Defining the optimal duration of maintenance mitomycin C in intermediate-risk Ta NMIBC: a multicenter retrospective landmark analysis

Purpose: While mitomycin C (MMC) is widely used for intravesical therapy, the optimal maintenance regimen for non-muscle invasive bladder cancer (NMIBC) remains unclear. This study assessed the impact of MMC maintenance on recurrence-free survival (RFS) in patients with intermediate-risk Ta NMIBC and aimed to identify the optimal number of instillations for improved outcomes. Methods: We conducted a retrospective multicenter analysis of patients with Ta NMIBC treated with transurethral resection and adjuvant MMC across 13 Italian centers (2010–2023). Patients were grouped based on MMC maintenance duration: no maintenance, short-term (≤ 6 instillations), and long-term (> 6 instillations). Kaplan–Meier curves, Cox regression, and CART analysis were used to evaluate RFS and high-grade RFS (HG-RFS). Results: Among 292 patients included, maintenance therapy significantly improved 2-year and 3-year RFS compared to no maintenance (78% vs. 55% and 67% vs. 30%, respectively; p < 0.001). CART analysis identified > 6 instillations as the threshold for optimal benefit. Long-term maintenance was associated with a lower risk of recurrence (HR 0.23 vs. no maintenance; HR 0.39 vs. short-term; both p < 0.001). No significant difference in HG-RFS was observed between no maintenance, long-term, and short-term groups. Conclusion: Long-term MMC maintenance (> 6 instillations) significantly prolongs RFS in patients with Ta NMIBC. These findings suggest that extended MMC regimens may improve patients’ outcomes and should be considered in clinical practice. Prospective studies are needed to confirm these results and guide evidence-based treatment strategies.