Immune Modulation in Prostate Cancer Patients Treated with Androgen Receptor (AR)-Targeted Therapy

Vincenza Conteduca, Orazio Caffo, Emanuela Scarpi, Pierangela Sepe, Luca Galli, Lucia Fratino, Francesca Maines, Vincenzo Emanuele Chiuri, Matteo Santoni, Elisa Zanardi, Francesco Massari, Ilaria Toma, Cristian Lolli, Giuseppe Schepisi, Andrea Sbrana, Stefania Kinspergher, Maria Concetta Cursano, Chiara Casadei, Caterina Modonesi, Daniele SantiniGiuseppe Procopio, Ugo De Giorgi

Research output: Contribution to journalArticlepeer-review

Abstract

Androgen deprivation therapy (ADT) is a cornerstone of treatment for prostate cancer and, in recent years, androgen receptor (AR)-targeted therapies (abiraterone and enzalutamide) have both been used for the treatment of castration-resistant prostate cancer (CRPC). In our study, we sought to investigate the association between ADT and immune disorders, considering a potential role of androgens in the immune modulation. We retrospectively evaluated CRPC patients treated with abiraterone/enzalutamide between July 2011 and December 2018. We assessed the risk of developing immune alterations and their impact on outcome. We included 844 CRPC patients receiving AR-directed therapies, of whom 36 (4.3%) had autoimmune diseases and 47 (5.6%) second tumors as comorbidities. Median age was 70 years [interquartile range (IQR) = 63-75)]. We showed higher significant incidence of autoimmune diseases during their hormone sensitive status (p = 0.021) and the presence of autoimmune comorbidities before starting treatment with abiraterone/enzalutamide was significantly associated with worse overall survival (OS) (10.1 vs. 13.7 months, HR = 1.59, 95% CI 1.03-2.27, p = 0.038). In a multivariate analysis, the presence of autoimmune disorders was an independent predictor of OS (HR = 1.65, 95% CI 1.05-2.60, p = 0.031). In conclusion, CRPC patients with autoimmune alterations before starting AR-directed therapies may have worse prognosis. Further prospective studies are warranted to assess the role of immune modulation in the management of prostate cancer patients.

Original languageEnglish
JournalJournal of Clinical Medicine
Volume9
Issue number6
DOIs
Publication statusPublished - Jun 22 2020

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