Evaluating the therapeutic role of lymph node dissection in variant histology bladder cancer.

749 Background: Outcome benefit associated with lymph node dissection (LND) at time of radical cystectomy have been suggested in urothelial bladder cancer (BC), but have not been evaluated in variant subtype BC. Our objective was to characterize the impact of LND on survival outcomes across variant subtype BC. Methods: The National Cancer Database was queried for cases of variant histology bladder cancers using International Classification of Disease-O-3 morphologic codes managed with radical cystectomy between 2004 and 2020. Cases were stratified by variant subtype and LND status. Primary outcome was overall survival associated pathologic nodal status and receipt of LND. Kaplan Meier analysis and Cox proportional hazards analysis were performed for survival analyses. Results: A total of 30,911 patients with variant UC histology were included in our analysis. that were managed with radical cystectomy. Rates for the no-LND group (pNx) were 33.1% in the micropapillary subtype, 42.2% in sarcomatoid, 68.4% in squamous, 48.9% in adenocarcinoma, and 56.2% in the neuroendocrine subtype. Median OS was higher in those that received a nodal dissection for squamous (91.3 [89.9, 92.7] vs. 62.8 [60.1, 65.6] months p<0.001) and adenocarcinoma (83.6 [73.1, 92.1] vs. 56.3 [43.5, 69.0] months p=0.020). On Cox proportional hazards regression, in T1/2 stage disease LN dissection was associated improved OS for sarcomatoid (0.50 [0.23-0.96] p=0.048), squamous (0.67 (0.61-0.76) p<0.001), adenocarcinoma (0.45 [0.23-0.85) p=0.015), and neuroendocrine (0.425 [0.21-0.85) p=0.017) variant histologies. In T3/4 disease, nodal dissection was statistically significant improved OS only for squamous histology (0.68 [0.59-0.77] p<0.001 and 0.70 [0.59-0.83] p<0.001 respectively). The survival benefit of LND appears to be attenuated following receipt of NAC across most histologic subtypes including micropapillary and sarcomatoid histologies. Conclusions: Our data highlights the varying degrees of therapeutic benefit across variant BC. LND particularly in sarcomatoid, neuroendocrine, and adenocarcinoma VHBC is correlated with improved survival, particularly in low clinical stages. The benefit also appears to be attenuated with receipt of NAC. These data help inform a variant subtype-informed surgical approach.