Histologic Subtypes and Response to PD-1/PD-L1 Blockade in Advanced Urothelial Cancer: A Retrospective Study.

Urinary tract cancer can be pure urothelial carcinoma (PUC), pure non-UC, or variant UC (VUC, defined here as mixed UC). Little is known regarding outcomes for patients with VUC receiving immune checkpoint inhibitors (ICI). We hypothesized that VUC does not compromise ICI efficacy in patients with advanced (a)UC.

We performed a retrospective cohort study across 18 institutions. Demographic, clinicopathologic, treatment and outcomes data were collected for patients with aUC who received ICI. Patients were divided into PUC vs. VUC; VUC further divided by type of variant (i.e. squamous, neuroendocrine, etc). We compared overall response rate (ORR) using univariate and multivariate logistic regression and progression free survival (PFS) and overall survival (OS) using Kaplan-Meier and univariate and multivariate Cox proportional hazards.

519 patients were identified; 395, 406 and 403 included in ORR, OS and PFS analyses, respectively. ORR to ICI between patients with PUC and VUC was comparable (28% vs. 29%, p=0.90) without significant differences for individual subtypes vs. PUC. Median OS for patients with PUC was 11.0 months vs. 10.1 months for VUC (p=0.60), but only 4.6 months for patients with neuroendocrine (NE) features (n=9; HR=2.75 [95% CI 1.40-5.40] vs. PUC; p=0.003). Median PFS was 4.1 months for PUC vs. 5.2 months for VUC (p=0.43) and 3.7 months for NE (HR=1.87 [95% CI 0.92-3.79] vs. PUC, p=0.09).

ORR to ICI was comparable across histologic types. However, OS was worse for patients with tumors containing NE features. VUC should not exclude patients from receiving ICI.

The Journal of urology. 2020 Jan 23 [Epub ahead of print]

Natalie J Miller, Ali Raza Khaki, Leonidas N Diamantopoulos, Mehmet A Bilen, Victor Santos, Neeraj Agarwal, Rafael Morales-Barrera, Michael Devitt, Ariel Nelson, Christopher J Hoimes, Evan Shreck, Hussein Assi, Benjamin A Gartrell, Alex Sankin, Alejo Rodriguez-Vida, Mark Lythgoe, David J Pinato, Alexandra Drakaki, Monika Joshi, Pedro Isaacsson Velho, Noah Hahn, Sandy Liu, Lucia Alonso Buznego, Ignacio Duran, Marcus Moses, Jayanshu Jain, Jure Murgic, Pedro Barata, Abhishek Tripathi, Yousef Zakharia, Matthew D Galsky, Guru Sonpavde, Evan Y Yu, Gary H Lyman, Petros Grivas

Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington., Winship Cancer Institute of Emory University, Atlanta, Georgia., Department of Medicine, University of Utah, Salt Lake City, Utah., Vall d´Hebron Institute of Oncology, Vall d´Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain., Division of Hematology/Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia., Division of Hematology/Oncology, Department of Medicine, Case Comprehensive Cancer Center, Cleveland, Ohio., Departments of Medical Oncology and Urology, Montefiore Medical Center, Bronx, New York., Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma., Medical Oncology Department, Hospital del Mar Research Institute, Barcelona, Spain., Division of Medicine, Imperial College London, London, UK., Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California., Division of Hematology/Oncology, Department of Medicine, Penn State Cancer Institute, Hershey, Pennsylvania., Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland., Hospital Universitario Marques de Valdecilla. IDIVAL. Santander, Spain., Department of Medicine and Oncology, Tulane University, New Orleans, Louisiana., Department of Medicine, University of Iowa, Iowa City, Iowa., Department of Oncology and Nuclear Medicine, University Hospital Center Sisters of Charity Zagreb School of Medicine, Zagreb, Croatia., Division of Oncology, Department of Medicine, University of Iowa, Iowa City, Iowa., Division of Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York., Genitourinary Oncology Program, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.