Prognostic Role of Different T1 Substaging Systems on Recurrence and Progression in Non-muscle-invasive Bladder...

Different substaging methods have been proposed for risk stratification of T1 non-muscle-invasive bladder cancer; however, no consensus exists. This systematic review and meta-analysis evaluates the prognostic value of various T1 substaging systems.

A systematic literature search was conducted using the PubMed/Medline, Embase, Scopus, and Web of Science databases to identify reports published until January 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The primary outcomes were disease recurrence and progression. A subgroup analysis evaluated histoanatomical and micrometric substaging within the same population.

Fifty-seven studies met the inclusion criteria. Muscularis mucosae invasion was associated with progression (hazard ratio [HR]: 2.65, 95% confidence interval [CI]: 1.79-3.92, p < 0.001) but not with recurrence (HR: 1.19, 95% CI: 0.88-1.61, p = 0.3). Micrometric substaging (T1m/T1e, 0.5 mm cutoff) correlated with both recurrence (HR: 2.01, 95% CI: 1.53-2.64, p < 0.001) and progression (HR: 3.33, 95% CI: 2.47-4.49, p < 0.001). Considering the substaging systems applied to the same population, the pooled risk ratio (RR) for T1a versus T1b/c was 0.60 (95% CI: 0.45-0.80, p < 0.001), while the RR for T1m versus T1e was 0.39 (95% CI: 0.29-0.52, p < 0.001). The main limitation was heterogeneity in postsurgery management.

Histoanatomical substaging significantly associate with progression but not with recurrence. Micrometric substaging demonstrated an association with both recurrence and progression, potentially enhancing patient stratification. Rete Oncologica Lombarda substaging shows some promising results in stratifying patients. These results may support a global pathological consensus on the optimal T1 substaging system.