Morphologic alterations post trimodal therapy in muscle-invasive urothelial carcinoma: understanding the impact of post-treatment changes on the pathological interpretation and their potential clinical correlates.

While surveillance biopsies play a critical role in management of patients with muscle invasive bladder cancer (MIBC) treated with trimodal therapy (TMT), their assessment is often confounded by pronounced post-treatment changes. The aim of this study was to characterize these morphologic alterations and their clinical implications. A single-center retrospective analysis of surveillance transurethral resection of bladder tumor (TURBT) samples was undertaken, assessing for post-treatment morphologic changes in non-neoplastic and neoplastic tissue, as well as the correlation between these changes and cancer recurrence and cancer-specific survival. The cohort consisted of 73 patients with 56 males (76.7%), with a median age of 72 years and stage cT2 in 84.9%. The median follow-up was 28 months (4-207 months), with 34 patients (46.6%) dead during follow-up. A wide spectrum of morphologic characteristics was documented in all post-TMT TURBTs, with most common features including fibrosis (63.0%), inflammation (56.2%), and epithelial denudation (45.2%). Presence of fibrosis inversely correlated with cancer-specific death (n = 68, p = 0.027). Among the 18 cases with residual MIBC, 12 cases (66.7%) showed morphologic changes in the neoplastic cells that deviated from usual morphology of urothelial carcinoma. Presence of these changes was enriched in patients with subsequent disease recurrence (n = 18, p = 0.05). Secondary pathology review identified two cases (2.7%) with diagnostic discrepancy, both due to omission of in situ component. Post-treatment changes in post-TMT TURBTs must be recognized to avoid diagnostic misinterpretation and accurately guide patient management. Also, poor cellular preservation and severe cytologic changes in the residual carcinoma are not associated with a better prognosis.