IMPACT OF VARIANT HISTOLOGY ON RESPONSE TO NEOADJUVANT CHEMOTHERAPY FOR UROTHELIAL BLADDER CANCER
Urothelial carcinoma comprises 90 percent of bladder cancers in the United States and can be further categorized as pure urothelial carcinoma (PUC) or variant histology. The addition of neoadjuvant chemotherapy (NAC) to cystectomy provides a survival benefit for PUC, however it is unclear if histologic variants receive the same benefit. Our primary objective was to assess the ability of NAC to downstage variants prior to radical cystectomy and secondary objective was to quantify variant subtype, extravesicular involvement, and overall survival (OS) for histologic variants.
Using our IRB approved, prospectively maintained bladder cancer database, we identified 1440 patients who underwent radical cystectomy with curative intent for urothelial carcinoma between 2003 and 2016. Clinical histology was identified at time of TURBT with final pathology following cystectomy. Multivariate Cox proportional hazards regression analysis was used to assess effect of variant histology on OS.
Of the 1440 patients, 1171 (81.3%) had PUC and 269 (18.7%) had variant histology. Variants were classified as squamous cell carcinoma 121 (44.9%), glandular 54 (20.0%), micropapillary 30 (11.2%), sarcomatoid 14 (5.2%), nested 10 (3.7%), clear cell 5 (1.9%), rhabdoid 3 (1.1%), and plasmacytoid 2 (0.7%). 28 (10.4%) patients had >1 variant. Specimens with variant histologic patterns had higher incidence of extravesicular involvement at time of clinical staging (20.8% vs 13.3%, p=0.003). 193 (16.5%) patients with PUC received NAC, of which 105 (54.4%) were downstaged. 69 (25.6%) patients with variant histology received NAC resulting in pathologic downstaging for 43 (62.3%). Variants were more likely to be downstaged in response to NAC compared to PUC (p<0.0001). Variant histology identified either during TURBT or cystectomy did not affect overall survival (HR=1.04, 95% CI (0.81-1.34), p=0.760; HR=0.79, 95% CI (0.61-1.02) p=0.070, respectively). </p>
Histologic variants compared to PUC are more likely to have extravesicular involvement at time of diagnosis and have a greater pathologic response to neoadjuvant chemotherapy. NAC should be offered to eligible patients regardless of the presence of histologic variants. Variant histology identified at either TURBT or radical cystectomy had no effect on overall survival.