Recurrence patterns in a large contemporary cohort of patients with non-muscle invasive bladder cancer

Background and ObjectivePatients 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. MethodsWe 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 LimitationsWe 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 ImplicationsOur 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. Patient SummaryOur research focused on the timing and characteristics of recurring tumours among patients with non-muscle invasive bladder cancer. We showed that a recurring tumour is often of a similar type as the previous tumour. We also found that for patients with initial low- or intermediate risk tumours, a progression to muscle-invasive bladder cancer is often preceded by a high risk recurrence. What does the study add?Existing literature extensively addresses the risk of first recurrence as clinical outcome, leaving the risk, timing and characteristics of subsequent recurrences relatively understudied. Our study addresses this gap by investigating patterns of subsequent recurrences in a large contemporary population-based cohort. We found that recurrence risk increases with number of prior recurrences, and subsequent tumours often manifest similar clinical characteristics within patients. Moreover, we discovered that over half of patients with primary low- or intermediate risk NMIBC who progress to muscle-invasive or metastatic disease experience a high risk recurrence before progression.