Daniel M Geynisman, Philip H Abbosh, Eric Ross, Matthew R Zibelman, Pooja Ghatalia, Fern Anari, James R Mark, Lambros Stamatakis, Jean H Hoffman-Censits, Rosalia Viterbo, Richard E Greenberg, Thomas M Churilla, Eric M Horwitz, Mark A Hallman, Marc C Smaldone, Robert Uzzo, David Y T Chen, Alexander Kutikov, Elizabeth R Plimack
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引用次数: 0
Abstract
Purpose: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy is the standard of care for patients with muscle-invasive bladder cancer (MIBC). Mutations in DNA damage repair genes are associated with pathologic downstaging after NAC. We hypothesized that a combination of biomarker selection and clinical staging would identify patients for cystectomy-sparing active surveillance (AS).
Patients and methods: We conducted a single-arm, phase II, noninferiority trial to evaluate a risk-adapted approach for MIBC. Patients with cT2-T3N0M0 MIBC underwent NAC with accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC). Pre-NAC transurethral bladder tumor specimens were sequenced for mutations in ATM, ERCC2, FANCC, and RB1. Patients with ≥1 mutation and cT0 post-NAC began AS. The primary end point was metastasis-free survival (MFS) at 2 years for the entire cohort with the null hypothesis rejected if the lower bound exact one-sided 95% CI exceeds 64%.
Results: Seventy patients were enrolled, 33 (47%) had a mutation, and 25 (36%) began per-protocol AS. With a median follow-up of 40 months, the 2-year MFS for all patients was 72.9% (lower bound exact one-sided 95% CI, 62.8). The 2-year MFS was 76.0% in the AS group (95% CI, 54.2 to 88.4) and 71.1% (95% CI, 55.5 to 82.1) in the remaining patients. In the AS group, 17 patients (68%) had some recurrence and 12 (48%) were metastasis-free with an intact bladder. The 2-year overall survival (OS) was 84.3% (95% CI, 73.4 to 91.0); OS was 88.0% (95% CI, 67.3 to 96.0) and 82.2% (95% CI, 67.6 to 90.7) in the AS and not-AS groups, respectively.
Conclusion: Patients with MIBC treated with AMVAC followed by a risk-adapted approach to local consolidation achieved a 2-year MFS rate of 73%. The primary end point was not met, but 17% of all enrolled patients and 48% of the AS group avoided cystectomy without metastatic disease.
期刊介绍:
The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.