Risk-Based Assessment Of the Impact Of Intravesical Therapy on Recurrence-Free Survival Rate Following Resection of Suspected Low-grade, Non-muscle-invasive Bladder Cancer (NMIBC): A Southwest Oncology Groups (SWOG) S0337 Posthoc Analysis.

ABSTRACT

BACKGROUND: Nonmuscle invasive bladder cancer (NMIBC) has an elevated risk of recurrence, and immediate postresection intravesical instillation of chemotherapy (IVC) significantly reduces the risk of recurrence. Questions remain about which subpopulation may maximally benefit from IVC. Our aim was to develop risk groups based on recurrence risk in NMIBC, and then evaluate the impact of a single, postoperative instillation of IVC on the subsequent risk of recurrence for each risk group. MATERIAL AND METHODS: Using the SWOG S0337 trial cohort, we performed a posthoc analysis of 345 patients who were diagnosed with suspected low-grade NMIBC, underwent transurethral resection of the bladder tumor (TURBT), and received post-operative IVC (gemcitabine vs. saline). Using regression tree analysis, the regression tree stratified patients based on their risk of recurrence into low-risk - single tumor and aged < 57 years, intermediate-risk - single tumor and aged ≥ 57 years, and high-risk - multiple tumors. We used Cox proportional hazard models to test the impact of recurrence-free rate, and after adjustment to available covariates. RESULTS: Median age of the cohort was 66.5 (IQR 59.7-75.8 years) with 85% of patients being males. Median overall follow-up time was 3.07 years (IQR 0.75-4.01 years). When testing the impact of treatment in each risk group separately, we found that patients in the intermediate-risk treated with gemcitabine had a 24-month recurrence free rate of 77% (95% CI 68%-86%) vs. 59% (95% CI 49%-70%) in the saline group. This survival difference was confirmed on multivariable analysis (hazard ratio 0.39, 95% CI 23%-66%, P < 0.001). This group represented 53% of our cohort. Conversely, we did not observe a significant difference in recurrence-free survival among patients in the low- (P = 0.7) and high-risk (P = 0.4) groups. CONCLUSION: Our findings indicate that older patients with a single tumor of suspected low-grade NMIBC at TURBT maximally benefit from immediate postresection IVC (gemcitabine).