Non-Conventional Histologic Components in Urothelial Carcinoma: Post-Neoadjuvant Chemotherapy Pathologic Outcomes in a Multi-institutional Radical Cystectomy Cohort

In urothelial carcinoma (UC), the presence of many form of divergent differentiation or histologic subtypes (henceforth collectively designated as UC with non-conventional components [UC-NCC]) negatively influences disease-specific clinical outcomes when compared to typical UC. Prior studies have suggested that UC-NCC may show lower rates of response to neoadjuvant chemotherapy (NAC), a factor that may partially explain their more aggressive course. However, data on post-NAC pathology outcomes in radical cystectomy (RC) are conflicting, and the influence of the number of UC-NCC on NAC response remains unknown. In this study, we evaluated the impact of UC-NCC on post-NAC RC outcomes, accounting for the number of UC-NCC components present within individual cases.

The pathology databases of the participating institutions were queried for post-NAC RCs. Those with pathology results available from the prior transurethral resection (TURBT) were selected for inclusion in the study. Cases were separated according to the presence or absence of UC-NCC in a pre-NAC TURBT showing muscle-invasive cancer. Those with UC-NCC were further stratified according to the number of UC-NCC present (1 versus 2 versus 3 or more). The following pathology outcomes were assessed on RCs: pathologic downstaging (

This multi-institutional cohort consisted of 206 patients: 92 with conventional UC, 73 with 1 UC-NCC, 30 with 2 UC-NCC, and 11 with 3 or more UC-NCC. The presence of UC-NCC was associated with lower rates of complete pathologic response (p=0.021) and downstaging (p=0.027), without significant differences in the rate of positive surgical margins. There was no correlation between the number of UC-NCCs and pathologic downstaging or complete response.

The presence of UC-NCC is associated with adverse pathologic outcomes following NAC and RC.