serous or clear cell endometrial cancer.
DuBeshter B, Estler K, Altobelli K, McDonald S, Glantz C, Angel C.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wilmot Cancer Center, University of Rochester School of Medicine, 125 Lattimore Road, Rochester, NY 14620, USA. Brent_DuBeshter@urmc.rochester.edu

OBJECTIVE: To determine the efficacy of high-dose rate brachytherapy as adjuvant treatment for Stage I/II papillary serous or clear cell endometrial cancer. METHODS: A retrospective study of all patients with Stage I/II papillary serous or clear cell endometrial cancer treated with high-dose rate brachytherapy between 1995 and 2001 was performed. Following surgical staging, which included hysterectomy with pelvic and aortic lymphadenectomy, all patients without extrauterine disease were treated with high-dose rate brachytherapy and followed for recurrence. The locations of recurrences were noted and were classified as local or distant. RESULTS: Three (13%) recurrences occurred among 24 patients with Stage I/II papillary serous or clear cell carcinoma. The risk of recurrence was similar for papillary serous and clear cell cancer (12% vs. 12%). Local control was achieved in 96%. The risk of recurrence for those with no myometrial invasion, less than 1/2, or more than 1/2 myometrial invasion was 0%, 10%, and 50%, respectively (P < 0.04). Two of the three recurrences were distant and all patients with recurrence died despite additional treatment. CONCLUSIONS: High-dose rate brachytherapy (HDR) as the sole adjuvant treatment of Stage I/II papillary serous or clear cell carcinoma is associated with a 13% risk of recurrence. Although local control with HDR is excellent, the risk of distant recurrence is increased with deep myometrial invasion. High-dose rate brachytherapy is adequate for Stage IA cases, but more aggressive treatment combining chemotherapy with HDR should be evaluated for more advanced Stage I/II cases.

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Gynecol Oncol. 2004 Aug;94(2):333-9.
Adjuvant chemotherapy as treatment of high-risk stage I and II endometrial cancer.
Aoki Y, Watanabe M, Amikura T, Obata H, Sekine M, Yahata T, Fujita K, Tanaka K.
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata 951-8510, Japan. yoichi@med.niigata-u.ac.jp

OBJECTIVE: This study was performed to define the subgroups of patients who benefit from postoperative adjuvant chemotherapy in stage I and II endometrial carcinoma. METHODS: A retrospective review of 170 International Federation of Gynecology and Obstetrics (FIGO) stage I and II endometrial carcinoma patients treated between 1988 and 2000 at Niigata University Hospital was performed. All patients underwent surgery, of which 41 patients underwent adjuvant chemotherapy, consisting of intravenous cisplatin, doxorubicin, and cyclophosphamide. Multivariate analysis was performed for the prognostic factors and actuarial techniques were used for the survival and recurrence rates. RESULTS: The patients were divided into low-risk and high-risk groups based on the number of prognostic factors (tumor grade G3, outer half myometrial invasion, lymph-vascular space involvement (LVSI), and cervical invasion). The 5-year disease-free survival and the 5-year overall survival for the low-risk group were 97.4%, and 100%, respectively, which were significantly better than 77.4% and 88.1% for the high-risk group (P < 0.0001, P < 0.0001), respectively. Among high-risk group patients, the 5-year disease-free survival and the 5-year overall survival were 88.5% and 95.2% in 26 patients treated with adjuvant chemotherapy, and 50.0% and 62.5% in eight cases who underwent only surgery (P = 0.0150, P = 0.0226). Disease recurrence occurred in 7 (20.6%) of 34 high-risk group patients. Four of seven recurrences occurred in patients who did not receive postoperative chemotherapy, in which all four were distant failure. In the remaining three patients who were in the CAP group, two had vaginal wall recurrence and only one had pulmonary recurrence. Three recurrences were also observed in the 133 low-risk group patients. Only isolated vaginal wall recurrence occurred in three patients without adjuvant chemotherapy after the initial surgery. CONCLUSIONS: There is possibility that postoperative adjuvant CAP may be omitted in surgical stage I or II endometrial cancer patients with 0 or 1 prognostic factor. The high-risk group of patients should be treated with postoperative adjuvant CAP to decrease distant failure and improve prognosis.

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Ann Oncol. 2004 Aug;15(8):1173-8.
Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study.
Fleming GF, Filiaci VL, Bentley RC, Herzog T, Sorosky J, Vaccarello L, Gallion H.
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA. gfleming@medicine.bsd.uchicago.edu

BACKGROUND: This study was performed to determine whether 24-h paclitaxel plus doxorubicin and filgrastim was superior to cisplatin plus doxorubicin in patients with endometrial cancer with respect to response, progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: Eligible chemotherapy-na??ve patients were randomly assigned to doxorubicin 60 mg/m2 intravenously (i.v.) followed by cisplatin 50 mg/m2 i.v. (arm 1, n=157) or doxorubicin 50 mg/m2 i.v. followed 4 h later by paclitaxel 150 mg/m2 i.v. over 24 h plus filgrastim 5 microg/kg on days 3-12 (arm 2, n=160). Starting doses were reduced for prior pelvic radiotherapy and age > 65 years. Both regimens were to be repeated every 3 weeks for a maximum of seven cycles. RESULTS: There was no significant difference in response rate (40% versus 43%), PFS (median 7.2 versus 6 months) or OS (median 12.6 versus 13.6 months) for arm 1 and arm 2, respectively. Toxicities were primarily hematological, with 54% (arm 1) and 50% (arm 2) of patients experiencing grade 4 granulocytopenia. Gastrointestinal toxicities were similar in both arms. CONCLUSIONS: Doxorubicin and 24-h paclitaxel plus filgrastim was not superior to doxorubicin and cisplatin in terms of response, PFS or survival in advanced endometrial cancer. Copyright 2004 European Society for Medical Oncology

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Expert Rev Anticancer Ther. 2004 Aug;4(4):679-89.
Current treatment options for endometrial cancer.
Santin AD, Bellone S, O'Brien TJ, Pecorelli S, Cannon MJ, Roman JJ.
University of Arkansas for Medical Sciences, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, 4301 West Markham Street, Slot 518, Little Rock, AR 72205, USA. santinalessandrod@uams.edu

In North America, endometrial cancer is the most prevalent cancer of the female genital tract. On the basis of clinical and histologic variables, two main types of endometrial cancer have been described: Type I tumors, which are usually well differentiated and endometrioid in histology and account for the majority of cases; and Type II, which are poorly differentiated tumors, often with serous papillary or clear cell histology. Due to the early declaration of the disease by vaginal bleeding, approximately 80% of endometrial cancers are diagnosed at an early stage. Total abdominal hysterectomy and bilateral salpingo-oophorectomy with or without lymph node dissection remains the cornerstone of treatment. Tumor stage, histologic grade and depth of myometrial invasion are the most important prognostic factors. If myometrial invasion to 50% or more of the myometrial width and/or grade 2 or 3 histology is present, pelvic radiotherapy is indicated to reduce the risk of pelvic recurrence. Postoperative radiation therapy may improve local control but does not affect survival for Stage I endometrial cancer patients. Systemic chemotherapy is typically reserved for women with disseminated primary disease or extrapelvic recurrence. Although the combination of cisplatin plus doxorubicin is commonly used, carboplatin plus paclitaxel represents an efficacious, low-toxicity regimen for managing advanced or recurrent endometrial cancer. Recently, a significant percentage of Type II uterine tumors have been found to overexpress the epidermal growth factor Type II receptor. Anti-HER-2/neu-targeted therapy might be a novel and attractive therapeutic strategy in patients harboring this biologically aggressive variant of endometrial cancer.

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Obstet Gynecol Surv. 2004 Jul;59(7):516-518.
A Phase III Trial of Surgery With or Without Adjunctive External Pelvic Radiation Therapy in Intermediate-Risk Endometrial Adenocarcinoma: A Gynecologic Oncology Group Study.
Keys HM, Roberts JA, Brunetto VL, Zaino RJ, Spirtos NM, Bloss JD, Pearlman A, Maiman MA, Bell JG.
Department of Radiation Oncology, Albany Medical College, Albany, New York; Stanford University School of Medicine, Stanford, California; the Gynecologic Oncology Group, Roswell Park Cancer Institute, Buffalo, New York; the Department of Pathology, The Milton S. Hershey Medical Center of Pennsylvania State University, Hershey, Pennsylvania; the Women's Cancer Center of Northern California, Palo Alto, California; Gynecologic Oncology, Ellis Fischel Cancer Center, the University of Missouri, Columbia, Missouri; the Radiation Oncology Department, Wake Forest University School of Medicine, Winston-Salem, North Carolina; Obstetrics and Gynecology, State University of New York Health Science Center at Brooklyn, Brooklyn, New York; and Gynecologic Oncology, OB-GYN, Riverside Hospital, Ohio State University, Columbus, Ohio.

Between June 1987 and July 1995, 448 women with endometrial cancer were enrolled in a prospective, randomized trial comparing the use of postoperative radiation versus no postoperative treatment. Participants had stage IB, IC, II, or IIB endometrial adenocarcinoma with an intermediate risk of recurrence (that is, tumor with any degree of myometrial invasion, adenocarcinoma of any grade, and no evidence of lymph node involvement). In addition, an analysis was performed of 2 subgroups. High-risk patients had all of these risk factors: moderate to poorly differentiated tumor, presence of lymphvascular invasion, and myometrial invasion to the outer third; they were 50 years of age or older with 2 of the 3 risk factors; or they were 70 years of age or older and had one additional risk factor. Women who did not qualify for the high-risk subgroup were considered in the low-risk subgroup. Three hundred ninety-two participants met all eligibility requirements for inclusion in the analysis. Two hundred two women were randomized to the whole pelvic radiation group, and 190 received no additional postoperative treatment. Otherwise, both groups had similar clinical and demographic characteristics. In the radiation therapy (RT) group, 13 patients refused postoperative treatment and 5 received less than the prescribed dose. In the no-treatment group, 2 patients received full-dose postoperative RT. Twenty-four participants were lost to follow up within a median of 50 months. Overall median follow up was 68 months. Forty-four patients, 31 in the unirradiated group and 13 in the radiation group, developed disease recurrence. After a median follow up of 80 months, 15 of the women who recurred were alive with disease. In all, 66 women in the study died, 32 from disease or treatment-related causes. Women who received postoperative radiation therapy were less likely to have a recurrence of disease than those who had no additional treatment. Among the 202 patients who had no postoperative treatment, 13 recurred in the vagina, 4 in the pelvis, 1 in the vagina and pelvis, and 13 had distant recurrences. In the RT group, 2 women, both of whom refused treatment with radiation, had a recurrence in the vagina. One other patient recurred in the vagina and pelvis, and 10 had distant recurrences. Patients who were treated with postoperative radiation therapy had a 58% lower risk of ever having a recurrence of disease than women who did not. The overall risk of recurrence in the first 24 months after treatment was 3% (90% confidence interval [CI], 0.02-0.06) for women who received RT and 12% (90% CI, 0.09-0.17) for women who had no additional treatment. The estimated cumulative risk of recurring in the vagina or pelvis within the first 24 months was 1.6% (90% CI, 0.6-3.9) for those in the RT group compared with 7.4% (90% CI, 4.9-11.0) for the no additional treatment group. In the 132 women who were in the high-risk subgroup, 28 (28 of 44; 64%) had a recurrence of disease and 22 died from disease (22 of 32; 67%). The estimated risk of recurrence for high-risk women was 0.46 (90% CI, 0.19-1.11) compared with 0.42 (90% CI, 0.21-0.83) for low-risk women. There were 2 deaths from intestinal injury associated with radiation treatment. Overall, there were 6 instances of bowel obstruction in the RT group and 1 in the no additional treatment group.

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Horm Res. 2004;62(1):40-8. Epub 2004 Jun 01.
Hormone therapy after endometrial cancer.
Mueck AO, Seeger H.
Section of Endocrinology and Menopause, Women's University Hospital, Tubingen, Germany. endo.meno@med.uni-tuebingen.de

Endometrial carcinoma is listed among the absolute contra-indications to hormone therapy. After all the existing opinions so far, hormone therapy after FIGO stage I or II endometrial cancer is still thought of as a possibility, and up to now the continuous combined oestrogen/progestogen replacement therapy would be recommended. However, until today, only observational studies have been put forward. Although no study has established an increased rate of recurrences or mortality, alternatives such as phytopreparations, tibolone, or, in, particular, psychotherapeutic drugs such as venlafaxine should be considered for the relief of climacteric complaints. Progestogen-only therapy also comes particularly into question. Indeed, the wider discussion about the gestagen effects regarding the risks of breast cancer is to be considered. Generally, after hysterectomy, at least for patients with cardiovascular risk factors, the preference today is to use low-dose oestrogen therapy (patches, gels) instead of continuous combined oestrogen/progestogen replacement therapy, and this also is now recommended for patients after endometrial cancer. This is to be noted because of the risk factors for endometrial carcinomas, such as hypertension, obesity, polycystic ovary syndrome, diabetes mellitus, etc. However, each form of hormone therapy should only be exceptionally recommended, and the patients must be informed about the risks that exist and the use of alternatives. Copyright 2004 S. Karger AG, Basel

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Gan To Kagaku Ryoho. 2004 Jun;31(6):949-51.
[Successful treatment of endometrial carcinoma associated with lung metastasis by paclitaxel and carboplatin chemotherapy]
[Article in Japanese]
Tohya T, Onoda C, Yoshimura T, Kagami T.
Dept. of Obstetrics, Kumamoto Rosai Hospital.

BACKGROUND: Prognosis of patients with advanced endometrial cancer accompanied by distant metastases is poor. Moreover, there is no established therapy for this cancer. CASE: We treated a 32-year-old woman with endometrial cancer with multiple lung metastases (pT4N0M1). In August 2001, this patient presented with a complaint of abnormal genital bleeding. Endometrial cytology and histology revealed endometrial carcinoma, and chest XP and CT scan detected multiple lung metastases. MRI indicated invasion to the uterine cervix. Therefore, radical hysterectomy with pelvic lymph node dissection was performed. Postoperatively, this patient underwent TJ chemotherapy (paclitaxel 300 mg/body over 3 h, carboplatin 600 mg/body, area under the curve (AUC 5). A total of 9 courses of the regimen were given. Multiple lung shadows on chest XP and computed tomography (CT) were reduced in number and size after 2 courses of TJ chemotherapy. The multiple lung metastases either disappeared or remained as scars after 6 courses. There has been no evidence of recurrence for 20 months after the chemotherapy. CONCLUSION: TJ chemotherapy is considered effective as a postoperative chemotherapy in patients with endometrial cancer with multiple lung metastases.

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J Clin Oncol. 2004 Jun 1;22(11):2159-66.
Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study.
Fleming GF, Brunetto VL, Cella D, Look KY, Reid GC, Munkarah AR, Kline R, Burger RA, Goodman A, Burks RT.
Gynecologic Oncology Group, Four Penn Center, 1600 JFK Blvd, Suite 1020, Philadelphia, PA 19103, USA. gfleming@medicine.bsd.uchicago.edu

PURPOSE: To determine whether the addition of paclitaxel to doxorubicin plus cisplatin improves overall survival (OS) in women with advanced or recurrent endometrial carcinoma. Secondary comparisons included progression-free survival (PFS), response rate (RR), and toxicities. PATIENTS AND METHODS: Eligible, consenting patients received doxorubicin 60 mg/m(2) and cisplatin 50 mg/m(2) (AP), or doxorubicin 45 mg/m(2) and cisplatin 50 mg/m(2) (day 1), followed by paclitaxel 160 mg/m(2) (day 2) with filgrastim support (TAP). The initial doxorubicin dose in the AP arm was reduced to 45 mg/m(2) in patients with prior pelvic radiotherapy and those older than 65 years. Both regimens were repeated every 3 weeks to a maximum of seven cycles. Patients completed a neurotoxicity questionnaire before each cycle. RESULTS: Two hundred seventy-three women (10 ineligible) were registered. Objective response (57% v 34%; P <.01), PFS (median, 8.3 v 5.3 months; P <.01), and OS (median, 15.3 v 12.3 months; P =.037) were improved with TAP. Treatment was hematologically well tolerated, with only 2% of patients receiving AP, and 3% of patients receiving TAP experiencing neutropenic fever. Neurologic toxicity was worse for those receiving TAP, with 12% grade 3, and 27% grade 2 peripheral neuropathy, compared with 1% and 4%, respectively, in those receiving AP. Patient-reported neurotoxicity was significantly higher in the TAP arm following two cycles of therapy. CONCLUSION: TAP significantly improves RR, PFS, and OS compared with AP. Evaluation of this regimen in the high-risk adjuvant setting is warranted, but close attention should be paid to the increased risk of peripheral neuropathy.

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Gynecol Obstet Fertil. 2004 May;32(5):433-41.
[Conservative treatment of endometrial cancer and atypical hyperplasia]
[Article in French]
Yazbeck C, Dhainaut C, Thoury A, Driguez P, Madelenat P.
Service de gynecologie-obstetrique, hopital Bichat-Claude-Bernard, Paris, France. chayaz@cyberia.net.lb

Endometrial carcinoma is the most frequent pelvic cancer encountered in women. The discovery of an endometrial carcinoma in a woman seeking pregnancy cannot be considered as exceptional. The medical alternative to the classic radical surgical treatment is studied in a review. Treatment with progestins might be considered and discussed with the couple in special indications. The oncologic risk to which this treatment exposes is limited. However, the application and the surveillance of this therapeutic protocol must obey strict rules, in order to recognize without delay any resistance to treatment. The spontaneous fertility of such patients seems weak, most probably because of their age, but assisted reproductive techniques (ART) could be considered in particular cases. Secondary hysterectomy is controversial, but a recent tendency is to widen this practice is becoming apparent.

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Eur J Gynaecol Oncol. 2004;25(3):379-80.
Results of cisplatin, adriamycin and etoposide chemotherapy in patients with recurrent and metastatic endometrial cancer.
Bilgin T, Ozan H, Kara HF.
Department of Obstetrics and Gynecology, Uludag University, Faculty of Medicine, Bursa, Turkey.

The efficacy of the combination treatment of cisplatin, adriamycin and etoposide were retrospectively evaluated in 26 recurrent or metastatic endometrial cancer patients. One hundred and twenty-three treatment courses were observed. Patients received 20 mg/m2 cisplatin and 80 mg/m2 etoposide by continuous i.v. infusion for three days and adriamycin 40 mg/m2 i.v. the second day. Treatment courses were repeated every four weeks. Megestrol acetate, 160 mg/day, was added in six patients who had positive progesterone receptors. Ten (38.5%) women had complete and three (11.5%) patients had partial response with an overall response rate of 50%. Median follow-up was 24 months. Surviving patients were alive for four months and six years. Toxicity was mainly hematological and gastrointestinal ulcerations and stomatitis were also observed.

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Gynecol Oncol. 2004 May;93(2):345-52.
Combined treatment with chemotherapy and radiotherapy in high-risk FIGO stage III-IV endometrial cancer patients.
Bruzzone M, Miglietta L, Franzone P, Gadducci A, Boccardo F.
Medical Oncology Unit C, National Cancer Research Institute, Genoa, Italy.

Objectives. We reviewed our series of very advanced FIGO stage III-IV endometrial cancer patients to assess the efficacy and toxicity of a platinum- and doxorubicin-containing chemotherapy followed by conventional radiotherapy. Methods. Forty-five patients with advanced FIGO stage III and IV endometrial cancer have been treated, after surgery, with four courses of chemotherapy containing cisplatin 50 mg/m(2), epidoxorubicin 60 mg/m(2) and cytoxan 600 mg/m(2) (day 1 every 21 days) in association with conventional external pelvic radiotherapy (50 Gy, with a 2 Gy daily dose administered with "box technique"). Results. Chemotherapy was well tolerated: WHO grade 4 neutropenia, without fever or other symptoms, has been recorded in six patients (8.8%) at nadir, but no patient required hospitalization or colony-stimulating factors support during chemotherapy. Radiotherapy timing was not delayed by systemic treatment. Toxicities observed during radiation treatment are superimposable to those referred for not pretreated patients. At a median follow-up time of 63 months (range 4-112), 18 patients progressed and 16 patients have died: actuarial 9 years progression-free survival and survival are 30% and 53%, respectively. Conclusions. The addition of chemotherapy to radiotherapy seems to be an effective and safe way to treat this subset of endometrial cancer patients.

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Gan To Kagaku Ryoho. 2004 Apr;31(4):549-53.
[A pilot study of combined chemotherapy with paclitaxel, doxorubicin and cisplatin for
endometrial cancer]
[Article in Japanese]
Honma H, Sagae S, Terasawa K, Tanaka R, Chida M, Mizumoto H, Ishioka S, Saito T, Kudo R.
Dept. of Obstetrics and Gynecology, School of Medicine, Sapporo Medical University.

A pilot trial of combined chemotherapy with paclitaxel, doxorubicin and cisplatin was conducted in patients with advanced endometrial cancer. Between June 2000 and March 2002 8 patients were treated with combined chemotherapy, consisting of paclitaxel, 135 mg/m2; doxorubicin, 30 mg/m2; and cisplatin, 50 mg/m2 (TAP therapy). Patients received 3 to 5 courses of TAP therapy every 4 weeks. The major adverse effect was myelosuppression. All patients had grade 3 or 4 neutropenia, but did not have any severe infection with uncontrollable fever. Only 1 patient discontinued additional therapy due to grade 3 thrombocytopenia after 3 cycles. Grade 2 neurotoxicity occurred in 5 patients, but grade 3 was not observed. Among 5 patients with measurable tumors, 4 achieved partial response and 1 had no change of tumor size, indicating a response rate of 80.0%. We found that TAP therapy was feasible with G-CSF support and shows potential for high efficacy in advanced endometrial cancer.

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Onkologie. 2004 Apr;27(2):207-10.
Hormone replacement therapy and endometrial cancer.
Emons G, Huschmand-Nia A, Krauss T, Hinney B.
Department of Obstetrics and Gynecology, Georg-August-Universitat Gottingen, Germany. emons@med.uni-goettingen.de

Postmenopausal hormone replacement therapy (HRT) using unopposed estrogens significantly increases endometrial cancer risk and should not be used in non-hysterectomized women. Even low-potency estrogens (oral estriol) or low-dose unopposed estrogens significantly enhance the risk to develop endometrial cancer. This risk is markedly reduced, when in addition to estrogens, progestins are administered for at least 10 days (better 14 days) per month. In some studies, a normalization of endometrial cancer risk to that of women receiving no HRT was only found when a continuous combined estrogen/progestin replacement was used. The use of progestins for less than 10 days per month and long-cycle regimens, where a progestin is added only every 3 months cannot be recommended. For women needing HRT, estrogen dose should be selected as low as possible and reassessment of the need of HRT should be performed annually. Copyright 2004 S. Karger GmbH, Freiburg

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Zhonghua Fu Chan Ke Za Zhi. 2004 Mar;39(3):165-8.
[Comparative analysis of laparoscopic surgery and laparotomy for early stage endometrial cancer]
[Article in Chinese]
Peng P, Huang HF, Shen K, Pan LY, Wu M, Yang JX, Lang JH.
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.

OBJECTIVE: To evaluate the feasibility of laparoscopic surgical treatment of early stage endometrial cancer. METHODS: From January 1998 to August 2003, 24 endometrial cancer cases treated by laparoscopy were analyzed as the study group. And 41 endometrial cancer cases treated by laparotomy during the same period were randomly selected as the control group. The two groups were compared in terms of the clinic data of perioperative periods. RESULTS: The clinicopathological characteristics before operation between both groups were similar. The mean operating time in the laparoscopy group (97 minutes) was significantly shorter (P < 0.001) than that in the laparotomy group (134 minutes). The blood loss during the operation in the laparoscopy group (163 ml) was fewer than that in the laparotomy group (259 ml). The numbers of the lymph nodes resected between the two groups were similar. The rate of complications in the laparoscopy group was lower than that in the laparotomy group. The laparoscopy group had shorter hospitalization (6.3 days) than that of the laparotomy group (9.6 days, P < 0.01). The pathological type and International Federation of Gynecology and Obstetrics (FIGO) stage between the two groups were similar. One case had recurrence and 1 case died in the control group but there was no such case in the laparoscopy group. The survival rate of the study group was 100% and that of the control group was 97% (P > 0.05). CONCLUSION: Laparoscopic surgery is feasible and safe in treatment of early stage endometrial cancer, and the clinic value should be confirmed by multicenter randomized clinic trial.

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Zhonghua Fu Chan Ke Za Zhi. 2004 Mar;39(3):156-8.
[Study of different surgeries for clinical stage I endometrial carcinoma]
[Article in Chinese]
Li MD, Huang YW, Huang H, Liu JH.
Department of Gynecology, Cancer Hospital, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.

OBJECTIVE: To compare the outcomes and the risk of post-operative complications in patients with stage I endometrial carcinoma who were treated with different surgeries. METHODS: A total of 211 cases with stage I endometrial cancer treated with surgery in our Cancer Center from Jan 1986 to Dec 1997 were analyzed retrospectively. Sixty-one patients (group 1) underwent simple hysterectomy and salpingo-oophorectomy and 150 patients (group 2) underwent radical hysterectomy. The 5-year survival rates and the risk of post-operative complications were compared between two groups. RESULTS: Five-year survival rates of the group 1 and 2 were 96.0% and 93.5% (P > 0.05), respectively. The recurrence rates of the two groups were 6.6% and 10.7% (P > 0.05), respectively. The overall rates of post-operative complications in the two groups were 11.5% and 24.7% (P < 0.05), respectively. CONCLUSION: The patients with stage I endometrial carcinoma who were treated with simple hysterectomy and salpingo-oophorectomy did almost as well as those who underwent radical hysterectomy.

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Gynecol Oncol. 2004 Mar;92(3):744-51.
A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study.
Keys HM, Roberts JA, Brunetto VL, Zaino RJ, Spirtos NM, Bloss JD, Pearlman A, Maiman MA, Bell JG.
Department of Radiation Oncology, Albany Medical College, Albany, NY 12208, USA.

Background. Despite their low risk for recurrence, many women with endometrial adenocarcinoma receive postoperative radiation therapy (RT). This study was developed to determine if adjunctive external beam irradiation lowers the risk of recurrence and death in women with endometrial cancer International Federation of Gynaecology and Obstetrics (FIGO) stages IB, IC, and II (occult disease). Methods. Four hundred forty-eight consenting patients with "intermediate risk" endometrial adenocarcinoma were randomized after surgery to either no additional therapy (NAT) or whole pelvic radiation therapy (RT). They were followed to determine toxicity, date and location of recurrence, and overall survival. A high intermediate risk (HIR) subgroup of patients was defined as those with (1) moderate to poorly differentiated tumor, presence of lymphovascular invasion, and outer third myometrial invasion; (2) age 50 or greater with any two risk factors listed above; or (3) age of at least 70 with any risk factor listed above. All other eligible participants were considered to be in a low intermediate risk (LIR) subgroup. Results. Three hundred ninety-two women met all eligibility requirements (202 NAT, 190 RT). Median follow-up was 69 months. In the entire study population, there were 44 recurrences and 66 deaths (32 disease or treatment-related deaths), and the estimated 2-year cumulative incidence of recurrence (CIR) was 12% in the NAT arm and 3% in the RT arm (relative hazard (RH): 0.42; P = 0.007). The treatment difference was particularly evident among the HIR subgroup (2-year CIR in NAT versus RT: 26% versus 6%; RH = 0.42). Overall, radiation had a substantial impact on pelvic and vaginal recurrences (18 in NAT and 3 in RT). The estimated 4-year survival was 86% in the NAT arm and 92% for the RT arm, not significantly different (RH: 0.86; P = 0.557). Conclusions. Adjunctive RT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence, but should be limited to patients whose risk factors fit a high intermediate risk definition.

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Arzneimittelforschung. 2004;54(1):1-8.
Hormone therapy after endometrial cancer.
Mueck AO, Seeger H.
Department of Endocrinology and Menopause, Women's University Hospital, Tubingen, Germany.

Endometrial carcinoma is one of the absolute contraindications of hormone therapy (HT). After all the existing opinions so far, HT after Stage I or II is still thought of as a possibility and up to now, the continuously combined estrogen (CAS 53-16-7) / progestogen (CAS 57-83-0) replacement therapy (CCEPT) has been recommended. However, only observational studies have been conducted as yet. Although no study established an increased rate of recurrence or mortality, alternatives such as phyto-preparations, tibolone, or particular psychotherapeutic drugs such as venlafaxine should be considered for the relief of climacteric complaints. In particular considered is progestogen-only therapy. However, the currently discussed possible progestogen effects regarding the risk of breast cancer have to be taken into account. Generally after hysterectomy, at least for patients with cardiovascular risk factors, the preference today is to use low-dose estrogen therapy (patches, gels) instead of CCEPT, and this also is now recommended for patients after endometrial cancer. This is important because of the risk factors for endometrial carcinoma, such as hypertension, obesity, polycystic ovary syndrome, diabetes mellitus etc. However, each form of HT should only be exceptionally recommended, and the patients must be informed about the risks that exist and the use of alternatives.

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Cancer. 2004 Jan 1;100(1):89-96.
Surgical treatment of recurrent endometrial carcinoma.
Campagnutta E, Giorda G, De Piero G, Sopracordevole F, Visentin MC, Martella L, Scarabelli C.
Scientific Institute for Research, Hospitalization, and Health Care, National Cancer Institute, Aviano, Italy.

BACKGROUND: Surgery does not have a definite role in the treatment of patients with recurrent endometrial carcinoma, except for those with central pelvic recurrences. The authors describe their experience with surgery in patients with abdominal endometrial recurrences. METHODS: Between 1988 and 2000, 75 patients with abdominal and pelvic endometrial recurrences underwent secondary rescue surgery. Patients were classified according to the presence or absence of residual tumor after surgery. Therapy after rescue surgery was undertaken at the discretion of the medical oncologist. The progression-free interval and overall survival were defined as the time from secondary rescue surgery to the specific event and were evaluated by the Kaplan-Meier method and the log-rank test. A Cox proportional hazards regression model was used to compare survival with covariates. RESULTS: Fifty-six patients (74.7%) underwent optimal debulking. Major surgical complications were observed in 23 patients (30.7%). Only 1 postoperative death was observed, although the mortality rate for surgical complications after the postoperative period was 8%. Patients who underwent optimal debulking had a significantly better cumulative survival rate compared with patients who had residual disease (36% vs. 0% at 60 months; P < 0.05). Residual disease, chemotherapy after rescue surgery, and central pelvis-vagina as the only site of recurrence were associated significantly with survival. CONCLUSIONS: The authors found that this approach was very challenging in terms of the procedures involved, the incidence of major surgical complications, and the high mortality rate. It was useful in increasing overall survival, provided that patients were free of macroscopic disease. Careful selection of patients is needed to minimize mortality. Copyright 2003 American Cancer Society.

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Clin Exp Obstet Gynecol. 2003;30(1):7-12.
The role of laparoscopy in the surgical treatment of endometrial cancer.
Holub Z.

OBJECTIVES: Endometrial cancer is the most common gynaecological cancer. Surgical treatment has traditionally been done by laparotomy, however the laparoscopic approach has gained wider acceptance by gynecologic surgeons. Whether in combination with laparoscopic-assisted or laparoscopic hysterectomy, laparoscopic staging, including lymph-node dissection, is a major component in the treatment of patients with early endometrial cancer. It remains to be proven if these techniques are associated with the greatest benefit. METHODS: Substantial recent studies on the topic of surgical laparoscopic treatment of endometrial cancer were identified from Medline. RESULTS AND DISCUSSION: Laparoscopically assisted surgical staging (LASS) has been reported in several case series totaling more than 600 cases. CONCLUSION: The report illustrates that laparoscopically assisted surgical staging of endometrial cancer is safe as an open procedure. The laparoscopic approach may also be considered for endometrial malignancy which typically occurs in obese and elderly high-risk women.

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Gynecol Oncol. 2003 Jul;90(1):64-9.
A phase II trial of arzoxifene, a selective estrogen response modulator, in patients with recurrent or advanced endometrial cancer.
McMeekin DS, Gordon A, Fowler J, Melemed A, Buller R, Burke T, Bloss J, Sabbatini P.
University of Oklahoma, Oklahoma City, OK 73190, USA. scott-mcmeekin@ouhsc.edu

OBJECTIVES: The goal of this study was to determine response rate and evaluate toxicity of LY353381 (arzoxifene) in patients with recurrent or advanced endometrial cancer (EC). METHODS: A phase II, open-labeled study with arzoxifene was performed at 13 centers. Patients with measurable recurrent/advanced EC not amenable to curative therapies were eligible if either the primary tumor or recurrent tumor was ER+ and/or PR+. If receptor status could not be determined, patients with well or moderately well-differentiated EC were also permitted. Prior use of salvage chemotherapy was not allowed; however, prior use of progestagens was permitted and patients were stratified by prior exposure to progestagen. Patients received 20 mg/day PO, and were treated for at least 8 weeks in the absence of disease progression or unacceptable toxicity. Efficacy was based on the frequency of complete (CR) and partial (PR) responses, and a 95% confidence interval (CI) was calculated. The Kaplan-Meier method was used to analyze time to progression and duration of response. RESULTS: From February 1999 through April 2001, 37 patients were entered of whom 34 received treatment. Efficacy was evaluated for the 29 patients who received at least 4 weeks of therapy and at least one tumor response assessment. Safety was assessed in all 34 patients who received any drug. Thirty patients were defined as progestagen sensitive, and 4 patients were defined as progestagen failures. Twenty-six patients were ER+, and 22 were PR+. Nine (1 CR + 8 PR) of 29 patients responded (31%, CI 25-51%), with a median duration of response of 13.9 months. All 9 responses occurred in progestagen-sensitive patients. Two additional patients (one from each progestagen cohort) had stable disease for >or=6 months. The median progression-free interval was 3.7 months (CI 1.9-6.6 months) for all 29 patients. Toxicity was minimal with no grade 3-4 toxic effects, and 9 patients had only grade 1-2 toxic effects (7 grade 1, 2 grade 2). Hot flashes were the most common toxic effect and, in all 3 reported cases, were grade 1. CONCLUSIONS: Arzoxifene has demonstrated a high response rate with the longest median duration of response reported in a phase II trial of this patient population. The ease of administration and extremely favorable toxicity profile make this an agent warranting further evaluation.

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Eur J Cancer. 2003 Jan;39(1):78-85.
Phase II study of carboplatin in patients with advanced or recurrent endometrial carcinoma. A trial of the EORTC Gynaecological Cancer Group.
van Wijk FH, Lhomme C, Bolis G, Scotto di Palumbo V, Tumolo S, Nooij M, de Oliveira CF, Vermorken JB; European Organization for Research and Treatment of Cancer. Gynaecological Cancer Group.
EORTC Data Center, Brussels, Belgium.

The aim of this study was to investigate the efficacy and toxicity of carboplatin given as monotherapy in endometrial adenocarcinoma. Cisplatin is one of the most active drugs in gynaecological cancer types, but at the cost of an associated high toxicity. In this high-risk population of endometrial cancer patients, it is necessary to have chemotherapy regimens with a low toxicity. Patients eligible for this study were those with histologically-confirmed endometrial adenocarcinoma with evidence of recurrent and/or metastatic disease. Carboplatin was administered every 4 weeks as a first- (dose: 400 mg/m(2)) or second- (dose: 300 mg/m(2)) line chemotherapy. Of the 64 patients who entered the trial, 60 were eligible, 53 patients were evaluable for toxicity and 47 for efficacy. A total of 169 cycles of carboplatin was given with a median of 2 cycles per patient (range 1-11 cycles) to a median cumulative dose of 798 mg/m(2) (range 290-3879 mg/m(2)). No grade 4 toxicity or toxic deaths occurred. White Blood Cell (WBC) toxicity grade 3 was noted five times, mainly in the radiotherapy pre-treated patients. Grade 3 non-haematological toxicity consisted mainly of nausea and vomiting (21%). There was a total of eight responses (3 Complete Responses (CR) and 5 Partial Responses (PR) with an overall response rate (ORR) of 13% (95% Confidence Interval (CI) 6-25). No responses occurred in patients treated with prior chemotherapy. In evaluable patients, the ORR in all patients (n=47) and in those receiving first-line chemotherapy (n=33) were, 17% (95% CI 8-31) and 24% (95% CI 11-42), respectively. After a median follow-up of 379 days, the median duration of response was 488 days (range 141-5303 days) with two very long responses in patients with a CR. Carboplatin has a low toxicity and is active in chemotherapy-naive advanced endometrial carcinoma patients. These results lead us to propose its use in association in first-line chemotherapy in recurrent or advanced endometrial carcinoma patients. The choice of the initial dose can be determined according to whether the patients have received prior radiotherapy treatment.

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Int J Radiat Oncol Biol Phys. 2003 Aug 1;56(5):1366-72.
Definitive radiotherapy for patients with isolated vaginal recurrence of endometrial carcinoma
after hysterectomy.
Jhingran A, Burke TW, Eifel PJ.
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. ajhingran@mdanderson.org

PURPOSE: To determine the outcome of patients after radical radiotherapy (RT) for isolated vaginal recurrence of endometrial carcinoma and to determine the clinical and pathologic predictors of outcome. METHODS AND MATERIALS: We reviewed the records of 91 patients treated at our institution between 1960 and 1997 with radical RT for vaginal recurrence after definitive surgery for endometrial carcinoma. Thirty-one percent of the patients received external beam RT (EBRT) alone, 12% received brachytherapy alone, and 57% received a combination. The median dose of radiation was 75 Gy (range 34-122). All end points were measured from the time of the first recurrence. The median duration of follow-up after recurrence was 58 months (range 1-289). RESULTS: The 2- and 5-year local control (LC) rate and overall survival rate was 82% and 75% and 69% and 43%, respectively. The median time from initial diagnosis of endometrial cancer to death from disease was 38 months. On univariate analysis, a dose to the relapse site of > or =80 Gy and EBRT plus brachytherapy vs. single-modality therapy were significant predictors of improved LC. On multivariate analysis, only the type of treatment correlated significantly with LC (p = 0.03). On univariate analysis, Grade 1 or 2 vs. Grade 3 tumor and EBRT plus brachytherapy vs. single-modality therapy were significant predictors of improved overall survival. CONCLUSION: RT provides excellent LC of isolated vaginal recurrences of endometrial carcinoma, particularly when high doses are given using a combination of EBRT and brachytherapy. However, distant metastases frequently develop despite local disease control, contributing to a 5-year overall survival rate of <50%. For patients who have an isolated vaginal recurrence, the time from initial diagnosis of endometrial cancer to death from disease is usually >3 years. For this reason, in studies of adjuvant RT, long-term follow-up is required to permit evaluation of the impact of treatment on survival.

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Am J Obstet Gynecol. 2003 Jun;188(6):1573-7; discussion 1577-8.
Endometrial carcinoma: treatment and outcomes in the regional hospital setting.
Hickerson JW.
Department of Surgery, Good Samaritan Hospital, Corvallis, OR, USA.

OBJECTIVE: Between 1986 and 2000, 204 cases of endometrial carcinoma were managed at Good Samaritan Hospital and Samaritan Regional Cancer Center, both located in Corvallis, Ore. Too often in the private practice setting, accurate outcome data and critical review of appropriateness of care are insufficient or lacking. The current review is the first in-depth examination of endometrial malignancies treated in Corvallis since the author's arrival in 1985. STUDY DESIGN: Data were retrieved through confidential review of hospital, Cancer Center, and office charts of all patients treated for endometrial carcinoma during the previous 15 years. RESULTS: Treatment modalities included surgery, radiation therapy, chemotherapy, hormonal therapy, and combinations thereof. Seventy-six percent of the cases were surgical stage I, 9% were stage II, 10% were stage III, and 5% were stage IV. Tumors were predominantly grade 1 or 2, which accounted for 69% of the total. Twenty-seven percent were grade 3 or undifferentiated. The overall 5-year disease-free survival was 86%. CONCLUSION: The outcomes for this patient population compare favorably with previously published survival data from larger studies.

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Bull Cancer. 2003 Apr;90(4):347-55.
[The choice of approach in the surgical management of endometrial carcinoma: a retrospective
series of 155 cases]
[Article in French]
Occelli B, Samouelian V, Narducci F, Leblanc E, Querleu D.
Centre Oscar-Lambret, rue Frederic Courbemale, 59020 Lille Cedex.

SETTING: Retrospective study of patients consecutively managed surgically for apparent stage I endometrial carcinoma in a comprehensive cancer center, using a standardized protocol for the choice of surgical approach: laparoscopically assisted vaginal hysterectomy (LAVH) as standard procedure, vaginal surgery in apparent stage IA grade 1 or in patients in poor medical condition, laparotomy in the case of subserous myometrial involvement at imaging or in patients with enlarged uteri or in the presence of a contra-indication to laparoscopy. MATERIALS AND METHODS: Excluding 2 patients in whom laparoscopy was converted in laparotomy, and 1 patient who had a full laparoscopic hysterectomy, the records of 155 patients were reviewed. All patients had a preoperative sonogram, and 74% had a preoperative MRI. Preoperative data, preoperative staging, operative data, pathological staging, postoperative complications, recurrence and survival were recorded. RESULTS: 69 patients (43.6%) had a LAVH procedure (group LAVH), 58 patients (36.7%) were treated by laparotomy (group TAH), and 28 patients (18%) were treated by simple vaginal hysterectomy (group VH). Patients in the vaginal group were significantly heavier (VH 91.3 kg 33, range 53-175) than those of the other two groups (TAH 76.5 12.7, range 48-142; LAVH 71.1 18.5, range 47-102). The number of large (> 10 cm) uteri was significantly greater in the TAH group (46.5%) than the LAVH group (26.1%, p = 0.02) or the VH group (14.3%, p = 0.007). Myometrial invasion was suspected in 53.6% of the VH group, 72.6% of the LAVH group, and 71.4% of the TAH group. Deep myometrial invasion was suspected in no patient of the VH group, 14.5% of the LAVH group and 70.7% of the TAH group. The LAVH group had a significantly longer mean operative time than the TAH group or the VH group.The number of perioperative complications was significantly higher in the TAH group (22.4%) compared to the LAVH group (5.6%) and the VH group (0%). Blood loss was significantly elevated in the laparotomy group compared to the other two groups. The mean number of nodes removed was significantly higher in the LAVH group (15.8 7.8, range 4-37) compared to the TAH group (11 5.3, range 2-25, p = 0.002). Of 155 patients, 100 (64.5%) had correct preoperative staging. In 19 (12.3%), FIGO stage was overestimated preoperatively, and in 36 (23.2%) the FIGO stage was underestimated preoperatively. Survival curves were not found significantly different between groups.

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Gynecol Oncol. 2003 Jun;89(3):470-4.
Phase II trial of danazol in advanced, recurrent, or persistent endometrial cancer: a Gynecologic Oncology Group study.
Covens A, Brunetto VL, Markman M, Orr JW, Lentz SS, Benda J; Gynecologic Oncology Group.
Division of Gynecology/Oncology, University of Toronto, Toronto, Ontario, M4N 3M5, Canada. al.covens@tsrcc.on.ca

OBJECTIVES: To evaluate the activity and toxicity of danazol in advanced, recurrent, or persistent endometrial carcinoma. METHODS: Eligible patients with advanced, recurrent, or persistent endometrial carcinoma not amenable to curative therapy were treated with danazol at a dose of 100 mg four times per day until disease progression or toxicity necessitated discontinuation. Eligibility criteria included the presence of measurable disease and no prior chemotherapy. Immunohistochemical analysis of metastatic tumor tissue for estrogen and progesterone receptors was required. RESULTS: Twenty-five patients were enrolled and 3 were excluded. Six patients had tumors staining positive for both estrogen and progesterone receptors. There were no responders among 22 eligible patients. Six patients (27%) demonstrated stable disease as their best response. The median progression-free survival and overall survival were 1.9 and 14.4 months, respectively. A median total dose of 21.7 (range: 1.4 to 67.2) of danazol was administered. Therapy was discontinued in 5 eligible patients due to toxicity. Four of these patients experienced hepatic toxicity. CONCLUSIONS: Danazol has minimal activity in advanced, recurrent, or persistent endometrial carcinoma.

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Int J Radiat Oncol Biol Phys. 2003 Jul 1;56(3):788-92.
Whole abdomen radiotherapy for patients with peritoneal dissemination of endometrial adenocarcinoma.
Lee SW, Russell AH, Kinney WK.
Radiological Associates of Sacramento Medical Group, Sacramento, CA 95815, USA. Lees@radiological.com

PURPOSE: No standard, universally accepted therapy exists for patients with adenocarcinoma of the endometrium with peritoneal dissemination. We report mature outcomes of selected patients with this uncommon pattern of spread treated with whole abdomen radiotherapy (RT). METHODS AND MATERIALS: A retrospective review was undertaken of all patients with a diagnosis of endometrial cancer referred to the Radiologic Associates of Sacramento Medical Group between January 1, 1988 and October 1, 1999. Eleven patients were identified who had surgically proven peritoneal dissemination (peritoneal seeding) treated with whole abdomen RT as the sole cytotoxic therapy after operative cytoreduction. Ten patients had International Federation of Obstetrics and Gynecology (1988) Stage IV disease at diagnosis, and one had peritoneal dissemination at the time of initial recurrence after hysterectomy for Stage I disease. RT was administered to the whole abdomen using 10-MV photons in fractions of 1.0 or 1.5 Gy. A cumulative dose of 30 Gy was given in all patients, with shielding used to reduce the dose to the liver and kidneys. Partial abdominal volumes (pelvis plus paraaortic nodes) received supplementary dose at 1.5-1.8 Gy/fraction to bring the cumulative dose within the limited volumes to 46.2-54 Gy. RESULTS: Four patients developed progressive cancer within 13 months of completion of whole abdomen RT. One additional patient died of hepatic venoocclusive disease (radiation hepatitis) 15 months after RT without evidence of cancer recurrence. Five patients were alive and clinically cancer free 55, 129, 131, 134, and 178 months after RT completion. One patient died of unrelated causes 79 months after treatment completion. CONCLUSION: Abdominal RT, in doses compatible with the acute and late tolerance of normal tissues, can eradicate small deposits of disseminated, intraperitoneal endometrial cancer. Currently, our patient selection criteria include limited peritoneal dissemination at diagnosis permitting complete surgical clearance (<1 mm residual) of visible and palpable disease, Grade 1 or 2 histologic features, lack of demonstrable extraabdominal metastasis, and absence of major medical contraindications.

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J Clin Oncol. 2003 Jun 1;21(11):2110-4.
Topotecan is an active agent in the first-line treatment of metastatic or recurrent endometrial carcinoma: Eastern Cooperative Oncology Group Study E3E93.
Wadler S, Levy DE, Lincoln ST, Soori GS, Schink JC, Goldberg G.
Department of Oncology, Division of Hematology-Oncology, Weill Medical College of Cornell University, 525 E 68th St, STARR 353, New York, NY 10021, USA. scw2004@med.cornell.edu

PURPOSE: To determine the clinical activity and the toxicity profile of the topoisomerase-I inhibitor, topotecan, in women with recurrent or advanced endometrial carcinoma. PATIENTS AND METHODS: A prospective, phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG). Patients had histologically confirmed advanced or recurrent endometrial carcinoma, measurable disease, no prior cytotoxic therapy, an ECOG performance status of 0 to 2, and evidence of disease progression while on progestins or after radiation therapy. Topotecan was administered at 1.5 mg/m(2) (or 1.2 mg/m(2) for patients with prior pelvic radiation) intravenously daily for 5 days every 3 weeks. RESULTS: A total of 44 patients were enrolled; 42 were eligible. The study was suspended because of unexpected toxicities, primarily sepsis and bleeding. After toxicity review, the study was reopened using lower doses of topotecan (1.0 mg/m(2) or 0.8 mg/m(2) for patients with prior radiation therapy). In addition, prophylactic use of growth factors was allowed after the first cycle, and patients with performance status of 2 were excluded. The major toxicities were hematologic and gastrointestinal. Among the 40 assessable patients, there were three (7.5%) complete responders and five partial responders (12.5%), for an overall response rate of 20%. The median duration of response was 8.0 months and of overall survival was 6.5 months. CONCLUSION: Topotecan is an active agent for the treatment of advanced endometrial carcinoma. At the doses and schedules initially used, toxicities were unacceptable; however, at the modified doses, toxicities were acceptable and clinical activity was preserved.

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Cancer Radiother. 2003 Apr;7(2):121-31.
[Brachytherapy of endometrial cancers]
[Article in French]
Peiffert D, Hoffstetter S, Charra-Brunaud C.
Unite de curietherapie, centre Alexis-Vautrin, 54500, Vandoeuvre-les-Nancy, France. peiffert@nancy.fnclcc.fr <peiffert@nancy.fnclcc.fr>

Endometrial adenocarcinomas rank third as tumoral sites en France. The tumors are confined to the uterus in 80% of the cases. Brachytherapy has a large place in the therapeutic strategy. The gold standard treatment remains extrafascial hysterectomy with bilateral annexiectomy and bilateral internal iliac lymph node dissection. However, after surgery alone, the rate of locoregional relapses reaches 4-20%, which is reduced to 0-5% after postoperative brachytherapy of the vaginal cuff. This postoperative brachytherapy is delivered as outpatients treatment, by 3 or 4 fractions, at high dose rate. The uterovaginal preoperative brachytherapy remains well adapted to the tumors which involve the uterine cervix. Patients presenting a localized tumor but not operable for general reasons (< 10%) can be treated with success by exclusive irradiation, which associates a pelvic irradiation followed by an uterovaginal brachytherapy. A high local control of about 80-90% is obtained, a little lower than surgery, with a higher risk of late complications. Last but not least, local relapses in the vaginal cuff, or in the perimeatic area, can be treated by interstitial salvage brachytherapy, associated if possible with external beam irradiation. The local control is reached in half of the patients, but metastatic dissemination is frequent. We conclude that brachytherapy has a major role in the treatment of endometrial adenocarcinomas, in combination with surgery, or with external beam irradiation for not operable patients or in case of local relapses. It should use new technologies now available including computerized afterloaders and 3D dose calculation.

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Ginekol Pol. 2003 Feb;74(2):91-7.
The effect of pelvic and paraaortic lymphadenectomy on intensity of pain and intraoperative and postoperative complications]
[Article in Polish]
Onichimowski D, Stefanowicz M, Wasniewski T.
Oddzialu Ginekologii Operacyjnej i Perinatologii Wojewodzkiego Szpitala Specjalistycznego, Olsztynie.

OBJECTIVES: The aim of the study was the estimation of effect of pelvic and paraaortic lymphadenectomy on intensity of pain complains, and comparison of quantity of intraoperative and postoperative complications in groups of patients subjected and not subjected the lymphadenectomy. MATERIAL AND METHODS: We studied to 80 patients divided into two groups: 40 people with endometrial cancer, who were treated with total abdominal hysterectomy, salpingo-oophorectomy and pelvic and paraaortic lymphadenectomy; and 40 people with uterine myomas or benign neoplasms of uterine adnexa, who were treated with abdominal hysterectomy and salpingo-oophorectomy, but without lymphadenectomy. The measure of intensity of pain complaints was twenty-four hour analgetic requirement of patients in postoperative period, counted by PCA (Patient Controlled Analgesia) pump (Perfusor fm Braun). RESULTS: Twenty-four hour consumption of morphine counted by PCA pump did not statistically differ in both groups of patients. Twenty-four hour consumption of morphine on kilogram of body mass was similarly too. We find 3 (3.8%) intraoperative and 15 (18.8%) postoperative complications. The number of complications did not statistical to differ in groups of patients subjected and not subjected lymphadenectomy. CONCLUSIONS: The inclusion of lymphadenectomy into the operation procedures did not increase of pain in the postoperative course. The percentage of intraoperative and postoperative complications in both groups was similar. The lymphadenectomy executed in specialised centres of oncological gynaecology is a safe intervention, with a low number of complications.

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Gynecol Oncol. 2003 May;89(2):288-94.
High-risk surgical stage 1 endometrial cancer: outcomes with vault brachytherapy alone.
Rittenberg PV, Lotocki RJ, Heywood MS, Jones KD, Krepart GV.
Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, Cancer Care Manitoba and University of Manitoba, Winnipeg, Canada. paularittenberg@shaw.ca

OBJECTIVE: Prior to 1995, in our center, patients with surgically staged endometrial cancer with greater than 50% myoinvasion (FIGO 1C) were treated with vault brachytherapy and whole pelvis (WP) radiotherapy despite negative nodes. After October 1, 1995, these patients were treated with vault brachytherapy alone. The aim of this study was to ensure that the survival and recurrence rate had not changed. METHODS: A retrospective review of Cancer Care Manitoba charts was undertaken. All patients diagnosed with endometrioid adenocarcinoma between October 1, 1995, and March 1, 2001, were reviewed. Data for all FIGO surgical stage 1 patients, and a subset of stage 1C patients, were analyzed and compared with those of a historical control group, composed of patient data previously collected in our center (1978 to 1990) [Gynecol. Oncol. 55 (1994), 51]. RESULTS: A total of 172 patients had negative selective pelvic lymphadenectomy and FIGO stage 1 disease. Fifty-three stage 1C patients were spared WP radiotherapy. Median follow-up was 32 months. Recurrence rate in FIGO stage 1 disease was 2.3% (4/172) and for the subset 1C was 5.7% (3/53). The recurrence rate was not statistically significantly different from that of the historical control group, 3.6% for stage 1 (P = 0.562) and 7.2% for stage 1C (P = 0.51). Two- and five-year survival rates for stage 1 patients in this study were 97 and 95%, respectively. In the historical group, 2- and 5-year survival rates were 97 and 94%. CONCLUSION: Whole pelvis radiotherapy can be safely omitted in patients with FIGO stage 1C endometrial cancer if nodal status is known.

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Eur J Gynaecol Oncol. 2003;24(2):126-8.
Role of pelvic lymphadenectomy in the management of stage I endometrial cancer: our experience.
Vizza E, Galati GM, Corrado G, Sbiroli C.
Division of Gynecology, S. Carlo di Nancy Hospital, Rome, Italy.

OBJECTIVES: To estimate the prognostic value of pelvic-node removal on survival of patients affected by endometrial carcinoma at presurgical FIGO Stage I. METHODS: A retrospective analysis was performed on a total of 111 patients recruited from 1990 to 1996 at the S. Carlo di Nancy Hospital. Thirty-nine (35%) of them underwent a total hysterectomy and bilateral salpingo-oophorectomy with removal of the vaginal cuff (group 1), while 72 (65%) underwent a total hysterectomy combined with pelvic lymphadenectomy (group 2). Prognostic features including tumor grade, depth of myometrial invasion and histologic subtype. Survival rates were calculated with Cox and Kaplan analyses. RESULTS: Overall survival rate at five years was 91.2%. The survival rate of group 1 and group 2 was 89% and 92.8%, respectively which is not statistically significant. Stage, grade, histotype, age at diagnosis, and presence of positive lymph nodes did not show any significant prognostic value on survival probability. CONCLUSIONS: The survival rate for patients submitted to lymphadenectomy (group 2) was the same of patients who did not undergo this treatment (group 1). Nevertheless, pelvic lymphadenectomy in endometrial carcinoma at presurgical FIGO stage I was worthwhile as it allowed correct staging to be performed. The prediction of nodal disease based only on preoperative investigations (such as TC, NMR) is often inaccurate.

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Eur J Gynaecol Oncol. 2003;24(1):41-4.
Laparoscopic management of early stage endometrial cancer.
Litta P, Fracas M, Pozzan C, Merlin F, Saccardi C, Sacco G, Mannici D.
Department of Gynaecology & Obstetrics, University of Padova, Italy.

PURPOSE OF INVESTIGATION: The purpose of this study was to evaluate the feasibility of laparoscopic hysterectomy versus the transabdominal approach with systemic pelvic lymphadenectomy in early stage endometrial cancer. METHODS: From January 1996 to April 2002, 59 women were treated for endometrial cancer at the Department of Gynecology in Padova, Italy (29 by the laparoscopic technique and 30 by laparotomy). Every patient underwent hysterosalpingo-oophorectomy with systemic pelvic lymphadenectomy. RESULTS: Comparing the two techniques, operating time was longer and hospital stay was significantly shorter for laparoscopy; no differences were observed about the number of removed lymph nodes (range 5-33) or intra-postoperatory complications. CONCLUSION: The laparoscopic approach to endometrial cancer is certainly to be considered appropriate and efficacious, even if it requires skilled surgeons and adequate oncologic training. It is important to perform pelvic lymphadenectomy in all cases of early stage cancer.

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Gan To Kagaku Ryoho. 2003 Feb;30(2):243-9.
[Paclitaxel and carboplatin with or without pirarubicin (THP-ADR) as first line chemotherapy
in elderly patients]
[Article in Japanese]
Nagao S, Okimoto N, Hongo A, Mizutani Y, Kodama J, Yoshinouchi M, Hiramatsu Y, Kudo T.
Dept. of Obstetrics and Gynecology, Okayama University Medical School.

To evaluate the validity of administration of paclitaxel and carboplatin with or without pirarubicin (THP-ADR) as first line chemotherapy in elderly patients with gynecologic cancer, we explored the efficacy and safety of these regimens. From October 1, 1998 to September 30, 2001, we administered paclitaxel and carboplatin with or without THP-ADR pursuant to the chart we prepared originally as first line chemotherapy in patients with gynecologic cancer. Eleven elderly patients (age > 70 years) and 62 younger patients (age < 70 years) were entered into the present study. Paclitaxel was administered as a 3-hour intravenous (i.v.) infusion at dosages of 135 to 180 mg/m2 immediately followed by carboplatin over 60 minutes at dosages of area under the curve (AUC) 3 to 5, administered intravenously or intraperitoneally. We observed grade 3/4 anemia more frequently in elderly patients receiving the regimen including paclitaxel and carboplatin without THP-ADR (9% v.s. 47%, p < 0.0001). Grade 3/4 anemia (10% v.s. 22%, p = 0.02) and grade 3/4 thrombocytopenia (7% v.s. 22%, p = 0.007), febrile neutropenia (14% v.s. 44%, p = 0.02) also occurred more frequently in elderly patients receiving the regimen including paclitaxel and carboplatin with THP-ADR. The overall response rates were equivalent among elderly and younger patients (69% and 78%), respectively. The regimen consisting of paclitaxel and carboplatin without THP-ADR was applied safely to elderly patients.

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Int J Clin Oncol. 2003 Feb;8(1):45-8.
Weekly 1-h paclitaxel infusion in patients with recurrent endometrial cancer: a preliminary study.
Nishio S, Ota S, Sugiyama T, Matsuo G, Kawagoe H, Kumagai S, Ushijima K, Nishida T, Kamura T.
Department of Obstetrics and Gynecology, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. nishio_shin@hotmail.com

BACKGROUND: The aim of this study was to evaluate the toxicity and efficacy of weekly paclitaxel in patients with recurrent endometrial cancer. METHODS: Nine patients with recurrent endometrial cancer who had previously received chemotherapy or radiotherapy participated in the study, between May 1999 and August 2001. Paclitaxel was given at a dose of 70 mg/m(2) as a 1-h infusion every week for at least 20 consecutive weeks unless lesions became progressive. Intravenous dexamethasone and cimetidine and oral diphenhydramine were administered 30 min before paclitaxel infusion. RESULTS: The nine patients received a total of 149 cycles of therapy. No hypersensitivity reactions were elicited. Grade 3 leukopenia, neutropenia, and anemia occurred in 22%, 33%, and 33% of the patients, respectively. Granulocyte colony-stimulating factor was required for two patients and no patients experienced febrile neutropenia. Neurotoxicity was commonly observed. Grade 1 peripheral neuropathy and myalgias were observed in 78% and 11% of the patients, respectively. No grade 3 or higher nonhematological toxicities were observed. Partial responses were seen in six of the nine patients (67%). The median progression-free interval was 8 months (range, 0-12 months) and the median overall survival was 10 months (range, 4-24 months). CONCLUSION: Weekly 1-h paclitaxel administration is considered safe and effective as a salvage therapy for recurrent endometrial cancer, with this schedule and delivery making its use more convenient and easier in the outpatient setting. The current results support further evaluation.

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Expert Rev Anticancer Ther. 2003 Feb;3(1):37-47.
Optimal therapy and management of endometrial cancer.
Sonoda Y.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, Gynecology Service Academic Office, New York, NY 10021, USA. gynbreast@mskcc.org

Carcinoma of the endometrium is the most common malignancy of the female genital tract. Fortunately, this neoplasm presents with abnormal clinical symptoms in its early stages. The majority of cases will be detected at a curable stage when the neoplasm is still confined to the uterus. Given this fact, surgical removal of the involved organ remains the cornerstone of treatment for this disease. Certain pathologic risk factors for recurrence have been identified and are the basis for which adjuvant therapy is recommended. Controversy in management exists as to the approach and extent of primary surgery as well as the indications for adjuvant therapy. Management of this disease is reviewed.

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Curr Treat Options Oncol. 2003 Apr;4(2):121-30.
Endometrial cancer: treatment of nodal metastases.
McMeekin DS, Tillmanns T.
University of Oklahoma, Health Science Center, PO Box 26901, Oklahoma City, OK 73190, USA. scott-mcmeekin@ouhsc.edu

Surgical staging has changed the method by which patients with endometrial cancer are managed. Before the routine use of lymph node dissection, patients were presumed to have nodal disease based on imaging studies, palpation, and biopsy. The move to a surgically based staging system in 1988 created a new subgroup of patients who had documented nodal disease. The risk of nodal involvement is related primarily to tumor grade and depth of myometrial invasion. Although patients with nodal disease are uncommon, treatment of these patients poses multiple challenges. It is our belief that unless nodes are surgically assessed, the clinician will not know whether the nodes are involved. A thorough lymphadenectomy with removal of nodal tissue from multiple pelvic sites and from bilateral para-aortic regions is recommended for most patients with endometrial cancer. Identification of positive nodes allows appropriate postoperative therapies to be used, and data support that nodal dissection may be therapeutic and prognostic. Patients with positive nodes should receive radiation therapy directed to the nodal distribution, with patients having involved para-aortic nodes receiving an extended field. Whole abdominal radiation has been used, especially in patients with adnexal disease or positive cytology. The role of whole abdominal radiation remains in question. The most promising treatment option is combination therapy with sequential radiation and chemotherapy. Active chemotherapy agents in endometrial cancer are doxorubicin, cisplatin, and paclitaxel.

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Eur J Gynaecol Oncol. 2002;23(6):553-6.
Surgical stage III endometrial cancer: analysis of treatment outcomes, prognostic factors
and failure patterns.
Ayhan A, Taskiran C, Celik C, Aksu T, Yuce K.
Department of Obstetrics and Gynecology, Hacettepe University Hospitals, Ankara, Turkey.

OBJECTIVE: The purpose of this study was to evaluate the survival estimates of stage III endometrial cancer patients, and also to detect the prognostic factors and failure patterns. MATERIALS AND METHODS: Sixty-eight surgical Stage III endometrial cancer patients treated at Hacettepe University Hospital were included. All patients underwent surgical staging procedures consisting of peritoneal cytology, infracolic omentectomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy and complete pelvic-paraaortic lymphadenectomy. By surgical staging 26 (38%) patients had Stage IIIA and 42 (62%) patients had Stage IIIC disease. The mean resected lymph node number was 26 (median, 25; range, 15-58). RESULTS: The median age was 60 years (range, 38-77), and the median follow-up period was 62 months (range, 36-90 months). The 5-year disease free survival rate was 58% and the 5-year overall survival rate was 64%. These figures for Stage IIIA were 60% and 68%, respectively; and for Stage IIIC they were 57% and 62%, respectively. No significant survival difference was detected between Stage IIIA and IIIC (p = 0.60 for disease-free survival and p = 0.48 for overall survival). High grade and positive peritoneal cytology predicted poor survival in both univariate (p = 0.004 and p = 0.006, respectively) and multivariate (p = 0.05 and p = 0.04, respectively) analysis. Twenty-eight patients (41%) had recurrence with a median time of 23 months (range, 10-54 months). Nine patients (13%) had only local, 13 patients (19%) had only distant and six patients (9%) had both local and distant relapse. CONCLUSION: Surgical staging is important in the management of Stage III endometrial cancer, and the main problem is still distant failure. In multivariate analysis high grade and positive peritoneal cytology predicted poor survival significantly.

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Ginekol Pol. 2002 Nov;73(11):976-9.
[Clinical value of pelvic lymphadenectomy in surgical treatment of endometrial cancer]
[Article in Polish]
Lapinska-Szumczyk S, Emerich J.
Kliniki Ginekologii Akademii Medycznej w Gdansku.

OBJECTIVES: The aim of the study was the clinical analysis of value of pelvic lymphadenectomy in surgical treatment of endometrial carcinoma. MATERIAL AND METHODS: The group of 420 women treated for of endometrial cancer in stage IA-IV by FIGO 1988 was analysed. All these women were operated in 2nd Dept. of Obstetrics and Gynecology Medical University of Gdansk between 1981-2000. The subgroup of patients with pelvic lymphadenectomy was selected. The data were obtained from case histories. RESULTS: The subgroup of patients on whom pelvic lymphadenectomy was performed was up 32.6% of all treated women (137 women). Neoplastic metastases were found in 27 cases (19.7%). All those patients were in clinical stage II-IV by FIGO 1988, and no earlier stage of endometrial cancer was found in that group. In every case myometrial invasion was more then 1/2 of myometrium. In 59.2% of neoplastic metastases high or medium differential adenocarcinoma were found. CONCLUSION: Pelvic lymphadenectomy has to be part of surgical treatment of endometrial cancer. Lymph nodes metastases are important prognostic factors. Myometrial invasion plays an important role as a risk factor of lymph nodes metastases.

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Am J Clin Oncol. 2002 Dec;25(6):625-6.
Hypersensitivity reaction to cisplatin during chemoradiation therapy for gynecologic malignancy.
Koren C, Yerushalmi R, Katz A, Malik H, Sulkes A, Fenig E.
Institute of Oncology, Rabin Medical Center, Beilinson Campus, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Hypersensitivity reactions to intravenous cisplatin are rare. The appearance of hypersensitivity reactions in 4 of 25 consecutive patients treated with concomitant pelvic radiation and weekly intravenous cisplatin for gynecologic malignancies is reported. The reactions appeared within hours of cisplatin delivery and included primarily fever, rash, and pruritus. Infection was ruled out by blood cultures and other laboratory studies. Affected patients were treated prophylactically with an antihistamine before subsequent courses of cisplatin, with excellent results. The high rate of hypersensitivity reactions in our series may be attributable to tumor necrosis and cytokine release caused by the pelvic irradiation. Clinicians should be aware of this potential side effect so that early premedication regimens can be instituted to prevent unnecessary toxicity.

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Am J Clin Oncol. 2002 Dec;25(6):557-60.
Goserelin acetate as treatment for recurrent endometrial carcinoma: a Gynecologic
Oncology Group study.
Asbury RF, Brunetto VL, Lee RB, Reid G, Rocereto TF; Gynecologic Oncology Group.
Interlakes Oncology Hematology, P.C., Rochester, New York 19107, USA.

This Gynecologic Oncology Group (GOG) study was designed to estimate the activity of goserelin acetate as treatment for advanced and recurrent endometrial carcinoma. Forty evaluable patients received monthly treatment with goserelin acetate at a dose of 3.6 mg, given subcutaneously. Standard GOG response and adverse effects criteria were used. The median age of patients was 71 years. Seventy-one percent of patients had received prior radiation therapy; 18% of patients were reported to have received prior progestational therapy for endometrial cancer. One patient had received prior chemotherapy. There were two complete responses (5%) and three partial responses (7%). One response occurred in a patient who previously did not respond to progestin therapy after having achieved a response. The overall response rate was 11% (95% CI: 4-27%). Median progression-free survival was 1.9 months and median overall survival was 7.3 months. No severe or life-threatening toxicities occurred because of goserelin. Deep venous thrombosis developed in two patients. This study confirmed the limited activity of goserelin acetate in endometrial carcinoma, with only one response in a patient previously treated with hormonal therapy. The activity is insufficient to warrant further study of the single agent at this time. Elucidation of the mechanism of action of this drug may allow more effective use in conjunction with other agents in the future.

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Gynecol Oncol. 2002 Dec;87(3):274-80.
Surgical stage I endometrial cancer: predictors of distant failure and death.
Mariani A, Webb MJ, Keeney GL, Lesnick TG, Podratz KC.
Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota 55905, USA.

OBJECTIVES: The objective was to analyze the effect of various histopathologic characteristics on prognosis in surgical stage I (node-negative) endometrial carcinoma. METHODS: During a 10-year period, 229 patients with stage I epithelial (all subtypes) endometrial cancer had hysterectomy and node dissection. Mean number of nodes harvested was 16.2 pelvic and 5.7 paraaortic. Median follow-up was 83 months. Sixty-seven patients (29%) received adjuvant radiotherapy. RESULTS: Five-year disease-related survival (DRS) was 95%, and 5-year relapse-free survival (RFS) 91%. We observed 7 (3%) isolated vaginal recurrences, 14 (6%) distant failures, and 1 (0.4%) simultaneous recurrence at both regional (pelvic sidewall) and distant sites. Only 1 of 7 patients (14%) with vaginal failure died of the disease (median follow-up of censored patients after failure was 110 months), compared with 10 of the 15 patients (67%) with distant failure. By univariate analysis, myometrial invasion (MI) >or= 66%, nonendometrioid histology, lymphovascular invasion, absence of associated hyperplasia, and tumor diameter >2 cm were significant predictors of poor prognosis with distant failure (P <or= 0.05). Cox regression analysis identified MI >or= 66% as the only independent predictor of DRS (P < 0.001, relative risk [RR] = 12.44), RFS (P < 0.001, RR = 8.67), and distant failure (P < 0.001, RR = 24.89). Only 2% of patients with MI < 66% had distant failure and died of the disease at 5 years, compared with a 29% 5-year distant failure rate and a 22% 5-year death rate among patients with MI >or= 66%. CONCLUSION: Stage I (negative nodes) endometrial cancer patients with MI >or= 66% are at significant risk for distant failure and death and should be considered candidates for new randomized trials of adjuvant systemic therapy.

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Gynecol Oncol. 2002 Dec;87(3):247-51.
A phase II trial of topotecan in patients with advanced, persistent, or recurrent endometrial carcinoma: a gynecologic oncology group study.
Miller DS, Blessing JA, Lentz SS, Waggoner SE.
Department of Obstetrics & Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032, USA.

OBJECTIVE: To estimate the antitumor activity of topotecan in women with advanced, persistent, or recurrent endometrial carcinoma previously treated with chemotherapy, and to determine the nature and degree of toxicity of topotecan in this cohort of patients. MATERIALS AND METHODS: Eligible patients were those who had failed one prior chemotherapy regimen. Topotecan 0.5 to 1.5 mg/m(2) was administered iv daily for 5 days, every 3 weeks, until progression of disease or adverse affects prohibited further therapy. RESULTS: Of 29 patients entered, 28 were evaluable for toxicity and 22 were evaluable for response. Patient characteristics included a median age of 65, with 41% having prior radiation and 14% having prior hormonal therapy. Nine patients (41%) had a performance status (PS) of 0, 11 (50%) had a PS of 1, and 2 (9%) had a PS of 2. Patients received from 2 to 11 (with a median of 4) courses of treatment. The most frequently observed grade 4 toxicities were neutropenia seen in 17 (61%) patients, leukopenia in 11 (39%), and thrombocytopenia in 7 (25%). Two deaths were considered potentially related to treatment. There was one (4.5%) complete and one (4.5%) partial response; 12 (55%) patients maintained stable disease and eight (36%) experienced increasing tumor. CONCLUSION: Topotecan at this dose and schedule does not appear to have major activity in patients with advanced or recurrent endometrial carcinoma previously treated with chemotherapy.

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Int J Gynecol Cancer. 2002 Nov-Dec;12(6):749-54.
Cisplatin-based chemotherapy regimen (DECAV) for uterine sarcomas.
Pautier P, Genestie C, Fizazi K, Morice P, Mottet C, Haie-Meder C, Le Cesne A, Lhomme C.
Department of Medical Oncology, Institut Gustave-Roussy, Villejuif, France. pautier@igr.fr

Uterine sarcomas are an extremely rare event. There is no standard therapy for cases of relapse, although chemotherapy is commonly used. We studied the use of a cisplatin-based chemotherapy regimen for uterine sarcomas with an unusually long follow-up. Thirty-nine women with a median age of 50 years (32-71) entered the study. Histologically, leiomyosarcomas (26), carcinosarcomas (8), and stromal sarcomas (5) were represented. Group 1 consisted of patients undergoing adjuvant therapy (for initial disease, eight patients; for pelvic recurrence, two patients); Group 2 consisted of patients with advanced disease (locoregional after initial local therapy, five patients; local recurrence, six patients) or metastatic disease (stage IV, four patients; recurrence, 14 patients). DECAV therapy consisted of doxorubicin 50 mg/m2 d1, dacarbazine (DTIC) 200 mg/m2/d d1-3, vindesine 2 mg/day d1-2, cisplatin 100 mg/m2 d3, and either cyclophosphamide (CPM) 200 mg/m2/d d1-3 (n = 21), or ifosfamide (IFM) 2 g/m2/d d1-3 with mesna every 4 weeks Toxicity included 18 hospital stays for cytopenia (nine patients), including 13 cases of febrile neutropenia. Twenty blood transfusions in 10 patients and 12 platelet transfusions in seven patients were required. One toxicity-related death (hemorrhage) occurred. The overall response rate was 54% (3 complete response, 11 partial response) with a median duration of 13 months (4-36). Median overall survival was 14 month overall, 45 months for Group 1 and 13 months for Group 2. We conclude that the DECAV regimen is clearly active in uterine sarcomas but is too toxic to be recommended routinely.

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Eur J Cancer. 2002 Nov;38(17):2265-71.
Adjuvant endocrine treatment with medroxyprogesterone acetate or tamoxifen in stage I and II endometrial cancer--a multicentre, open, controlled, prospectively randomised trial.
von Minckwitz G, Loibl S, Brunnert K, Kreienberg R, Melchert F, Mosch R, Neises M, Schermann J, Seufert R, Stiglmayer R, Stosiek U, Kaufmann M.
Department of Gynaecology and Obstetrics, Johann Wolfgang Goethe-Universitat Frankfurt/Main, Germany.

Endometrial cancer is a hormone-dependent disease and therefore an adjuvant hormonal therapy might improve the outcome in the early stages of the disease. Between 1983 and 1989, we conducted a randomised trial of 388 patients who received either medroxyprogesterone acetate (MPA) (n=133) or tamoxifen (n=121) orally for 2 years, or were observed only (n=134) after surgical therapy. The aim was to evaluate whether an adjuvant treatment can improve disease-free and overall survival rates. After a median follow-up period of 56 months (range 3-199 months), we observed no differences in the disease-free and overall survival rates for the tamoxifen group compared with the control or the MPA group. Side-effects were more frequent and severe in the MPA-group than in the tamoxifen group. In patients with early endometrial cancer, adjuvant endocrine treatment did not significantly improve the outcome. However, tamoxifen did have some beneficial effects on coexisting morbidity.

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Zentralbl Gynakol. 2002 Jul;124(7):356-61.
[Actual aspects of endometrial carcinoma]
[Article in German]
Dietl J.
Universitats-Frauenklinik Wurzburg, Germany. j.dietl@mail.uni-wuerzburg.de

The endometrial carcinoma is meanwhile the most common malignant tumor of the female genital tract. 2 subtypes can be divided according the pathogenesis: the classical estrogen related endometroid type and the nonclassical estrogen unrelated serous type. The endometrial adenomatous hyperplasia as a precancerous lesion must be identified by subjective criteria. Therefore the histological diagnosis is worse reproducible. An improvement would be helpful by morphometric and molecular genetic methods. The golden standard of diagnosis of the endometrial carcinoma is fractional dilatation and curettage. Immunohistochemical staining with a limited panel of antibodies can discriminate between an endometrial and an endocervical origin of an adenocarcinoma. The corner stone of the therapy is surgery. An individual decision about postoperative treatment is very important and depends on histological criteria. The adjuvant postoperative whole pelvic radiation is under discussion whereas the vaginal brachytherapy is established as standard therapy. This article outlines an overview of the actual situation for pathogenesis, diagnosis and treatment endometrial cancer.

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Radiother Oncol. 2002 Oct;65(1):23-8.
Outcome after salvage radiotherapy (brachytherapy +/- external) in patients with a vaginal recurrence from endometrial carcinomas.
Hasbini A, Haie-Meder C, Morice P, Chirat E, Duvillard P, Lhomme C, Delapierre M, Gerbaulet A.
Department of Radiotherapy, Brachytherapy Service, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France.

BACKGROUND AND PURPOSE: The vagina is the site most commonly affected by loco-regional failure in endometrial carcinoma (EC). The aim of this study was to evaluate the efficacy of vaginal brachytherapy (BT) combined or not with whole pelvic external radiotherapy (RT) for the treatment of patients with vaginal recurrences from endometrial cancer. PATIENTS AND METHODS: Between 1986 and 1999 25 women were treated at the Institut Gustave Roussy (IGR) for a vaginal relapse (VR) from EC. Patient characteristics were as follows: median age 65 years (range 43-84), histologic type: adenocarcinoma (21 patients); endometrioid carcinoma (three patients); adenoacanthoma (one patient); FIGO staging for initial disease: Ia, three; Ib, eight; Ic, four; II, seven; IIIa, two; IVa, one. The initial tumor was treated by surgery alone in 18 patients, or surgery combined with RT and/or BT in seven patients. A VR occurred in a median interval of 21 months (range 2-89); 10/25 (40%) occurred within the first year following initial treatment. The recurrence was exclusively in the vagina in 18 patients and was associated with parametrial and or nodal involvement in seven patients; it was localized in the upper 1/3 of the vagina in nine patients, in the upper 2/3 or the entire vagina in 11 patients or in the lower 1/3 in five patients. The largest tumor diameter ranged from 10 to 70 mm (median: 25 mm). The treatment of the VR included low-dose rate endocavitary BT in all cases: three patients received endocavitary BT alone, or it was associated with external RT in 22 patients or delivered after surgical removal of the lesion in nine patients. Seven patients were submitted to further irradiation combining endocavitary and interstitial BT. RESULTS: Local control was achieved in 23 patients (92%). With a follow-up ranging from 4 to 154 months, 13 patients have died (ten due to metastasis, two of intercurrent disease and two due to local tumor progression) and ten patients are alive and disease free. The 3-year actuarial survival was 48%. Late radiation-related sequelae were observed in nine patients (mucous necrosis in one patient, moderate sclerosis in six patients) in an interval varying between 8 and 45 months. The majority of recurrences occurred in patients who had not previously received irradiation, which emphasizes the role of systematic prophylactic post-operative vaginal BT. Extra-vaginal extension (P < 0.001), the tumor size (P < 0.03) and the stage of initial disease (P < 0.01) appeared to have a significant impact on the prognosis. CONCLUSION: BT combined with external RT is an efficient treatment for VR from EC even in previously irradiated patients. Poor survival remains related to metastatic dissemination. Copyright 2002 Elsevier Science Ireland Ltd.

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Int J Radiat Oncol Biol Phys. 2002 Nov 15;54(4):1153-9.
Interstitial brachytherapy for salvage treatment of vaginal recurrences in previously unirradiated endometrial cancer patients.
Nag S, Yacoub S, Copeland LJ, Fowler JM.
Division of Radiation Oncology, Arthur G. James Cancer Hospital and Solove Research Institute, Ohio State University, 300 W. Tenth Avenue, Columbus, OH 43210, USA. nag.1@osu.edu

PURPOSE: To evaluate whether interstitial brachytherapy can effectively salvage vaginal recurrence from endometrial carcinoma. METHODS AND MATERIALS: Between September 1989 and September 2000, 13 previously unirradiated patients (mean age 70 years) with isolated vaginal recurrences from endometrial adenocarcinoma were treated with interstitial low-dose-rate brachytherapy with or without additional external beam radiotherapy. Brachytherapy was delivered using a modified perineal Syed template loaded with (192)Ir. The central cylinder was loaded with high-activity (192)Ir (n = 12) or (137)Cs (n = 1). RESULTS: The patients had initially presented with FIGO Stage I (n = 11) or III (n = 2) cancer. Vaginal recurrences were diagnosed at a mean interval of 27.5 months after hysterectomy (range 2-83). The patients were followed for a median of 60 months (range 15-105). Ten patients had recurrence at the vaginal apex and three had recurrence in the lower two-thirds of the vagina. The median time to recurrence was 22 months. The tumor size ranged from 1.5 to 6 cm (mean 2.2, median 2.5). Eleven of 13 patients received 45-50-Gy pelvic external beam radiotherapy, followed by a mean interstitial brachytherapy boost of 28.3 Gy (range 18-35). The 2 other patients received brachytherapy only of 40 Gy and 50 Gy, respectively. All tumors were locally controlled. Three (23%) of 13 patients had a relapse at distant sites (two in the paraaortic region and one in the liver). The overall 8-year actuarial disease-specific survival rate was 77%. Major (Grade 3 and 4) long-term morbidity occurred in 2 patients (15%) and included Grade 3 vaginal ulceration in 1 patient, and Grade 4 colovesical fistula requiring surgical intervention in 1 patient. Additional long-term morbidity included Grade 2 proctitis in 1 patient. CONCLUSION: Interstitial brachytherapy with or without supplementary external beam radiotherapy can effectively salvage vaginal recurrence from endometrial cancer with very favorable local control and overall survival and acceptable morbidity.

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Wien Klin Wochenschr. 2002 Jan 15;114(1-2):44-9.
Surgery and adjuvant radiation therapy of endometrial stromal sarcoma.
Weitmann HD, Kucera H, Knocke TH, Potter R.
Department of Radiotherapy and Radiobiology, University of Vienna, General Hospital Vienna, Austria. Dirk.Weitmann@str.akh.magwien.gv.at

OBJECTIVE: In the treatment of endometrial stromal sarcoma, it is still not clear whether adjuvant radiation therapy improves the outcome. We wish to summarize the experiences we gathered from treating 15 patients over a period of 18 years, and to compare these to results from literature. PATIENTS AND METHODS: According to the 1989 FIGO classification for endometrial carcinoma, 11 (73%) of the 15 patients analyzed presented stage I, 1 presented stage II, and 3 presented stage III sarcoma. Of these, 11 patients (73%) had high grade stromal sarcoma and 4 had low grade stromal sarcoma. All patients were treated with surgery and adjuvant radiation therapy. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed on 11 patients (73%), vaginal hysterectomy and bilateral salpingo-oophorectomy on 2 patients, and total abdominal hysterectomy on 2 patients. Combined radiotherapy was performed on 13 patients (93%), while isolated brachytherapy and isolated external beam therapy were each performed on 1 patient. External beam therapy was administrated in daily fractions of 1.6-2.0 Gy up to a total dose of 37-57 Gy to the pelvis. RESULTS: Follow up ranged from 23 to 170 months (mean: 80 mths). 10 patients (67%) are still alive without tumor, and 5 patients have died. Of these, one died due to intercurrent disease, one due to breast-cancer, and 3 due to endometrial stromal sarcoma, presenting distant metastases within one year after therapy. Only one patient presented with an additional local recurrence. The overall actuarial survival and the disease specific survival rate was 72% and 79% respectively after 5 years, and 60% and 79% after 10 years. The overall local control rate was 93% after 5 years. There were no severe acute side effects and no late side effects. CONCLUSION: In our experience, the most effective treatment for patients with endometrial stromal sarcoma is total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by adjuvant radiation therapy, due to the excellent local monitoring possibilities in all stages of disease, and a good disease specific survival in early stages.

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Cancer. 2002 Nov 1;95(9):1894-901.
Analysis of survival after laparoscopy in women with endometrial carcinoma.
Eltabbakh GH.
Division of Gynecologic Oncology, University of Vermont College of Medicine, Burlington, USA.

BACKGROUND: The effect of the laparoscopic surgical approach on the survival of women with endometrial carcinoma remains unclear. The objectives of the current study were to assess the effect of laparoscopic surgery on the survival of women with early-stage endometrial carcinoma and to analyze the factors that affect such survival. METHODS: A retrospective review of women presenting with clinical stage I endometrial carcinoma (according to the 1988 International Federation of Gynecology and Obstetrics Staging System) was performed. Women treated with laparoscopy were compared with those treated with laparotomy with regard to their characteristics, surgical procedure, treatment, surgical stage, histology, tumor grade, and recurrence-free and overall survival. Factors affecting survival (surgical approach, histology, grade, and surgical stage) were evaluated using multivariate analysis and survival curves were constructed using Kaplan-Meier analyses. RESULTS: One hundred women underwent laparoscopy and 86 underwent laparotomy. Both groups were similar with regard to age, parity, menopausal status, lymphadenectomy, surgical stage, tumor grade, histology, and postoperative radiation therapy. Women who underwent laparoscopy and those who underwent laparotomy had similar 2-year and 5-year estimated recurrence-free survival rates (93% vs. 94% and 90% vs. 92%, respectively), as well as similar 2-year and 5-year overall survival rates (98% vs. 96% and 92% vs. 92%, respectively). There was no apparent difference with regard to the sites of recurrence between both groups. In univariate and multivariate analyses, surgical stage, tumor grade, and histology (but not the surgical approach) were found to have a significant effect on survival. CONCLUSIONS: Although longer follow-up is needed, the survival of women with early-stage endometrial carcinoma does not appear to be worsened by laparoscopy. Surgical stage, tumor histology, and tumor grade were found to significantly affect survival regardless of the surgical approach used. Copyright 2002 American Cancer Society.

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Int Surg. 2002 Jul-Sep;87(3):185-90.
Clinical assessment of neoadjuvant chemotherapy and interval cytoreductive surgery for unresectable advanced ovarian cancer.
Ushijima K, Ota S, Komai K, Matsuo G, Motoshima S, Honda S, Tomonari R, Sugiyama T, Kamura T.
Department of Obstetrics and Gynecology, Kurume University School of Medicine, Japan. kimi@med.kurume-u.ac.jp

Sixty-five patients with unresectable advanced epithelial ovarian cancer who underwent exploratory laparotomy or unilateral oophorectomy were reviewed. Forty-five of 65 patients received 3.8 cycles of neoadjuvant chemotherapy (NAC) and were successfully debulked at interval cytoreductive surgery (IRS); 31 of 45 showed no evidence of disease. Patients with residuals <1 cm at IRS had a high possibility of achieving clinical remission. Patients who failed to receive IRS showed poor prognosis. Also, 63 patients who underwent conventional primary debulking surgery with residuals >1 cm were investigated as a contrast. No significant difference was observed in patient survival between the NAC group and the conventional treatment group. NAC and IRS offered patients with unresectable tumors survival similar to that of those with suboptimally resectable tumors at primary debulking. We conclude that this strategy has potential benefits for the patients with clinically aggressive ovarian cancer who are unable to receive standard treatment.

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Eur J Obstet Gynecol Reprod Biol. 2002 Nov 15;105(2):161-5.
Neoadjuvant therapy of endometrial cancer with the aromatase inhibitor letrozole:
endocrine and clinical effects.
Berstein L, Maximov S, Gershfeld E, Meshkova I, Gamajunova V, Tsyrlina E, Larionov A, Kovalevskij A, Vasilyev D.
Laboratory Oncoendocrinology, N.N. Petrov Research Institute of Oncology, St. Petersburg 197758, Russia. levmb@endocrin.spb.ru

OBJECTIVE: To investigate the short-term hormonal and clinical effects of the aromatase inhibitor letrozole (Femara) in patients with endometrial cancer. MATERIALS AND METHODS: Ten previously untreated, post-menopausal patients (mean age 59 years) with endometrial cancer, predominantly stage I disease, received letrozole 2.5mg per day for 14 days before surgery. Clinical, sonographic, morphologic, cytologic, and hormonal-metabolic parameters (blood estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), glucose, and cholesterol by radioimmunoassay, enzyme immune assay, or enzyme-colorimetric methods; tumor progesterone receptors by ligand-binding assay; and aromatase activity by 3H-water release assay) were evaluated before and after treatment. RESULTS: Treatment was well-tolerated in all patients. In two patients, pain relief in the lower part of the belly and/or decrease in intensity of uterine discharge was reported. In the three cases, substantial decreases in endometrial M-echo (ultrasound) signal were noted; the mean value of this parameter after treatment was 31.1% lower than before treatment. Blood estradiol concentration decreased by an average of 37.8% after letrozole therapy, and tumor progesterone receptor levels and aromatase activity decreased by 34.4 and 17.5%, respectively. Treatment with letrozole did not influence surgery. CONCLUSIONS: These data show that short-term treatment with letrozole in the neoadjuvant setting resulted in some positive clinical changes. Longer-term and larger-scale trials of neoadjuvant letrozole in endometrial cancer are warranted.

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Int J Gynecol Cancer. 2002 Sep-Oct;12(5):459-64.
Concomitant cisplatin and extended field radiation therapy in patients with cervical and
endometrial cancer.
Sood BM, Timmins PF, Gorla GR, Garg M, Anderson PS, Vikram B, Goldberg GL.
Department of Radiation Oncology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA. brijmsood@aol.com

The purpose of this study is to evaluate the toxicity and safety of concomitant cisplatin (CDDP) and extended field radiation therapy (EFRT) in patients with cervical cancer (CxCA) and endometrial cancer (EnCA). Twenty-five patients were analyzed retrospectively for treatment-related morbidity from 1989 to 1998. Fourteen patients had CxCA and 11 patients had EnCA. Eighteen patients (72%) had surgery prior to radiotherapy and chemotherapy. EFRT was delivered by a four-field technique to the pelvis and para-aortic regions. CDDP at 100 mg/m2 was given over 5 days during 1st and 4th week of EFRT. EFRT dose for EnCA and CxCA was 45 Gy. Toxicity was analyzed using the RTOG toxicity criteria. Twenty-four (96%) of the 25 patients completed the prescribed therapy. Of the 14 patients with CxCA, three (21%) had no toxicity, three (21%) had grade 1-2, and eight (58%) had grade 3-4 hematologic toxicities. Overall six (24%) had grade 3-4 acute gastrointestinal toxicities, three (21%) of these patients were treated for cervix cancer and three (27%) patients were treated for endometrial cancer. The worst (Grade 3-4) toxicities in 15 patients occurred after the 4th week of radiotherapy. In six of 25 (24%) patients radiation treatments had to be delayed due to toxicities. The median delay of treatment was 10.5 days (range 7-31 days). Of the six patients who had grade 3-4 acute gastrointestinal toxicities, four (66%) had undergone exploratory laparotomy and lymph node sampling prior to start of chemoradiation. We conclude that concomitant EFRT and CDDP appears to be safe with moderate but manageable toxicity. Toxicity is most severe after the 4th week of treatment. Morbidity may be worse in patients with prior laparotomy.

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Int J Gynecol Cancer. 2002 Sep-Oct;12(5):448-53.
The influence of cytoreductive surgery on survival and morbidity in stage IVB endometrial cancer.
Ayhan A, Taskiran C, Celik C, Yuce K, Kucukali T.
Department of Obstetrics and Gynecology, Hacettepe University Hospitals, Ankara, Turkey. cagataytaskiran@yahoo.com

The purpose of this study was to detect possible survival advantages of surgical cytoreduction and different adjuvant treatment regimens for stage IVB endometrial cancer patients, and also to evaluate the prognostic importance of surgico-pathological risk factors and surgical morbidity rates. Thirty-seven FIGO stage IVB endometrial cancer patients treated at the Hacettepe University Hospital between 1977 and 1998 were included in this study. Clinical data were obtained from the private oncology files and all specimens were re-evaluated by the co-author pathologist. Optimal cytoreduction was defined as a surgical procedure leaving the patient with < or =1 cm residual disease in maximal diameter. All patients were subjected to initial cytoreductive surgery, but it had been achieved for 22 (60%) patients. Fourteen (38%) patients received both radiotherapy and chemotherapy, 10 (27%) patients received only radiotherapy and the other 10 (27%) patients received only chemotherapy. Three patients refused any type of adjuvant therapy. The median survival of the suboptimally cytoreduced patients was 10 months, while the median survival in the optimal group was 25 months (P = 0.001). In optimal cytoreduction group, the median survival for 12 (55%) patients without visible tumor was 48 months compared to 13 months in 10 (45%) patients with visible tumor. As an adjuvant treatment, concomitant cisplatin and radiotherapy revealed 54 months median survival compared to 15 and 13 months in patients treated with only radiotherapy and only chemotherapy, respectively. By univariate analysis, extra-abdominal metastases, suboptimal cytoreduction, visible tumoral mass after cytoreduction, pelvic-para-aortic lymphatic metastases, and cervical invasion were found to be significant predictors of poor survival. In multivariate analysis, optimal cytoreduction, concomitant cisplatin-radiotherapy treatment, and extra-abdominal metastases were significant. Morbidity was mild in six (16%), and severe in nine (24%) patients. We conclude that optimal cytoreduction achieved significant survival benefit for stage IVB endometrial cancer patients with a reasonable surgical morbidity rate. As an adjuvant treatment, concomitant cisplatin and radiotherapy was the best choice.

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Oncologist. 2002;7 Suppl 5:36-45.
Update on the treatment of cervical and uterine carcinoma: focus on topotecan.
Fiorica JV.
H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL 33612-9497, USA. fiorica@moffitt.usf.edu

Carcinomas of the uterine cervix and corpus are significant causes of morbidity and mortality among women in the U.S. and are expected to contribute 10,700 deaths in 2002. Despite the widespread use of cytologic screening and improvements in early diagnosis, mortality rates have changed little over the past 25 years, and the management of cervical and uterine cancers remains a significant unmet medical need. Currently available modalities, including radiotherapy and cisplatin-based chemotherapy, provide suboptimal control of disease, and there are no effective treatments for recurrent disease. The antitumor activity and tolerability of a number of novel agents, including topoisomerase I inhibitors, vinca alkaloids, taxanes, and gemcitabine, have been of considerable interest in treatment of these cancers. This review discusses current trends in the treatment of cervical and endometrial carcinomas, focusing on the potential role of topotecan in the treatment of non-ovarian gynecologic malignancies.

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