The value and limitations of urothelial bladder carcinoma molecular classifications to predict oncological outcomes and cancer treatment response: A systematic review and meta-analysis

Aim: To evaluate the predictive value of molecular subtypes on oncological outcomes and response to cancer treatment in patients with urothelial bladder carcinoma (UBC). Materials and Methods: A literature search using PubMed, Scopus, and Cochrane Library was conducted on April 2020 to identify relevant studies according to the preferred reporting items for systematic review and meta-analysis guidelines. The pooled overall survival (OS), cancer-specific survival (CSS), and progression-free survival were calculated using a fixed or random effects model. Results: We identified 66 studies (including 21,447 molecular subtype records) evaluating the impact of molecular classification on oncologic outcomes in patients with UBC. We found significant association of different molecular subtypes with OS, CSS, progression-free survival, recurrence-free survival, and response to treatment. Totally, 11 studies were included in the meta-analysis. Basal group and NE-like subtypes were associated with worse OS (pooled HR: 1.78, 95%CI: 1.49–2.12, and pooled HR: 2.67, 95%CI: 1.08–6.60, respectively) in patients with muscle invasive bladder cancer. Luminal group was also associated with worse CSS (pooled HR of 3.67, 95%CI: 2.19–6.14). Conclusions: Based on these data, UBC molecular classifications are significant predictors of oncological outcomes and identify patients who are most likely to benefit from intensified or different therapies. The optimal consensus on molecular classification remains to be verified in well-designed prospective studies to allow precise prognostic and predictive value assessment.