Predictors of Benign Ureteroenteric Anastomotic Strictures After Radical Cystectomy and Urinary Diversion.

OBJECTIVE: To determine predictors of symptomatic ureteroenteric anastomotic strictures (UAS) formation following radical cystectomy (RC) and urinary diversion (UD). MATERIALS AND METHODS: A total of 2,888 consecutive patients who underwent open RC at our institution from 1995 to 2014 were included for analysis. Data were collected from institutional databases and individual medical records. Symptomatic benign UAS was defined as percutaneous nephrostomy tube insertion for rising creatinine or unilateral hydronephrosis by comparing preoperative and postoperative imaging. Univariate and multivariable Cox proportional hazards models were utilized to identify features associated with UAS formation. RESULTS: UAS developed in 123 of 2888 patients following RC. There were 94 symptomatic and 29 asymptomatic strictures. Median follow-up was 32 months (IQR 12, 72) for patients without stricture. Higher BMI (P = 0.002), ASA score >2 (P < 0.0001), lymph node positive disease (P = 0.027), and 30-day postoperative grade 3I+ complications (P = 0.017) on univariate analysis and male gender on multivariable analysis were significantly associated with time to stricture development. However, history of prior abdominal surgery (PAS) had the strongest association with time to stricture formation (HR 3.25, 95% CI 1.78, 5.94, P = 0.0001). Risk of developing a stricture within 10 years was 1.9% for patients without PAS vs 9.3% with PAS. CONCLUSION: Associated factors with an increased risk of benign UAS include higher BMI, ASA score >2, lymph node involvement, grade 3/4 complications within 30 days, male sex, and a history of PAS. We conclude that while surveillance is important for patients who undergo cystectomy for malignancy, it may be beneficial for patients with history of PAS to undergo more intensive follow-up compared to those patients without history of PAS.

The Impact of Plasmacytoid Variant Histology on the Survival of Patients with Urothelial Carcinoma of Bladder after Radical Cystectomy.

BACKGROUND: The clinical significance of the plasmacytoid variant (PCV) in urothelial carcinoma (UC) is currently lacking. OBJECTIVE: To compare clinical outcomes of patients with any PCV with that of patients with pure UC treated with radical cystectomy (RC). DESIGN, SETTING, AND PARTICIPANTS: We identified 98 patients who had pathologically confirmed PCV UC and 1312 patients with pure UC and no variant history who underwent RC at our institution between 1995 and 2014. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable Cox regression and Cox proportional hazards regression to determine if PCV was associated with overall survival (OS). RESULTS AND LIMITATIONS: Patients with PCV UC were more likely to have advanced tumor stage (p=0.001), positive lymph nodes (p=0.038), and receive neoadjuvant chemotherapy than those with pure UC (46% vs 22%, p<0.0001). The rate of positive soft tissue surgical margins was over five times greater in the PCV UC group compared with the pure UC group (21% vs 4.1%, respectively, p<0.0001). Median OS for the pure UC versus the PCV patients were 8 yr and 3.8 yr, respectively. On univariable analysis, PCV was associated with an increased risk of overall mortality (hazard ratio=1.34, 95% confidence interval: 1.02-1.78, p=0.039). However, on multivariable analysis adjusted for age, sex, neoadjuvant chemotherapy received, lymph node status, pathologic stage, and soft margin status, the association between PCV and OS was no longer significant (hazard ratio=1.06, 95% confidence interval: 0.78, 1.43, p=0.7). This retrospective study is limited by the lack of pathological reanalysis, and the impact of other concurrent mixed histology cannot be determined in this study. CONCLUSIONS: Patients with PCV features have a higher disease burden at RC compared with those with pure UC. However, PCV was not an independent predictor of survival after RC on multivariable analysis, suggesting that PCV histology should not be used as an independent prognostic factor. PATIENT SUMMARY: Plasmacytoid urothelial carcinoma is a rare and aggressive form of bladder cancer. Patients with plasmacytoid urothelial carcinoma had worse adverse pathologic features, but this was not associated with worse overall mortality when compared with patients with pure urothelial carcinoma.

Reduced Recurrence of Low-grade Papillary Bladder Tumors Associated With Asymptomatic Bacteriuria.

OBJECTIVE: To determine tumor recurrence rate of low-grade, papillary, and non-muscle-invasive (TaLG) bladder tumors in patients who have asymptomatic bacteriuria (ABU). Microbes in the urine trigger immune responses like intravesical Bacillus Calmette-Guerin, suggesting that common bacteria may also exert an antitumor effect. METHODS: We investigated recurrence rates in 387 patients with low-grade, papillary noninvasive bladder tumors TaLG, with or without ABU. They were followed every 6 months for 36 months, and did not receive antibiotics or intravesical chemotherapy. Recurrent tumors were treated generally by outpatient fulguration. Before cystoscopy, patients submitted a voided urine sample for culture, stratified as no growth, <104, >104, or >105 CFU/mL single organism. Any degree of bacteria on culture was classified as ABU. We also measured absolute neutrophil counts (ANC) and the presence of pyuria, as surrogate indicators of local immune response. RESULTS: Of the 387 cases, 200 (52%) had ABU, including 102 (27%) with >104 CFU/mL bacteriuria. With absolute 3-year follow-up, 75% of patients with ABU survived tumor-free compared to 40% of 187 uninfected patients (P = .001). Sixty percent of patients with negative cultures recurred vs 25%, 14%, and 29% of patients with <104, >104, or >105 CFU/mL. (P = .001). Mean number of recurrent tumors in colonized patients was 4.2 vs 8.4 in uninfected patients (P = .009). ANC averaged 6.3 K/mcL in bacteriuric vs 4.1 K/mcL in uninfected patients (P = .01). CONCLUSION: Patients with papillary TaLG tumors and chronic ABU had fewer recurrences, fewer numbers of recurrent tumors, and longer tumor-free survival times than similarly staged uninfected patients. Bladder-resident bacteria may reduce bladder tumor recurrences through local immune mechanisms.

Idiographic quality of life assessment before radical cystectomy.

BACKGROUND: We sought to determine if idiographic, or self-defined, measures added to our understanding of patients with bladder cancer's quality of life (QOL) prior to radical cystectomy (RC). We tested whether idiographic measures increased prediction of global QOL beyond standard (nomothetic) measures of QOL components. METHODS: We administered the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (QLQ)-C30 and QLQ-BLM30, and our own idiographic Quality of Life Appraisal Profile prior to RC. Idiographic measures included number of goal statements, distance from goal attainment, and ability to complete goal attainment activities. Multivariate linear regression was used to predict measures of global QOL and related constructs of life satisfaction and mental health. RESULTS: Two hundred fiftheen patients reported a median of 8 (interquartile range [IQR] 6, 11) goals and half had an average goal attainment rating above 6.9 out of 10 (IQR 5.5, 8.2). On multivariable analysis, QLQ-C30 role functioning and QLQ-BLM30 future perspective explained 15.7% of the variability in preoperative global QOL. Including goal attainment and activity difficulty explained an additional 12% of global QOL variance. Smaller gains were seen on measures of global health, life satisfaction, mental health, and activity, suggesting that idiographic measures capture aspects of QOL distinct from health and functional status defined by nomothetic scales. CONCLUSIONS: Idiographic assessment of QOL added to prediction of global QOL above and beyond health-related components measured using nomothetic instruments. This self-defined information may be valuable in communicating with cancer patients about their QOL. Copyright © 2015 John Wiley & Sons, Ltd.

A 10-Item Checklist Improves Reporting of Critical Procedural Elements during Transurethral Resection of Bladder Tumor.

PURPOSE: Previous studies have demonstrated significant variation in recurrence rates after transurethral resection of bladder tumor, likely due to differences in surgical quality. We sought to create a framework to define, measure and improve the quality of transurethral resection of bladder tumor using a surgical checklist. MATERIALS AND METHODS: We formed a multi-institutional group of urologists with expertise with bladder cancer and identified 10 critical items that should be performed during every high quality transurethral bladder tumor resection. We prospectively implemented a 10-item checklist into practice and reviewed the operative reports of such resections performed before and after implementation. Results at all institutions were combined in a meta-analysis to estimate the overall change in the mean number of items documented. RESULTS: The operative notes for 325 transurethral bladder tumor resections during checklist use were compared to those for 428 performed before checklist implementation. Checklist use increased the mean number of items reported from 4.8 to 8.0 per resection, resulting in a mean increase of 3.3 items (95% CI 1.9-4.7) on meta-analysis. With the checklist the percentage of reports that included all 10 items increased from 0.5% to 27% (p <0.0001). Surgeons who reported more checklist items tended to have a slightly higher proportion of biopsies containing muscle, although not at conventional significance (p = 0.062). CONCLUSIONS: The use of a 10-item checklist during transurethral resection of bladder tumor improved the reporting of critical procedural elements. Although there was no clear impact on the inclusion of muscle in the specimen, checklist use may enhance surgeon attention to important aspects of the procedure and be a lever for quality improvement.

Narrow-band imaging cystoscopy to evaluate bladder tumours--individual surgeon variability.

STUDY TYPE: Diagnosis (exploratory cohort) Level of Evidence 2b. OBJECTIVE: To assess individual urologist variability using narrow-band imaging (NBI) cystoscopy to evaluate bladder tumours. PATIENTS AND METHODS: In all, 50 patients underwent white-light and NBI cystoscopy to evaluate for recurrent bladder tumours. Endoscopic images in each patient were independently viewed by four urologists assessing presence or absence of tumour. Their findings were correlated with biopsy results. RESULTS: In all, 26 patients had recurrent tumour and 24 had benign histology. There were no significant differences among urologists detecting recurrent tumour or in determining final pathology. CONCLUSIONS: There does not appear to be a 'learning curve' for adapting to NBI-surveillance cystoscopy in patients with bladder cancer.

Sequential adjuvant chemotherapy after surgical resection of high-risk urothelial carcinoma.

BACKGROUND: Despite definitive surgery, the survival of patients with high-risk urothelial carcinoma (UC) is poor. Adjuvant cisplatin-based chemotherapy may be beneficial, but it is restricted by the need for normal renal function (RF). Sequential administration of adjuvant chemotherapy facilitates drug delivery and improves survival in patients with breast cancer. The objective of this study was to evaluate the feasibility and survival impact of adjuvant, sequential chemotherapy in patients with high-risk UC. METHODS: Fifty patients were treated on 2 simultaneous protocols between 1997 and 2004. The patients on Protocol A (normal RF) received doxorubicin and gemcitabine (AG) followed by paclitaxel and cisplatin. The patients on Protocol B (impaired RF) received AG followed by paclitaxel plus carboplatin. Overall survival (OS) and disease-specific survival (DSS) were compared with a group of 203 contemporary control patients who had similar pathology and RF and who underwent surgery alone. RESULTS: The median follow-up of protocol patients was 6.5 years (range, 0.9-8.6 years), and 25 patients remained alive. The median follow-up of the control group was 4.7 years (0.0-9.2), and 68 patients remained alive. The median OS for patients on Protocol A was greater than that for controls who had good RF (4.6 years vs 2.5 years; P = .03). The median OS for patients on Protocol B was greater than that for controls who had impaired RF (3.4 years vs 2 years; P = .04). DSS for the protocol and matched control groups was similar (good RF: 4.6 years vs 3 years; P = .24; impaired RF: 3.4 years vs 3.3 years; P = .40). CONCLUSIONS: In this nonrandomized study, adjuvant, sequential chemotherapy for patients with high-risk UC did not improve DSS over that observed with surgery alone.

Positive surgical margins in soft tissue following radical cystectomy for bladder cancer and cancer specific survival.

PURPOSE: We evaluated risk factors for positive soft tissue surgical margins and the impact of soft tissue surgical margins on metastatic progression and disease specific survival in patients treated with radical cystectomy for bladder cancer. MATERIALS AND METHODS: A total of 1,589 patients who underwent radical cystectomy for primary urothelial cancer at our institution were included in the study. Several variables were analyzed including gender, age, use of perioperative chemotherapy, tumor stage, tumor grade, presence of carcinoma in situ, pathological vascular invasion, bladder pathology, status of soft tissue surgical margins, lymph node status, number of lymph nodes removed and number of positive lymph nodes. End points were freedom from progression to metastases and disease specific survival. RESULTS: Positive soft tissue surgical margins were detected in 67 patients (4.2%). Risk factors for positive soft tissue surgical margins were female gender (p = 0.04), pathological stage, vascular invasion in the radical cystectomy specimen, lymph node metastases (all p < or = 0.001) and median number of positive lymph nodes (p = 0.002). In addition, nonpure transitional cell carcinoma histology (p = 0.001) was associated with positive soft tissue surgical margins. In the 5 years after cystectomy, rates of disease specific survival for the negative and positive soft tissue surgical margin groups were 72% (95% CI 69-75) and 32% (95% CI 19-54), respectively. On multivariate analysis disease specific death was associated with tumor stage, positive soft tissue surgical margins, vascular invasion, presence of positive lymph nodes, number of nodes removed and number of positive nodes. CONCLUSIONS: Risk factors for positive soft tissue surgical margins are female gender, locally advanced cancer, presence of vascular invasion and mixed histology. Patients with positive soft tissue surgical margins have poor prognosis, and positive soft tissue surgical margins were found to be independently associated with disease specific death.

Favorable clinical outcomes of three-dimensional computer-optimized high-dose-rate prostate brachytherapy in the management of localized prostate cancer.

PURPOSE: To report PSA relapse-free survival and toxicity outcomes of prostate cancer patients who have undergone three-dimensional computer-optimized high-dose-rate (HDR) brachytherapy with external beam radiotherapy as definitive treatment. METHODS AND MATERIALS: One hundred five patients consecutively treated between 1998 and 2004 are reported. All patients were treated with HDR boost with lr 192 (5.5-7.0 Gy), based upon postimplant CT three-dimensional treatment planning using an in-house treatment plan optimization algorithm. Three-dimensional conformal external beam radiotherapy (45-50.4 Gy) was also administered 3 weeks after the HDR procedure. Toxicity was measured using National Cancer Institutes Common Toxicity Criteria and International Prostate Symptom Score indices. RESULTS: With a median followup of 44 months (8-79 months), the 5-year PSA relapse-free survival outcomes for low, intermediate and high-risk patients were 100%, 98%, and 92%, respectively, Median urinary toxicity, and 93% of patients denied rectal problems at the time of last followup. Erectile dysfunction was noted in 47% patients at the time of last followup, but overall 80% were able to achieve vaginal penetration when those who responded to sildenafil were included. CONCLUSION: Computer-optimized three-dimensional HDR prostate brachytherapy provides excellent disease control for even high risk localized prostate cancer. Significant toxicity has been minimal.

Prospectively packaged lymph node dissections with radical cystectomy: evaluation of node count variability and node mapping.

PURPOSE: Accumulating evidence supports the relationship between an increased number of lymph nodes (LNs) reported following radical cystectomy (RC) and overall outcome. We prospectively evaluated RC cases with transitional cell carcinoma of the bladder to determine which factors may contribute to the variability in the number of reported LNs. MATERIALS AND METHODS: We conducted a prospective evaluation in which 144 patients undergoing RC and pelvic lymph node dissection (PLND) between June 2001 and April 2003 were included. Lymph nodes were processed as individual packets. A standard method of evaluating nodal submissions was used. A mixed statistical model was used with neoadjuvant chemotherapy, node status, pathological stage, bacillus Calmette-Guerin exposure, age and number of days from transurethral resection as the fixed effects. Surgeon and pathologist were treated as random effects. RESULTS: The extended PLND group had a significantly greater lymph node yield (median 22.5 nodes) compared to standard PLND (median 8), however, no staging advantage was observed in the extended dissection group. Only the type of PLND performed was associated with node yield (p <0.001). Subset analysis of patients with unexpected microscopic nodal involvement revealed that 33% had involvement of the common iliac nodes. CONCLUSIONS: In our series only the extent of the lymph node dissection was found to influence node yield significantly after radical cystectomy. Additionally, the observed risk of involvement of the common iliac chain in microscopically node positive cases suggests a need to include this region as part of the PLND for bladder cancer for cases without grossly involved LNs.