European urology oncology, 20 3 2025, Pages S2588-9311(25)00104-X Towards Defining Follow-up Strategies for Patients with Primary Intermediate-risk Non-muscle-invasive Bladder Cancer. Contieri R, Martini A, Beijert IJ, Mertens LS, Hentschel AE, Bründl J, Compérat EM, Plass K, Rodríguez O, Subiela Henríquez JD, Hernández V, de la Peña E, Alemany I, Turturica D, Pisano F, Soria F, Čapoun O, Bauerová L, Pešl M, Maxim Bruins H, Runneboom W, Herdegen S, Breyer J, Brisuda A, Calatrava A, Rubio-Briones J, Seles M, Mannweiler S, Bosschieter J, Kusuma VRM, Ashabere D, Huebner N, Seisen T, Claps F, Masson-Lecomte A, Liedberg F, Cohen D, Lunelli L, Cussenot O, Sheikh SE, Volanis D, Côté JF, Rouprêt M, Haitel A, Shariat SF, Mostafid AH, Nieuwenhuijzen JA, Zigeuner R, Dominguez-Escrig JL, Hacek J, Zlotta AR, Burger M, Evert M, de Kaa CAH, van der Heijden AG, Kiemeney LALM, Soukup V, Molinaro L, Hurle R, Paciotti M, Moschini M, Pradere B, Perdonà S, Gontero P, Llorente C, Algaba F, Palou J, N'Dow J, Ribal MJ, van der Kwast TH, Babjuk M, Sylvester RJ, van Rhijn BWG
Background and objective
The current European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC) categorize patients into four risk groups. In 2024, a specific follow-up schedule was introduced for intermediate-risk (IR) disease. However, recommendations are based on expert opinion and restricted to patients with IR-NMIBC who have primary low-grade or high-grade/grade 2 disease. Our aim was to identify a subgroup of patients with IR-NMIBC who may require more stringent follow-up.
Methods
We conducted a retrospective analysis of 2086 patients with IR-NMIBC classified according to the World Health Organization 1973 grading scheme. Multivariable Cox-regression models were fitted to identify predictors of recurrence, which were then used to dichotomize groups with low risk of recurrence (IR-Low) versus high risk of recurrence (IR-High). Kaplan-Meier curves were plotted to estimate recurrence-free survival (RFS) and progression-free survival (PFS). Smoothed hazard estimates of first recurrence were plotted by risk group.
Key findings and limitations
Multifocality and tumor size ≥3 cm were significantly associated with higher risk of first recurrence and were used to define the IR-High and IR-Low (unifocal, size <3 cm; n = 1087) groups. The 3-yr RFS rate was significantly worse for the IR-High group (51%, 95% confidence interval [CI] 48-54%) than for IR-Low (68%, 95% CI 65-71%). The risk of progression was low (5-yr PFS rate 96%) with no significant difference between the IR-High and IR-Low groups.
Conclusions and clinical implications
During IR-NMIBC follow-up for recurrence, tumor size and focality should be considered rather than grade. If the primary objective is to ensure prompt detection of recurrence, follow-up schedules should be tailored according to the risk of recurrence, with more stringent protocols for patients with IR-NMIBC at higher risk of recurrence.
