Enhanced prognostic value of four‐tier hybrid grading system in Ta non‐muscle‐invasive bladder cancer
Matteo Ferro, Michele Catellani, Roberto Contieri, Giuseppe Fallara, Marco Tozzi, Martina Maggi, Francesco Chierigo, Alessandro Uleri, L. Da Pozzo, Ludovica Cella, Rodolfo Hurle, M. Stasi, Enrico Checcucci, Pierluigi Bove, Francesco Maiorino, Mihai Dorin Vartolomei, E. Montanari, Giancarlo Albo, E. De Lorenzis, Luca Boeri, Giovanni Liguori, Francesca Vedovo, Beat Roth, Gian Maria Busetto, Ugo Giovanni Falagario, Riccardo Mastroianni, Massimo Madonia, Alessandro Tedde, Pasquale Di Tonno, Giuseppe Lucarelli, Saverio Forte, Giorgio Ivan Russo, Arturo Lo Giudice, Fabrizio Verweij, Marco Racioppi, Francesco Pio Bizzarri, Alessandro Crestani, Marco Rinaldi, Maria Angela Cerruto, Francesco Claps, Andrea Conti, Sisto Perdonà, Fabrizio Moro, Fabio Zattoni, Ciro Imbimbo, Felice Crocetto, Achille Aveta, Savio Domenico Pandolfo, Angelo Porreca, Giuseppe Carrieri, Luca Carmignani, Cosimo De Nunzio, Giuseppe Simone, Luigi Cormio, Marco Borghesi, Alessandro Antonelli, Francesco Porpiglia, Bernardo Rocco, Biagio Barone, Roberto Contieri
Abstract
OBJECTIVES: To compare the predictive performance of the World Health Organization (WHO) 1973, WHO 2004/2022, the three-tier (low grade [LG]/Grade 1 [G1]-G2, high grade [HG]/G2, and HG/G3), and four-tier (LG/G1, LG/G2, HG/G2, and HG/G3) hybrid grading systems in Ta non-muscle-invasive bladder cancer (NMIBC), by evaluating recurrence-free survival (RFS) and progression-free survival (PFS). PATIENTS AND METHODS: This retrospective multicentre study included 1233 patients with pTa NMIBC treated with transurethral resection of bladder tumour, eventually followed by intravesical instillations as determined by their physicians, between 2010 and 2023, across 18 Italian hospitals. Pathologists graded resected tissues using the WHO 1973, WHO 2004/2022 classifications, and hybrid three-tier (LG, HG/G2, HG/G3) and four-tier (LG/G1, LG/G2, HG/G2, HG/G3) systems. Kaplan-Meier curves estimated RFS and PFS. Discriminative performance was assessed using Harrell's concordance index (C-index). RESULTS: Among 1233 patients with pTa NMIBC, 890 were classified as LG and 343 as HG according to the WHO 2004/2022 grading system, while 586, 405, and 242 were categorised as G1, G2, and G3, respectively, under the WHO 1973 system. With a median (interquartile range) follow-up of 26 (14-48) months, 418 patients experienced recurrence, including 184 with HG recurrence and 42 who progressed to MIBC. The C-index values for RFS were 0.60, 0.56, 0.57, and 0.61 for the WHO 1973, WHO 2004/2022, hybrid three-tier, and four-tier grading systems, respectively. For progression, the C-index values were 0.80, 0.74, 0.75, and 0.81 across the same systems, underscoring the superior predictive capacity of the four-tier classification. Nonetheless, the low number of MIBC progression events limits the robustness of these analyses. CONCLUSION: Our findings highlight the superior prognostic accuracy of the four-tier hybrid classification in predicting recurrence and progression in patients with stage Ta NMIBC. By combining strengths from the WHO 1973 and 2004/2022, this hybrid model shows promise as tool for enhancing NMIBC patient management in clinical practice.