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Latest Research on
Endometrial Cancer
     
J Minim Invasive Gynecol. 2008 March - April;15(2):181-187.
Analysis of Survival After Laparoscopic Management of Endometrial Cancer.
Nezhat F, Yadav J, Rahaman J, Gretz H, Cohen C.
Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Science, The Mount Sinai School of Medicine, New York, New York; Division of Minimally Invasive Surgery, Department of Obstetrics, Gynecology, and Reproductive Science, The Mount Sinai School of Medicine, New York, New York.

STUDY OBJECTIVE: To assess the effect of laparoscopic surgery on the survival of women with early-stage endometrial cancer and to analyze the factors that affect survival. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Tertiary teaching hospital. PATIENTS: Women with clinical stage I and II endometrial cancer (International Federation of Gynecology and Obstetrics staging, 1971) from January 1993 through June 2003. INTERVENTION: Demographic, surgical, perioperative, and pathologic characteristics of women treated with laparoscopy or laparotomy were compared by use of Fisher's exact test or the Student t test. Recurrence-free and overall survival was calculated by use of the Kaplan-Meier method. Stratified analyses were performed with the log-rank test for factors affecting survival (surgical stage, histologic study, and grade). MEASUREMENTS AND MAIN RESULTS: Sixty-seven and 127 women were treated with laparoscopy and laparotomy, respectively. Median follow-up was 36.3 months for the laparoscopy group and 29.6 months for the laparotomy group. The complication rates in the 2 groups were comparable. Women undergoing laparoscopy had shorter hospital stay and less morbidity related to infection. The 2- and 5-year estimated recurrence-free survival rates for the laparoscopy and laparotomy groups (93 % vs 91.7% and 88.5% vs 85%, respectively), as well as the overall 2- and 5-year survival rates (100% vs 99.2% and 100% vs 97%, respectively) were similar. CONCLUSIONS: Laparoscopic surgery in women with early-stage endometrial carcinoma resulted in survival rates similar to laparotomy, although a small sample size precludes definitive conclusions. A larger randomized comparison of the 2 techniques is needed to validate these findings.

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Brachytherapy. 2008 Mar 19 [Epub ahead of print]
Vaginal vault brachytherapy as sole postoperative treatment for low-risk endometrial cancer.
Chong I, Hoskin PJ.
Mount Vernon Cancer Centre, Northwood, Middlesex, UK.

PURPOSE: To evaluate the efficacy and side effect profile of adjuvant vaginal vault brachytherapy alone after hysterectomy in Stage I endometrial carcinoma. METHODS AND MATERIALS: Between 23/11/1992 and 16/05/2005, a total of 173 patients with early endometrial carcinoma treated with vaginal vault brachytherapy alone postoperatively were identified. Patients were treated using a single-line source vaginal stump applicator (Varian Medical Systems) to deliver a dose of 5.5Gy per fraction at a depth of 5mm from the applicator surface. A total of four fractions were delivered treating twice a week giving an overall treatment time of 10 days to deliver the total dose of 22Gy in four fractions. RESULTS: There were 19 deaths in this series, 6 (3.5%) from disseminated endometrial cancer and 13 (7.5%) from unrelated causes. High-risk features of Stage 1C, Grade G3, or clear cell histology were present in all 6 patients who developed metastatic disease. One patient developed a local recurrence alone, which was salvaged with external beam pelvic radiotherapy. The low-risk group defined by Stage 1B and G1 or G2 did not develop distant relapse in this series. Late morbidity was rare except for vaginal stenosis seen in 13%. CONCLUSIONS: This series confirms that vaginal vault brachytherapy is associated with a high rate of pelvic control and survival after simple hysterectomy for low- and intermediate-risk endometrial cancer with minimal toxicity.

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Int J Gynaecol Obstet. 2008 Mar 13 [Epub ahead of print]
Synchronous early-stage endometrial and ovarian cancer.
Signorelli M, Fruscio R, Lissoni AA, Pirovano C, Perego P, Mangioni C.
Clinic of Obstetrics and Gynecology, San Gerardo Hospital, University of Milan-Bicocca, Monza, Italy.

OBJECTIVE: To explore the clinicopathologic findings and oncological outcome of early-stage synchronous endometrial and ovarian malignancies. METHODS: A retrospective study of 93 women with synchronous stage I ovarian and stage I-II endometrial cancer treated between December 1981 and August 2005 in the gynecologic oncology department of San Gerardo Hospital, Italy. RESULTS: Fifty-one percent of the ovarian tumors were stage Ia and 71% of the endometrial cancers had minimal myometrial invasion. Endometrioid histology and grade 2 disease were prevalent in both sites. Hyperplasia and endometriosis coexisted in 71% and 22% of endometrial and ovarian cancers, respectively. The actuarial 5-year disease-free and overall survival rates were 83% and 96%, respectively. CONCLUSION: The incidence of synchronous endometrial and ovarian cancer is not negligible, especially among young women. Synchronous cancers show very favorable pathologic features and have an excellent oncologic outcome. Adjuvant therapy should be tailored according to surgical staging and histology.

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Int J Clin Oncol. 2008 Feb;13(1):62-5. Epub 2008 Feb 29.
A phase II trial of weekly 1-hour paclitaxel as second-line therapy for endometrial and cervical cancer.
Homesley HD, Meltzer NP, Nieves L, Vaccarello L, Lowendowski GS, Elbendary AA.
The Brody School of Medicine of East Carolina University, 2S-12 Brody Medical Sciences Building, Greenville, NC, 27834, USA, homesleyh@ecu.edu.

BACKGROUND: The efficacy of weekly paclitaxel has not been well characterized in either cervical or endometrial cancer. METHODS: Eligible women had disseminated endometrial or squamous cell cancer of the cervix, one prior chemotherapy regimen, measurable disease, and a Gynecologic Oncology Group (GOG) performance status of 0-2. At entry, all laboratory results were within normal limits. Paclitaxel 80 mg/m(2) was administered by intravenous infusion over 1 h every 7 days. Response served as the endpoint of the trial. RESULTS: Forty-four patients were registered, and 15 of 16 patients with endometrial cancer and 20 of 28 patients with cervical cancer were evaluable for response. Four of the 15 (26.7%) endometrial cancer patients responded to treatment, with one complete response of 22 weeks and three partial responses. Stable disease was present in 26.7%. Two of the 20 (10%) cervical cancer patients responded to treatment, with one complete response of 25 weeks and one partial response of 14 weeks. Stable disease was present in 35%. Adverse effects were minimal and easily managed with dose adjustments as needed. CONCLUSION: Although confirmatory larger trials are needed, weekly paclitaxel appears promising for advanced endometrial carcinoma, and possibly for squamous cell carcinoma of the cervix.

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Gynecol Oncol. 2008 Feb 23 [Epub ahead of print]
Carboplatin and paclitaxel in advanced or metastatic endometrial cancer.
Pectasides D, Xiros N, Papaxoinis G, Pectasides E, Sykiotis C, Koumarianou A, Psyrri A, Gaglia A, Kassanos D, Gouveris P, Panayiotidis J, Fountzilas G, Economopoulos T.
Second Department of Internal Medicine, Propaedeutic, Oncology Section, University of Athens, “Attikon” University Hospital, Haidari, 1 Rimini, Athens, Greece.

OBJECTIVES: The purpose of this study was to evaluate the activity and toxicity of carboplatin and paclitaxel combination in advanced or recurrent endometrial carcinoma. METHODS: Forty-seven eligible patients with measurable advanced or recurrent endometrial carcinoma were treated with carboplatin [area under the curve (AUC) 5] and paclitaxel 175 mg/m(2) every 3 weeks for 6-9 cycles or until disease progression or unacceptable toxicity. RESULTS: There were 10 complete responses (CRs) (21%) and 19 partial responses (PRs) (41%) for an overall response rate (RR) of 62% (29 patients) (95% confidence interval [CI], 47-76%). The median progression-free survival (PFS) was 15 months (95% CI, 7.3-22.7 months) and the median overall survival (OS) was 25 months (95% CI, 19.0-31.0 months). No difference was found in RR and OS in patients with primary advanced disease and those with recurrent tumors. Similarly, no difference was found in PFS and OS for patients with serous/clear tumors an
d those with endometrioid tumors. Toxicity was generally mild except for myelotoxicity. Neutropenia grade 3/4 was recorded in 36% of patients and 6% experienced febrile neutropenia. One patient each developed grade 4 thrombocytopenia and anemia. Grade 3 sensory neuropathy was recorded in 6% of patients. CONCLUSION: The combination of carboplatin and paclitaxel appears to have activity in advanced or recurrent endometrial carcinoma with an acceptable toxicity profile.

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Int J Radiat Oncol Biol Phys. 2008 Feb 5 [Epub ahead of print]
High-Dose-Rate Rotte "Y" Applicator Brachytherapy for Definitive Treatment of Medically Inoperable Endometrial Cancer: 10-Year Results.
Coon D, Beriwal S, Heron DE, Kelley JL, Edwards RP, Sukumvanich P, Zorn KK, Krivak TC.
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA.

PURPOSE: To assess the intermediate clinical outcomes of medically inoperable patients with endometrial cancer treated with definitive Rotte "Y" applicator high-dose-rate brachytherapy (HDRB) over a 10-year period. METHODS AND MATERIALS: Forty-nine inoperable patients were treated with HDRB from 1997 to 2007. Forty three (84%) were markedly obese (body mass index >35 kg/m(2)). Thirty-one patients (63.3%) underwent two-dimensional treatment planning, whereas 18 patients (36.7%) underwent three-dimensional treatment planning. Thirty five of the patients (71.4%) were first treated with external beam radiotherapy (EBRT). For patients receiving EBRT in addition to HDRB, the median Y-applicator dose was 20 Gy in 5 fractions; for patients receiving HDRB alone it was 35 Gy in 5 fractions. All patients received two Y-applicator treatments per day. RESULTS: Median follow-up time for all patients was 33 months. Acute HDRB toxicities were limited to Grade 1 and 2 occurring in 5 patients.
One patient had a myocardial infarction. Four patients had late Grade 2 or 3 toxicity. Three patients had local recurrence (median time to recurrence, 16 months). The 3- and 5-year actuarial cause-specific survival rates were 93% and 87%, respectively; the overall survival rate was 83% and 42%, respectively, at 3 and 5 years. CONCLUSIONS: Twice-daily HDRB using a Y-applicator is a well-tolerated and efficacious regimen for the definitive treatment of medically inoperable patients with early-stage endometrial cancer. The recent incorporation of three-dimensional treatment planning has the potential to further decrease treatment morbidities.

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Gynecol Oncol. 2008 Feb 1 [Epub ahead of print]
Feasibility and effectiveness of a lifestyle intervention program in obese endometrial cancer patients: A randomized trial.
von Gruenigen VE, Courneya KS, Gibbons HE, Kavanagh MB, Waggoner SE, Lerner E.
University Hospitals Case Medical Center, Division of Gynecologic Oncology, 11100 Euclid Avenue, Room 7128, Cleveland, Ohio 44106, USA; Case Western Reserve University, Cleveland, OH, USA; Department of Reproductive Biology, USA.

OBJECTIVE: The majority of endometrial cancer survivors (ECS) are obese and at risk for premature death. The purpose of this study was to assess feasibility of a lifestyle intervention program for promoting weight loss, change in eating behaviors, and increased physical activity in obese ECS. STUDY DESIGN: Early stage ECS (n=45) were randomized to a 6-month lifestyle intervention (LI; n=23) or usual care (UC; n=22). The LI group received group and individual counseling for 6 months. The primary endpoint was weight change. Secondary endpoints were physical activity, [Leisure score index (LSI)] and nutrient intake (3-day food records). Quantitative vitamin C and folate intake were used to assess fruit/vegetable intake. RESULTS: Recruitment was 29%, adherence (LI group) was 73% and 84% of participants completed follow-up assessments. At 12 months, the intervention group lost 3.5 kg compared to a 1.4 kg gain in the control group [mean difference=-4.9 kg; 95% CI: -9.0 to -0.9 kg; p=.018] and had an increased LSI score of 16.4 versus -1.3 in the control group from baseline [mean group difference=17.8; 95% CI=7.1 to 28.4; p=.002]. There were no differences in vitamin C and folate intake. The LI group had lower intake of kilocalories, although differences were not significant. CONCLUSION(S): A lifestyle intervention program in obese ECS is feasible and can result in sustained behavior change and weight loss over a 1-year period.

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Obstet Gynecol. 2008 Feb;111(2 Pt 1):436-47.
Endometrial cancer.
Sorosky JI.
Department of Obstetrics and Gynecology, Hartford Hospital, the University of Connecticut, Hartford, Connecticut 06102, USA. jsorosk@harthosp.org

This review summarizes the epidemiology, prevention, diagnosis and treatment, and prognosis of endometrial carcinoma. Although the incidence of disease has remained stable, the death rate has increased over 100% over the last two decades. Precursor lesions of complex hyperplasia with atypia are associated with an endometrial carcinoma in over 40% of cases. The percentage of obese women with endometrial cancer is increasing. The incidence of endometrial cancer in white women is twice the incidence in African-American women, but stage for stage, African-American women have a less favorable prognosis. Preoperative imaging cannot accurately assess lymph node involvement. Gross examination of depth of myometrial invasion does not have the sensitivity, specificity, and positive or negative predictive value to select women who can have lymphadenectomy safely omitted from the surgical procedure. In the absence of ideal noninvasive preoperative testing, surgical staging remains the most accurate method of determining the extent of disease. There has been an increase in surgical staging and a decrease in postoperative adjuvant pelvic radiation therapy over the past two decades. Women with a family history of hereditary nonpolyposis colorectal colon cancer are at increased risk for endometrial cancer. Conservative treatment to allow for childbearing is possible in select situations. Women with endometrial cancer should be managed by physicians experienced in the treatment of this disease.

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Int J Radiat Oncol Biol Phys. 2007 Dec 28 [Epub ahead of print]
Stage II Adenocarcinoma of the Endometrium: Adjuvant Radiotherapy and Recurrence Patterns.
Cozad SC.
Therapeutic Radiologists, Inc., Liberty Radiation Oncology Clinic, Liberty, MO.

PURPOSE: Review patterns of recurrence for Stage II endometrial cancer in a community practice. METHODS AND MATERIALS: A retrospective review of patients with endometrial cancer diagnosed between 1985-2002. Patients were excluded for Stages I, III, or IV or treatment with preoperative pelvic radiation (external beam radiation therapy [EBRT]). RESULTS: Eighty-six patients with a mean follow-up of 70 months are reported. Higher risk patients were selected for adjuvant radiation with no apparent differences for those receiving only EBRT compared with EBRT with brachytherapy. Five-year actuarial vaginal, pelvic sidewall/nodal, and metastatic control rates were 100% and 100%, 96.9% and 100%, and 79% and 84.2% for patients receiving EBRT or EBRT with brachytherapy. Overall survival rates were 70.5% and 75.8%, and cause-specific survival rates were 78.8% and 82.9% for those receiving EBRT or EBRT with brachytherapy. A select group was observed and experienced one vaginal recurrence with overall and cause-specific survival rates of 100%. CONCLUSION: In higher risk patients with Stage II, adjuvant EBRT achieves excellent vaginal and pelvic sidewall/nodal control without apparent benefit from additional brachytherapy. Select patients may not require adjuvant treatment.

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Int J Gynecol Cancer. 2007 Dec 13 [Epub ahead of print]
The outcome of patients with stage I endometrial cancer involving the lower uterine segment.
Lavie O, Uriev L, Gdalevich M, Barak F, Peer G, Auslender R, Anteby E, Gemer O.
Department of Obstetrics and Gynecology, Carmel Medical Center, Haifa, Israel.

The objective of this study was to evaluate whether lower uterine segment involvement (LUSI) correlates with recurrence and survival in women with stage I endometrial adenocarcinoma and whether it is associated with poor prognostic histopathologic features. Three hundred seventy-five consecutive patients with endometrial carcinoma stage I compromised the study population. The patients were divided into two groups according to the presence of LUSI with endometrial carcinoma. The two groups were compared with regard to prognostic factors and outcome measures by using the Pearson chi(2) test, log-rank test, and Cox proportional hazards model. LUSI was present in 89 (24%) patients with stage I endometrial carcinoma. LUSI was significantly associated with grade 3 tumor (P= 0.022), deep myometrial invasion (P < 0.0001), and the presence of capillary space-like involvement (CSLI) (P= 0.003). Kaplan-Meier survival curves demonstrated that patients with LUSI had a lower recurrence-free survival (log-rank test; P= 0.009) and a worse overall survival (log-rank test; P= 0.0008). In the Cox proportional hazards model, only a trend toward higher recurrence rate (HR = 2.4, 95% CI 0.7, 8.2; P= 0.16) and a trend toward poorer overall survival (HR = 1.54, 95% CI 0.82, 2.91; P= 0.18) were noted when LUSI was present. In patients with stage I endometrial cancer, the presence of LUSI is associated with grade 3 tumor, deep myometrial invasion, and the presence of CSLI. A larger group of patients is necessary to conclude whether higher recurrence rate and poorer overall survival are associated with the presence of LUSI.

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Prev Med. 2007 Nov 28 [Epub ahead of print]
Vitamin D and calcium intake in relation to risk of endometrial cancer: A systematic review of the literature.
McCullough ML, Bandera EV, Moore DF, Kushi LH.
Epidemiology and Surveillance Research, American Cancer Society, 1599 Clifton Rd NE, Atlanta, GA 30329, USA.

OBJECTIVE: In response to a recent ecologic study of UV exposure and endometrial cancer incidence, we present the epidemiologic evidence on the relation between intake of vitamin D and its metabolically related nutrient, calcium, and the occurrence of endometrial cancer. METHODS: We conducted a systematic literature review and meta-analysis of vitamin D and calcium in relation to endometrial cancer, including peer-reviewed manuscripts published up to May 2007. Random and fixed effects summary estimates were computed. RESULTS: Pooled analyses of the three case-control studies of dietary vitamin D and endometrial cancer uncovered heterogeneous results that were not significant in random or fixed effects analyses. Cut-points for the highest vitamin D intakes ranged from >244 to >476 IU/day. Qualitatively similar findings were observed for dietary calcium. Only two studies provided estimates for calcium supplements (random effects OR=0.62, 95% CI 0.39-0.99; fixed effects OR=0.62, 95% CI 0.42-0.93, for top vs. bottom category, p for heterogeneity=0.25). CONCLUSIONS: The limited epidemiological evidence suggests no relation between endometrial cancer in the ranges of dietary vitamin D examined, and suggests a possible inverse association for calcium from supplements. Prospective studies, ideally including plasma 25(OH) D to estimate vitamin D input from diet and sun exposure, are needed to further explore these hypotheses.

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Curr Oncol Rep. 2007 Nov;9(6):494-8.
Treatment considerations in advanced endometrial cancer.
Kendrick JE, Huh WK.
Division of Gynecologic Oncology, University of Alabama at Birmingham, 618 20th Street South, OHB Room 538, Birmingham, AL 35233, USA. warner.huh@ccc.uab.edu.

An estimated 39,080 new cases of endometrial cancer will occur in the United States in 2007, along with 7400 deaths associated with this disease. Fortunately, with surgical staging, the majority of women are diagnosed with disease at an early stage and are often completely treated with a hysterectomy alone. However, 13% of women who are surgically staged have stage III disease, and 3% to 13% have stage IV disease identified at that time. Over the past 10 years, the role of cytoreductive surgery, radiotherapy, and chemotherapy in endometrial cancer have been actively investigated. This review outlines and summarizes some of these important developments and findings.

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Strahlenther Onkol. 2007 Nov;183(11):600-604.
Stage IB Endometrial Cancer : Does Lymphadenectomy Replace Adjuvant Radiotherapy?
Bottke D, Wiegel T, Kreienberg R, Kurzeder C, Sauer G.
Department of Radiotherapy and Radiation Oncology, University Hospital, Ulm, Germany.

BACKGROUND: The role of surgical lymph node dissection and adjuvant radiation therapy (RT) in early stage endometrial cancer is no longer clearly defined. The increased appreciation of lymphadenectomy and the absence of survival advantage from adjuvant RT rise controversies how patients should adequately be treated in stage IB endometrial cancer. The aim of this review is to rule out the validity of either treatment option and determine which preference provides the best therapeutic benefit. METHODS: Reports of relevant studies obtained from a search of PubMed and studies referenced in those reports were reviewed. RESULTS: Based on the available data in the literature, for stage IB grade 1 or 2, the risk of pelvic relapse is considered too low to justify pelvic RT. However, intravaginal RT (IVRT) should be recommended for those >/= 60 years old or with lymphovascular invasion (LVI). For patients with stage IB grade 3 (and IC all grades), the treatment recommendation is mainly based on whether surgical lymph node staging was performed. These patients have - without surgical lymph node staging - a high risk of pelvic recurrence and should therefore primarily undergo relaparotomy for lymphadenectomy or pelvic RT as second choice. If these patients had a surgical lymph node staging, then IVRT alone is a reasonable alternative to pelvic RT. CONCLUSION: Overall survival may not be the only ideal endpoint for stage IB endometrial cancer since causes of death are mostly other than endometrial cancer. Conventional pelvic RT may be overtreatment in some patients, in particular in those patients with a large number of negative lymph nodes after lymphadenectomy. However, negative surgical staging should not be understood as adjuvant RT can be omitted in all patients.

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Int J Gynecol Cancer. 2007 Oct 18 [Epub ahead of print]
Vaginal versus abdominal hysterectomy in endometrial cancer: a retrospective study in a selective population.
Berretta R, Merisio C, Melpignano M, Rolla M, Ceccaroni M, de Ioris A, Patrelli TS, Nardelli GB.
Department of Gynecology, Obstetrics and Neonatology, University of Parma, Parma, Italy.

The purpose of this study was to analyze the outcome of vaginal and abdominal hysterectomy for the treatment of early-stage endometrial cancer in a selected group of elder patients. This retrospective study analyzed a total of 154 patients: 113 (group I) underwent vaginal surgery and 41 (group II) underwent laparotomy. In both groups, we investigated the following parameters: intra- and postoperative complications, mean operative time, mean hospital stay, disease-free survival (DFS), overall survival (OS), and time of local or retroperitoneal recurrence. Medically compromised patients were significantly more frequent in the vaginal surgery group (P= 0.005), and the operative duration in this group was significantly shorter (P= 0.01). Intra- and postoperative complications, along with local and distant recurrence, did not show a statistically significant difference in the two groups. Total survival in the two populations, 85% at 5 years, did not reach statistically significant difference either in terms of DFS or in terms of OS. Vaginal surgery compared to traditional abdominal approach is feasible also in patients with high surgical risk; it does not require general anesthesia, abolishes abdominal trauma correlated to laparotomy, and allows a quicker reprise of the bladder and rectal function; therefore, it achieves high eradication rates and low intra- and postoperative morbidity rates.

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Best Pract Res Clin Obstet Gynaecol. 2007 Sep 18; [Epub ahead of print]Hormonal therapies and gynaecological cancers.
Garrett A, Quinn MA.
Mercy Hospital for Women, Heidelberg, Victoria 3084, Australia.

Hormonal therapy has an established place in the management of women with gynaecological malignancies, including first-line therapy for recurrent receptor-positive endometrial cancer and low-grade stromal sarcoma. There is no place for adjuvant hormonal treatment of these cancers after primary surgery. Primary treatment with either oral or intra-uterine progestagens to preserve fertility in younger women with endometrial carcinoma is effective in about 70% of cases. Response rates to tamoxifen in advanced/recurrent ovarian cancers approximates 10%. To the authors' knowledge, no studies that reasonably compare different progestagens, different routes of therapy, different doses and different hormonal preparations have been published.

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Int J Radiat Oncol Biol Phys. 2007 Sep 11; [Epub ahead of print]
Adjuvant Brachytherapy Removes Survival Disadvantage of Local Disease Extension in Stage IIIC Endometrial Cancer: A SEER Registry Analysis.
Rossi PJ, Jani AB, Horowitz IR, Johnstone PA.
Department ofRadiation Oncology, Emory University School of Medicine, Atlanta, GA.

PURPOSE: To assess the role of radiotherapy (RT) in women with Stage IIIC endometrial cancer. METHODS AND MATERIALS: The 17-registry Survival, Epidemiology, and End Results (SEER) database was searched for patients with lymph node-positive non-Stage IV epithelial endometrial cancer diagnosed and treated between 1988 and 1998. Two subgroups were identified: those with organ-confined Stage IIIC endometrial cancer and those with Stage IIIC endometrial cancer with direct extension of the primary tumor. RT was coded as external beam RT (EBRT) or brachytherapy (BT). Observed survival (OS) was reported with a minimum of 5 years of follow-up; the survival curves were compared using the log-rank test. RESULTS: The therapy data revealed 611 women with Stage IIIC endometrial cancer during this period. Of these women, 51% were treated with adjuvant EBRT, 21% with EBRT and BT, and 28% with no additional RT (NAT). Of the 611 patients, 293 had organ-confined Stage IIIC endometrial cancer and 318 patients had Stage IIIC endometrial cancer with direct extension of the primary tumor. The 5-year OS rate for all patients was 40% with NAT, 56% after EBRT, and 64% after EBRT/BT. Adjuvant RT improved survival compared with NAT (p <0.001). In patients with organ-confined Stage IIIC endometrial cancer, the 5-year OS rate was 50% for NAT, 64% for EBRT, and 67% for EBRT/BT. Again, adjuvant RT contributed to improved survival compared with NAT (p = 0.02). In patients with Stage IIIC endometrial cancer and direct tumor extension, the 5-year OS rate was 34% for NAT, 47% for EBRT, and 63% for EBRT/BT. RT improved OS compared with NAT (p <0.001). Also, in this high-risk subgroup, adding BT to EBRT was superior to EBRT alone (p = 0.002). CONCLUSION: Women with Stage IIIC endometrial cancer receiving adjuvant EBRT and EBRT/BT had improved OS compared with patients receiving NAT. When direct extension of the primary tumor was present, the addition of BT to EBRT was even more beneficial.

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BJOG. 2007 Sep 5; [Epub ahead of print]
Survival and recurrent disease after postoperative radiotherapy for early endometrial cancer: systematic review and meta-analysis.
Johnson N, Cornes P.
Department of Gynaecologic Oncology, Royal United Hospital, Bath, UK.

Objective To clarify the effect of postoperative (adjuvant) external-beam pelvic radiotherapy (EBRT) for different grades of early endometrial cancer. Search strategy Meta-analysis of data from randomised trials stratified by histological risk factors supported by cohort studies. Selection criteria Cochrane methodology. Data Seven randomised trials were identified. Five were eligible for meta-analysis. Homogeneity was confirmed (I(2) < 25%). Main outcome measures Survival, site of recurrence and added complications. Main results EBRT after hysterectomy for low-risk disease increases the odds of death (OR for overall survival 0.71; 95% CI 0.52-0.96). EBRT does not appear to alter survival for intermediate-risk cancers (stage ICG1/2 and IBG3) (OR 0.97; 95% CI 0.69-1.35). In contrast, EBRT offers a significant disease-free survival advantage for high-risk cancer (OR 1.76; 95% CI 1.07-2.89). The survival advantage benefits one in ten women. The definition of high risk is variable across studies but focuses on ICG3 (deeply invasive, poorly differentiated) tumours. Pelvic EBRT reduces the risk of pelvic recurrent disease in all types of invasive endometrial cancer (OR 0.27; 95% CI 0.16-0.44), but local recurrence may respond to salvage treatment. The risk of distant metastasis appears to be increased significantly by prophylactic EBRT (OR 1.58; 95% CI 1.07-2.35), but this might be because pelvic relapse in untreated women alters reporting of metastatic disease. Authors' conclusions Adjuvant EBRT should not be used for low- (IA, IBG1) or intermediate-risk (IBG2) cancer, but it is associated with a 10% survival advantage for high-risk (stage ICG3) endometrial cancer. This challenges the role of a staging lymphadenectomy.

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Curr Opin Oncol. 2007 Sep;19(5):479-85.
Treatment modalities in endometrial cancer.
Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I.
Leuven Cancer Institute (LKI), UZ Gasthuisberg, Katholieke Universiteit, Leuven, Belgium.

PURPOSE OF REVIEW: Endometrial cancer is the most common malignancy of the female genital tract. This review highlights new insights and these will change current practice. RECENT FINDINGS: Surgery is the cornerstone of the treatment of endometrial cancer but the metastatic pattern is different for types 1 and 2. The surgical staging procedure therefore depends on subtype. Type 2 endometrial cancers often metastasize to the lymph nodes and peritoneal cavity and patients should undergo a staging procedure similar to that performed for ovarian cancer. Laparoscopic staging and treatment for endometrial cancer appears to be safe and effective. Adequate staging also serves to appropriately tailor adjuvant treatment modalities that benefit high-risk patients only. Recent data suggest adequate staging to improve the overall survival. In addition, following complete surgical staging, recent studies emphasize the benefit for adjuvant chemotherapy in early stage serous endometrial cancer. Adjuvant chemotherapy appears to be more effective than radiotherapy for type 1 cancers. In the primarily advanced or recurrent setting, hormonal treatment may be beneficial. Doxorubicin-cisplatin is still the standard chemotherapy regime used in many centres; paclitaxel-containing regimes also appear to show promise. SUMMARY: Recent data shed new light on the current concepts of tumour spread, surgical staging and adjuvant treatment modalities for endometrial cancer.

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J Steroid Biochem Mol Biol. 2007 Aug-Sep;106(1-5):76-80. Epub 2007 May 24.
Aromatase inhibitors in gynecologic cancers.
Krasner C.
Gillette Center for Women's Oncology, Massachusetts General Hospital, United States.

The female genital tract is hormonally responsive, and consequently some tumors, which arise within in it, may be treated at least in part, with hormonal manipulation. The range of responses in clinical trials and case reports will be reviewed. Many of these diseases are too rare for clinical trial testing, and in some cases evidence is anecdotal at best. Recurrences of ovarian cancer have been treated with tamoxifen and megesterol acetate with variable response rates from 0 to 56%. The favorable toxicity profile of aromatase inhibitors led to trials of these agents for the treatment of relapsed epithelial ovarian cancer. These agents have proved tolerable with minor response rates but a significant disease stabilization rate, which may be prolonged in a minority of cases. It is unclear if these responses may be predicted by estrogen receptor expression or aromatase expression. Anastrazole has also been tried in combination with an EGFR receptor-inhibitor, again showing minor responses but possibly an increase in TTT in some patients. Granulosa cell tumors of the ovary are rare, hormonally sensitive tumors, with reported responses to a variety of hormonal manipulations, including aromatase inhibition. In addition, combined endocrine blockade, including aromatase inhibition, has been tried with reports of success. Endometrial cancers, particularly type I lesions, are often treated with hormonal manipulation, most commonly with progestins, but also with antiestrogens such as tamoxifen. A trial of aromatase inhibition in the treatment of recurrent endometrial cancer showed minimal responses. Endometrial stromal sarcoma, an uncommon uterine malignancy, has shown response to hormonal treatments, with multiple case reports of efficacy of aromatase inhibition. Despite the rarity of some of these tumor types, rare tumor study groups, such as within the Gynecologic Oncology Group, should make an effort to prospectively define the utility of these treatments.

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Am J Obstet Gynecol. 2007 Aug;197(2):202.e1-6; discussion 202.e6-7.
The role of vaginal hysterectomy in the treatment of endometrial cancer.
Smith SM, Hoffman MS.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa, FL 33606, USA.

OBJECTIVE: The objective of the study was to evaluate the role of vaginal hysterectomy in the treatment of endometrial cancer. STUDY DESIGN: Medical records were retrospectively reviewed for patients undergoing vaginal hysterectomy for endometrial cancer at the University of South Florida. The medical data were reviewed for medical comorbidities, preoperative and postoperative diagnosis, hospital course, surgical and postoperative complications, adjuvant treatments, and follow-up. RESULTS: Sixty-three women underwent vaginal hysterectomy for endometrial carcinoma between May 1987-September 2006. Mean age was 62.1 years and body mass index [BMI] was 40; 73% of patients were obese (BMI > or = 30 or greater). Medical comorbidities included hypertension (76.2%), cardiovascular disease (34.9%), diabetes mellitus (31.7%), and pulmonary disease (28.6%). Eighty-one percent of patients had at least 2 and 55.5% had 3 or more comorbid surgical risk factors. Postoperative complications included infection (4.8%), blood transfusion (11.1%), and prolonged hospital stay (6.3%). Of patients with intrauterine pathology, 89.5% had endometrioid adenocarcinoma. CONCLUSION: Vaginal hysterectomy may be appropriate treatment of endometrial carcinoma for select patients.

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Gynecol Oncol. 2007 Aug 3; [Epub ahead of print]
The role of multi-modality adjuvant chemotherapy and radiation in women with advanced stage endometrial cancer.
Alvarez Secord A, Havrilesky LJ, Bae-Jump V, Chin J, Calingaert B, Bland A, Rutledge TL, Berchuck A, Clarke-Pearson DL, Gehrig PA.
Division of Gynecologic Oncology, Duke University Medical Center, Box 3079, Durham, NC 27710, USA.

OBJECTIVE.: The optimal adjuvant therapy for women with stages III and IV endometrial cancer following surgical staging and cytoreductive surgery is controversial. We sought to determine the outcome of patients with advanced stage endometrial cancer treated with postoperative chemotherapy+/-radiation to determine whether there was an advantage to combining treatment modalities. METHODS.: A retrospective analysis of patients with surgical stages III and IV endometrial cancer from 1975 to 2006 was conducted at Duke University and the University of North Carolina. Inclusion criteria were comprehensive staging procedure including hysterectomy, bilateral salpingo-oophorectomy, +/-selective pelvic/aortic lymphadenectomy, surgical debulking, and treatment with adjuvant chemotherapy and/or radiotherapy. Progression-free (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazards model. RESULTS.: 356 Patients with advanced stage endometrial cancer were identified who received postoperative adjuvant therapies; 48% (n=171) radiotherapy alone, 29% (n=102) chemotherapy alone, 23% (n=83) chemotherapy and radiation. The median age was 66 years; 38% had endometrioid tumors; and 83% were optimally debulked. There was a significant difference between the adjuvant treatment groups for both OS and PFS (p<0.001), with those receiving chemotherapy alone having poorer 3-year OS (33%) and PFS (19%) compared to either radiotherapy alone (70% and 59%) or combination therapy (79% and 62%). After adjusting for stage, age, grade, and debulking status the hazard ratio (HR) for OS was 1.60 (95% CI, 0.88 to 2.89; p=0.122) for chemotherapy alone and 2.01 (95% CI, 1.17 to 3.48; p=0.012) for radiotherapy alone, compared to combination therapy. When the analysis was restricted to optimally debulked patients the adjusted HR for patients who were treated with either chemotherapy or radiation alone indicated a significantly higher risk for disease progression [HR=1.84 (95% CI, 1.03 to 3.27; p=0.038); HR=1.80 (95% CI, 1.10 to 2.95; p=0.020)] and death [HR=2.33 (95% CI, 1.12 to 4.86; p=0.024); HR=2.64 (95% CI, 1.38 to 5.07; p=0.004)], respectively, compared to patients who received combination therapy. CONCLUSION.: Combined adjuvant chemotherapy and radiation was associated with improved survival in patients with advanced stage disease compared to either modality alone. Future clinical trials are needed to prospectively evaluate multi-modality adjuvant therapy in women with advanced staged endometrial cancer to determine the appropriate sequencing and types of chemotherapy and radiation.

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Brachytherapy. 2007 Jul-Sep;6(3):201-6.
An analysis of simulation for adjuvant intracavitary high-dose-rate brachytherapy in early-stage endometrial cancer.
Barney BM, MacDonald OK, Lee CM, Rankin J, Gaffney DK.
Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, 1950 Circle of Hope, Salt Lake City, UT 84112, USA.

PURPOSE: The utility of serial simulations in vaginal vault irradiation is controversial. Our primary endpoint was to assess the significance of simulation in women who received adjuvant intracavitary high-dose-rate brachytherapy (HDR-BT) for early-stage endometrial adenocarcinoma. Secondary endpoints included assessment of acute and late treatment toxicity, medication requirements, and charges related to the HDR-BT simulation and procedure. METHODS AND MATERIALS: Twenty-four consecutive women with early-stage endometrial cancer treated with adjuvant HDR-BT were evaluated. Descriptive statistical analyses were performed on the ratio of calculated to prescription BT dose at predefined dosimetric points. Data on acute and late toxicities, medication usage, and simulation charges were evaluated and compared. RESULTS: The intravaginal cylinder was placed three times over 10-14 days (median 6.5Gy prescribed to 5mm). No substantial deviation in the means of the calculated ratios was observed except at the bladder point (mean 0.77+/-0.23). Early toxicity was found to be no greater than Grade 1 (n=5). Serious late toxicities were uncommon; one woman developed a Grade 3 gastrointestinal toxicity. Half of the women required prescription medication incident to simulation. The average simulation charge was $1252.80. CONCLUSIONS: Despite the broad range of doses calculated at the bladder point, genitourinary toxicity was minimal. Simulation proved useful in recording dose and represented a small, yet important portion of the total treatment charge but did not alter treatment in this series. The necessity of simulation for intracavitary high-dose-rate vaginal brachytherapy remains unclear.

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Brachytherapy. 2007 Jul-Sep;6(3):195-200.
Intravaginal 1-week high-dose-rate brachytherapy alone for Stages I-II endometrial cancer.
Martinez-Monge R, Nagore G, Cambeiro M, Garran C, Villafranca E, Jurado M.
Department of Oncology, Clinica Universitaria de Navarra, University of Navarre, Avenida Pio XII s/n, E-31080 Pamplona, Navarre, Spain. rmartinezm@unav.es

OBJECTIVE: To evaluate the feasibility and intermediate-term results of a short course of high-dose-rate (HDR) intravaginal brachytherapy only after hysterectomy. METHODS AND MATERIALS: From December 1999 to February 2005, 50 patients with International federation of gynecology and obstetrics Stages IA-IIB endometrioid endometrial adenocarcinoma were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by postoperative HDR brachytherapy alone. The mean age of the patients was 62.6 years (range 42-86). International federation of gynecology and obstetrics patient grouping included IaG3N(x) (n=1), IbG1N(0) (n=1), IbG1N(x) (n=2), IbG2N(0) (n=10), IbG2N(x) (n=20), IbG3N(0) (n=3), IbG3N(x) (n=1), IcG1N(x) (n=2), IcG2N(0) (n=3), IcG3N(0) (n=3), IIaG1N(x) (n=2), IIaG2N(x) (n=1), and IIbG1N(0) (n=1). Twenty-one patients (42.0%) had been surgically staged. Four to 16 weeks after surgery (median 42d, range 28-112), all patients received HDR intravaginal brachytherapy to 25Gy in five consecutive 5-Gy daily fractions prescribed at 0.5-cm depth. Median HDR brachytherapy treatment duration was 5 days (range 5-12). RESULTS: After a median followup of 37 months (range 12-80), the overall survival and disease-free survival were 96%. No vaginal or pelvic recurrences have been observed. One patient (2%) developed distant metastases. No late toxicities of Grade 3 or greater have been reported. CONCLUSIONS: The results reported in this study are in agreement with previous reports of postoperative HDR brachytherapy alone in early-stage endometrial cancer. HDR brachytherapy alone seems to provide adequate tumor control. The fractionation schedule proposed (25Gy in five consecutive daily treatments) was well tolerated and is convenient for patients living far from the radiation center.

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Gynecol Oncol. 2007 May 4; [Epub ahead of print]
External radiotherapy versus vaginal brachytherapy for patients with intermediate risk endometrial cancer.
Lin LL, Mutch DG, Rader JS, Powell MA, Grigsby PW.
Department of Radiation Oncology, Washington University School of Medicine, USA; Alvin J. Siteman Cancer Center, St. Louis, MO, USA.

PURPOSE.: To determine if brachytherapy alone is adequate adjuvant local therapy in patients classified as intermediate risk after complete surgical staging for endometrioid adenocarcinoma. METHODS.: Between 1991 and 2004, 78 patients with FIGO stage IA-II (occult) disease meeting the eligibility criteria of GOG 99 received adjuvant radiotherapy following complete surgical staging (total abdominal hysterectomy and bilateral salpingo-oophorectomy, peritoneal cytology, and pelvic+/-para-aortic lymphadenectomy) for endometrioid adenocarcinoma at Washington University in St. Louis. Forty-two patients received postoperative vaginal brachytherapy alone and 36 received postoperative pelvis external radiotherapy (XRT) and vaginal brachytherapy. Fifty-two patients were classified as having high intermediate risk disease and 26 patients had low intermediate risk disease as defined by GOG 99. Median follow-up for all patients was 55 months. RESULTS.: The 5-year overall and disease-free survivals for all patients were 86% and 89%, respectively. There was no difference in 5-year disease-free survivals among patients classified as high intermediate risk vs. low intermediate risk (p=0.26) or in terms of radiation treatment received (p=0.95). There were two patients that had >grade 2 gastrointestinal complications, both were treated with external radiotherapy and vaginal brachytherapy. CONCLUSIONS.: Vaginal brachytherapy alone results in minimal morbidity and is adequate local therapy for intermediate risk patients with endometrioid adenocarcinoma after complete surgical staging.

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Cochrane Database Syst Rev. 2007 Apr 18;(2):CD003916.
Adjuvant radiotherapy for stage I endometrial cancer.
Kong A, Johnson N, Cornes P, Simera I, Collingwood M, Williams C, Kitchener H.

BACKGROUND: The role of adjuvant radiotherapy (both pelvic external beam radiotherapy and vaginal intracavity brachytherapy) in stage I endometrial cancer following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH and BSO) remains unclear. OBJECTIVES: To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CancerLit, Physician Data Query (PDQ) of National Cancer Institute. Handsearching was also carried out where appropriate. SELECTION CRITERIA: Randomised controlled trials (RCTs) which compared adjuvant radiotherapy versus no radiotherapy following surgery for patients with stage I endometrial cancer were included. DATA COLLECTION AND ANALYSIS: Quality of the studies was assessed and data collected using a predefined data collection form. The primary endpoint was overall survival. Secondary endpoints were locoregional recurrence, distant recurrence and endometrial cancer death. Data on quality of life (QOL) and morbidity were also collected. A meta-analysis on included trials was performed using the Cochrane Collaboration Review Manager Software 4.2. MAIN RESULTS: The meta-analysis was performed on four trials (1770 patients). The addition of pelvic external beam radiotherapy to surgery reduced locoregional recurrence, a relative risk (RR) of 0.28 (95% confidence interval (CI) 0.17 to 0.44, p < 0.00001), which is a 72% reduction in the risk of pelvic relapse (95% CI 56% to 83%) and an absolute risk reduction of 6% (95% CI of 4 to 8%). The number needed to treat (NNT) to prevent one locoregional recurrence is 16.7 patients (95% CI 12.5 to 25). The reduction in the risk of locoregional recurrence did not translate into either a reduction in the risk of distant recurrence or death from all causes or endometrial cancer death. A subgroup analysis of women with multiple high risk factors (including stage 1c and grade 3) showed a trend toward the reduction in the risk of death from all causes and endometrial cancer death in patients who underwent adjuvant external beam radiotherapy. AUTHORS' CONCLUSIONS: Patients with stage I endometrial carcinoma have different risks of local and distant recurrence depending on the presence of risk factors including stage 1c, grade 3, lymphovascular space invasion and age. Though external beam pelvic radiotherapy reduced locoregional recurrence by 72%, there is no evidence to suggest that it reduced the risk of death. In patients with multiple high risk factors, including stage 1c and grade 3, there was a trend towards a survival benefit and adjuvant external beam radiotherapy may be justified. For patients with only one risk factor, grade 3 or stage 1c, no definite conclusion can be made and data from ongoing studies ( ASTEC; Lukka) are awaited. External beam radiotherapy carries a risk of toxicity and should be avoided in stage 1 endometrial cancer patients with no high risk factors.

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Int J Gynecol Cancer. 2007 Apr 18; [Epub ahead of print]
Hormone therapy in advanced and recurrent endometrial cancer: a systematic review.
Decruze SB, Green JA.
Department of Gynecological Oncology, Liverpool Women's Hospital NHS Foundation Trust, Liverpool, United Kingdom.

Endometrial cancer is a hormone-dependent malignancy, and the majority has a precursor phase of endometrial hyperplasia. Histologic subtypes have been recognized with differing natural history. The relationship between hormone response, histology, and molecular profile is not established, but the relevant biology is summarized. This study was a systematic review of the literature to identify which populations should be considered for hormone interventions. Systematic searches were carried out in the English literature for randomized controlled trials and phase II studies of hormone interventions in endometrial cancer. Five randomized trials and 29 phase II studies were identified comprising a total of 2471 patients. In previously untreated patients with grade 1 (G1) or G2 tumors, the response rate for progestogens and the progression-free survival is in the range of 11-56% and 2.5-14 months, respectively. Higher response rates are seen in progesterone receptor-positive cases. Phase II studies comprise the majority of the data and many are of poor quality. There was considerable heterogeneity in patient selection, prior treatment, and type of regimen, and meta-analysis was not possible. G3 or G4 toxicity was less than 5%. We conclude that hormone receptor assessments should be carried out in all patients entered on clinical trials and may aid clinical management in selected cases. Receptor-negative status should not be an absolute contraindication to hormone intervention. Integration of hormone treatment with conventional chemotherapy and growth factor-targeted therapy needs to be explored.

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J Minim Invasive Gynecol. 2007 Mar-Apr;14(2):205-10.
Hysteroscopic surgery does not adversely affect the long-term prognosis of women with endometrial adenocarcinoma.
Vilos GA, Edris F, Al-Mubarak A, Ettler HC, Hollett-Caines J, Abu-Rafea B.
Department of Obstetrics and Gynecology, The University of Western Ontario, London, Ontario, Canada. george.vilos@sjhc.london.on.ca

STUDY OBJECTIVE: To determine the effect of hysteroscopic surgery on the long-term clinical outcome of women diagnosed with endometrial cancer. DESIGN: Prospective cohort study (Canadian Task Force classification II-3). SETTING: University-affiliated teaching hospital. PATIENTS: From January 1990 through December 2005, the principal author (GAV) performed primary hysteroscopic surgery in 3401 women with abnormal uterine bleeding. Among these women, there were 16 occult and 3 known endometrial cancers. INTERVENTIONS: All women underwent hysteroscopic evaluation and partial (n = 8) or complete (n = 11) rollerball electrocoagulation and/or endomyometrial resection. After diagnosis of endometrial malignancy, women were counseled regarding their disease and management, in accordance with established clinical practice guidelines. Follow-up ranged from 1 to 14 years and was conducted by office visits and telephone interviews. MEASUREMENTS AND MAIN RESULTS: Among the 3401 women, there were 19 women with endometrial adenocarcinoma, 3 of whom were known to harbor cancer before hysteroscopic surgery. One woman refused hysterectomy and remains alive and well 5 years after total hysteroscopic endomyometrial resection. Two women wished to maintain fertility; 1 consented to hysterectomy after incomplete resection of her lesion. The other was treated with progestins. Her cancer reverted to complex hyperplasia, and she requested hysterectomy 4 years later. No residual cancer was found. After 5 years of follow-up, 1 patient died from carcinoma of the gallbladder (2 years), and 2 died at 4 years; 1 at the age of 87 years of natural causes and the other at the age of 86 years from acute renal failure unrelated to her cancer. Fourteen women remain alive and well at 5 to 14 years of follow-up. Two additional women remain alive and well at 1 and 4 years of follow-up. CONCLUSION: Resectoscopic surgery did not adversely affect the 5-year survival and the long-term prognosis in 14 women with endometrial cancer.

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Am J Obstet Gynecol. 2007 Mar;196(3):248.e1-8.
Laparoscopy-assisted vaginal hysterectomy compared with abdominal hysterectomy in clinical stage I endometrial cancer: safety, recurrence, and long-term outcome.
Kalogiannidis I, Lambrechts S, Amant F, Neven P, Van Gorp T, Vergote I.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.

OBJECTIVE: To determine the feasibility of laparoscopic-assisted vaginal hysterectomy (LAVH) in the treatment of clinical FIGO stage I endometrial adenocarcinoma and long-term survival outcome. STUDY DESIGN: Prospective cohort study without randomization of 169 consecutive patients. Laparoscopy or laparotomy was selected based on size and mobility of the uterus and Body Mass Index (BMI). Lymphadenectomy was only performed in cases at high-risk for nodal metastases. RESULTS: Sixty-nine patients (41%) treated successfully by LAVH (LAVH group) while 100 (59%) by total abdominal hysterectomy (TAH) (laparotomy group). Four out of 73 patients initially approached by laparoscopy were converted to laparotomy (5.5%). Lymphadenectomy was performed in 40% of the LAVH and 57% of TAH group (P = 0.03). The median number of pelvic lymph nodes removed by LAVH and laparotomy was 15 (range 2-31) and 21 (range 2-65), respectively (P = 0.05). LAVH was associated with more surgical FIGO stage IA disease and a smaller tumor diameter. Operative time was significantly longer with laparoscopy compared with laparotomy, while blood loss and duration of hospitalization was significantly lower in the LAVH group. The recurrence rate in the LAVH group was 8.7%, compared with 16% in the laparotomy group (not significant, NS). The actuarial overall survival (OS) and disease-free survival (DFS) for the LAVH were 93% and 91% compared with 86% and 84% in the TAH, respectively (NS). In the multivariate analyses histological subtype was the only independent prognostic factor for DFS, while surgical technique was not. CONCLUSION: LAVH with lymphadenectomy in selected population in high-risk patients with clinical stage I endometrial adenocarcinoma and with favorable body mass index of less than 35 kg/m2, appears to be safe procedure.

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Ann Oncol. 2007 Mar 19; [Epub ahead of print]
Adjuvant radiotherapy for stage I endometrial cancer: systematic review and meta-analysis.
Kong A, Simera I, Collingwood M, Williams C, Kitchener H.
Radiotherapy Department, St Bartholomew's Hospital, London EC1.

The role of adjuvant radiotherapy in stage I endometrial cancer following surgery remains unclear. The management for these patients varies widely, particularly in stage I patients with different risk factors. Using the methodology of Cochrane Collaboration, we did a systematic and meta-analysis of all know randomised controlled trials which compared adjuvant radiotherapy versus no radiotherapy following surgery for patients with stage I endometrial cancer. The meta-analysis was carried out on four trials (three published and one unpublished) and a total of 1770 patients. The addition of pelvic external beam radiotherapy to surgery reduced locoregional recurrence, a relative risk (RR) of 0.28 [95% confidence interval (CI) 0.17-0.44, P < 0.00001], which is a 72% reduction in the risk of pelvic relapse (95% CI 56% to 83%) and an absolute risk reduction of 6% (95% CI of 4% to 8%). The reduction in the risk of locoregional recurrence did not translate into a reduction in the risks of death from all causes, endometrial cancer death or distant recurrence. A subgroup analysis showed a trend towards the reduction in the risks of death from all causes and endometrial cancer in patients with multiple high risk factors (including stage 1c and grade 3). External beam pelvic radiotherapy should be considered in patients with multiple high-risk features including stage 1c and grade 3. However, it carries an inherent risk of damage and toxicity and should be avoided in stage 1 endometrial cancer patients with no high risk factors.

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Int J Clin Oncol. 2007 Feb;12(1):31-6. Epub 2007 Feb 25.
Weekly low-dose paclitaxel and carboplatin in the treatment of advanced or recurrent cervical and endometrial cancer.
Secord AA, Havrilesky LJ, Carney ME, Soper JT, Clarke-Pearson DL, Rodriguez GC, Berchuck A.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Box 3079, Duke University Medical Center, Durham, NC 27710, USA. secor002@mc.duke.edu

BACKGROUND: The purpose of this study was to evaluate the toxicity profile of weekly low-dose paclitaxel and carboplatin in patients with gynecologic malignancies. METHODS: Patients had measurable disease defined by clinical examination or radiographic studies. Each cycle of treatment consisted of carboplatin at an AUC of 2 and paclitaxel at 80 mg/m2 on days 1, 8, and 15 of a 28-day cycle. RESULTS: Twenty-eight patients with advanced or recurrent cervical and endometrial cancers were included in this study. The overall response rate (ORR) was 39% (2 CR, 9 PR). Among the 15 cervical cancers the ORR was 20%, while the 13 endometrial cancers had a 62% ORR. Median time to progression and overall survival was 3.4 and 7.6 months for those with cervical cancer and 5.5 and 15.4 months for those with endometrial cancer. Grade 3 or 4 hematologic toxicity was uncommon (7% grade 3 anemia, 21% grade 3 or 4 neutropenia, 7% grade 3 or 4 thrombocytopenia). CONCLUSION: A regimen of weekly low-dose paclitaxel and carboplatin has an acceptable toxicity profile that is easily managed by dose adjustment and the use of erythropoietic therapy. This regimen appears to have activity in advanced or recurrent endometrial cancer which warrants further evaluation.

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Qual Life Res. 2007 Feb;16(1):89-100. Epub 2006 Oct 11.
Randomized trial results of quality of life comparing whole abdominal irradiation and combination chemotherapy in advanced endometrial carcinoma: A gynecologic oncology group study.
Bruner DW, Barsevick A, Tian C, Randall M, Mannel R, Cohn DE, Sorosky J, Spirtos NM.
Departments of Population Science and Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.

OBJECTIVE: To prospectively compare quality of life (QOL) outcomes in patients with advanced endometrial cancer treated with whole abdominal irradiation (WAI) or doxorubicin-cisplatin (AP) chemotherapy. METHODS: Using the Fatigue Scale (FS), Assessment of Peripheral Neuropathy (APN), Functional Alterations due to Changes in Elimination (FACE), and Functional Assessment of Cancer Therapy-General (FACT-G), QOL was measured at: pre-treatment, end of treatment (EOT), and 3 and 6 months post-treatment. RESULTS: 317 of 396 eligible patients provided a baseline QOL assessment. The AP arm produced a statistically significant survival benefit along with greater toxicities, including peripheral neuropathy persisting up to 6 months. WAI patients reported worse FS (p < 0.001) and FACE (p < 0.001) scores at EOT and poorer FACE scores 3 months post-treatment (p = 0.004) compared to AP patients. APN scores were significantly worse among AP patients at EOT, and 3 and 6 months post-treatment (p < 0.001 for all). There is no indication that FACT-G scores differed between the two arms at any assessment point. CONCLUSIONS: The trade-off for increased survival with AP is its potential for clinically significant peripheral neuropathy. This should be discussed with patients, particularly those who work with their hands or on their feet, in weighing therapeutic choices. Further research is needed to manage side effects having an enduring impact on QOL.

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Gynecol Oncol. 2006 Dec 29; [Epub ahead of print]
Twelve-year experience in the management of endometrial cancer: A change in surgical and postoperative radiation approaches.
Barakat RR, Lev G, Hummer AJ, Sonoda Y, Chi DS, Alektiar KM, Abu-Rustum NR.
Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.

OBJECTIVE.: Over the past 12 years, the primary management of endometrial cancer at a comprehensive cancer center has undergone changes characterized by the increased use of laparoscopic surgery with comprehensive staging resulting in a decreased reliance on postoperative adjuvant whole pelvic radiation therapy (WPRT). The purpose of this study was to analyze the results of these changes. MATERIALS AND METHODS.: Between 1/93 and 12/04, 1312 patients underwent surgery for endometrial cancer consisting of either abdominal or laparoscopic hysterectomy/bilateral salpingo-oophorectomy (TAH/BSO or LAVH/BSO). Pelvic and para-aortic lymph node dissection was performed at the discretion of the attending physician. Postoperative adjuvant treatment employed in patients with high-risk features consisted mainly of WPRT+/-intravaginal radiation therapy (IVRT). Total direct medical charges incurred from 10 days prior to surgery through 75 days after surgery were determined with charges converted to direct medical costs, taking into account inflationary changes. RESULTS.: The median age at diagnosis for all patients was 62 years (range, 21-93 years), with a median follow-up of 31.6 months (range, 0-140 months). There was a significant increase in LAVH/BSO versus TAH/BSO (P<0.001) until 2001 when we began participating in a national randomized trial of laparoscopic versus abdominal surgery. In addition, there was a significant increase in the percentage of patients undergoing lymph node dissection as well as the median number of nodes removed (P<0.001). This was associated with a significant decrease in the use of WPRT during 1993-1998 versus 1999-2004 (P<0.001). The use of IVRT remained the same during these time periods. There was no significant difference in 1-, 2-, or 5-year survival for patients treated in either time period. Cost data were available from 1995 to 2004. There was a significant increase in the median total direct medical costs when comparing periods 1995-1998 with 1999-2004 (P<0.001), although the median cost of pelvic radiation therapy was lower in the later time period. CONCLUSION.: Over a 12-year period, the primary management of endometrial cancer changed to include an increased use of laparoscopy and comprehensive surgical staging and a decrease in the use of postoperative adjuvant WPRT, with no appreciable negative effect on overall survival.

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Cancer. 2006 Oct 15;107(8):1823-30.
Therapeutic role of lymph node resection in endometrioid corpus cancer: a study of 12,333 patients.
Chan JK, Cheung MK, Huh WK, Osann K, Husain A, Teng NN, Kapp DS.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford Cancer Center, Stanford, California 94305, USA. johnchan@stanford.edu

BACKGROUND: The purpose of the current study was to determine the potential therapeutic role of lymphadenectomy in women with endometrioid corpus cancer. METHODS: Demographic and clinicopathologic information were obtained from the Surveillance, Epidemiology, and End Results Program between 1988-2001. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression. RESULTS: In all, 12,333 women (median age, 64) underwent surgical staging with lymph node assessment, including 9,009, 1,211, 1,223, and 890 with Stage I-IV disease. Over the time intervals 1988-1992, 1993-1997, and 1998-2001, the percentage of patients undergoing lymph node staging increased from 22.6%, 29.6%, to 40.9% (P < .001). In the intermediate/high-risk patients (Stage IB, Grade 3; Stage IC and II-IV, all grades), a more extensive lymph node resection (1, 2-5, 6-10, 11-20, and >20) was associated with improved 5-year disease-specific survivals across all 5 groups at 75.3%, 81.5%, 84.1%, 85.3%, and 86.8%, respectively (P < .001). For Stage IIIC-IV patients with nodal disease, the extent of node resection significantly improved the survival from 51.0%, 53.0%, 53.0%, 60.0%, to 72.0%, (P < .001). However, no significant benefit of lymph node resection in low-risk patients could be demonstrated (Stage IA, all grades; Stage IB, Grades 1 and 2 disease; P = .23). In multivariate analysis, a more extensive node resection remained a significant prognostic factor for improved survival in intermediate/high-risk patients after adjusting for other factors including age, year of diagnosis, stage, grade, adjuvant radiotherapy, and the presence of positive nodes (P < .001). CONCLUSIONS: The findings of the current study suggest that the extent of lymph node resection improves the survival of women with intermediate/high-risk endometrioid uterine cancer. 2006 American Cancer Society

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Int Semin Surg Oncol. 2006 Sep 13;3:28.
Laparoscopic hysterectomy with or without pelvic lymphadenectomy or sampling in a high-risk series of patients with endometrial cancer.
Willis SF, Barton D, Ind TE.
Department of Gynaecological Oncology, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK. ThomasInd@ThomasInd.co.uk.
Full free text at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16968556

ABSTRACT: BACKGROUND: The purpose of the study was to determine the outcome of all patients with endometrial adenocarcinoma cancer treated by laparoscopic hysterectomy at our institution, many of whom were high-risk for surgery. METHODS: Data was collected by a retrospective search of the case notes and Electronic Patient Records of the thirty eight patients who underwent laparoscopic hysterectomy for endometrial cancer at our institutions. RESULTS: The median body mass index was 30 (range 19-67). Comorbidities were present in 76% (29 patients); 40% (15 patients) had a single comorbid condition, whilst 18% (7 patients) had two, and a further 18% (7 patients) had more than two. Lymphadenectomy was performed in 45% (17 patients), and lymph node sampling in 21% (8 patients). Median operating time was 210 minutes (range 70-360 minutes). Median estimated blood loss was 200 ml (range 50-1000 ml). There were no intraoperative complications. Post-operative complications were seen in 21% (2 major, 6 minor). Blood transfusion was required in 5% (2 patients). The median stay was 4 post-operative nights (range 1-25 nights). In those patients undergoing lymphadenectomy, the mean number of nodes taken was fifteen (range 8-26 nodes). The pathological staging was FIGO stage I 76% (29 patients), stage II 8% (3 patients), stage III 16% (6 patients). The pathological grade was G1 31% (16 patients), G2 45% (17 patients), G3 24% (8 patients). CONCLUSION: Laparoscopic hysterectomy can be safely carried out in patients at high risk for surgery, with no compromise in terms of outcomes, whilst providing all the benefits inherent in minimal access surgery.

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Oncologist. 2006 Sep;11(8):895-901.
Role of minimally invasive surgery in gynecologic cancers.
Schlaerth AC, Abu-Rustum NR.
Memorial Sloan-Kettering Cancer Center, Gynecology Service, Department of Surgery, 1275 York Avenue, New York, New York 10021, USA.

The role of minimally invasive surgery in the management of gynecologic cancers continues to expand. Radical vaginal trachelectomy with laparoscopic pelvic lymphadenectomy has emerged as a safe, reasonable option for women with early-stage cervical cancer desiring fertility preservation. Similarly, laparoscopically assisted radical vaginal hysterectomy has been systematically described, is feasible, and can be offered to women with early-stage cervical cancer who do not desire future childbearing. In the treatment of early-stage endometrial cancer, the surgical approach of laparoscopic hysterectomy, peritoneal washings, and pelvic and para-aortic lymph node dissection, with or without an omentectomy, is being compared with the same surgery performed via laparotomy in the cooperative Gynecologic Oncology Group LAP 2 study, which has completed accrual, and appears to be a reasonable surgical option. In ovarian cancer, minimally invasive surgery has been incorporated to manage early-stage, advanced-stage, and recurrent disease, as well as second-look procedures. Hand-assisted laparoscopy has also recently been described in managing larger volume primary and recurrent gynecologic cancers. Extraperitoneal laparoscopy for para-aortic and pelvic lymph node dissections has been shown to yield adequate nodal counts and to be safe and feasible in the management of gynecologic cancers.
 

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