ctDNA-Guided Adjuvant Atezolizumab in Muscle-Invasive Bladder Cancer

作者：Thomas Powles, Ariel Galapo Kann, Daniel Castellano, Marine Gross‐Goupil, Hiroyuki Nishiyama, Sergio Bracarda, Jørgen Bjerggaard Jensen, Lydia Makaroff, Shusuan Jiang, Ja Hyeon Ku, Se Hoon Park, Òscar Reig, Dingwei Ye, Marco Maruzzo, Andrea Necchi, Rafael Morales‐Barrera, Emilio Francesco Giunta, Jae‐Lyun Lee, Giampaolo Tortora, Yüksel Ürün, Łukasz Dołowy, Di̇lek Erdem, Álvaro Pinto, F. Pontes Grando, Wei Zou, Zoe J. Assaf, Jacqueline Vuky, Viraj Degaonkar, Elizabeth E. Steinberg, Joaquim Bellmunt, Jürgen E. Gschwend · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2511885 · 被引用次数：117 · 研究领域：Bladder and Urothelial Cancer Treatments、Single-cell and spatial transcriptomics、Cancer Genomics and Diagnostics

BACKGROUND: Patients with muscle-invasive bladder cancer have varied outcomes after cystectomy. Circulating tumor DNA (ctDNA)-based detection of molecular residual disease may identify patients at high risk for recurrence after cystectomy who can benefit from adjuvant immunotherapy, thus sparing patients at lower risk from unnecessary treatment burden. METHODS: In a phase 3, double-blind, randomized trial, we used serial ctDNA testing to monitor (for up to 1 year) patients with muscle-invasive bladder cancer and no radiographic evidence of disease after surgery. Eligible patients who tested ctDNA-positive during surveillance were randomly assigned in a 2:1 ratio to receive intravenous atezolizumab or placebo every 4 weeks for up to 1 year. The primary end point was investigator-assessed disease-free survival. Overall survival was a secondary end point that was assessed in a hierarchical fashion to control for alpha. Patients who persistently tested ctDNA-negative did not receive atezolizumab or placebo. RESULTS: A total of 761 patients were enrolled; 250 eligible patients who tested ctDNA-positive underwent randomization (167 to the atezolizumab group and 83 to the placebo group). The median disease-free survival was 9.9 months with atezolizumab, as compared with 4.8 months with placebo (hazard ratio for first event of disease recurrence or death, 0.64; 95% confidence interval [CI], 0.47 to 0.87; P = 0.005). The median overall survival was 32.8 months with atezolizumab, as co...