Statistical analysis

Given the unclear functional impact of many DDR gene alterations, correlation with clinical characteristics was focused on alterations likely to be deleterious. These were defined as nonsense, frameshift, or splice site mutations, or missense alterations at recurrent sites associated with chemotherapy response in prior work. Only ERCC2 was demonstrated to harbor such missense alterations, occurring at or near previously reported recurrent alteration sites within UCB ^{19, 20} or associated with chemotherapy response ¹⁰, as discussed further in the results. Bivariate comparisons of mutation frequency were performed using Fisher's exact test and comparisons of means with ANOVA testing.

Analyzed clinical endpoints were time to bladder recurrence (superficial or MIBC), metastatic recurrence, and any recurrence, as measured from the end of radiotherapy. Censoring was performed at last follow up or death. Bladder intact survival was not analyzed because not all patients were medically able to undergo salvage cystectomy. Kaplan-Meier method was used to estimate cumulative probability of each event, and the log-rank statistic tested differences between groups. Hazard ratios and confidence intervals were estimated using Cox regression. Analyses were conducted using SPSS v. 20 (IBM) and R software version 3.2.1 (R Core Development Team, Vienna, Austria). An alpha of 0.05 was used to define statistical significance, with two-sided testing.

Genomic and associated clinicopathologic data are publically available through the MSKCC cBioPortal (www.cbioportal.com) ²¹.