Important Note: The following information is provided for your education. It should not be relied upon for personal diagnosis or treatment. If you believe that a particular therapy applies to you or someone you care about, be sure to consult a doctor before trying it.
   

On Downloading (Please Read Carefully)   
To download or print the Bladder Cancer File, point your mouse to "File" in the top bar of your Explorer or Netscape window, and click once. Now click once on either "Save As" (download), or "Print" (print), and follow the appropriate prompts.
 

Latest Research on Bladder Cancer
     
Aktuelle Urol. 2008 Jan;39(1):58-61.
[Bladder Preservation or Initial Cystectomy in T1G3 Bladder Cancer: Which Parameters Help in Therapeutic Decision-Making?]
[Article in German]
Denzinger S, Burger M, Fritsche HM, Ganzer R, Blana A, Wieland WF, Otto W.
Klinik und Poliklinik für Urologie, Universität Regensburg.

PURPOSE: T1G3 bladder cancers show the clinical and biological behaviour of muscle invasive tumours with progression rates of about 30 %. While radical cystectomy in some cases is indicated, other patients can achieve healing with organ preservation. We present a study analysing the influence of the risk factors multifocality, tumour diameter >/= 3 cm and associated carcinoma in situ (Cis) on the outcome of initial T1G3 bladder cancers treated in various ways. MATERIALS AND METHODS: Of 223 patients with initial T1G3 bladder cancer, 125 patients underwent transurethral resection of the tumour (TURB), second resection and adjuvant bacille Calmette-Guérin (BCG) instillations (TURB group), 98 patients chose initial radical cystectomy (CX group). RESULTS: Median follow-up times were 56 months (TURB group) and 51 months (CX group). 5- and 10-year survival rates (82 % and 65 % in TURB group vs. 75 % and 48 % in CX group) did not show statistically significant differences. In Cox reg
ression analysis no single risk factor showed a prognostic value. While in TURB group the combination of all risk factors (multifocality, tumour diameter >/= 3 cm and associated carcinoma in situ) was associated with a statistically significantly lower survival rate, the same combination in the CX group was not oncologically relevant. CONCLUSIONS: While initial T1G3 bladder cancer with up to two risk factors after organ-preserving therapy is not associated with a lower tumour specific survival rate in comparison to radical cystectomy, patients with a combination of the three analysed risk factors would profit by an early radical cystectomy.

-----

J Urol. 2008 Jan 24 [Epub ahead of print]
Outcome After Radical Cystectomy With Limited or Extended Pelvic Lymph Node Dissection.
Dhar NB, Klein EA, Reuther AM, Thalmann GN, Madersbacher S, Studer UE.
Department of Urology, University of Bern, Bern, Switzerland (NBD, GNT, SM, UES); Glickman Urological Institute, Cleveland Clinic, Cleveland, Ohio (NBD, EAK, AMR).

PURPOSE: We compared recurrence patterns and survival of patients with urothelial bladder cancer undergoing radical cystectomy who either had limited or extended pelvic lymph node dissection at 2 institutions between 1987 and 2000. MATERIALS AND METHODS: Two consecutive series of patients treated with radical cystectomy and limited pelvic lymph node dissection (336; Cleveland Clinic) and extended pelvic lymph node dissection (322; University of Bern) were analyzed. All cases were staged N0M0 prior to radical cystectomy, and none were treated with neoadjuvant radiotherapy or chemotherapy. Patients with PTis/pT1 and pT4 disease were excluded from analysis. Pathological characteristics based on the 1997 TNM system and recurrence patterns were determined. RESULTS: The overall lymph node positive rate was 13% for patients with limited and 26% for those who had extended pelvic lymph node dissection. The 5-year recurrence-free survival of patients with lymph node positive disease was 7% for limited and 35% for extended pelvic lymph node dissection. The 5-year recurrence-free survival for pT2pN0 cases was 67% for limited and 77% for extended pelvic lymph node dissection, and the respective percentages for pT3pN0 cases were 23% and 57% (p <0.0001). The 5-year recurrence-free survival for pT2pN0-2 cases was 63% for limited and 71% for extended pelvic lymph node dissection, and for pT3pN0-2 cases the respective figures were 19% and 49% (p <0.0001). Incidence of local and systemic failure correlated closely with pathological stage for both series. CONCLUSIONS: Our data suggest that limited pelvic lymph node dissection is associated with suboptimal staging, poorer outcome for patients with node positive and node negative disease, and a higher rate of local progression. Extended pelvic lymph node dissection allows for more accurate staging and improved survival of patients with nonorgan confined and lymph node positive disease.

-----

Eur Urol. 2008 Jan 15 [Epub ahead of print]
The Schedule and Duration of Intravesical Chemotherapy in Patients with Non-Muscle-Invasive Bladder Cancer: A Systematic Review of the Published Results of Randomized Clinical Trials.
Sylvester RJ, Oosterlinck W, Witjes JA.
EORTC Data Center, Brussels, Belgium.

OBJECTIVES: Intravesical chemotherapy has been studied in randomized clinical trials for >30 yr; however, the optimal schedule and duration of treatment are unknown. The objective is to determine the effect of schedule and duration of intravesical chemotherapy on recurrence in patients with stage Ta T1 bladder cancer. METHODS: A systematic review was conducted of the published results of randomized clinical trials that compared intravesical instillations with respect to their number, frequency, timing, duration, dose, or dose intensity. RESULTS: One immediate instillation after transurethral resection (TUR) is recommended in all patients. In low-risk patients, no further treatment is recommended before recurrence. In patients with multiple tumors, one immediate instillation is insufficient treatment. Additional instillations may further reduce the recurrence rate; however, no recommendations can be made concerning their optimal duration. A short intensive schedule of instillations within the first 3-4 mo after an immediate instillation may be as effective as longer-term treatment schedules (grade C). Instillations during >/=1 yr in intermediate-risk patients seem advisable only when an immediate instillation has not been given (grade C). Higher drug concentrations and optimization of the drug's concentration in the bladder may provide better results (grade C). CONCLUSIONS: The optimal schedule and duration of intravesical chemotherapy after an immediate instillation remain unknown. Future studies should focus on the eradication of residual disease after TUR and the prevention of late recurrences.

-----

Clin Cancer Res. 2008 Jan 1;14(1):224-229.
Phase III Prevention Trial of Fenretinide in Patients with Resected Non Muscle-Invasive Bladder Cancer.
Sabichi AL, Lerner SP, Atkinson EN, Grossman HB, Caraway NP, Dinney CP, Penson DF, Matin S, Kamat A, Pisters LL, Lin DW, Katz RL, Brenner DE, Hemstreet GP 3rd, Wargo M, Bleyer A, Sanders WH, Clifford JL, Parnes HL, Lippman SM.
Authors' Affiliations: Departments of Clinical Cancer Prevention, Biostatistics and Applied Mathematics, Urology, Pathology, Community Clinical Oncology Program, and Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center.

PURPOSE: The study aims to evaluate the efficacy and toxicity of fenretinide in preventing tumor recurrence in patients with transitional cell carcinoma (TCC) of the bladder. EXPERIMENTAL DESIGN: We conducted a multicenter phase III, randomized, placebo-controlled trial of fenretinide (200 mg/day orally for 12 months) in patients with non-muscle-invasive bladder TCC (stages Ta, Tis, or T1) after transurethral resection with or without adjuvant intravesical Bacillus Calmette-Guerin (BCG). Patients received cystoscopic evaluation and bladder cytology every 3 months during the 1-year on study drug and a final evaluation at 15 months. The primary endpoint was time to recurrence. RESULTS: A total of 149 patients were enrolled; 137 were evaluable for recurrence. The risk of recurrence was considered to be "low" in 72% (no prior BCG) and intermediate or high in 32% (prior BCG) of the evaluable patients. Of the lower-risk group, 68% had solitary tumors and 32% had multifocal, low-gra
de papillary (Ta, grade 1 or grade 2) tumors. The 1-year recurrence rates by Kaplan-Meier estimate were 32.3% (placebo) versus 31.5% (fenretinide; P = 0.88 log-rank test). Fenretinide was well tolerated and had no unexpected toxic effects; only elevated serum triglyceride levels were significantly more frequent on fenretinide (versus placebo). The Data Safety and Monitoring Board recommended study closure at 149 patients (before reaching the accrual goal of 160 patients) because an interim review of the data showed a low likelihood of detecting a difference between the two arms, even if the original accrual goal was met. CONCLUSIONS: Although well tolerated, fenretinide did not reduce the time-to-recurrence in patients with Ta, T1, or Tis TCC of the bladder.

-----

J Endourol. 2007 Dec;21(12):1533-42.
Retrospective analysis of transurethral resection, second-look resection, and long-term chemo-metaphylaxis for superficial bladder cancer: indications and efficacy of a differentiated approach.
Schulze M, Stotz N, Rassweiler J.
Department of Urology, SLK-Kliniken Heilbronn, University of Heidelberg, Germany.

Background and Purpose: Because of controversy concerning risk factors for progression, recurrence, and persistence of bladder cancer, we reviewed the data of our patients with superficial bladder tumors. Based on a differentiated approach with second-look transurethral resection (TUR) and/or intravesical metaphylaxis, we wanted to answer the following questions: Was this approach efficient? What risk factors demand a second-look TUR? Is surveillance appropriate for patients at low risk? Materials and Methods: Retrospectively we analyzed the data of 251 patients with superficial bladder cancer with a mean follow-up time of 69 (range 20 to 107) months. We focused on recurrence rates, tumor-persistence and progression, and types of adjuvant treatment. An early reintervention within 6 to 8 weeks after primary resection was defined as a second-look TUR. To judge the necessity of early reintervention and metaphylaxis, we performed a matched-pair analysis for the low-risk group. Results: Tumor stages included T(a) (170 patients, 68%); T(1) (72 patients, 29%); carcinoma in situ (CIS) (9 patients, 4%). Grades included grade 1 (58 patients, 23%); grade 2 (117 patients, 47%); and grade 3 (76 patients, 30%). Thirty-eight (15%) tumors were already classified as recurrent. A second-look TUR was performed on 222 (88%) patients, indicating a persistence rate of 25%. Persistence rates for low-risk tumors (T(a) grade 1/2) were 9%; rates for T(a) grade 3 tumors were significantly higher. Risk factors for persistence were multilocularity and higher grade and stage. Matched-pair analysis for the low-risk group did not show any significant advantage for second-look TUR. After complete resection of T(1) grade 3 tumors, the risk of progression is similar to that for tumors of lower grade and stage. The overall recurrence rate was 25%, with a higher risk of upstaging in cases of higher stage or grade and multilocular and persisting tumors. Conclusion: The overall tumor recurrence rate of 25% reflects the efficacy of our differentiated approach with selective use of second-look TUR and intravesical metaphylaxis (intravesical chemotherapy). Second-look TUR is indicated for multifocal and recurrent tumors or in patients whose tumors put them at high risk. Patients with grade 2/3 tumors, multifocal grade 1 tumors, and all T(1) tumors received metaphylaxis; intravesical bacillus Calmette-Guerin was instilled in patients with CIS. With this regimen, even in T(1) grade 3 stages, organ preservation can be achieved.

-----

Urology. 2007 Dec;70(6):1091-5.
Recurrence-free survival after radical cystectomy of patients downstaged by transurethral resection.
Nielsen ME, Bastian PJ, Palapattu GS, Trock BJ, Schoenberg MP, Chan T, Rogers CG.
James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, Maryland 21287-2101, USA. nielsen@jhmi.edu

OBJECTIVES: The finding of bladder cancer invading the detrusor muscle on transurethral resection (TUR) is one of the clearest indications for radical cystectomy. To the extent that detrusor invasion is, in practical effect, a binary variable, the variety of outcomes after radical cystectomy in these patients belies the simplicity of this approach. In this context, we assessed bladder cancer recurrence-free survival among patients noted to have muscle-invasive urothelial carcinoma (transitional cell cancer [TCC]) on staging TUR subsequently found to have non-muscle-invasive TCC at radical cystectomy (downstaged). METHODS: The records of 248 consecutive patients who underwent radical cystectomy for TCC at a single academic institution from 1994 to 2002 were retrospectively reviewed. Of these patients, 112 (45%) had documented muscle-invasive disease by TUR and were clear of gross residual tumor on cystoscopy before radical cystectomy. RESULTS: Of the 112 patients, 25 (22.3%) were downstaged to non-muscle-invasive disease (Stage pT1 or less) at cystectomy and 87 (77.7%) had persistent muscle-invasive disease (Stage pT2 or greater) at cystectomy. Recurrence occurred in 4 downstaged patients (16.0%) compared with 29 patients (33.3%) who were not downstaged (P = 0.094). Kaplan-Meier analysis demonstrated a statistically significant improvement in recurrence-free survival with downstaging (log-rank P = 0.008). Multivariate analysis demonstrated a threefold reduction in recurrence risk with tumor downstaging (hazard ratio 0.33, 95% confidence interval 0.10 to 1.12) that approached statistical significance (P = 0.075). Nodal status was the strongest predictor of RFS. CONCLUSIONS: Downstaging from muscle-invasive TCC on TUR to non-muscle-invasive TCC at radical cystectomy can be associated with a reduced risk of recurrence even after adjusting for lymph node status and adjuvant chemotherapy.

-----

Urology. 2007 Dec;70(6):1053-6.
Gum chewing stimulates bowel motility in patients undergoing radical cystectomy with urinary diversion.
Kouba EJ, Wallen EM, Pruthi RS.
Division of Urologic Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

OBJECTIVES: Several studies have shown that gum chewing may stimulate bowel motility after gastrointestinal surgery. Because urinary diversion typically uses a segment of bowel, it is conceivable that patients undergoing cystectomy and diversion may benefit from gum chewing. This study aimed to determine whether gum chewing in the immediate postoperative period facilitates a return to bowel function in patients undergoing cystectomy and urinary diversion. METHODS: A total of 102 patients underwent radical cystectomy and urinary diversion for clinically localized bladder cancer. Each patient followed our institution's perioperative cystectomy care plan. The first cohort of patients underwent surgery between July 2004 and August 2005 and served as a comparison (control) group in which no gum was dispensed. The second cohort underwent surgery during September 2005 to July 2006. These patients were given chewing gum to begin on postoperative day 1. Outcome measures included time to flatus, time to bowel movement, length of hospital stay, and complications. RESULTS: The time to flatus was shorter in patients who received gum compared with controls (2.4 versus 2.9 days; P <0.001). Also, time to bowel movement was reduced in patients who received gum (3.2 versus 3.9 days; P <0.001). There was no significant difference in length of hospital stay between gum-chewing patients and controls (4.7 versus 5.1 days, respectively; P = 0.067). Gum chewing was well tolerated in all patients. CONCLUSIONS: Gum chewing may speed the recovery of bowel function after cystectomy and diversion. These findings are consistent with outcomes in the colorectal surgery published data that support the use of chewing gum as an easy and inexpensive way to enhance recovery after surgery.

-----

BJU Int. 2007 Dec;100(6):1221-4.
Improving the prognosis of patients after radical cystectomy. Part I: the role of lymph node dissection.
Suttmann H, Kamradt J, Lehmann J, Stöckle M.
Department of Urology and Paediatric Urology, Saarland University Hospital, Homburg/Saar, Germany. henrik.suttmann@uniklinikum-saarland.de

The first two reviews are from the same unit in Germany and describe the well-known but still much discussed ways of improving the prognosis of patients undergoing cystectomy for bladder cancer. The authors review the roles of lymph node dissection and perioperative chemotherapy, and draw conclusions which will be of help for patients having this form of therapy. In a further review, authors from Egypt debate the requirement for a refluxing or non-refluxing uretero-ileal anastomosis in low-pressure reservoirs, drawing on their extensive experience in this field. The optimum treatment for patients with muscle-invasive bladder cancer remains a matter of intense debate; some authors still question the role of radical cystectomy (RC) per se, as it can be a potentially mutilating procedure with subsequent impairment in quality of life. However, the impairment has not been investigated using validated quality-of-life studies. By contrast, it is commonly accepted that no alternative treatment yields similar long-term survival data to RC. However, survival rates after RC are far from satisfying, particularly for patients with >/= pT3 and/or pN+ disease. Therefore, various strategies were introduced to improve survival in these patients, i.e. extension of lymph node dissection during radical surgery and perioperative chemotherapy. Both strategies are analysed and discussed in two mini-reviews, based on data from current publications and from theoretical considerations.

-----

J Urol. 2007 Nov 9; [Epub ahead of print]
Conservative Management of Low Risk Superficial Bladder Tumors.
Pruthi RS, Baldwin N, Bhalani V, Wallen EM.
Division of Urologic Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

PURPOSE: The most common approach for nonmuscle invasive urothelial cancers of the bladder is transurethral resection of the bladder tumor, often under regional or general anesthesia. Due to the high rate of recurrence, many such patients experience the potential risks and morbidity of frequent surgical intervention, despite the often slow growth rate and low risk of progression of such tumors. Recent experiences have suggested that some patients with low grade superficial tumors may be treated expectantly. We report on our experience with expectant management of low risk superficial bladder tumors. MATERIALS AND METHODS: We retrospectively evaluated 173 patients with superficial bladder cancer who are currently actively treated at our institution and who have complete clinical information. From this population we identified 22 cases (12.7%) under expectant management for bladder tumors in the last 12 months. Demographic and clinical information on this cohort are described as well as clinical and pathological outcomes, and disease interventions on followup. RESULTS: All patients had a prior history of recurrent low risk (Ta, low grade) bladder tumors. The mean followup was 25 months. Of the 22 patients 8 had no growth, 9 had minimal growth and 5 had moderate growth of their tumors. Fifteen patients have required no intervention, 3 have undergone office fulguration and 4 have undergone repeat transurethral bladder tumor resection. Two men (9%) had evidence of grade progression on followup transurethral bladder tumor resection, and 1 of these men (4.5%) had stage progression (T1 disease). Both men had evidence of moderate tumor growth and suspicious/malignant cytology which resulted in the repeat transurethral bladder tumor resection. Interestingly, these 2 men had a 6 and 11 year history of recurrent Ta, low grade disease before progression and had been under expectant management for 18 and 12 months before progression. Interestingly all smokers had a recurrence during the surveillance period and this represented a 3.3-fold increased rate of recurrence over nonsmokers. CONCLUSIONS: Expectant management of recurrent bladder tumors may be an appropriate option for some patients with a history of Ta, low grade tumors, especially those who are older and with significant medical comorbidities. Such a strategy may avoid potential risks and morbidities associated with frequent, repeat transurethral bladder tumor resection. However, under such an expectant management strategy, patients should remain under careful cystoscopic and cytologic surveillance as there remains some risk for grade and stage progression in this patient population.

-----

Br J Cancer. 2007 Nov 6; [Epub ahead of print]
Activity of endovesical gemcitabine in BCG-refractory bladder cancer patients: a translational study.
Gunelli R, Bercovich E, Nanni O, Ballardini M, Frassineti GL, Giovannini N, Fiori M, Pasquini E, Ulivi P, Pappagallo GL, Silvestrini R, Zoli W.
1Department of Urology, Morgagni-Pierantoni Hospital, Forlì, Italy.

Intravesical gemcitabine (Gem) has shown promising activity against transitional cell carcinomas (TCC) of the bladder, with moderate urinary toxicity and low systemic absorption. The present phase II study evaluated the activity of biweekly intravesical treatment with Gem using a scheme directly derived from in vitro preclinical studies. Patients with Bacille Calmette-Guérin (BCG) -refractory Ta G3, T1 G1-3 TCC underwent transurethral bladder resection and then intravesical instillation with 2000 mg Gem diluted in 50 ml saline solution on days 1 and 3 for 6 consecutive weeks. Thirty-eight (95%) of the 40 patients showed persistent negative post-treatment cystoscopy and cytology 6 months after Gem treatment, while the remaining 2 patients relapsed at 5 and 6 months. At a median follow-up of 28 months, recurrences had occurred in 14 patients. Among these, four had downstaged (T) disease, three had a lower grade (G) lesion and three had a reduction in both T and G. Urinary and systemic toxicity was very low, with no alterations in biochemical profiles. In conclusion, biweekly instillation of Gem proved active in BCG-refractory Ta G3, T1 G1-3 TCC. Our results highlight the importance of preclinical studies using in vitro systems that adequately reproduce the conditions of intravesical clinical treatment to define the best therapeutic schedule. British Journal of Cancer advance online publication, 6 November 2007; doi:10.1038/sj.bjc.6604074 www.bjcancer.com.

-----

BJU Int. 2007 Nov 6; [Epub ahead of print]
Does photodynamic transurethral resection of bladder tumour improve the outcome of initial T1 high-grade bladder cancer? A long-term follow-up of a randomized study.
Denzinger S, Wieland WF, Otto W, Filbeck T, Knuechel R, Burger M.
Department of Urology, University of Regensburg, Regensburg, and Institute of Pathology, University Hospital RWTH Aachen, Aachen, Germany.

OBJECTIVE To evaluate, in a long-term follow-up of T1 high-grade bladder cancer treated in a prospective, randomized trial, whether fluorescence diagnosis (FD) increases recurrence-free survival (RFS) or reduces progression to muscle-invasive stages. PATIENTS AND METHODS In all, 191 patients with suspected superficial bladder cancer were treated with transurethral resection under white light (WL) or with FD; 46 presented with initial T1 high-grade BC (WL, 25; FD, 21). There were no differences in multifocality of tumours, concomitant carcinoma in situ or tumour size in either group. RESULTS Patients were followed for a median of 7.3 (WL) and 7.5 (FD) years to evaluate RFS. In the WL group there were 11, and in the FD group three, recurrent tumours of the same stage and grade. The RFS at 4 and 8 years was 69% and 52% in the WL, and 91% and 80% in FD group, respectively. With FD, the RFS was significantly longer according to Kaplan-Meier analysis (P = 0.025). In the WL group, three (12%), and in the FD group four (19%) patients progressed to muscle-invasive stages (>/= T2). CONCLUSION In initial T1 high-grade bladder cancer, FD is significantly better than conventional WL transurethral resection for RFS. However, the progression rate to muscle-invasive disease was not reduced by FD. Thus the clinical course (progression) of T1 high-grade bladder cancer remains unaffected by FD.

-----

Clin Genitourin Cancer. 2007 Sep;5(6):386-9.
Long-term follow-up of intravesical bacillus Calmette-Guérin treatment for superficial transitional-cell carcinoma of the bladder involving the prostatic urethra.
Taylor JH, Davis J, Schellhammer P.
Department of Urology, Eastern Virginia Medical School, Norfolk, VA 23501, USA. intuition97@gmail.com

BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) is a treatment option for superficial (<or=T1) transitional cell carcinoma. Transitional cell carcinoma involving the prostatic urethra presents a treatment dilemma. Whereas prostatic urethral involvement might require radical cystectomy, select patients can be offered BCG and careful surveillance to preserve the bladder. We report long-term experience with BCG in this subset of patients with >5-year follow-up. PATIENTS AND METHODS: Twenty-eight patients with high-risk superficial bladder cancer and prostatic urethral involvement were treated with once-weekly BCG for 6 weeks. Patients with prostatic stromal involvement were excluded. Maintenance was not used before 1995. Currently, we use maintenance BCG after induction. Patients were followed by cystoscopy/cytology and repeat biopsy to detect persistent and/or progressive disease. RESULTS: After 1 or 2 courses of once-weekly BCG for 6 weeks, 64.3% (18 of 28 of patients) exhibited a complete response in the bladder and prostate at their 6-month followup. Of those obtaining a complete response, 55.6% (10 of 18) experienced recurrence. Three recurrences were in the prostate: 1 isolated and 2 associated with multifocal bladder involvement. Twenty-eight percent (8 of 28 patients) underwent cystectomy because of failure of treatment to eradicate superficial disease or disease progression. Disease-specific survival was 89% (25 of 28 patients) at a median follow-up of 7.5 years. CONCLUSION: Our long-term data support the durability of intravesical BCG in select patients with superficial bladder transitional cell carcinoma with prostatic urethral involvement. Follow-up biopsy of the prostatic urethra is mandatory and, if positive, cystectomy is indicated. One third of patients will require cystectomy for persistent or progressive disease; therefore, careful surveillance is critical.

-----

Urol Int. 2007;79(3):200-3.
Primary invasive versus progressive invasive transitional cell bladder cancer: multicentric study of overall survival rate.
Ferreira U, Matheus WE, Nardi Pedro R, Levi D'Ancona CA, Reis LO, Stopiglia RM, Denardi F, Rodrigues Netto N Jr, de Cássio Zequi S, da Fonseca FP, Lopes A, Cardoso Guimarães G, de Carvalho Fernandes R, Cardenuto Perez MD.
Division of Urology UNICAMP, São Paulo, Brazil.

INTRODUCTION AND OBJECTIVE: When feasible, the treatment for all-invasive bladder cancer is radical cystectomy. The aim of the present study was to analyze the prognostic difference, disease-specific survival rate, of muscle-invasive transitional cell cancer of the bladder (TCCB) for progressive invasive TCCB. PATIENTS AND METHODS: A retrospective multicentric analysis was performed studying a total of 242 patients who underwent radical cystectomy for invasive TCCB from 1993 to 2005. The patients were divided into two groups: group 1 included 57 patients with progressive invasive TCCB, and group 2 included 185 patients with primary invasive TCCB. Both groups were further divided according to the pathological findings in pT2/3 (muscle and/or perivesical fat invasion), pT4 (adjacent organs/structure invasion), N+ (positive lymphatic nodes) and M+ (distant organ metastasis). Several tests were employed for statistical analysis: chi2, Mann-Whitney, Kaplan-Meier method and Wilcoxon (Breslow) method were used to compare the possible survival curve differences of groups 1 and 2. Multivariated analysis determined by proportional risk regression excluded sex, age and disease stage interferences in the final results. RESULTS: The average time for a superficial TCCB to become muscle-invasive was 37.4 months, and the average number of transurethral resections performed in each patient was 3. The average and median global survival rates were, respectively, 96 and 88 months in group 1 and 98 and 90 months in group 2, without a statistically significant difference (p = 0.0734). The 1-year survival rate was 84.32% in group 1 and 76.54% in group 2. After 3 years of follow-up the survival rate fell to 74.50% in group 1 and to 59.05% in group 2. Finally, the 5-year survival rate was 57.94% in group 1 and 52.24% in group 2. CONCLUSION: In the present study, patients with primary invasive and progressive invasive TCCB showed a similar 5-year disease-specific survival rate. Pathological stage (pTN, N and M) and patient demography did not interfere with the results. Copyright 2007 S. Karger AG, Basel.

-----

Urol Int. 2007;79(3):191-9.
Lymphadenectomy in bladder cancer: a review.
Buscarini M, Josephson DY, Stein JP.
Department of Urology, Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, Los Angeles, Calif 90089, USA.

BACKGROUND: Radical cystectomy is the standard treatment for muscle invasive bladder cancer, however the role and appropriate extent of an associated lymphadenectomy continues to change. METHODS: We performed a detailed review of the medical literature pertaining to the development and rationale for an extended lymphadenectomy in patients undergoing radical cystectomy. RESULTS: A perspective of lymphadenectomy and an anatomic account of bladder lymphatic drainage are presented. The technique of an extended lymphadenectomy is also highlighted. Autoptic contemporary clinical data are presented to suggest that a more extensive lymphadenectomy has both prognostic and therapeutic utility. Furthermore, the stage of the primary bladder tumor, total number of lymph nodes removed, and the lymph node tumor burden are shown to be important prognostic variables in patients undergoing cystectomy with pathologic evidence of lymph node metastasis. CONCLUSIONS: Radical cystectomy provides excellent local cancer control with the Lowe's pelvic recurrence rates and the best long-term survival. Radical cystectomy with an appropriate extended lymphadenectomy, while surgically more challenging, does not significantly increase the morbidity or mortality of the procedure. The limits of lymph node dissection are still subject to debate and there is growing evidence that an extended lymphadenectomy provides further diagnostic and therapeutic benefit. Copyright 2007 S. Karger AG, Basel.

-----

BJU Int. 2007 Jul;100(1):137-42.
Laparoscopic radical cystectomy for cancer: oncological outcomes at up to 5 years.
Haber GP, Gill IS.
Section of Laparoscopic and Robotic Surgery, Glickman Urological Institute, The Cleveland Clinic Foundation, Cleveland, OH, USA.

OBJECTIVE To report the oncological outcomes at </= 5 years after laparoscopic radical cystectomy (LRC), as open RC is the reference standard treatment for muscle-invasive bladder cancer, but interest in LRC is increasing at selected centres worldwide and as yet there are no long-term follow-up data. PATIENTS AND METHODS Between December 1999 and January 2005, 37 patients (mean age 66 years) had LRC with urinary diversion for invasive bladder cancer; 26 patients (70%) also had an extended pelvic lymphadenectomy. Overall and cancer-specific survival data were obtained from patient charts, radiographic reports, telephone contact, and a check of the Social Security Death Index. RESULTS Most tumours were transitional cell carcinoma (32, 86%), high-grade (grade III in 29, 78%) and high-stage (>/=pT2 in 26, 70%). Two patients had a positive surgical margin. The median (range) number of lymph nodes excised was 14 (2-24); seven patients (17%) had node-positive disease (pN1). Follow-up data were available for 35 patients (95%); eight (22%) completed >/= 5 years of follow-up, and the mean (range) follow-up was 31 (1-66) months. At the last follow-up, 24 patients (65%) were alive with no evidence of disease and 11 (30%) were dead, two (5%) from metastasis and nine (24%) from unrelated causes. The 5-year actuarial overall, cancer-specific and recurrence-free survival was 63%, 92% and 92%, respectively. CONCLUSION To our knowledge, this is the first report of </= 5-year follow-up after LRC; the data suggest that LRC provides oncological outcomes comparable to contemporary series of open RC.

-----

BJU Int. 2007 Jul;100(1):33-6.
The increasing use of intravesical therapies for stage T1 bladder cancer coincides with decreasing survival after cystectomy.
Lambert EH, Pierorazio PM, Olsson CA, Benson MC, McKiernan JM, Poon S.
Urology, Columbia University Medical Center, New York, NY, USA.

OBJECTIVE Intravesical therapy (IVT), chemo and immunotherapy, has made conservative, bladder-sparing strategies a viable option for managing patients with high grade T1 bladder cancer. However, many of these patients will have recurrence and occasionally progression, questioning delayed intervention. This study examines the patterns of use of IVT in high-grade T1 bladder cancer and the subsequent impact on survival for patients ultimately proceeding to radical cystectomy (RC). PATIENTS AND METHODS Between 1990 and 2005, 104 patients were identified with T1 high-grade transitional cell carcinoma (TCC) and who underwent RC. Patients were divided into two groups; those having RC before 1998 (median year of surgery) and those after 1998. Trends in time from diagnosis to RC, courses of IVT, recurrence and pathological stage were analysed using two-sample t-tests with 95% confidence intervals. Kaplan-Meier analysis was used to determine the disease-free and overall survival rates. RESULTS Before 1998, 28 of 38 patients (74%) proceeded directly to RC with no IVT, vs 20 of 47 (43%) after 1998 (P = 0.004). The mean number of IVT courses per patient was 0.53 before 1998 and 1.2 afterward (P = 0.016). Patients who had RC before 1998 had a 69.7% disease-free survival at 5 years, vs 39.6% for those after 1998 (P = 0.05). CONCLUSION In the past 15 years, our experience indicates that patients having RC for T1 high-grade TCC after 1998 were more likely to receive IVT. These same patients had a worsening disease-free survival. In very few other cancers has disease-free survival decreased over time. We postulate that the decrease in survival might be related to an increased use of IVT.

-----

J Urol. 2007 Jun;177(6):2088-94.
Upper tract urothelial recurrence following radical cystectomy for transitional cell carcinoma of the bladder: an analysis of 1,069 patients with 10-year followup.
Sanderson KM, Cai J, Miranda G, Skinner DG, Stein JP.
Department of Urology, Keck School of Medicine, University of Southern California, University of Southern California/Norris Cancer Center, Los Angeles, California.

PURPOSE: Risk factors for upper tract recurrence following radical cystectomy for transitional cell carcinoma of the bladder are not yet well-defined. We reviewed our population of patients who underwent radical cystectomy to identify prognostic factors and clinical outcomes associated with upper tract recurrence. MATERIALS AND METHODS: From our prospective database of 1,359 patients who underwent radical cystectomy we identified 1,069 patients treated for transitional cell carcinoma of the bladder between January 1985 and December 2001. Univariate analysis was completed to determine factors predictive of upper tract recurrence. RESULTS: A total of 853 men and 216 women were followed for a median of 10.3 years (maximum 18.5). There were 27 (2.5%) upper tract recurrences diagnosed at a median of 3.3 years (range 0.4 to 9.3). Only urethral tumor involvement was predictive of upper tract recurrence. In men superficial transitional cell carcinoma of the prostatic urethra was associated with an increased risk of upper tract recurrence compared with prostatic stromal invasion or absence of prostatic transitional cell carcinoma (p <0.01). In women urethral transitional cell carcinoma was associated with an increased risk of upper tract recurrence (p = 0.01). Despite routine surveillance 78% of upper tract recurrence was detected after development of symptoms. Median survival following upper tract recurrence was 1.7 years (range 0.2 to 8.8). Detection of asymptomatic upper tract recurrence via surveillance did not predict lower nephroureterectomy tumor stage, absence of lymph node metastases or improved survival. CONCLUSIONS: Patients with bladder cancer are at lifelong risk for late oncological recurrence in the upper tract urothelium. Patients with evidence of tumor involvement within the urethra are at highest risk. Surveillance regimens frequently fail to detect tumors before symptoms develop. However, radical nephroureterectomy can provide prolonged survival.

-----

World J Urol. 2007 May 25; [Epub ahead of print]
The rationale for radical cystectomy as primary therapy for T4 bladder cancer.
Nagele U, Anastasiadis AG, Merseburger AS, Corvin S, Hennenlotter J, Adam M, Sievert KD, Stenzl A, Kuczyk MA.
Department of Urology, Eberhard-Karls University Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany, markus.kuczyk@med.uni-tuebingen.de.

Treatment of T4 bladder cancer patients remains a clinical challenge. Conservative management is often insufficient regarding local control, neoadjuvant chemotherapy delays definite treatment while leading to increased therapy-associated morbidity and mortality during the course of the disease. Primary cystectomy has also been reported to be associated with a high complication rate and unsatisfactory clinical efficacy. Herein, we report postoperative outcome, including therapy-related complications, in 20 T4 bladder cancer patients subjected to primary cystectomy. Twenty patients underwent radical cystectomy for T4 bladder cancer. At the time of surgery, 8 patients had regional lymph node metastases. The median postoperative follow-up was 13 months for the whole group. Mean duration of postoperative hospitalization was 19 days. Ten patients received no intra- or postoperative blood transfusions, whereas an average number of 3 blood units were administered in the remaining cases. Major therapy-associated complications were paresthesia affecting the lower extremities (n = 3) as well as insignificant pulmonary embolism, enterocutaneous fistulation and acute renal failure in one patient, respectively. At the time of data evaluation, 11 patients were still alive after a follow-up of 20 months. Four patients >/=70 years at the time of cystectomy were still alive after 11, 22 and 31 months following surgery, respectively. The current data demonstrate primary cystectomy for T4 bladder cancer as a technically feasible approach that is associated with a tolerable therapy-related morbidity. Additionally, satisfying clinical outcome is observed even in a substantial number of elderly patients.

-----

Cancer Epidemiol Biomarkers Prev. 2007 May;16(5):984-90.
Associations between Exercise and Quality of Life in Bladder Cancer Survivors: A Population-Based Study.
Karvinen KH, Courneya KS, North S, Venner P.
Faculty of Physical Education and Recreation, University of Alberta, E-488 Van Vliet Center, Edmonton, Alberta, Canada, T6G 2H9. kerry.courneya@ualberta.ca.

BACKGROUND: Exercise has been shown to improve quality of life (QoL) in some cancer survivor groups, but it is unknown if the unique QoL issues faced by bladder cancer survivors are also amenable to an exercise intervention. This study provides the first data examining the association between exercise and QoL in bladder cancer survivors. METHODS: Bladder cancer survivors identified through a provincial cancer registry were mailed a survey that included the Godin Leisure Time Exercise Questionnaire, the Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) scale, and the Fatigue Symptom Inventory. RESULTS: Of the 525 bladder cancer survivors (51% response rate) that completed the survey, 22.3% were meeting public health exercise guidelines in the past month, 16.0% were insufficiently active (i.e., some exercise but less than the guidelines), and 61.7% were completely sedentary. ANOVA indicated a general linear association between meeting guidelines and QoL, with those meeting guidelines reporting more favorable scores than completely sedentary survivors on the FACT-Bl (mean difference, 7.6; 95% confidence interval, 3.6-11.7; P < 0.001), the FACT (P = 0.001), the trial outcome index (P < 0.001), functional well-being (P < 0.001), additional concerns (P = 0.001), sexual functioning (P < 0.001), erectile function (P < 0.001), body image (P < 0.001), and various fatigue indicators (P < 0.05). Adjusting for key medical and demographic factors slightly attenuated the magnitude of the associations but did not alter the substantive conclusions. CONCLUSIONS: Exercise is positively associated with QoL in bladder cancer survivors, although few are meeting public health exercise guidelines. Studies testing the causal effects of exercise on QoL issues unique to this population are warranted. (Cancer Epidemiol Biomarkers Prev 2007;16(5):984-90).

-----

Wien Med Wochenschr. 2007 Apr;157(7-8):162-9.
[Therapy and follow-up of bladder cancer.]
[Article in German]
Meyer D, Schmid HP, Engeler DS.
Klinik für Urologie, Kantonsspital St. Gallen, St. Gallen, Switzerland, daniel.meyer@kssg.ch.

Treatment and follow up of bladder cancer strongly depends on stage and differentiation of the tumour. Superficial bladder tumours can mostly be controlled by transurethral resection followed by early intravesical application of a chemotherapeutic agent and a further close meshed follow-up. Generally, for muscle-invasive tumours radical cystectomy is indicated, whereas organ-spearing treatment due to combined therapeutic concepts can be offered in selected cases. For advanced and metastatic tumours, despite good response of bladder cancer to chemotherapy, prognosis is still poor. However, implementation of new chemotherapeutic agents indicate a trend towards improved survival rates.

-----

Wien Med Wochenschr. 2007 Apr;157(7-8):157-61.
[Systemic oncological treatment of bladder cancer.]
[Article in German]
Meran JG, Kudlacek S, Beke D.
Medizinische Abteilung des Krankenhaus der Barmherzigen Brüder, Wien, Austria, johannes.meran@bbwien.at.

M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) and Cisplatin/Gemzar are potent therapies in the treatment of advanced bladder cancer. C/G provides similar efficacy in terms of overall survival compared with M-VAC, but does so with a superior safety profile. Therefore C/G is widely accepted as standard of care in locally advanced and metastatic bladder cancer. Despite potentially curative surgery almost half of the patients with muscle-invasive bladder cancer will have recurrence of disease. Based on a recent meta-analysis with data from 3005 patients, and 2 randomised studies, neoadjuvant cisplatin-containing therapy has shown to improve overall survival. Thus, the use of neoadjuvant systemic treatment should be considered state-of-the-art. The question whether adjuvant treatment will improve the outcome is still not sufficiently answered.

-----

Eur Urol. 2007 Apr 27; [Epub ahead of print]
A Multicentre, Randomised Prospective Trial Comparing Three Intravesical Adjuvant Therapies for Intermediate-Risk Superficial Bladder Cancer: Low-Dose Bacillus Calmette-Guerin (27 mg) versus Very Low-Dose Bacillus Calmette-Guerin (13.5 mg) versus Mitomycin C.
Ojea A, Nogueira JL, Solsona E, Flores N, Gómez JM, Molina JR, Chantada V, Camacho JE, Piñeiro LM, Rodríguez RH, Isorna S, Blas M, Martínez-Piñeiro JA, Madero R; Members of the Cueto Group (Club Urológico Español De Tratamiento Oncológico).
Complejo Hospitalario Universitario de Vigo, Vigo, Spain.

OBJECTIVE: The primary aim was to search for lower doses of Bacillus Calmette-Guerin (BCG) that are effective and have lower toxicity. METHODS: A low dose of BCG 27mg was compared with BCG 13.5mg, using mitomycin C (MMC) 30mg as the third arm of comparison. A total of 430 patients with intermediate-risk superficial bladder cancer were randomised into three groups. Instillations were repeated once a week for 6 wk followed by another six instillations given once every 2 wk during 12 wk. RESULTS: There was a significantly longer disease-free interval for BCG 27mg versus MMC 30mg (p=0.006). There were no statistically significant differences between BCG 27mg and BCG 13.5mg (p=0.165) or between BCG 13.5mg and MMC 30mg (p=0.183). Cox proportional hazards regression showed that disease-free interval in the multivariate analysis was significantly better for primary disease and treatment with BCG 27mg. There were no significant differences among the three groups with regards to time to progression and cancer-specific survival time. Local and systemic toxicity were higher in both BCG treatment groups. CONCLUSIONS: One third of the standard dose, BCG 27mg, seems to be the minimum effective dose as adjuvant treatment for intermediate-risk superficial bladder cancer, being more effective than MMC 30mg. One sixth of the standard dose, BCG 13.5mg, has the same efficacy as MMC 30mg but it is more toxic.

-----

J Urol. 2007 Feb;177(2):437-43.
Defining optimal therapy for muscle invasive bladder cancer.
Herr HW, Dotan Z, Donat SM, Bajorin DF.
Department of Urology and Genitourinary Oncology Service, Division of Solid Tumor Oncology, Memorial Sloan-Kettering Cancer Center, Cornell University Weill Medical College, New York, New York 10021, USA. herrh@mskcc.org

PURPOSE: We defined an optimal curative strategy for muscle invasive bladder cancer and to determine how best to deliver curative therapy. MATERIALS AND METHODS: We reviewed published reports from 1985 to 2006 dealing with the treatment of muscle invasive (stage T2-T4a) bladder cancer. We analyzed all cohort, phase II and randomized phase III studies providing level 1 to 3 evidence impacting survival. RESULTS: Cisplatin based chemotherapy combined with high quality radical cystectomy and complete pelvic lymph node dissection improves survival over that of cystectomy alone. Surgery quality is an important predictor of survival even in patients receiving chemotherapy. Neoadjuvant chemotherapy is favored over adjuvant chemotherapy because it is better tolerated and more patients are able to receive effective therapy before rather than after surgery. CONCLUSIONS: Neoadjuvant chemotherapy followed by radical cystectomy and complete pelvic lymph node dissection is the optimal curative strategy in most patients presenting with muscle invasive bladder cancer.

-----

Urol Oncol. 2007 Jan-Feb;25(1):76-84.
Benchmarks achieved in the delivery of radiation therapy for muscle-invasive bladder cancer.
Coen JJ, Zietman AL, Kaufman DS, Shipley WU.
Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.

Radiation therapy has a multifaceted role in the treatment of muscle-invasive bladder cancer, from being a component of bladder sparing regimens to adjuvant therapy for patients after partial cystectomy, to palliative treatment in patients with metastatic disease. Here, we review the techniques currently used and the settings in which these techniques are applied. Advances in imaging and radiation delivery have allowed for definition of more precise treatment volumes, permitting the delivery of higher tumor doses and lesser doses to critical targets. Better tumor control, fewer therapeutic complications, and better quality of life outcomes are anticipated. In the United States, the most rapidly growing use of radiation in the treatment of bladder cancer is as a component of selective bladder conservation. It uses trimodality therapy, consisting of a maximal transurethral resection followed by concurrent chemotherapy and radiation. Careful cystoscopic surveillance by an experienced urologist ensures a prompt cystectomy at the fist sign of treatment failure. The majority of patients retain a well-functioning bladder with no survival decrement. Radiation therapy is also used as adjuvant therapy after partial cystectomy in select patients. In this setting, it decreases the risk of local or incisional recurrence. It is also used in patients with pelvic recurrences after cystectomy, often combined with concurrent chemotherapy. Radiation is a very effective palliative agent for patients with locally advanced or metastatic disease. It can palliate bleeding and pain for patients with local progression or alleviate pain from bony metastases.

-----

Urol Oncol. 2007 Jan-Feb;25(1):72-5.
Chemotherapy for muscle-invasive bladder cancer in the perioperative setting: current standards.
Dreicer R.
Department of Solid Tumor Oncology, Taussig Cancer Center and the Glickman Urologic Institute, Cleveland Clinic, Cleveland, OH 44195, USA. dreicer@ccf.org

Radical cystectomy remains the gold standard treatment for muscle-invasive bladder cancer. Although surgery achieves excellent local control, within 5 years, almost 50% of patients have a relapse and, subsequently, progression to systemic disease developing. Randomized trials of cisplatin-based chemotherapy regimens in the neoadjuvant setting have shown the potential to improve survival. Suboptimal trial design, insufficient numbers of patients, and lack of standardization of the chemotherapy regimens used have plagued adjuvant studies. Given the lethality of recurrent transitional cell carcinoma of the bladder, perioperative cisplatin-based chemotherapy should be considered a standard of care.

-----

Urol Oncol. 2007 Jan-Feb;25(1):66-71.
Surgical benchmarks for the treatment of invasive bladder cancer.
Skinner EC, Stein JP, Skinner DG.
Department of Urology, Keck University of Southern California School of Medicine and the Kenneth Norris Jr. Comprehensive Cancer Center, Los Angeles, CA 90089, USA. skinner@hsc.usc.edu

Radical cystectomy is the gold standard for treatment of localized invasive bladder cancer in the United States. In recent years, there has been increasing focus on the importance of surgical technique as a factor that may influence the clinical and oncologic outcome of the operation, beyond the classically recognized patient and tumor-related factors. There is still insufficient high-quality evidence to support the absolute standardization of the surgical technique or the establishment of firm benchmarks by which the individual surgeon can measure performance. However, there is considerable evidence suggesting that 3 aspects of surgical technique have an impact on outcome: (1) Positive surgical margins nearly always result in ultimate cancer death. The rate of positive margins varies with surgeon experience as well as with cancer-specific variables. (2) The extent of lymphadenectomy has a significant impact on recurrence rates of the cancer, regardless of whether the lymph nodes are pathologically positive or not. (3) Higher volume surgeons have lower operative mortality and fewer positive surgical margins than low-volume surgeons. Higher volume hospitals also have lower operative mortalities and shorter hospital stays for patients who have undergone radical cystectomy. In this review, the authors evaluate the evidence supporting each of these statements and suggest potential areas of standardization of surgical technique that could translate into improved patient outcomes.

-----

Urology. 2007 Jan;69(1 Suppl):80-92.
Radiotherapy for bladder cancer.
Milosevic M, Gospodarowicz M, Zietman A, Abbas F, Haustermans K, Moonen L, Rodel C, Schoenberg M, Shipley W.
Radiation Medicine Program, Princess Margaret Hospital, and Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.

The radiotherapy panel met to develop international consensus about the optimal use of radiotherapy, alone or in combination with surgery and chemotherapy, in the radical treatment of patients with bladder cancer. A consensus meeting of experts in the treatment of bladder cancer was convened by the Societe Internationale d'Urologie (SIU). The radiotherapy committee, which had international representation from 6 countries, performed a critical review of the English-language literature and developed evidence-based guidelines for the use of radiotherapy in the treatment of patients with bladder cancer. The strength of the evidence supporting each recommendation was ranked according to a 4-point scale. Consensus statements were developed that address (1) the effectiveness of radiotherapy in the treatment of bladder cancer, (2) the most appropriate patients for curative treatment with radiotherapy, (3) the optimal method of delivery of radiotherapy, (4) the best radiation prescription for treating bladder cancer, and (5) optimal management of the patient's condition after radiotherapy has been provided. Radiotherapy is effective treatment for selected patients with bladder cancer; it produces long-term disease control with preservation of normal bladder function. Modern radiotherapy treatment techniques offer the potential to improve cure rates and reduce adverse effects. All patients in whom the condition is newly diagnosed should be assessed in a multidisciplinary setting, where the relative merits of surgery, radiotherapy, and chemotherapy can be considered on an individual basis with the aim of optimizing overall outcomes.

-----

Urology. 2007 Jan;69(1 Suppl):62-79.
Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer.
Sternberg CN, Donat SM, Bellmunt J, Millikan RE, Stadler W, De Mulder P, Sherif A, von der Maase H, Tsukamoto T, Soloway MS.
Department of Oncology, San Camillo Forlanini Hospital, Rome, Italy.

To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Societe Internationale d'Urologie (SIU) to critically review the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed, as is chemotherapy for patients with metastatic urothelial cancer. The conference panel consisted of 10 medical oncologists and urologists from 3 continents who are experts in this field and who reviewed the English-language literature through October 2004. Relevant English-language literature was identified with the use of Medline; additional cited works not detected on the initial search regarding neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and chemotherapy for patients with metastatic urothelial cancer were reviewed. Evidence-based recommendations for diagnosis and management of the disease were made with reference to a 4-point scale. Results of the authors' deliberations are presented as a consensus document. Meta-analysis of randomized trials on cisplatin-containing combination neoadjuvant chemotherapy revealed a 5% difference in favor of neoadjuvant chemotherapy. No randomized trials have yet compared survival with transurethral resection of bladder tumor alone versus cystectomy for the management of patients with muscle-invasive disease. Collaborative international adjuvant chemotherapy trials are needed to assist researchers in assessing the true value of adjuvant chemotherapy. Systemic cisplatin-based combination chemotherapy is the only current modality that has been shown in phase 3 trials to improve survival in responsive patients with advanced urothelial cancer. A panel of international experts has formulated grade A through D recommendations for the management of patients with locally advanced and metastatic urothelial cancer on the basis of level 1 to 3 evidence and the findings of phase 2 trials, prospective randomized clinical trials, and meta-analyses.

-----

J Clin Oncol. 2006 Dec 10;24(35):5545-51.
Systemic chemotherapy for advanced bladder cancer: update and controversies.
Garcia JA, Dreicer R.
Department of Solid Tumor Oncology, Glickman Urologic Institute, Cleveland Clinic Taussig Cancer Center, Cleveland, OH 44195, USA. garciaj4@ccf.org

Despite improvements in surgical techniques and outcomes, 5-year survival rates for patients with muscle-invasive bladder cancer remain suboptimal. Almost 50% of patients will eventually progress and develop systemic disease. Although various single agents have shown activity in patients with advanced or metastatic disease, randomized trials have demonstrated the utility of cisplatin-based combinations regimens. Despite relatively high objective response rates, the impact on survival in patients with advanced disease has been quite limited. Surgical resection in selected patients achieving significant objective response to cytotoxic therapy can contribute to long-term survival rates. The role of salvage therapy in advanced disease remains undefined. Evaluation of several active compounds has yielded unimpressive results with low objective response rates and overlapping CIs. Recognition that the maximum benefit from conventional cytotoxics has been achieved has led to the recent initiation of a number of clinical trials evaluating targeted agents in the management of advanced urothelial cancer.

-----

J Clin Oncol. 2006 Dec 10;24(35):5536-44.
Trimodality treatment and selective organ preservation for bladder cancer.
Rodel C, Weiss C, Sauer R.
Department of Radiation Therapy, University of Erlangen, Erlangen, Germany. claus.roedel@strahlen.med.uni-erlangen.de

Standard treatment for muscle-invasive bladder cancer is cystectomy. Trimodality treatment, including transurethral resection of the bladder tumor (TURBT), radiation therapy and chemotherapy, has been shown to produce survival rates comparable to those of cystectomy. With these programs, cystectomy has been reserved for patients with incomplete response or local relapse. During the past 15 years, organ preservation by trimodality treatment has been investigated in prospective series from single centers and cooperative groups, with more than 1,000 patients included. Five-year overall survival rates in the range of 50% to 60% have been reported, and approximately three quarters of the surviving patients maintained their bladder. Clinical criteria helpful in determining ideal patients for bladder preservation include early tumor stage (including high-risk T1 disease), a visibly complete TURBT, and absence of ureteral obstruction. Close coordination among all disciplines is required to achieve optimal results. Future investigations will focus on (1) optimizing radiation techniques and incorporating more effective systemic chemotherapy, and (2) the proper selection of patients based on molecular makers.

   

The Bladder Cancer FileSM Compiled and Maintained by    The Center for Current Research, Inc. 708 Aubrey Avenue • Ardmore PA USA 19003 Phone: 610-649-3165 Email: customerservice@lifestages.com Website: www.lifestages.com

©Copyright 1992-date by The Center for Current Research. The Bladder Cancer File is a proprietary compilation of the Center for Current Research. The information in the File is solely for your use, and the use of your family, friends, and doctors. The information is the property of the individual researchers and institutions that produced it. It is an infringement of copyright law to attempt to "resell" the information as it is presented here.