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. 2026 Jan 2.
doi: 10.1007/s11255-025-04946-9. Online ahead of print.

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

Roberto Contieri  1 , Letizia Maria Ippolita Jannello  2   3 , Mihai Dorin Vartolomei  4   5 , Beat Roth  4 , Roberto Bianchi  2   3 , Giuseppe Fallara  2   3 , Marco Tozzi  2   3 , Martina Maggi  2   3 , Francesco Chierigo  2   3 , Francesco Pellegrino  2   3 , Ludovica Cella  6 , Alessandro Uleri  6   7 , Luigi Da Pozzo  8   9 , Francesco Claps  10 , Achille Aveta  11 , Gianluca Spena  11 , Enrico Checcucci  12 , Cecilia Gatti  12 , Pierluigi Bove  13   14 , Francesca Vedovo  15 , Gian Maria Busetto  16 , Ugo Falagario  17 , Riccardo Mastroianni  18 , Alessandro Tedde  19 , Massimo Madonia  19 , Pasquale Di Tonno  20 , Giuseppe Lucarelli  20 , Saverio Forte  20 , Giorgio Ivan Russo  21 , Fabrizio Verweij  22 , Marco Racioppi  23 , Francesco Pio Bizzarri  24 , Marco Borghesi  25 , Marco Rinaldi  26 , Fabio Zattoni  27 , Luca Boeri  2   28 , Elisa De Lorenzis  2   28 , Andrea Conti  29 , Maria Angela Cerruto  30   31 , Felice Crocetto  32 , Giuseppe Simone  18 , Savino Mauro Di Stasi  13 , Cosimo De Nunzio  16 , Luca Carmignani  29 , Giovanni Liguori  15 , Angelo Porreca  33 , Biagio Barone  34 , Emanuele Montanari  28 , Albo Giancarlo  28 , Alessandro Antonelli  30   31 , Alessandro Veccia  30   31 , Fabrizio Dal Moro  27 , Giuseppe Carrieri  17 , Luigi Cormio  17 , Carlo Terrone  25 , Francesco Porpiglia  12 , Sisto Perdonà  11 , Bernardo Rocco  23 , Rodolfo Hurle  35 , Michele Catellani  8 , Matteo Ferro  36   37
Affiliations

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

Roberto Contieri et al. Int Urol Nephrol. .

Abstract

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.

Keywords: Bladder cancer; Instillation duration; Landmark analysis; Mitomycin C; Ta NMIBC.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare that there are no competing interests.

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