Multicenter phase 3 trial of intensification of androgen blockade for high-risk biochemically relapsed castration-sensitive prostate cancer

Patients with biochemically recurrent prostate cancer (BRPC) after radical prostatectomy and a short PSA doubling time are at risk for distant metastases. Apalutamide and abiraterone acetate plus prednisone (AAP) prolong survival in the metastatic setting. The multicenter phase 3 PRESTO trial in the USA randomized BRCP patients with PSA doubling time ≤ 9 months 1:1:1 to androgen deprivation therapy (ADT; control group), ADT plus apalutamide, or ADT plus apalutamide plus AAP for 52 weeks. The PSA-PFS was significantly prolonged in both experimental groups compared to the control group (HR 0.52 and HR 0.48, respectively). Median time to testosterone recovery did not differ across the groups. The most common grade 3 or higher adverse events was hypertension (7.5%, 7.4%, and 18% in te groups with ADT, ADT + apalutamide, and ADT + apalutamide + AAP, respectively. The authors conclude that intensified androgen receptor blockade for a finite duration prolongs PSA-PFS with a manageable safety profile, without adversely affecting time to testosterone recovery.