{"doi":"10.1200/jco-24-01214","title":"Phase II Trial of Risk-Enabled Therapy After Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer (RETAIN 1)","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 ≥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%.\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>","journal":"Journal of Clinical Oncology","year":2025,"id":618146,"datarank":0.5983476069846413,"base_score":3.9889840465642745,"endowment":3.9889840465642745,"self_citation_contribution":0.5983476069846413,"citation_network_contribution":0.0,"self_endowment_contribution":0.5983476069846413,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":53,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":568424,"name":"Philip H. Abbosh","orcid":"0000-0003-3611-9532","position":1,"is_corresponding":false},{"id":339896,"name":"Eric A. Ross","orcid":"0000-0002-0890-2418","position":2,"is_corresponding":false},{"id":579719,"name":"Matthew R. Zibelman","orcid":"0000-0003-1475-6477","position":3,"is_corresponding":false},{"id":394993,"name":"Pooja Ghatalia","orcid":"0000-0001-6229-7581","position":4,"is_corresponding":false},{"id":1594466,"name":"Fern Anari","orcid":null,"position":5,"is_corresponding":false},{"id":937242,"name":"James Ryan Mark","orcid":"0000-0001-7675-3437","position":6,"is_corresponding":false},{"id":1430740,"name":"Lambros Stamatakis","orcid":"0000-0002-2955-6411","position":7,"is_corresponding":false},{"id":529079,"name":"Jean Hoffman‐Censits","orcid":"0000-0002-6970-6509","position":8,"is_corresponding":false},{"id":1594467,"name":"Rosalia Viterbo","orcid":null,"position":9,"is_corresponding":false},{"id":932197,"name":"Richard E. Greenberg","orcid":"0000-0002-8609-1307","position":10,"is_corresponding":false},{"id":1594468,"name":"Thomas M. Churilla","orcid":null,"position":11,"is_corresponding":false},{"id":557291,"name":"Eric M. Horwitz","orcid":"0000-0003-2187-317X","position":12,"is_corresponding":false},{"id":798019,"name":"M.A. Hallman","orcid":"0000-0002-2825-0656","position":13,"is_corresponding":false},{"id":971289,"name":"Marc C. Smaldone","orcid":"0000-0003-4160-0005","position":14,"is_corresponding":false},{"id":1594469,"name":"Robert Uzzo","orcid":null,"position":15,"is_corresponding":false},{"id":458989,"name":"David Y.T. Chen","orcid":"0000-0002-2587-2214","position":16,"is_corresponding":false},{"id":878780,"name":"Alexander Kutikov","orcid":"0000-0003-1525-6247","position":17,"is_corresponding":false},{"id":226676,"name":"Elizabeth R. Plimack","orcid":"0000-0002-7618-0744","position":18,"is_corresponding":false},{"id":579720,"name":"Daniel M. Geynisman","orcid":"0000-0002-1423-5295","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Phase II Trial of Risk-Enabled Therapy After Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer (RETAIN 1)","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 ≥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%.\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>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39680823","pmcid":"PMC11908952","openalex_id":null,"authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"P30 CA006927","title":null}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":null,"oa_locations":[{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11908952/","host_type":"repository"},{"url":"https://ascopubs.org/doi/pdfdirect/10.1200/JCO-24-01214","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Humans","Neoplasm Invasiveness","Cisplatin","Vinblastine","Methotrexate","Doxorubicin","Antineoplastic Combined Chemotherapy Protocols","Neoplasm Staging","Chemotherapy, Adjuvant","Neoadjuvant Therapy","Cystectomy","Mutation","Adult","Aged","Middle Aged","Female","Male","Urinary Bladder Neoplasms"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T03:36:03.901956Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}