The availability of multiple treatments for metastatic castration-resistant prostate cancer (mCRPC) mandates the need to identify prognostic factors applicable to clinical practice. Variations in (PSA) levels are widely used in the monitoring of response to treatment with abiraterone acetate (AA) or enzalutamide, but are not validated as an early biomarker for overall survival (OS). Objective: To evaluate the association between early PSA changes and OS following enzalutamide or AA treatments in mCRPC.
We retrospectively evaluated mCRPC patients treated with AA or enzalutamide, before or after docetaxel, in 11 reference hospitals between 2011 and 2017. A descriptive and multivariate analysis of the data was carried out in order to establish the association of PSA variations at 4 and 12 weeks (expressed as 30% and 50% percentage modifications, respectively, relative to baseline value at the start of AA or enzalutamide) with OS. Association with OS was analyzed using multivariate Cox regression and log-rank analyses. Spearman’s rho correlation coefficient (r) was calculated to evaluate the association between PSA changes at 4 and 12 weeks.
We analyzed 450 mCRPC patients with a median follow-up of 16 months (1-65). A 30% PSA decline at 4 weeks was associated with longer OS (30 vs 20 months; hazard ratio [HR] 0.55 (0.42-0.73), p < 0.001), as well as a 50% PSA decrease at 12 weeks (39 vs 19 months; HR 0.42 (0.31-0.56), p < 0.001). We found a detriment in survival in patients with a 30% PSA rise at 4 weeks, with shorter OS (22 vs 26 months; HR 1.5 (1.07-2.21), p = 0.025) and a 50% PSA increase at 12 weeks after starting treatment (14 vs 29 months; 2.66 (1.93-3.67) p < 0.001), in both univariate and multivariable models. The percentage PSA decline at 4 weeks was significantly correlated with the percentage PSA change at 12 weeks (r = 0.635; p < 0.001). Limitations include the retrospective design of this analysis.
PSA changes as early as 4 weeks after enzalutamide or AA initiation are highly associated with OS in mCPRC. Prospective multicentre validation studies are needed to confirm these findings.
Clinical trial identification
Legal entity responsible for the study
Fernando López Campos.
Has not received any funding.
All authors have declared no conflicts of interest.