Clinical risk stratification in patients with surgically resectable micropapillary bladder cancer.

OBJECTIVE: To analyse survival in patients with clinically localised, surgically resectable micropapillary bladder cancer (MPBC) undergoing radical cystectomy (RC) with and without neoadjuvant chemotherapy (NAC) and develop risk strata based on outcome data. PATIENTS AND METHODS: A review of our database identified 103 patients with surgically resectable (≤cT4acN0 cM0) MPBC who underwent RC. Survival estimates were calculated using Kaplan-Meier method and compared using log-rank tests. Classification and regression tree (CART) analysis was performed to identify risk groups for survival. RESULTS: For the entire cohort, estimated 5-year overall survival and disease-specific survival (DSS) rates were 52% and 58%, respectively. CART analysis identified three risk subgroups: low-risk: cT1, no hydronephrosis; high-risk: ≥cT2, no hydronephrosis; and highest-risk: cTany with tumour-associated hydronephrosis. The 5-year DSS for the low-, high-, and highest-risk groups were 92%, 51%, and 17%, respectively (P < 0.001). Patients down-staged at RC

Outcome of patients with clinically node-positive bladder cancer undergoing consolidative surgery after preoperative chemotherapy: The M.D. Anderson Cancer Center Experience.

PURPOSE: Patients with urothelial cancer with nodal metastasis have a poor prognosis, with many deemed incurable. We report outcomes of a prospective clinical protocol of patients with clinically node-positive disease treated via a multimodality treatment approach. PATIENTS AND METHODS: A total of 55 patients with bladder urothelial carcinoma with concurrent node-positive disease including pelvic nodal and retroperitoneal lymph node (RPLN) involvement underwent preoperative chemotherapy followed by consolidative surgery between 1995 and 2010. Associations between clinicopathologic factors and outcomes were analyzed using log-rank test and Cox regression analysis. RESULTS: Median cancer-specific survival (CSS) was 26 months (95% CI: 12.9-not applicable) for all patients. A total of 30 (55%) patients had pN0 category disease at the time of surgical extirpation. Despite radiologic complete response after chemotherapy, 6 of 21 patients (29%) had pN+category disease. The 5-year CSS rate was 66% for pN0 category disease vs. 12% for pN+category disease (P<0.001). Radiologic complete response to chemotherapy was associated with a 5-year CSS rate of 60% vs. 33% for a partial response (P = 0.038). Although no recurrences occurred within the lymphadenectomy template, 2 (14%) patients with cM1 RPLN disease who did not undergo RPLN dissection had recurrences in the RPLN basin and died within 6 months. CONCLUSION: Multimodality treatment approach with upfront chemotherapy followed by surgery can result in a 66% 5-year CSS rate for patients rendered as having pN0 category disease despite initially presenting with node-positive disease. However, as those with residual disease do so poorly, further efforts in refining selection of patients for surgical consolidation are needed.

Novel fluorescence in situ hybridization-based definition of bacille Calmette-Guérin (BCG) failure for use in enhancing recruitment into clinical trials of intravesical therapies.

OBJECTIVES: To present a molecular definition of bacille Calmette-Guérin (BCG) failure that incorporates fluorescence in situ hybridization (FISH) testing to predict BCG failure before it becomes clinically evident, which can be used to enhance trial designs for patients with non-muscle-invasive bladder cancer. PATIENTS AND METHODS: We used data from 143 patients who were followed prospectively for 2 years during intravesical BCG therapy, during which time FISH assays were collected and correlated to clinical outcomes. RESULTS: Of the 95 patients with no evidence of tumour at 3-month cystoscopy, 23 developed tumour recurrence and 17 developed disease progression by 2 years. Patients with a positive FISH test at both 6 weeks and 3 months were more likely to develop tumour recurrence (17/37 patients [46%] and 16/28 patients [57%], respectively) than patients with a negative FISH test (6/58 patients [10%] and 3/39 patients [8%], respectively; both P < 0.001). Using hazard ratios for recurrence with positive 6-week and 3-month FISH results, we constructed clinical trial scenarios whereby patients with a negative 3-month cystoscopy and positive FISH result could be considered to have 'molecular BCG failure' and could be enrolled in prospective, randomized clinical trials comparing BCG therapy (control) with an experimental intravesical therapy. CONCLUSIONS: Patients with positive early FISH and negative 3-month cystoscopy results can be considered to have molecular BCG failure based on their high rates of recurrence and progression. This definition is intended for use in designing clinical trials, thus potentially allowing continued use of BCG as an ethical comparator arm.

Clinical outcomes of cT1 micropapillary bladder cancer.

PURPOSE: While many urologists recommend radical cystectomy for micropapillary bladder cancer invading the lamina propria (cT1), contradictory small reports exist on the efficacy of conservative management with intravesical bacillus Calmette-Guérin for this disease. We report our updated experience in what to our knowledge is the largest series of patients with cT1 micropapillary bladder cancer. MATERIALS AND METHODS: An institutional review board approved review of our cancer database identified 283 patients with micropapillary bladder cancer, including 72 staged with cT1N0M0 disease at diagnosis and initiation of therapy. Survival analysis was performed using the Kaplan-Meier estimator and compared using the log rank test. RESULTS: In this cohort of 72 patients 40 received primary intravesical bacillus Calmette-Guérin and 26 underwent up-front radical cystectomy. Of patients who received bacillus Calmette-Guérin 75%, 45% and 35% experienced disease recurrence, progression and lymph node metastasis, respectively. Patients treated with up-front cystectomy had improved survival compared to patients treated with primary bacillus Calmette-Guérin (5-year disease specific survival 100% vs 60% p = 0.006) and patients who underwent delayed cystectomy after recurrence (5-year disease specific survival 62%, p = 0.015). Prognosis was especially poor in patients who waited for progression before undergoing radical cystectomy with an estimated 5-year disease specific survival of only 24% and a median survival of 35 months. In patients treated with up-front cystectomy pathological up-staging was found in 27%, including 20% with lymph node metastasis. CONCLUSIONS: While certain patients with T1 micropapillary bladder cancer may respond to intravesical bacillus Calmette-Guérin, survival is improved in those who undergo early radical cystectomy. Further molecular studies are needed to identify subsets of patients in whom the bladder can be safely spared.

Micropapillary bladder cancer: current treatment patterns and review of the literature.

OBJECTIVES: No guidelines exist for the management of micropapillary bladder cancer (MPBC) and most reports of this variant of urothelial carcinoma are case series comprising small numbers of patients. We sought to determine current practice patterns for MPBC using a survey sent to the Society of Urologic Oncology (SUO) and to present those results in the setting of a comprehensive review of the existing literature. MATERIALS AND METHODS: A survey developed by the Translational Science Working Group of the Bladder Cancer Advocacy Network-sponsored Think Tank meeting was distributed to members of the SUO. The results from 118 respondents were analyzed and presented with a literature review. RESULTS: Most survey respondents were urologists, with 80% considering bladder cancer their primary area of interest. Although 78% of the respondents reported a dedicated genitourinary pathologist at their institution, there were discrepant opinions on how a pathologic diagnosis of MPBC is determined as well as variability on the proportion of MPBC that is clinically significant. Among them, 78% treat MPBC differently than conventional urothelial carcinoma, with 81% reporting that they would treat cT1 MPBC with upfront radical cystectomy. However, the respondents had split opinions regarding the sensitivity of MPBC to cisplatin-based chemotherapy, which affected utilization of neoadjuvant chemotherapy in muscle-invasive disease. CONCLUSIONS: The management of MPBC is diverse among members of the SUO. Although most favors early cystectomy for cT1 MPBC, there is no consensus on the use of neoadjuvant chemotherapy for muscle-invasive MPBC.

Should histologic variants alter definitive treatment of bladder cancer?

PURPOSE OF REVIEW: The clinical significance of variant histology is controversial and diagnosis is challenging. If variant architecture truly identifies high-risk patients, or those with a differential response to therapy, than treatment algorithms should be altered. This review outlines the current evidence and determines whether histologic variants should indeed alter definitive treatment. RECENT FINDINGS: For patients with pure squamous cell, adenocarcinoma, or small cell carcinoma, there is clear evidence to alter treatment paradigms. In adenocarcinoma or squamous cell carcinoma, there is a focus on local control and multimodal therapy with radiation. In small cell carcinoma all stages should be treated with primary chemotherapy followed by surgical extirpation. For patients with other variants of urothelial differentiation (i.e., micropapillary, sarcomatoid, squamous/glandular differentiation, etc.), management guidelines are less clear and radical cystectomy remains the mainstay of treatment at this time. SUMMARY: The management of variant histology is challenging as it not only depends on accurate diagnosis and staging, but on assumptions regarding sensitivity to multimodal therapy (i.e., chemotherapy, radiation, intravesical agents) based on a handful of retrospective case series. This will need to be the focus of future studies and collaborative efforts in order to make significant advancements in the field.

Comparison of outcomes between pure laparoscopic vs robot-assisted laparoscopic radical prostatectomy: a study of comparative effectiveness based upon validated quality of life outcomes.

OBJECTIVE: To compare perioperative, oncological and functional outcomes of laparoscopic radical prostatectomy (LRP) and robot-assisted laparoscopic radical prostatectomy (RALP) with emphasis on health-related quality of life (HRQOL) data as few studies exist. PATIENTS AND METHODS: Patients underwent RALP or LRP by a single, fellowship trained surgeon with a standard clinical care pathway. HRQOL data using the Expanded Prostate Cancer Index Composite (EPIC) were collected at 0, 3, 6 and 12 months after 175 consecutive LRP and 174 RALP procedures. Urinary and sexual function outcomes were compared using two methods: (1) EPIC summary/subscale analyses described as percent return to baseline function and (2) traditional single-question analysis. RESULTS: The two groups were statistically similar with respect to demographics, clinical stage, perioperative outcomes, stage-specific surgical margin rates, and baseline urinary and sexual function scores. There was no statistical difference in postoperative urinary function between RALP and LRP using EPIC or single-question analyses at 3, 6 and 12 months. EPIC questionnaire data showed a greater return to baseline sexual function over time (mixed model analysis) in RALP than in LRP patients who had a bilateral nerve sparing procedure (Sexual Summary Score, P= 0.005; Sexual Function and Bother Subscales, P= 0.007). Using EPIC, RALP patients receiving a bilateral nerve sparing procedure showed improved percent return to baseline potency at 3 and 6 months (P < 0.025) compared with LRP patients, but had similar outcomes at 12 months (73.7% vs 66.2%, P= 0.3). Single-question analysis suggested improved potency after RALP compared with LRP, with a greater percentage of RALP patients reporting successful sexual intercourse in the past 4 weeks (87.5% vs 66.7% at 12 months, P= 0.06). CONCLUSIONS: When comparing surgical techniques, RALP and LRP groups showed statistically similar postoperative urinary function outcomes. RALP patients had an earlier return of sexual function when compared with LRP patients after a bilateral nerve sparing procedure.

Predictors of citations in the urological literature.

To assess the factors associated with increased citation rates in the urological literature by reviewing articles published in the four major urological journals to help authors improve the impact of their work. A random sample of 200 original research articles published between January and June 2004 was analysed from The Journal of Urology, Urology, European Urology and BJU International. Study information was abstracted by two independent reviewers and citation counts within 4 years of publication were collected using Web of Science(TM) . Study characteristics and citation rates were analysed using median and interquartile ranges (IQRs), and logistic regression analysis was used to evaluate which factors predicted greater citation rates. The overall median number of citations per published article was 6.0 (IQR 3-12). After univariate analysis, we found that study design, study topic, continent of origin and sample size were associated with greater median citation rates. In a multivariate linear regression model, study design and study topic (oncology) predicted increased citation rates. Randomized controlled trials were cited a median of 13.5 times and were the strongest predictor of citation rates with an odds ratio of 115.5 (95% confidence interval 9.4-1419.6). Citation rates are associated with study design and study topic in the urological literature. Authors may improve the impact of their work by designing clinical studies with greater methodological safeguards against bias.