The Response of Urothelial Cancer Variants to PD-1/PD-L1 Blockade - Expert Commentary

Some histologic variants of urothelial cancer (UC) are associated with an aggressive clinical course. Understanding whether these variants respond differently to immune checkpoint inhibitors compared to conventional UC.


A recent study published by Miller et al. in The Journal of Urology evaluated clinical outcomes in advanced UC patients with variants treated with immune checkpoint inhibitors. In this retrospective study, the investigators included 519 patients across 18 institutions. Patients were classified into pure urothelial carcinoma (PUC) or variant urothelial carcinoma (VUC) subgroups, including squamous, neuroendocrine, and glandular variants. After exclusions, the investigators included 395 patients for overall response rate analysis using univariate and multivariate logistic regression, 403 patients for progression-free survival rate, and 406 patients for overall survival (OS) analyses using the Kaplan-Meier method.

There was no significant difference in overall response rate to immune checkpoint inhibitors between PUC and VUC (28% vs. 29%, odds ratio (OR) 1.03, 95% confidence interval (CI) 0.64 -1.66, p=0.90) or between variants. OS was not significantly different between PUC and VUC (hazard ratio [HR] 1.07, 95% CI 0.82-1.41, p=0.60). OS was not significantly different between PUC and VUC (HR 1.07, 95% CI 0.82-1.41, p=0.60) but was significantly worse for patients with tumors containing neuroendocrine features.

The investigators conclude that UC variants should not exclude patients from receiving immune checkpoint inhibitors. Ongoing trials are prospectively testing immune checkpoint inhibitors combined with targeted agents in rare genitourinary cancers, including UC variants. 

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York

Reference:

  1. Miller, Natalie J., Ali Raza Khaki, Leonidas N. Diamantopoulos, Mehmet A. Bilen, Victor Santos, Neeraj Agarwal, Rafael Morales-Barrera et al. "Histological Subtypes and Response to PD-1/PD-L1 Blockade in Advanced Urothelial Cancer: A Retrospective Study." The Journal of Urology (2020): 10-1097.
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