dc.contributor.author | Hall, E | |
dc.contributor.author | Hussain, SA | |
dc.contributor.author | Porta, N | |
dc.contributor.author | Lewis, R | |
dc.contributor.author | Crundwell, M | |
dc.contributor.author | Jenkins, P | |
dc.contributor.author | Rawlings, C | |
dc.contributor.author | Tremlett, J | |
dc.contributor.author | Sreenivasan, T | |
dc.contributor.author | Wallace, J | |
dc.contributor.author | Syndikus, I | |
dc.contributor.author | Sheehan, D | |
dc.contributor.author | Lydon, A | |
dc.contributor.author | Huddart, R | |
dc.contributor.author | James, N | |
dc.contributor.author | BC2001 Investigators, | |
dc.coverage.spatial | Switzerland | |
dc.date.accessioned | 2022-07-19T10:11:52Z | |
dc.date.available | 2022-07-19T10:11:52Z | |
dc.date.issued | 2022-05-13 | |
dc.identifier | S0302-2838(22)02265-5 | |
dc.identifier.citation | European Urology, 2022, pp. S0302-2838(22)02265-5 - | |
dc.identifier.issn | 0302-2838 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5238 | |
dc.identifier.eissn | 1873-7560 | |
dc.identifier.eissn | 1873-7560 | |
dc.identifier.doi | 10.1016/j.eururo.2022.04.017 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.format.extent | S0302-2838(22)02265-5 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER | |
dc.relation.ispartof | European Urology | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Bladder cancer | |
dc.subject | Chemoradiotherapy | |
dc.subject | Phase 3 | |
dc.subject | Randomised controlled trial | |
dc.title | Chemoradiotherapy in Muscle-invasive Bladder Cancer: 10-yr Follow-up of the Phase 3 Randomised Controlled BC2001 Trial. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-04-17 | |
dc.date.updated | 2022-07-19T10:11:26Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.eururo.2022.04.017 | |
rioxxterms.licenseref.startdate | 2022-05-13 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/35577644 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Clinical Academic Radiotherapy (Huddart) | |
pubs.publication-status | Published online | |
icr.researchteam | Clin Trials & Stats Unit | |
icr.researchteam | Clinic Acad RT Huddart | |
dc.contributor.icrauthor | Hall, Emma | |
dc.contributor.icrauthor | Porta, Nuria | |
dc.contributor.icrauthor | Lewis, Rebecca | |
dc.contributor.icrauthor | Huddart, Robert | |
dc.contributor.icrauthor | James, Nicholas | |
icr.provenance | Deposited by Mr Arek Surman on 2022-07-19. Deposit type is initial. No. of files: 1. Files: 1-s2.0-S0302283822022655-main.pdf | |