Pathologic and Survival Outcomes Associated with Variant Histology Bladder Cancers Managed with Cystectomy with or Without Neoadjuvant Chemotherapy.

Although neoadjuvant chemotherapy (NAC) is associated with a survival advantage in pure urothelial (PUC) muscle-invasive bladder cancer (MIBC), the role of NAC is less clear in variant histology (VH) or urothelial carcinoma with divergent differentiation (UDD). We compared chemotherapy response and survival outcomes of patients with non-PUC histology who were managed with NAC followed by cystectomy compared to cystectomy alone.

We analyzed 768 patients with clinical MIBC (cT2-4N0M0) who were treated with cystectomy at a tertiary care center from 2007-2017. Patients were stratified by histology and treatment strategy. Adjusted logistic and Cox regression models were used to evaluate pathologic downstaging, cancer-specific survival (CSS), and overall survival (OS).

The cohort consisted of 410 (53%) patients with PUC, 185 (24%) with UDD, and 173 (23%) with VH. Overall, 314 (41%) patients received NAC prior to cystectomy. There were similar rates of complete (18-30%) and partial (37-46%) pathologic downstaging with NAC across all histologic subgroups (p = 0.30 and p = 0.40, respectively). However, while patients with PUC experienced an OS benefit (HR 0.71; 95% CI 0.51-0.98, p = 0.0013) and VH experienced a CSS benefit (HR 0.55; 95% CI 0.30-0.99, p = 0.0495) with NAC, patients with UDD did not experience OS or CSS survival benefits with the use of NAC prior to cystectomy.

In MIBC cases with non-PUC histology, patients with VH achieved nearly equivalent response rates and survival benefits with the use of NAC as patients with PUC, while patients with UDD experienced significantly worse survival outcomes regardless of the use of NAC prior to cystectomy.

The Journal of urology. 2020 Aug 12 [Epub ahead of print]

Ali Hajiran, Mounsif Azizi, Ahmet M Aydin, Logan Zemp, Charles C Peyton, Jasreman Dhillon, Samantha Nealon, Richard R Reich, Biwei Cao, Roger Li, Brandon J Manley, Wade J Sexton, Scott M Gilbert

Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida., Department of Pathology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida., Department of Biostatistics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.