TY - JOUR
T1 - Histological Subtypes and Response to PD-1/PD-L1 Blockade in Advanced Urothelial Cancer
T2 - A Retrospective Study
AU - Miller, Natalie J.
AU - Khaki, Ali Raza
AU - Diamantopoulos, Leonidas N.
AU - Bilen, Mehmet A.
AU - Santos, Victor
AU - Agarwal, Neeraj
AU - Morales-Barrera, Rafael
AU - Devitt, Michael
AU - Nelson, Ariel
AU - Hoimes, Christopher J.
AU - Shreck, Evan
AU - Assi, Hussein
AU - Gartrell, Benjamin A.
AU - Sankin, Alex
AU - Rodriguez-Vida, Alejo
AU - Lythgoe, Mark
AU - Pinato, David J.
AU - Drakaki, Alexandra
AU - Joshi, Monika
AU - Isaacsson Velho, Pedro
AU - Hahn, Noah
AU - Liu, Sandy
AU - Alonso Buznego, Lucia
AU - Duran, Ignacio
AU - Moses, Marcus
AU - Jain, Jayanshu
AU - Murgic, Jure
AU - Barata, Pedro
AU - Tripathi, Abhishek
AU - Zakharia, Yousef
AU - Galsky, Matthew D.
AU - Sonpavde, Guru
AU - Yu, Evan Y.
AU - Lyman, Gary H.
AU - Grivas, Petros
N1 - Publisher Copyright:
© 2020 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Purpose:Urinary tract cancer can be pure urothelial carcinoma, pure nonurothelial carcinoma or variant urothelial carcinoma (defined here as mixed urothelial carcinoma). Little is known regarding outcomes for patients with variant urothelial carcinoma receiving immune checkpoint inhibitors. We hypothesized that variant urothelial carcinoma does not compromise immune checkpoint inhibitor efficacy in patients with advanced urothelial carcinoma.Materials and Methods:We performed a retrospective cohort study across 18 institutions. Demographic, clinicopathological, treatment and outcomes data were collected for patients with advanced urothelial carcinoma who received immune checkpoint inhibitors. Patients were divided into pure vs variant urothelial carcinoma subgroups, with variant urothelial carcinoma further divided by type of variant (ie squamous, neuroendocrine etc). We compared overall response rate using univariate and multivariate logistic regression and progression-free survival and overall survival using Kaplan-Meier and univariate and multivariate Cox proportional hazards.Results:Overall 519 patients were identified, with 395, 406 and 403 included in overall response rate, overall survival and progression-free survival analyses, respectively. Overall response rate to immune checkpoint inhibitors between patients with pure vs variant urothelial carcinoma was comparable (28% vs 29%, p=0.90) without significant differences for individual subtypes vs pure urothelial carcinoma. Median overall survival for patients with pure urothelial carcinoma was 11.0 months vs 10.1 months for variant urothelial carcinoma (p=0.60), but only 4.6 months for patients with neuroendocrine features (9 patients, HR 2.75, 95% CI 1.40-5.40 vs pure urothelial carcinoma, p=0.003). Median progression-free survival was 4.1 months for pure vs 5.2 months for variant urothelial carcinoma (p=0.43) and 3.7 months for neuroendocrine features (HR 1.87, 95% CI 0.92-3.79 vs pure urothelial carcinoma, p=0.09).Conclusions:Overall response rate to immune checkpoint inhibitors was comparable across histological types. However, overall survival was worse for patients with tumors containing neuroendocrine features. Variant urothelial carcinoma should not exclude patients from receiving immune checkpoint inhibitors.
AB - Purpose:Urinary tract cancer can be pure urothelial carcinoma, pure nonurothelial carcinoma or variant urothelial carcinoma (defined here as mixed urothelial carcinoma). Little is known regarding outcomes for patients with variant urothelial carcinoma receiving immune checkpoint inhibitors. We hypothesized that variant urothelial carcinoma does not compromise immune checkpoint inhibitor efficacy in patients with advanced urothelial carcinoma.Materials and Methods:We performed a retrospective cohort study across 18 institutions. Demographic, clinicopathological, treatment and outcomes data were collected for patients with advanced urothelial carcinoma who received immune checkpoint inhibitors. Patients were divided into pure vs variant urothelial carcinoma subgroups, with variant urothelial carcinoma further divided by type of variant (ie squamous, neuroendocrine etc). We compared overall response rate using univariate and multivariate logistic regression and progression-free survival and overall survival using Kaplan-Meier and univariate and multivariate Cox proportional hazards.Results:Overall 519 patients were identified, with 395, 406 and 403 included in overall response rate, overall survival and progression-free survival analyses, respectively. Overall response rate to immune checkpoint inhibitors between patients with pure vs variant urothelial carcinoma was comparable (28% vs 29%, p=0.90) without significant differences for individual subtypes vs pure urothelial carcinoma. Median overall survival for patients with pure urothelial carcinoma was 11.0 months vs 10.1 months for variant urothelial carcinoma (p=0.60), but only 4.6 months for patients with neuroendocrine features (9 patients, HR 2.75, 95% CI 1.40-5.40 vs pure urothelial carcinoma, p=0.003). Median progression-free survival was 4.1 months for pure vs 5.2 months for variant urothelial carcinoma (p=0.43) and 3.7 months for neuroendocrine features (HR 1.87, 95% CI 0.92-3.79 vs pure urothelial carcinoma, p=0.09).Conclusions:Overall response rate to immune checkpoint inhibitors was comparable across histological types. However, overall survival was worse for patients with tumors containing neuroendocrine features. Variant urothelial carcinoma should not exclude patients from receiving immune checkpoint inhibitors.
KW - bladder cancer
KW - carcinoma
KW - immunotherapy
KW - neuroendocrine tumors
KW - transitional cell
UR - http://www.scopus.com/inward/record.url?scp=85086346750&partnerID=8YFLogxK
U2 - 10.1097/JU.0000000000000761
DO - 10.1097/JU.0000000000000761
M3 - Article
SN - 0022-5347
VL - 204
SP - 63
EP - 69
JO - Journal of Urology
JF - Journal of Urology
IS - 1
ER -
