With the shortage of bacillus Calmette-Guérin (BCG) vaccine, it is urgent to find an alternative to BCG instillation, which is the most commonly used adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC) patients after transurethral resection of bladder tumor treatment (TURBt) to delay tumor recurrence. Hyperthermia intra-vesical chemotherapy (HIVEC) with mitomycin C (MMC) is a good choice for NMIBC patients as an adjuvant treatment after TURBt. We aim to compare HIVEC with BCG instillation in the preventive efficacy of bladder tumor recurrence and progression by a network meta-analysis (NMA) taking MMC instillation and TURBt as the attached comparators.

PubMed (Medline), Ovid (Embase) and Cochrane Library were searched, and the network meta-analysis process followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Articles with BCG unresponsible patients and combined therapies were excluded. Evaluation was based on the recurrence free survival (RFS) and progression free survival (PFS).

72 clinical trials were eligible. A Bayesian consistency network model was generated under a random-effects model. HIVEC played a nonsignificant 22% relative reduction in bladder tumor recurrence compared with BCG instillation (HIVEC vs. BCG: HR 0.78, 95% credible interval [CrI] 0.55–1.08), and a nonsignificant higher risk of bladder tumor progression (BCG vs. HIVEC: HR 0.77, 95% credible interval [CrI] 0.22–3.03). Notably, in subgroup analysis of RFS, HIVEC plays significant 30% relative reduction compared with BCG perfusion (HR 0.70, 95% credible interval [CrI] 0.48–0.99) for patient groups with a higher portion of male. For articles with longer follow-up (median follow-up ≥ 2.5yr), HIVEC shows significant efficacy in the tumor recurrence prevention (HR 0.38, 95% credible interval [CrI] 0.17–0.85).

HIVEC is a potential alternative to BCG especially for males and long-term efficacy, and it is expectable to be standard therapy for NMIBC patients after TURBt during the global shortage of BCG.