Long-Term Results of Bladder Preservation with Twice-Daily Radiation plus 5-Flourouracil/Cisplatin or Daily Radiation plus Gemcitabine for MIBC - Updated Report of NRG/RTOG 0712: A Randomized Phase 2 Trial.

5-FU/cisplatin and twice-daily radiation (FCT) or gemcitabine and once daily radiation (GD) are effective chemoradiation (CRT) regimens for bladder sparing treatment of muscle-invasive bladder cancer (MIBC). This trial evaluated these regimens and demonstrated efficacy with either regimen at 3 years. With further follow-up, longer term results are reported here. Patients with cT2-4a MIBC were randomized to FCT or GD. Patients had a transurethral resection and induction CRT to 40 Gy. Patients with a complete response (CR) received consolidation CRT to 64 Gy. Others had cystectomy. Adjuvant gemcitabine/cisplatin chemotherapy was administered. The primary endpoint was freedom from distant metastasis (FDM). This updated analysis reports 7-year data. Toxicity and efficacy endpoints, including bladder intact distant metastasis free survival (BI-DMFS) were also assessed. From 12/2008 to 4/2014, 70 patients were enrolled; 66 eligible for analysis, 33 per arm. Median follow-up was 9.1 years for eligible living patients. At 7 years, FDM was 65% and 73% for FCT and GD, respectively. BI-DMFS was 58% (95% CI: 41 - 76) and 68% (95% CI: 51-84), respectively. The post-hoc hazard ratio of 0.75 (95% CI: 0.37-1.55) showed no difference between treatments (p=0.44). Overall survival at 7 years was 48% and 59%. There were 4 and 5 cystectomies performed for FCT and GD, respectively. In the FCT arm, there were 5 (16%), 1 (3%) and 0 grade 3, 4 and 5 late toxicities reported. In the GD arm, there were 7 (23%), 0 and 0. Both regimens maintained high FDM rates at 7 years. Cystectomy rates were low and overall survival rates high on both arms. Late toxicity rates were low. Either gemcitabine and daily radiation or a cisplatin-based regimen are effective bladder sparing therapies.

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Conflicts of Interest Drs Coen, Jani, Kucuk, Lautenschlaeger, Pugh, Saylor, Shipley and Mr. Rodgers have nothing to disclose. Dr Efstathiou declares in the last 36 months consulting fees from Blue Earth Diagnostics, Boston Scientific, AstraZeneca, Genentech, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from IBA and Elekta, participation on a data safety monitoring board or advisory board at Merck, Roivant Pharma, Myovant, Sciences, Janssen, Bayer Healthcare, Progenics Pharmaceuticals, Pfizer, Gilead, Lantheus, Blue Earth Diagnostics and Angiodynamics and leadership or fiduciary role in other board, society, committee or advocacy group as unpaid board member at Massachusetts Prostate Cancer, Coalition (MPCC); American College of Radiation Oncology (ACRO); Radiation Oncology Institute (ROI). Dr Lee declares in the last 36 months grants or contracts from any entity in the form of payments made to me as an active WebMD podcast host, and consulting fees (expired) from Merck. Dr Parker declares in the last 36 months support for attending meetings and/or travel from employer, McGill University Health Centre. Dr Sandler declares in the last 36 months consulting fees as a member of a clinical trial steering committee at Janssen, support for attending meetings and/or travel to XIV International Uro-Oncology Conference from Nonpharma travel to cancer congress in Brazil and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid at ASTRO as a member of the board of directors. Dr Souhami declares in the last 36 months payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from Varian Medical Systems and support for attending meetings and/or travel from Varian Medical Systems. Dr Wu declares in the last 36 months consulting fees from OrigiMed Co. Ltd, payment for expert testimony for Conrad Trosch & Kemmy, P.A. and stock in GoPath Diagnostics, LLC. Dr Zeitman declares in the last 36 months leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as Editor-in-Chief of International Journal of Radiation Oncology, Biology, Physics from 2011 through 2021.