Low-Cost Pathology Signals for Risk Stratification in High-Risk Non-Muscle-Invasive Bladder Cancer: A Narrative...

T1 high-grade (T1HG) urothelial carcinoma of the bladder presents a persistent clinical challenge: despite uniform high-risk classification under EAU guidelines, BCG failure and disease progression rates range from 10% to 40% across published series. Standard clinicopathological variables do not adequately explain this heterogeneity. Three pathological parameters evaluable from routine TURBT specimens-T1 substaging by lamina propria invasion depth, tumour budding at the invasion front, and E-cadherin (CDH1) immunohistochemistry-share a common mechanistic basis in CDH1-driven partial epithelial-to-mesenchymal transition and may refine escalation-oriented risk stratification without requiring additional tissue or molecular testing. We conducted a narrative critical review of PubMed/MEDLINE (January 2000-February 2026; 28 included studies) to evaluate the quantitative evidence for each parameter, with emphasis on reproducibility and BCG-specific outcome data. T1 substaging carries the strongest evidence: pooled progression HR 3.29 (95% CI 2.39-4.51) across 36 studies (n = 6781), with BCG failure of 41% vs. 21% in a centralised BCG-treated registry cohort of 264 patients on multivariable analysis. Tumour budding shows consistent adverse associations in BCG-treated pT1 NMIBC; zero progression was observed in the low-budding subgroup in the only available BCG-specific full-text cohort. CDH1 IHC is directionally supportive but limited by scoring heterogeneity (I² = 63%). All three parameters are mechanistically coherent and assessable from routine TURBT slides. Prospective validation with pre-specified thresholds and standardised scoring protocols is required before clinical implementation can be recommended.