Impact of Variant Histology on Occult Nodal Metastasis after Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: A Review of the National Cancer Database.

Abstract

Up to 14% of bladder urothelial carcinoma has variant histology (VH), which is associated with a higher incidence of occult regional lymph node metastasis. Neoadjuvant chemotherapy (NAC) is the gold-standard for resectable cT2-4 disease as it achieves pathologic complete response (pCR) in select patients at the time of radical cystectomy (RC). A landmark trial demonstrated chemosensitivity and pT0 status in the setting of VH. pT0N+ pathology in patients undergoing subsequent RC has prompted concerns about post-chemotherapy bladder preservation. We investigate how VH impacts pathologic primary site and nodal downstaging post-NAC. We queried the National Cancer Database for cT2-4N0M0 patients who underwent NAC and RC between 2004 and 2016. These patients were stratified into pure urothelial cell carcinoma (UCC) and VH. The rate of downstaging to ≤pT1 was analyzed, along with pN+ status. Overall survival was analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards regression model. Multivariable models were adjusted for demographic and clinicopathologic variables. Of 5,335 patients, 92.1% were UCC and 7.9% VH. UCC was associated with better unadjusted survival and lower adjusted odds of being pN+ (aOR=0.60, P < .001). Squamous cell, glandular, and sarcomatoid histologies were significantly associated with decreased adjusted odds of any pT downstage. Neuroendocrine histology (NE) trended towards increased adjusted odds of downstage to pT0N0. Patients with VH were more likely to harbor occult regional lymph node metastasis in the setting of intravesical pCR. NE had the highest pT0N0 rate, with potential implications on post-NAC bladder preservation. These findings reinforce the role of RC after NAC especially for VH.