Long-Term Results of Bladder Preservation With Twice-Daily Radiation Plus 5-Fluorouracil/Cisplatin or Daily Radiation Plus Gemcitabine for Muscle-Invasive Bladder Cancer-Updated Report of NRG/RTOG 0712: A Randomized Phase 2 Trial

Int J Radiat Oncol Biol Phys. 2025 Jan 1;121(1):153-161. doi: 10.1016/j.ijrobp.2024.08.007. Epub 2024 Aug 13.

Abstract

Purpose: For bladder-sparing treatment of muscle-invasive bladder cancer, 5-fluorouracil/cisplatin with twice-daily radiation (FCT) or gemcitabine plus daily radiation (GD) are effective chemoradiation (CRT) regimens. This trial evaluated these regimens and demonstrated efficacy with either regimen at 3 years. With further follow-up, longer-term results are reported here.

Methods and materials: Patients with cT2 to cT4a muscle-invasive bladder cancer were randomized to FCT or GD. Patients had a transurethral resection and induction CRT to 40 Gy. Patients with a complete response 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.

Results: From December 2008 to April 2014, 70 patients were enrolled; 66 were 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. Bladder-intact distant metastasis-free survival 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 = .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, respectively. In the GD arm, there were 7 (23%), 0, and 0 grade 3, 4, and 5 late toxicities reported, respectively.

Conclusions: Both regimens maintained high FDM rates at 7 years. Cystectomy rates were low and overall survival rates were high on both arms. Late toxicity rates were low. Either gemcitabine and daily radiation or a cisplatin-based regimen are effective bladder-sparing therapies.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Chemoradiotherapy* / methods
  • Cisplatin* / administration & dosage
  • Cystectomy / methods
  • Deoxycytidine* / administration & dosage
  • Deoxycytidine* / analogs & derivatives
  • Female
  • Fluorouracil* / administration & dosage
  • Gemcitabine*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness*
  • Organ Sparing Treatments* / methods
  • Time Factors
  • Urinary Bladder / pathology
  • Urinary Bladder / radiation effects
  • Urinary Bladder Neoplasms* / drug therapy
  • Urinary Bladder Neoplasms* / mortality
  • Urinary Bladder Neoplasms* / pathology
  • Urinary Bladder Neoplasms* / therapy

Substances

  • Gemcitabine
  • Deoxycytidine
  • Cisplatin
  • Fluorouracil