Third-line Hormonal Therapy to Treat Prostate Cancer Relapse after Initial and Second-line Hormonal Therapy: Report of 52 Cases and Literature Review

The aim of this study was to evaluate the efficacy of third-line combined androgen blockade (CAB) therapyfor castration-resistant prostate cancer that relapsed after primary and second-line CAB. We retrospectivelyreviewed the medical records of 52 patients who received first-, second-, and third-line CAB therapy (medicalor surgical castration, plus steroidal antiandrogen of chlormadinone acetate, or nonsteroidal antiandrogen offlutamide or bicalutamide). For cumulative analysis, we searched the PubMed database and identified a totalof 50 cases published in English. Including our cases, this provided a total of 102 cases for analysis. In ourstudy cohort, 11 cases (21.2%) achieved more than 50% reduction of serum prostate-specific antigen (PSA) oninitiation of third-line CAB. We found that third-line CAB with nonsteroidal antiandrogen after second-line CABwith steroidal antiandrogen exhibited favorable results, with a positive response in six of 13 patients (46.2%).Cumulative analysis findings were comparable. Regarding the timing of third-line CAB administration, 15 patientshad started at a PSA equal to or less than 4.0 ng/ml, and eight of them (53.3%) showed a positive response totreatment, compared to only three of 37 patients (8.1%) whose PSA at the initiation of third-line therapy washigher than 4.0 ng/ml (p<0.001). We conclude that third-line CAB with nonsteroidal antiandrogen would beparticularly useful for patients whose cancer progressed after second-line CAB with steroidal antiandrogen.The timing of treatment seems to be important because the higher the PSA at the start of third-line therapy, thelower the PSA response rate.