{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:51:28Z","timestamp":1793130688046,"version":"4.5.0"},"reference-count":46,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,3,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>ATM<\/jats:italic>\n                      ,\n                      <jats:italic>ERCC2<\/jats:italic>\n                      ,\n                      <jats:italic>FANCC<\/jats:italic>\n                      , and\n                      <jats:italic>RB1<\/jats:italic>\n                      . Patients with \u22651 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%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-24-01214","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T15:59:23Z","timestamp":1734364763000},"page":"1113-1122","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":64,"title":["Phase II Trial of Risk-Enabled Therapy After Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer (RETAIN 1)"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct02710734","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1423-5295","authenticated-orcid":true,"given":"Daniel M.","family":"Geynisman","sequence":"first","affiliation":[{"name":"Fox Chase Cancer Center, Philadelphia, 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