Combination of Radiation Therapy and Short-Term Androgen Blockade With Abiraterone Acetate Plus Prednisone for Men With High- and Intermediate-Risk Localized Prostate Cancer.

Purpose: Long-term androgen-deprivation therapy (ADT) is the standard of care in combination with radiation therapy (RT) in high-risk prostate cancer (PC), despite substantial toxicity from the resulting hypogonadism. We hypothesized that a combination of more potent but shorter-term androgen inhibition in men with intermediate- or high-risk localized PC would synergize with definitive RT to provide short-term testosterone recovery and improve disease control.

Methods And Materials: This prospective phase 2 single-arm trial enrolled men with low-volume unfavorable intermediate or high-risk localized PC. Treatment included 6 months of ADT concurrent with abiraterone acetate plus prednisone (AAP) once daily and RT to prostate and seminal vesicles. The primary endpoint was the proportion of men with an undetectable prostate-specific antigen (PSA) at 12-months; secondary objectives included biochemical progression-free survival (PFS), testosterone recovery, toxicity, and sexual and hormonal quality of life.

Results: We enrolled 37 men between January 2014 and August 2016, 45% of whom were high risk. All patients had T1-2 disease and PSA < 20 ng/mL. Median follow-up is 37 months (95% confidence interval [CI], 35.7-39.1). Treatment noted 32% grade 3 toxicities related to AAP, predominantly hypertension, with no toxicities ≥G4. The rate of undetectable PSA at 12 months was 55% (95% CI, 36%-72%). With 46 months of median follow-up, 2 of 37 patients developed PSA progression (36-month PFS = 96%; 95% CI, 76%-99%), and 81% of patients recovered testosterone with a median time to recovery of 9.2 months. Hormonal or sexual function declined at 6 months with subsequent improvement by 24 months.

Conclusions: The combination of RT and 6 months of ADT and AAP demonstrated acceptable toxicity and a high rate of testosterone recovery with restoration of quality of life and excellent disease control in men with low-volume, intermediate- or high-risk localized prostate cancer. Prospective comparative studies are justified.