Neoadjuvant Intravesical Therapy for Patients with Non-muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis.

Patients with non-muscle-invasive bladder cancer (NMIBC) have a significant risk of recurrence after trans-urethral resection of bladder tumor (TURBT). The use of neoadjuvant intravesical therapy prior to TURBT has been investigated previously as a possible treatment alternative, but the prospective evidence remains fragmented and heterogeneous. OBJECTIVES: This systematic review and meta-analysis aimed to synthesize the literature and assess whether outcomes differ compared with upfront TURBT. EVIDENCE ACQUISITION: We performed a comprehensive search in PubMed, Scopus, Embase, and Web of Science for prospective studies investigating recurrence-free survival (RFS) among patients with primary or recurrent NMIBC who received neoadjuvant intravesical treatment before TURBT. Only studies with an interventional treatment arm that used neoadjuvant treatment with subsequent TURBT were included in the meta-analysis. Cochrane Q test was used to assess heterogeneity of estimates across studies. EVIDENCE SYNTHESIS: Overall, eight studies were eligible for systematic review and six for meta-analysis with RFS as outcome. Estimates of 1-, 2- and 3-yr RFS were 96% (Confidence Interval [CI]: 92-100%), 82% (95% CI: 60-100%), and 77% (95% CI: 56-97%) for patients who received any neoadjuvant treatment (intravesical mitomycin C [MMC], electromotive drug administration MMC, and hyperthermic intravesical chemotherapy MMC) followed by TURBT, whereas for patients who received upfront TURBT the 1-, 2- and 3-yr RFS estimates were 76% (95% CI: 61-91%), 55% (95% CI: 32-77%), and 54% (95% CI: 31-78%), respectively. The use of neoadjuvant intravesical therapy provided benefit in terms of RFS compared with upfront TURBT (Hazard Ratio: 0.42, 95% CI: 0.29-0.61, p < 0.001). No grade 3-5 adverse events (AEs) were observed in patients treated with neoadjuvant intravesical therapy across different studies. CONCLUSIONS: The use of neoadjuvant intravesical therapy before TURBT results in higher short-term RFS compared with upfront TURBT in patients with NMIBC without causing grade 3-5 AEs. These findings support the need for adequately powered randomized trials to define patient selection, optimal regimens, and the durability of any observed benefit before routine clinical adoption.