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.
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).
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.
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.
International urology and nephrology. 2026 Jan 02 [Epub ahead of print]
Roberto Contieri, Letizia Maria Ippolita Jannello, Mihai Dorin Vartolomei, Beat Roth, Roberto Bianchi, Giuseppe Fallara, Marco Tozzi, Martina Maggi, Francesco Chierigo, Francesco Pellegrino, Ludovica Cella, Alessandro Uleri, Luigi Da Pozzo, Francesco Claps, Achille Aveta, Gianluca Spena, Enrico Checcucci, Cecilia Gatti, Pierluigi Bove, Francesca Vedovo, Gian Maria Busetto, Ugo Falagario, Riccardo Mastroianni, Alessandro Tedde, Massimo Madonia, Pasquale Di Tonno, Giuseppe Lucarelli, Saverio Forte, Giorgio Ivan Russo, Fabrizio Verweij, Marco Racioppi, Francesco Pio Bizzarri, Marco Borghesi, Marco Rinaldi, Fabio Zattoni, Luca Boeri, Elisa De Lorenzis, Andrea Conti, Maria Angela Cerruto, Felice Crocetto, Giuseppe Simone, Savino Mauro Di Stasi, Cosimo De Nunzio, Luca Carmignani, Giovanni Liguori, Angelo Porreca, Biagio Barone, Emanuele Montanari, Albo Giancarlo, Alessandro Antonelli, Alessandro Veccia, Fabrizio Dal Moro, Giuseppe Carrieri, Luigi Cormio, Carlo Terrone, Francesco Porpiglia, Sisto Perdonà, Bernardo Rocco, Rodolfo Hurle, Michele Catellani, Matteo Ferro
Department of Urology, Istituto Nazionale Tumori di Napoli IRCCS Fondazione "G. Pascale", Via Mariano Semmola, 52, 80131, Naples, NA, Italy. ., Università degli Studi di Milano, Milan, Italy., Department of Urology, University of Bern, Bern, Switzerland., Department of Biomedical Sciences, Humanitas University, Milan, Italy., Department of Urology, ASST Papa Giovanni XXIII, Piazza OMS, 1, 24127, Bergamo, BG, Italy., Department of Oncological Urology, Veneto Institute of Oncology (IOV) IRCCS, Padua, Italy., Department of Urology, Istituto Nazionale Tumori di Napoli IRCCS Fondazione "G. Pascale", Via Mariano Semmola, 52, 80131, Naples, NA, Italy., Division of Urology, Department of Oncology, School of Medicine, San Luigi Hospital, University of Turin, Turin, Italy., Department of Experimental Medicine, Torvergata Oncoscience Research Centre of Excellence, TOR, University of Rome Tor Vergata, via Montpellier 1, 00133, Rome, Italy., Urology Clinic, Department of Medical, Surgical and Health Science, University of Trieste, Trieste, Italy., Department of Urology, Sapienza Rome University, Rome, Italy., Department of Urology and Kidney Transplantation, University of Foggia, Foggia, Italy., Department of Urology, IRCCS "Regina Elena" National Cancer Institute, Via Elio Chianesi 43, 00143, Rome, Italy., Dipartimento di Medicina, Chirurgia e Farmacia, Università degli Studi di Sassari, Sassari, Italy., Unit of Urology, Andrology and Kidney Transplantation, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy., Department of Urology, University of Catania, Catania, Italy., U.O.C. Urologia, ASST Cremona, Cremona, Italy., U.O.C. Clinica Urologica, Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy., Department of Urology, Ospedale Isola Tiberina - Gemelli Isola, Università Cattolica del Sacro Cuore, Rome, Italy., Department of Surgical and Integrated Diagnostic Sciences, University of Genoa, 16126, Genoa, Italy., Department of Urology, Santa Maria Della Misericordia Hospital, Udine, Italy., Urology Unit, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy., Department of Urology, IRCCS Ospedale Galeazzi - Sant'Ambrogio, Milan, Italy., University of Verona, Verona, Italy., Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, 80131, Naples, Italy., Department of Urology, Humanitas Gavazzeni, Humanitas University, Bergamo, Italy., Division of Urology, Department of Surgical Sciences, AORN Sant'Anna e San Sebastiano, 81100, Caserta, Italy., Department of Urology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Department of Urology, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy., Università degli Studi di Milano, Milan, Italy. .