PMID- 37442672 OWN - NLM STAT- MEDLINE DCOM- 20240131 LR - 20240218 IS - 2588-9311 (Electronic) IS - 2588-9311 (Linking) VI - 7 IP - 1 DP - 2024 Feb TI - Long-term Outcomes of Chemoradiation for Muscle-invasive Bladder Cancer in Noncystectomy Candidates. Final Results of NRG Oncology RTOG 0524-A Phase 1/2 Trial of Paclitaxel + Trastuzumab with Daily Radiation or Paclitaxel Alone with Daily Irradiation. PG - 83-90 LID - S2588-9311(23)00115-3 [pii] LID - 10.1016/j.euo.2023.05.013 [doi] AB - BACKGROUND: Chemo-radiation is a well-established alternative to radical cystectomy in patients with muscle-invasive bladder cancer. Many patients due to age or medical comorbidity are unfit for either radical cystectomy, or standard cisplatin- or 5-fluorouracil-based chemoradiation, and do not receive appropriate treatment with curative intent. We treated patients with a less aggressive protocol employing seven weekly doses of paclitaxel and daily irradiation. In those whose tumors showed overexpression of her2/neu, seven weekly doses of trastuzumab were also administered. OBJECTIVE: To report the long-term survival outcomes and toxicity results of the of NRG Oncology RTOG 0524 study. DESIGN, SETTING, AND PARTICIPANTS: Seventy patients were enrolled and 65 (median age: 76 yr) were deemed eligible. Patients were assigned to daily radiation and weekly paclitaxel + trastuzumab (group 1, 20 patients) or to daily radiation plus weekly paclitaxel (group 2, 45 patients) based on tumor her2/neu overexpression. Radiation was delivered in 1.8 Gy fractions to a total dose of 64.8 Gy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was unresolved treatment-related toxicity. The secondary endpoints were complete response rate, protocol completion rate, and disease-free and overall survival. RESULTS AND LIMITATIONS: Protocol therapy was completed by 60% (group 1) and 76% (group 2); complete response rates at 12 wk were 62% in each group. Acute treatment-related adverse events (AEs) of grade >/=3 were observed in 80% in group 1 and 58% in group 2. There was one treatment-related grade 5 AE in group 1. Unresolved acute treatment-related toxicity was 35% in group 1 and 31% in group 2. The median follow-up was 2.3 yr in all patients and 7.2 yr in surviving patients. Overall survival at 5 yr was 25.0% in group 1 and 37.8% in group 2 (33.8% overall). At 5 yr, disease-free survival was 15.0% in group 1 and 31.1% in group 2. CONCLUSIONS: In a cohort of patients with muscle-invasive bladder cancer who are not candidates for cystectomy or cisplatin chemotherapy, chemoradiation therapy offers a treatment with a significant response rate and 34% 5-yr overall survival. While there were many AEs in this medically fragile group, there were few grade 4 events and one grade 5 event attributable to therapy. PATIENT SUMMARY: Patients with invasive bladder cancer who cannot tolerate surgery were treated with radiation and systemic therapy without surgically removing their bladders. Most patients tolerated the treatment, were able to keep their bladders, and showed a significant treatment response rate. CI - Copyright (c) 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved. FAU - Dahl, Douglas M AU - Dahl DM AD - Massachusetts General Hospital Cancer Center, Boston, MA, USA. Electronic address: ddahl@mgh.harvard.edu. FAU - Karrison, Theodore G AU - Karrison TG AD - NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA; University of Chicago, Chicago, IL, USA. FAU - Michaelson, M Dror AU - Michaelson MD AD - Massachusetts General Hospital Cancer Center, Boston, MA, USA. FAU - Pham, Huong T AU - Pham HT AD - Virginia Mason Medical Center, Seattle, WA, USA. FAU - Wu, Chin-Lee AU - Wu CL AD - Massachusetts General Hospital Cancer Center, Boston, MA, USA. FAU - Swanson, Gregory P AU - Swanson GP AD - Scott and White Memorial Hospital, Temple, TX, USA. FAU - Shipley, William U AU - Shipley WU AD - Massachusetts General Hospital Cancer Center, Boston, MA, USA. FAU - Vuky, Jacqueline AU - Vuky J AD - OHSU Knight Cancer Institute, Accrual-Virginia Mason CCOP, Portland, OR, USA. FAU - Lee, R Jeffrey AU - Lee RJ AD - Intermountain Medical Center, Salt Lake City, UT, USA. FAU - Zietman, Anthony L AU - Zietman AL AD - Massachusetts General Hospital Cancer Center, Boston, MA, USA. FAU - Souhami, Luis AU - Souhami L AD - The Research Institute of the McGill University Health Centre (MUHC), Montreal, QC, Canada. FAU - Chang, Brian K AU - Chang BK AD - Parkview Research Center, Fort Wayne, IN, USA. FAU - Deming, Richard L AU - Deming RL AD - Mercy Medical Center - Des Moines, Accrual-Penrose Cancer Center, Penrose-St. Francis Health Services, Des Moines, IA, USA. FAU - Ellerton, John A AU - Ellerton JA AD - Nevada Cancer Research Foundation NCORP, Las Vegas, NV, USA. FAU - Sandler, Howard M AU - Sandler HM AD - Cedars-Sinai Medical Center, Los Angeles, CA, USA. FAU - Rodgers, Joseph P AU - Rodgers JP AD - NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA. FAU - Feng, Felix Y AU - Feng FY AD - UCSF Medical Center-Mission Bay, San Francisco, CA, USA. FAU - Efstathiou, Jason A AU - Efstathiou JA AD - Massachusetts General Hospital Cancer Center, Boston, MA, USA. LA - eng GR - U10 CA180822/CA/NCI NIH HHS/United States GR - U10 CA180868/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article DEP - 20230711 PL - Netherlands TA - Eur Urol Oncol JT - European urology oncology JID - 101724904 RN - P88XT4IS4D (Paclitaxel) RN - Q20Q21Q62J (Cisplatin) RN - P188ANX8CK (Trastuzumab) SB - IM MH - Humans MH - Aged MH - *Paclitaxel/therapeutic use MH - Cisplatin/therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - *Urinary Bladder Neoplasms/drug therapy/pathology MH - Trastuzumab/therapeutic use MH - Muscles/pathology PMC - PMC10782593 MID - NIHMS1911895 OTO - NOTNLM OT - Bladder cancer OT - Chemotherapy OT - Radiation therapy OT - Targeted therapy EDAT- 2023/07/14 13:07 MHDA- 2024/01/31 06:42 PMCR- 2025/02/01 CRDT- 2023/07/13 21:58 PHST- 2022/10/31 00:00 [received] PHST- 2023/04/27 00:00 [revised] PHST- 2023/05/30 00:00 [accepted] PHST- 2025/02/01 00:00 [pmc-release] PHST- 2024/01/31 06:42 [medline] PHST- 2023/07/14 13:07 [pubmed] PHST- 2023/07/13 21:58 [entrez] AID - S2588-9311(23)00115-3 [pii] AID - 10.1016/j.euo.2023.05.013 [doi] PST - ppublish SO - Eur Urol Oncol. 2024 Feb;7(1):83-90. doi: 10.1016/j.euo.2023.05.013. Epub 2023 Jul 11.