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Predicting Recurrence and Progression in Patients with Non-Muscle-Invasive Bladder Cancer: Systematic Review on the Performance of Risk Stratification Models

BACKGROUND: Several classifications have been reported to stratify non-muscle-invasive bladder cancer (NMIBC) in risk groups according to the probability of recurrence and progression. OBJECTIVE: To systematically review the current evidence regarding risk stratification of NMIBC. METHODS: The systematic review was performed in accordance with the PRISMA statement. Studies providing data on development and/or external validation cohorts of models and risk stratification tables for recurrence and/or progression for patients with NMIBC, reporting at least one discrimination measure (AUC or C-Index) were included. RESULTS: Twenty-five studies involving 22,737 patients were included. Six classifications were identified, three of them were predictive models (EORTC, CUETO, EAU 2021) and three were based on expert opinion (EAU 2020, AUA, NCCN). A high risk of bias was present in the majority of the studies. Certain heterogenicity was found among the studies regarding adjuvant therapy, postoperative instillation or second resection. The definition of oncological outcomes was not standardized in the included studies. CUETO and EORTC scoring systems are the most validated. In general, validations showed a poor discrimination capability to predict recurrence, slightly better for progression. The EAU 2021 model overestimates the risk of progression in patients treated with BCG. Carcinoma in situ is underrepresented in all the studies analyzed. CONCLUSIONS: The existing classifications show poor discrimination capability for recurrence and possibly helpful discrimination capability for progression in NMIBC patients. These results highlight the unmet need to develop novel accurate risk models for patients with NMIBC, which could be improved with the combination of clinicopathological and molecular information.