Intravesical bacillus Calmette-Guérin (BCG) plus mitomycin (MM) had not been compared rigorously with BCG alone in BCG-naïve, non-muscle-invasive bladder cancer (NMIBC) patients.
Participants with BCG-naïve NMIBC (high-grade pTa or any grade pT1; concurrent carcinoma in situ [CIS] allowed) were assigned randomly (1:1) to either the BCG + MM or the BCG-alone group after maximal transurethral resection.
The primary endpoint was disease-free survival (DFS); the secondary endpoints included a complete response on cystoscopy at 3 mo (CR3mos), recurrence, progression, adverse events (AEs), and deaths from any cause.
We randomised 501 participants (249 to BCG + MM and 252 to BCG alone), with pTa in 53%, pT1 in 47%, and concurrent CIS in 28%. The median follow-up was 48 mo. DFS was not superior for BCG + MM versus BCG alone (2-yr DFS rate: 75% vs 71%; hazard ratio 0.87, 95% confidence interval 0.65-1.16; p = 0.3). The numbers of events for BCG + MM versus BCG alone were as follows: 214 versus 210 (CR3mos), 79 versus 86 (recurrence), 28 versus 44 (progression), and 26 versus 23 (death). Those assigned BCG + MM had more instillations (4033 vs 3383) but fewer doses of BCG (total 2056 vs 3383; median nine vs 16) than BCG alone. Grade 3-5 AEs occurred in 43 assigned BCG + MM versus 37 assigned BCG alone. A higher number of participants assigned BCG + MM than those assigned BCG alone had ≥75% of their planned doses (78% vs 68%, p = 0.02).
BCG + MM was not proved superior to BCG alone, but required 39% fewer doses of BCG and fewer treatment discontinuations. These findings support consideration of BCG + MM as a pragmatic alternative to BCG alone, which could mitigate the global shortage of BCG.
European urology. 2026 Feb 02 [Epub ahead of print]
Dickon Hayne, Alison Y Zhang, Hayley Thomas, Laurence Krieger, Joseph Ischia, Paul Anderson, Ratnesh K Srivastav, William Green, Jeremy Grummet, Patricia A Bastick, Emma K Beardsley, Alison Blatt, Manish Patel, Lewis Chan, Andrew Mitterdorfer, Matthew Roberts, Shomik Sengupta, Matthew Winter, Gavin Marx, Conrad Bishop, Leanna Cheung, Cynthia Hawks, Andrew Martin, Steve P McCombie, Andrew D Redfern, Ian D Davis, Martin R Stockler
UWA Medical School, University of Western Australia, Perth, WA, Australia. Electronic address: ., NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia., Department of Medical Oncology, Northern Cancer Institute, St Leonards, Sydney, NSW, Australia., Department of Urology, Austin Health, Melbourne, Victoria, Australia., Department of Urology, Royal Melbourne Hospital, Melbourne, Victoria, Australia., Department of Medical Oncology, Tweed Valley Hospital, Cudgen, NSW, Australia., Department of Urology, Nottingham University Hospital, Nottingham, UK., Department of Urology, The Alfred Hospital, Melbourne, Victoria, Australia., Department of Medical Oncology, Southside Cancer Care Centre, Sydney, NSW, Australia., Department of Medical Oncology, Frankston Hospital, Melbourne, Victoria, Australia., Department of Urology, John Hunter Hospital, Newcastle, NSW, Australia., Department of Urology, Westmead Hospital, Sydney, NSW, Australia., Department of Urology, Concord Repatriation General Hospital, Sydney, NSW, Australia., Department of Urology, Redcliffe Hospital, Redcliffe, Queensland, Australia., Department of Urology, Epworth HealthCare - Richmond, Melbourne, Victoria, Australia., Department or Urology, Nepean Hospital, Sydney, NSW, Australia., SAN Clinical Trials Unit, Sydney Adventist Hospital, Sydney, NSW, Australia., Department of Urology, Footscray Hospital, Melbourne, Victoria, Australia., Department of Urology, Fiona Stanley Hospital, Perth, WA, Australia., ULTRA The University of Queensland Clinical Trials Capability, Centre for Clinical Research, Queensland, Australia., Department of Oncology, UWA Medical School, Perth, WA, Australia., Monash University Eastern Health Clinical School, Melbourne, Australia., NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia; Department of Urology, Concord Repatriation General Hospital, Sydney, NSW, Australia.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/41633899