The role of fPSA, [-2]proPSA and the Prostate Health Index for the early prediction of outcome in patients with metastatic castration resistant prostate cancer on therapy with abirateroneacetate.

Abstract

241 Background: Abiraterone acetate (AA) prolongs overall survival (OS) in pre- and post-chemotherapy setting in patients with metastatic castration resistant prostate cancer (mCRPC). Biomarkers to predict response to therapy are limited. Prostate-specific antigen (PSA) and lactate dehydrogenase (LDH) are commonly used as response-indicators but are often misleading during early therapy. Assays for circulating tumor cells, which can be surrogate for poor survival, are not routinely available at most places. In this retrospective study we evaluated the role of the PSA-derivatives free PSA (fPSA), [-2]proPSA (p2PSA) and the prostate health index (PHI) in addition to PSA as indicators of response during early AA-therapy. Methods: Twenty-five men with mCRPC receiving AA between March 2012 and July 2015 at the University Hospital of Muenster were included and analyzed. The PSA response rate (RR) was monitored according to PCWG2-criteria. Dynamic PSA-, fPSA-, p2PSA- and PHI-changes at 8-12 weeks under therapy were analyzed as predictors of progression free survival (PFS) and OS using Kaplan-Meier-analysis (KMA) and uni- and multivariate cox-regression analysis (UVA and MVA). Results: Twenty men were chemotherapy naïve, 5 pretreated with docetaxel. The PSA RR was 44%. In patients with < or ≥ 12 months of PFS the relative change of median PSA and fPSA at 8-12 weeks compared to baseline differed significantly (p = 0.022 and 0.030). For men with ≤ or > 15 months of OS there was a trend for a difference in relative change of median fPSA (p = 0.058). In KMA declining fPSA at 8-12 weeks was associated with a median OS of 32 months compared to 21 months in men with rising fPSA. In UVA rising PSA and fPSA were non-significant predictors of poor OS (Hazard ratio (HR) = 1.3 and 2.5 (p = 0.717 and 0.159)). In MVA PSA and fPSA were independent predictors of poor survival (HR 6.7 and 12.8 (p = 0.050 and 0.012)). Conclusions: fPSA is easily available and cheap. When added to PSA information, change of fPSA at 8-12 weeks of AA therapy may be a promising therapy control marker to help physicians to make decisions weather to stop or to continue AA therapy in men with mCRPC.