A phase II trial of risk-enabled therapy after initiating neoadjuvant chemotherapy for bladder cancer (RETAIN).

作者：Daniel M. Geynisman, Philip H. Abbosh, Eric A. Ross, Matthew R. Zibelman, Pooja Ghatalia, Fern M. Anari, Katherine Ansel, James Ryan Mark, Lambros Stamatakis, Jean H. Hoffman-Censits, Rosalia Viterbo, Eric Mark Horwitz, Mark A. Hallman, R. Katherine Alpaugh, Richard Evan Greenberg, Marc C. Smaldone, Robert G. Uzzo, David Chen, Alexander Kutikov, Elizabeth R. Plimack · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.2023.41.6_suppl.438 · 被引用次数：37 · 研究领域：Bladder and Urothelial Cancer Treatments、Urinary and Genital Oncology Studies、Multiple and Secondary Primary Cancers

438 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy or chemoradiation is the standard of care for urothelial carcinoma (UC) patients with MIBC. Both cystectomy and chemoradiation have short and long-term toxicity and QOL implications. Mutations in DNA damage repair/response genes are associated with pathologic downstaging after NAC. We hypothesized that a combination of biomarker selection and clinical staging would identify patients prospectively for a cystectomy or chemoradiation avoidance algorithm. Methods: We conducted a single-arm, phase II, non-inferiority trial (NCT02710734) to evaluate a risk-adapted approach for MIBC. Patients with cT2-T3N0M0 UC underwent NAC with accelerated MVAC. Pre-NAC TURBT specimens were sequenced (Caris) for mutations in ATM, ERCC2, FANCC or RB1. Patients with ≥ 1 mutations and no clinical evidence of disease by restaging TUR, urine cytology and imaging post-NAC began pre-defined active surveillance (AS). Remaining patients underwent bladder-directed therapy. The primary endpoint was metastasis-free survival (MFS) at 2 years for the entire cohort. The risk-adapted approach would be declared non-inferior to the standard of care if the lower bound of an exact 1-sided 95% CI for MFS was > 64%. The study required 70 patients with a 4.5% type I error and 81.6% power. Results: 71 (ITT) patients were enrolled over 33 months at four academic centers. Median age was 70 years (47-83), 74% were male, 92% Caucasian, 81% ...