Objective: To explore risk factors including prostate-specific antigen (PSA) kinetics for the prediction of castration-resistant prostate cancer (CRPC), and to build a practical model for predicting the progression to CRPC after androgen deprivation therapy (ADT) so as to facilitate clinicians in decision-making for prostate cancer patients receiving ADT.
Methods: A total of 185 patients with prostate cancer who had received ADT as the primary therapy in Department of Urology of Peking University First Hospital from 2003 to 2014 were enrolled retrospectively. All the patients were diagnosed with prostate cancer via prostate biopsy and followed up every four weeks from the initiation of ADT. All the patients received ADT with luteinizing hormone-releasing hormone agonists (LHRH-A) or surgical castration accompanied with an antiandrogen (bicalutamide or flutamide, combined androgen blockade). The clinical information of the patients were collected including age, clinical TNM stage, Gleason score (GS), risk groups of prostate cancer, PSA at the initiation of ADT, PSA nadir after ADT, PSA decline velocity, and the time to PSA nadir. The end point of this study was the diagnosis of CRPC, which was based on the European Association of Urology (EAU) Guideline 2016. Cox proportional hazards regression models were established to analyze and estimate their effects on the time of progression to CRPC.
Results: In this study, 185 patients with prostate cancer who had received ADT as the primary therapy were included. The mean age was (71.02±8.67) years. The median time to progression to CRPC in this cohort was 38 months (ranging from 4 to 158 months). On univariate analysis, we found clinical T stage, N stage, the metastasis state before ADT, risk groups of prostate cancer, PSA decline velocity, and PSA nadir were all related to the time to CRPC progression, P<0.01 for all the above variables. And on multivariate analysis, the presence of distant metastasis before ADT (HR=6.030, 95% CI: 3.229-11.263, P=0.001), higher PSA nadir (HR=1.185, 95% CI: 1.080-1.301, P=0.001), higher PSA decline velocity>11 μg/(L×month) (HR=2.124, 95% CI: 1.195-3.750, P=0.001), and time to PSA nadir ≤9 months (HR=3.623, 95% CI: 1.640-4.817, P=0.004) were found to be significantly associated with an increased risk of progression to CRPC.
Conclusion: Patients with rapid decreasing of PSA in the initial ADT were more likely to progress to CRPC.