Use of elevated baseline IL-8, CCL-2, and TNFα to predict for shorter overall survival (OS) in men with metastatic prostate cancer initiating androgen-deprivation therapy (ADT).

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13 Background: Inflammation associated chemokines and cytokines have been shown in preclinical models to lead to the induction of castration resistance. We assessed whether higher blood cytokines and chemokines were associated with shorter time to CRPC and OS in patients initiating ADT for metastatic prostate cancer. Methods: A retrospective analysis of inflammatory markers including IL1β, IL-6, IL-8, TNFα and CCL-2 was undertaken in men initiating ADT for metastatic prostate cancer. Proteins were measured using multiplex electrochemiluminescence assays. The analytical cohort of 122 patients included a prospective trial (50 patients) and chart review (72 patients). A multivariate COX model was used to investigate the relationship between serum markers of inflammation and time to CRPC and OS. The covariates were age at time of ADT, ECOG score, race, baseline PSA, and extent of disease. Results: At time of initiating ADT, the median age of the cohort was 67 years, median PSA was 27.4, 82% had an ECOG PS of 0, 62% had extensive metastatic disease and 91% were Caucasian. Median OS was 42.2 months. The median (med) baseline levels for IL8 was 9.3pg/ml, TNFα was 2.4 pg/ml and CCL-2 was 507.5 pg/ml. As detailed below, patients with elevated IL-8, TNFα and CCL-2 had a significantly shorter OS and showed a non-significant shorter time to CRPC. Conclusions: In men with metastatic prostate cancer starting ADT, higher serum inflammatory markers are associated with poorer OS. This correlative data suggests that anti-inflammatory strategies which improved ADT efficacy in preclinical models may be relevant to the clinical setting. [Table: see text]