2823 - Time to castration resistant prostate cancer (CRPC) and the risk of developing immune disorders

Background

Androgen deprivation therapy (ADT) is a cornerstone of treatment for prostate cancer, but limited studies have been performed to investigate the association between ADT and immune alterations, such as autoimmune diseases and risk of second tumours, considering that androgens may also play a role in the immune modulation.

Methods

We retrospectively evaluated patients (pts) treated with abiraterone (abi) and enzalutamide (enza) in 12 Italian Institutes between July 2011 and December 2018. In particular, we assessed the risk of systemic or single-organ autoimmune diseases [according to the International Classification of Diseases 10th Revision (ICD-10)] and second tumors, by performing a logistic regression analysis.

Results

We included 844 pts receiving abi/enza, whose 36 (4.3%) had diagnosis of autoimmune diseases at baseline [13 (1.5%) arthritis (rheumatoid or psoriatic), 12 (1.4%) autoimmune thyroiditis, 4 (0.5%) gastrointestinal autoimmune disease, 4 (0.5%) psoriasis, and 3 (0.4%) vasculitis] and 58 (6.9%) had second tumors (45 solid and 13 hematological). Median age was 70 years [interquartile range (IQR) 63-75]. Median duration of hormone sensitive of prostate cancer was 29 months (IQR 14-59), while median CRPC duration was 22 months (IQR 13-39). Most pts (N = 764, 90.5%) did ≤ 2 therapeutic lines, whose 477 (56.5%) and 367 (43.5%) were treated with abi and enza, respectively, and 359 (42.5%) were chemotherapy naive.

We observed a significant increase in the risk of autoimmune diseases and a trend for higher incidence of second tumors in pts showing a shorter time to CRPC [odd ratio (OR) 0.98 (95% CI 0.96-0.99) p = 0.01, and OR 0.99 (95% CI 0.98-1.01) p = 0.09, respectively], whereas no association was reported between CRPC duration and the incidence of immune disorders. Clinical outcome associated with abi/enza in CRPC was independent from pre-treatment presence of immune diseases, but a worse overall survival was observed from diagnosis of prostate cancer in pts developing autoimmune diseases (HR 1.69, 95% CI 1.10-2.61, p = 0.016) .

Conclusions

Time to CRPC may represent a risk factor of developing immune alterations with a negative prognostic role in the overall survival of prostate cancer pts. Further larger prospective studies are warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

V. Conteduca: Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Janssen-Cilag; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas. O. Caffo: Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen-Cilag; Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca. E. Zanardi: Advisory / Consultancy: Janssen. G. Procopio: Travel / Accommodation / Expenses: Bayer; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: BMS. U.F.F. De Giorgi: Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS. All other authors have declared no conflicts of interest.