Immediate intravesical chemotherapy for low-grade bladder tumors in California: An underutilized practice and its impact on recurrence.

OBJECTIVES: To demonstrate patterns of uptake and impact on recurrence of intravesical chemotherapy (IC) immediately following transurethral resection of bladder tumor (TURBT) for low-grade non-muscle-invasive bladder cancer (NMIBC) at a population level. METHODS: Incident cases of low-grade (LG) Ta or T1 NMIBC from 2005 to 2012 were identified from the California Cancer Registry. We determined rates of IC utilization following TURBT. Multivariable logistic regression models were utilized to assess predictors of IC utilization. Multivariable Cox proportional hazards regression was used to assess the association of IC utilization with recurrence-free survival, bladder cancer-specific survival, and overall survival. RESULTS: Ten thousand thirty-one patients with LG NMIBC diagnosed in California between 2005 and 2012. The overall rate of IC utilization was 5.1%, and increased from 1.7% (2005-2006) to 9.6% (2011-2012). More recent year of diagnosis (Odds ratio 1.74, confidence interval 1.60-1.90 for 2-year increments) was associated with an increased likelihood of undergoing immediate postoperative IC. The cumulative incidence of recurrence at 24 months for patients who received IC was 25.2% compared to 30.2% among those who did not receive IC. Use of IC was significantly associated with improved recurrence-free survival (Hazards ratio 0.82, confidence interval 0.70-0.97). CONCLUSION: Utilization of IC for LG NMIBC remains dismally low, with less than 10% of patients receiving this standard of care. Low utilization is associated with increased rates of recurrence. We demonstrate a major shortcoming in quality of care with potential widespread impact on outcomes and cost of care.

The Promise and Disappointment of Neoadjuvant Chemotherapy and Transurethral Resection for Muscle Invasive Bladder Cancer: Updated Results and Long-Term Followup.

INTRODUCTION: Radical cystectomy with neoadjuvant chemotherapy is the standard of care for patients with localized muscle invasive urothelial carcinoma of the bladder. One of the strongest predictors of survival in these patients is pathological response to initial treatment. Our objective was to determine whether we could stratify the need for radical cystectomy based on pathological response to neoadjuvant chemotherapy. METHODS: We present a cohort of patients with muscle invasive urothelial carcinoma of the bladder to whom surveillance and bladder preservation were offered if complete response was achieved following neoadjuvant chemotherapy. Descriptive statistics and survival analysis were performed to assess overall, cancer specific and metastasis-free survival. Patients were stratified based on pathological response to neoadjuvant chemotherapy. RESULTS: A total of 60 patients were included in the cohort, of whom 32 (55%) had absence of residual disease on post-neoadjuvant chemotherapy transurethral resection and 27 (45%) had persistent disease. Of patients undergoing surveillance 52% maintained the bladder without evidence of recurrence. By comparison, of those with recurrence only 20% preserved the bladder and were without evidence of disease. CONCLUSIONS: Long-term followup shows a subset of patients achieving good outcomes while preserving the bladder. However, we also observed an inability to reliably identify this subset of patients given current clinical and pathological markers. Until we are able to achieve that goal, the safest oncologic approach remains neoadjuvant chemotherapy followed by radical cystectomy.

Utility of Anterior Zone Biopsy in Men Enrolled in Active Surveillance for Prostate Cancer.

BACKGROUND: Anterior zone (AZ) disease is present in one-fifth of men with newly diagnosed prostate cancer and has been associated with poor pathologic features. However, anterior targeted biopsies are not a routine part of active surveillance (AS) protocols. Our purpose is to assess the utility of AZ sampling for prostate biopsy in patients undergoing surveillance for low-risk prostate cancer. METHODS: A prospective data collection of men enrolled in AS between 2006 and 2014 was performed. Patient and disease characteristics were collected, including number of positive cores and Gleason score on all diagnostic and surveillance biopsies. Progression was defined as incident Gleason > 6 in any core and/or receipt of definitive therapy including radical prostatectomy or radiotherapy. Rate of anterior disease and relationship to subsequent disease progression was assessed. RESULTS: A total of 85 men were included, of which 45% demonstrated progression. Median follow-up was 40 months. Among those undergoing AZ sampling at initial diagnosis, 37% presented with AZ disease. A total of 47% of men with AZ-only disease progressed, whereas 78% of men with AZ and peripheral zone disease progressed. This compares with a 39% rate of progression among men with only peripheral zone disease. Multivariable logistic regression identified increasing body mass index as a significant predictor of disease progression (odds ratio, 5.18; 95% confidence interval, 1.06-25.31; P = .04). CONCLUSIONS: Over one-third of men enrolled in AS for low-risk prostate cancer had AZ disease on diagnostic biopsy. Progression occurred in the majority of these men. AZ sampling should be considered in biopsy surveillance strategies.

Effect of Neoadjuvant Chemotherapy on Renal Function following Radical Cystectomy: Is there a Meaningful Impact?

Objective: To evaluate the patterns of impact of neoadjuvant chemotherapy (NAC) on renal function across the initial year following treatment for muscle-invasive bladder cancer (MIBC) with radical cystectomy (RC). Methods: We reviewed the charts of 241 patients who underwent RC for urothelial carcinoma of the bladder between 2003-14 at our institution. Renal function was evaluated at multiple time points (pre-chemotherapy, pre-operatively, post-operatively, 6-12 months follow-up), and then classified by CKD staging. Univariable and multivariable logistic regression analyses were performed to determine relationship between NAC and change in CKD stage. Results: Of the 241 patients who underwent RC for urothelial carcinoma of the bladder, 66 (27%) received NAC and 175 (73%) did not. In multivariable analysis, NAC was significantly associated with a decrease of at least one CKD stage from baseline to post-op (p = 0.009), but not to the 6-12 months follow-up time point (p = 0.050). The loss of GFR in the NAC cohort occurs up-front with chemotherapy, but the peri-operative course is similar to those who underwent cystectomy alone. Of the 15 NAC patients (26.8%) who were Stage 3 CKD prior to chemotherapy, none progressed to a higher stage CKD. Conclusion: NAC is associated with an initial decline in GFR, which then remains stable through the first year following RC. Despite an initial insult, patients receiving NAC are not vulnerable to further deterioration. When appropriately selected, NAC does not appear to result in a clinically significant deterioration of renal function.

Perioperative Outcomes following Neoadjuvant Chemotherapy and Radical Cystectomy-Is There Room for Improvement?

INTRODUCTION: We identify the impact of neoadjuvant chemotherapy before open radical cystectomy on perioperative outcomes and identify actionable areas for improvement. METHODS: The impact of neoadjuvant chemotherapy on perioperative outcomes after radical cystectomy for muscle invasive bladder cancer from 2003 to 2014 was assessed using an institutional database. Individual outcomes (venous thromboembolism, surgical site infection, cardiac event) and a composite score using the Clavien-Dindo classification were identified. Univariable and multivariable logistic regression models were used to identify predictors of perioperative complication and 30-day readmission rates. RESULTS: A total of 241 patients were included in the study, of whom 175 underwent radical cystectomy alone (72.6%) and 66 were treated with neoadjuvant chemotherapy plus radical cystectomy (27.4%). The 30-day readmission rate for the neoadjuvant chemotherapy cohort was 30.5% compared to 17.2% for radical cystectomy alone. Multivariable logistic regression analysis identified neoadjuvant chemotherapy as an independent predictor of 30-day readmission (OR 3.47, p=0.01). Of the patients on neoadjuvant chemotherapy readmitted within 30 days 72.2% were readmitted with infections. All other outcomes were not significantly associated with neoadjuvant chemotherapy. CONCLUSIONS: While the administration of neoadjuvant chemotherapy did not significantly increase perioperative complications, patients receiving neoadjuvant chemotherapy had an increased rate of 30-day readmission, with infection being the most common etiology. This increased readmission rate has not been previously identified in this patient population to our knowledge and is an important focus for quality improvement.

Metastatic signet-ring cell carcinoma of the urinary bladder: A novel management approach to a rare tumour.

Primary signet-ring cell carcinoma (SRCC) of the urinary bladder, a variant of adenocarcinoma, is exceedingly rare and as a result no gold standard exists for its management. We report a case of primary SRCC of the bladder with recurrent metastases; we utilized an innovative diagnostic approach and the patient exhibited a treatment response to palliative FOLFOX-6 chemotherapy.