Chemoradiotherapy in Muscle-invasive Bladder Cancer: 10-yr Follow-up of the Phase 3 Randomised Controlled BC2001 Trial.

Abstract

BACKGROUND:

BC2001, the largest randomised trial of bladder-sparing treatment for muscle-invasive bladder cancer (MIBC), demonstrated improvement in locoregional control by adding fluorouracil and mitomycin C to radiotherapy (James ND, Hussain SA, Hall E, et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med 2012;366:1477-88). There are limited data on long-term recurrence risk.

OBJECTIVE:

To determine whether benefit of adding chemotherapy to radiotherapy for MIBC is maintained in the long term.

DESIGN, SETTING, AND PARTICIPANTS:

A phase 3 randomised controlled 2 × 2 factorial trial was conducted. Between 2001 and 2008, 458 patients with T2-T4a N0M0 MIBC were enrolled; 360 were randomised to radiotherapy (178) or chemoradiotherapy (182), and 218 were randomised to standard whole-bladder radiotherapy (108) or reduced high-dose-volume radiotherapy (111). The median follow-up time was 9.9 yr. The trial is registered (ISRCTN68324339).

INTERVENTION:

Radiotherapy: 55 Gy in 20 fractions over 4 wk or 64 Gy in 32 fractions over 6.5 wk; concurrent chemotherapy: 5-fluorouracil and mitomycin C.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

Locoregional control (primary endpoint), invasive locoregional control, toxicity, rate of salvage cystectomy, disease-free survival (DFS), metastasis-free survival (MFS), bladder cancer-specific survival (BCSS), and overall survival. Cox regression was used. The analysis of efficacy outcomes was by intention to treat.

RESULTS AND LIMITATIONS:

Chemoradiotherapy improved locoregional control (hazard ratio [HR] 0.61 [95% confidence interval {CI} 0.43-0.86], p = 0.004) and invasive locoregional control (HR 0.55 [95% CI 0.36-0.84], p = 0.006). This benefit translated, albeit nonsignificantly, for disease-related outcomes: DFS (HR 0.78 [95% CI 0.60-1.02], p = 0.069), MFS (HR 0.78, [95% CI 0.58-1.05], p = 0.089), overall survival (HR = 0.88 [95% CI 0.69-1.13], p = 0.3), and BCSS (HR 0.79 [95% CI 0.59-1.06], p = 0.11). The 5-yr cystectomy rate was 14% (95% CI 9-21%) with chemoradiotherapy versus 22% (95% CI 16-31%) with radiotherapy alone (HR 0.54, [95% CI 0.31-0.95], p = 0.034). No differences were seen between standard and reduced high-dose-volume radiotherapy.

CONCLUSIONS:

Long-term findings confirm the benefit of adding concomitant 5-fluorouracil and mitomycin C to radiotherapy for MIBC.

PATIENT SUMMARY:

We looked at long-term outcomes of a phase 3 clinical trial testing radiotherapy with or without chemotherapy for patients with invasive bladder cancer. We concluded that the benefit of adding chemotherapy to radiotherapy was maintained over 10 yr.

• Authors: Emma Hall, Syed A Hussain, Nuria Porta, Rebecca Lewis, Malcolm Crundwell, Peter Jenkins, Christine Rawlings, Jean Tremlett, Thiagarajan Sreenivasan, Jan Wallace, Isabel Syndikus, Denise Sheehan, Anna Lydon, Robert Huddart, Nicholas James, BC2001 Investigators
• Journal: European urology (Eur Urol) Vol. 82 Issue 3 Pg. 273-279 (09 2022) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 35577644 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Mitomycin
• Fluorouracil

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Chemoradiotherapy (adverse effects)
• Fluorouracil (therapeutic use)
• Follow-Up Studies
• Humans
• Mitomycin (therapeutic use)
• Muscles
• Urinary Bladder Neoplasms (drug therapy)