Mitomycin combined with Bacillus Calmette-Guérin (BCG) demonstrated comparable efficacy and safety to BCG alone as adjuvant intravesical therapy for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). The combination required fewer BCG doses, suggesting that broader adoption of this regimen could help mitigate the global BCG shortage.
Intravesical BCG induction and maintenance therapy remains the standard of care for patients with high-risk NMIBC who underwent transurethral resection of the bladder (TURB).1 However, the ongoing global BCG shortage, estimated at 30-50% below demand, has raised concerns. Previous evidence has suggested a potential benefit of adding intravesical chemotherapy to BCG in high-risk NMIBC.2,3 At ASCO 2025, results of a phase III ANZUP 1301 trial, conducted by the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, were presented.4
The open-label, phase III ANZUP 1301 trial enrolled patients with high-risk papillary NMIBC (high-grade pTa or any grade pT1) who were eligible for intravesical chemotherapy. Concurrent carcinoma in situ (CIS) was allowed. Patients were randomised 1:1 to receive either intravesical BCG plus mitomycin (induction and maintenance) or intravesical BCG alone (induction and maintenance). The primary endpoint was disease-free survival (DFS). Secondary endpoints included complete response on cystoscopy and biopsy at three months, time to recurrence, time to progression, overall survival (OS), and safety.
Of the 501 randomised patients (mitomycin plus BCG: N= 249, BCG: N= 252), 47% had pT1 disease, 53% had pTa disease, and 28% presented with concurrent CIS.
At a median follow-up of 48 months, efficacy endpoints were similar between both groups. The 24-month DFS was 75% with mitomycin plus BCG and 71% with BCG alone (HR[95% CI]: 0.87[0.65-1.16], p= 0.34). An exploratory post hoc analysis showed that the benefit was more pronounced in higher-risk patients (all T1, any CIS) (HR[95% CI]: 0.69[0.48-0.99]). The complete response at three months was 90% with mitomycin plus BCG and 86% with BCG alone (RR[95% CI]: 1.05[0.98-1.12], p= 0.22). Time to recurrence at 24 months was 80% vs 75% (HR[95% CI]: 0.85[0.61-1.19], p= 0.35), and time to progression at 24 months was 92% vs 90% (HR[95% CI]: 0.68[0.41-1.11], p= 0.12), for mitomycin plus BCG vs BCG, respectively. Five-year OS was 88% in the combination group and 87% in the BCG alone group (HR[95% CI]: 1.06[0.60-1.86], p= 0.85).
The total number of instillations was higher in the mitomycin plus BCG arm (4,033 vs 3,383), while the total number of BCG doses and the median number of BCG doses per patient were lower (2,056 vs 3,383; median 9 vs 16). A greater proportion of patients in the mitomycin plus BCG arm completed all planned doses (75% vs 64%).
The most commonly reported any-grade adverse events were fatigue, flu-like symptoms, haematuria, urinary tract infection, diarrhoea and nausea. Few grade ≥3 adverse events were seen in either arm. Three deaths occurred while on treatment: myocardial infarction and sepsis in the BCG arm, and BCG-related mycotic aortic aneurysm in the mitomycin plus BCG arm.
Mitomycin plus BCG showed similar efficacy and safety compared to BCG alone in patients with high-risk NMIBC. The combination required fewer BCG doses and resulted in fewer treatment discontinuations, offering a potential strategy to optimise care in the context of a global BCG shortage.
References
1. Gontero P, Birtel A, Compérat E, et al. EAU Guidelines on non-muscle-invasive bladder cancer (TaT1 and CIS). Update March 2025. Available at: https://uroweb.org/guidelines/non-muscle-invasive-bladder-cancer (last accessed 5 June 2025).
2. Cui J, Chen S, Yang Y, et al. Combination of intravesical chemotherapy and Bacillus Calmette-Guerin versus Bacillus Calmette-Guerin monotherapy in intermediate- and high-risk non-muscle invasive bladder cancer: a systematic review and meta-analysis. Transl Androl Urol 2016;5(Suppl 1):AB152.
3. Solsona E, Madero R, Chantada V, et al. Sequential combination of mitomycin C plus bacillus Calmette-Guérin (BCG) is more effective but more toxic than BCG alone in patients with non-muscle-invasive cancer in intermediate- and high-risk patients: final outcome of CUETO 93009, a randomized prospective trial. Eur Urol 2015;76(3):508-16.
4. Hayne D, Zhang AY, Thomas H, et al. Mitomycin plus BCG as adjuvant intravesical therapy for high-risk, non-muscle-invasive bladder cancer: a randomized phase 3 trial (ANZUP 1301). Presented at ASCO 2025; Abstract LBA4504.
Top
