Urine Tumor DNA to Stratify the Risk of Recurrence in Patients Treated with Atezolizumab for Bacillus Calmette-Guérin–unresponsive Non–muscle-invasive Bladder Cancer
Marie-Pier St-Laurent, Parminder Singh, David J. McConkey, M. Scott Lucia, Vadim S. Koshkin, Kelly Stratton, Trinity J. Bivalacqua, Wassim Kassouf, Sima P. Porten, Rick Bangs, Melissa Plets, Ian M. Thompson, Joshua Meeks, Vincent M. Caruso, Ceressa T. Ward, Brian C. Mazzarella, Kevin G. Phillips, Vincent T. Bicocca, Trevor G. Levin, Seth P. Lerner, Peter C. Black
Abstract
As new treatments for bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) emerge, better methods are needed to guide therapeutic decisions. This study analyzed urine tumor DNA (utDNA) from patients treated with atezolizumab in the SWOG S1605 trial to determine whether utDNA profiling can stratify the risk of treatment failure. Urine samples were analyzed using the UroAmp assay at baseline and 3 mo from 89 and 77 patients, respectively. Only 13% of UroAmp-positive patients at baseline achieved a complete response at 6 mo compared with 71% of UroAmp-negative patients (p < 0.001). The 18-mo event-free survival (EFS) was significantly lower for UroAmp-positive patients at baseline (23%) than for UroAmp-negative patients (51%; hazard ratio [HR] 2.8, p < 0.001). Among patients with no clinical evidence of disease at 3 mo (n = 51), the 18-mo EFS was 38% for UroAmp-positive and 86% for UroAmp-negative (HR 3.5, p = 0.01) patients. These findings suggest that utDNA profiling at baseline and after 3 mo of treatment can help identify patients with BCG-unresponsive NMIBC who are less likely to benefit from systemic immunotherapy.