Adding 2 years of antiandrogen therapy to salvage radiation may harm men with low PSA after radical prostatectomy (RP), according to new research presented at the 61st Annual Meeting of the American Society for Radiation Oncology (ASTRO) in Chicago.
Daniel Spratt, MD, of the University of Michigan Rogel Cancer Center, and colleagues performed a secondary analysis of the NRG Oncology/RTOG 9601 double-blind, placebo-controlled, randomized, phase 3 trial (NCT00002874). In the original trial conducted 1998 to 2003, men with adverse pathology (positive surgical margin or pathologic T3 disease) and a PSA of 0.2 to 4.0 ng/mL after RP were randomly assigned to salvage radiation treatment (SRT) plus the nonsteroidal antiandrogen bicalutamide (150 mg/d) or placebo for 2 years.
In the new study, the 761 patients were stratified by entry PSA for analyses. Group 1, comprising 85% of the cohort, had PSA levels of 0.2 to 1.5 ng/mL, and group 2 had PSA levels of 1.6 to 4.0 ng/mL.
Group 2 experienced a significant 55% improvement in overall survival with bicalutamide as in the original trial, but group 1 had no significant benefit, Dr Spratt’s team reported. Specifically, men with post-operative PSA levels less than 0.6 ng/mL had nearly double the risk for other-cause mortality from bicalutamide, and men with PSA levels of 0.2 to 0.3 mg/mL had quadruple the risk. Furthermore, bicalutamide users with the lowest PSA values had greater likelihood of grade 3 to 5 cardiac events and neurological problems by nearly 4-fold.
“What we showed for the first time is that a patient’s PSA level is a predictive biomarker,” Dr Spratt stated in an ASTRO news release. “That is, you can use a patient’s PSA to better select which men should receive hormone therapy, and to predict who will benefit and who will not benefit from this treatment, and who may actually be harmed by it. We found that the lower the PSA, the more harm the patient experienced. The higher the PSA, the more likely the patient was to benefit from hormone therapy because it decreased their chances of dying from prostate cancer and resulted in improved overall survival rates.”
The ongoing NRG GU006 trial (NCT03371719) may identify which patients receiving early SRT will benefit from hormone therapy, the investigators added.
Spratt DE, Dess RT, Efstathiou JA, et al. Two years of anti-androgen treatment increases other-cause mortality in men receiving early salvage radiotherapy: A secondary analysis of the NRG Oncology/RTOG 9601 randomized phase III trial. Presented at the American Society for Radiation Oncology 2019 annual meeting held September 15 to 18 in Chicago. Abstract 2019. LBA1.
Long-term hormone therapy increases mortality risk for men with low PSA levels after prostate surgery [news release]. American Society for Radiation Oncology (ASTRO); September 26, 2019.
Shipley WU, Seiferheld W, Lukka H, et al. Report of NRG Oncology/RTOG 9601, A phase 3 trial in prostate cancer: Anti-androgen therapy (AAT) with bicalutamide during and after radiation therapy (RT) in patients following radical prostatectomy (RP) with pT2-3pN0 disease and an elevated PSA. Inl J Radiol Oncol. 2016;94:3.