Evaluating the Therapeutic Role of Lymph Node Dissection in Variant Subtype Bladder Cancer.

Background: The importance of lymph node dissection (LND) at the time of radical cystectomy for urothelial carcinoma (UC) is widely accepted despite known risks. The therapeutic benefits of LND for variant subtype bladder cancer (VBC), a heterogenous and distinct set of diseases, are not well established. We aim to characterize the impact of LND on overall survival across VBC subtypes.

Methods: The National Cancer Database was queried for all cases of variant subtype bladder cancer managed with radical cystectomy between 2004 and 2020, using the International Classification of Disease-O-3 morphological codes. The cases were stratified by receipt of individual variant subtypes. The primary outcome was overall survival associated with pathologic nodal status and receipt of nodal dissection. A Kaplan-Meier analysis and Cox proportional hazards analysis were used for survival analyses.

Results: A total of 30,911 patients with VBC that were managed with radical cystectomy were included in our analysis. The pNx rates ranged from 33.1% in the micropapillary subtype, 42.2% in the sarcomatoid subtype, 68.4% in the squamous subtype, 48.9% in the adenocarcinoma subtype, and 56.2% in the neuroendocrine subtype. The median OS was higher in those that received a nodal dissection across subtypes but was statistically significant only for the squamous (71.0 [68.0 vs. 74.0] vs. 37.2 [33.6 vs. 40.9] months < 0.001) and adenocarcinoma (45.9 [32.9 vs. 59.0] vs. 37.9 [28.6 vs. 47.1] months = 0.037) subtypes. Using Cox proportional hazards regression, LN dissection was associated with improved OS for the squamous (0.50 (0.44-0.58) < 0.001) and adenocarcinoma (0.65 [0.45-0.93) = 0.030) subtypes.

Conclusions: The role of LND across VBC subtypes is not clearly defined and warrants further investigation to develop a more risk-adaptive approach. We demonstrate heterogeneity with respect to the OS benefit associated with LND at the time of surgery. Among certain VBC subtypes, LND may not offer a significant therapeutic benefit, while LND in squamous and adenocarcinoma VBCs is correlated with improved survival.