Background and Objective: Patients with non-muscle invasive bladder cancer (NMIBC) frequently experience recurrences, yet, the timing and characteristics of subsequent recurrences are understudied. We aim to describe subsequent recurrences in a large, contemporary, population-based cohort. Methods: We included 1,915 patients from the UroLife study and the Nijmegen Bladder Cancer Study, diagnosed with primary NMIBC between 2011 and 2021. The conditional 1-, 3- and 5-year risks of first to fourth recurrence were calculated using Kaplan-Meier risks, stratified by clinicopathological factors. Patterns of subsequent tumours were described and visualised. Key Findings and Limitations: We observed 671 first recurrences and 400 subsequent recurrences. The 3-year conditional recurrence risks for first, second and third recurrence were 31%, 45% and 54%, respectively, and were similar for NMIBC risk groups. Recurrence after a low-, intermediate- or high-risk tumour (either primary or recurrent) was again of low-, intermediate- or high-risk in 74%, 62% and 44% of cases, respectively. Ten patients with low/intermediate-risk NMIBC and 89 patients with high-risk NMIBC progressed to muscle-invasive or metastatic bladder cancer. Seven out of these ten (70%) and 13 out of these 89 (15%) patients had a high-risk recurrence before progression. This study was limited to a patient cohort from The Netherlands. Conclusions and Clinical Implications: Our study provides novel and reliable estimates of recurrence rates and patterns in NMIBC from a large, contemporary, population-based cohort. Recurring NMIBC tumours often exhibit similar clinicopathological characteristics, and patients with primary low- or intermediate-risk NMIBC who progress to MIBC/mBC often have a high-risk recurrence before progression. These results can inform research into NMIBC recurrences and surveillance schedules.

The authors have declared no competing interest.

SHV is supported by a grant from the Netherlands Organization for Scientific Research (NWO Vidi 91717334). The UroLife study was financially supported by Alpe dHuZes/Dutch Cancer Society (KUN 2013-5926) and Dutch Cancer Society (2017-2/11179).

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Ethics committee for Human Research of region Arnhem-Nijmegen gave ethical approval for this work

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