Association of Presalvage Radiotherapy PSA Levels After Prostatectomy With Outcomes of Long-term Antiandrogen Therapy in Men With Prostate Cancer. JAMA Oncol 2020 May 01;6(5):735-743
Date
03/28/2020Pubmed ID
32215583Pubmed Central ID
PMC7189892DOI
10.1001/jamaoncol.2020.0109Scopus ID
2-s2.0-85082524498 (requires institutional sign-in at Scopus site) 56 CitationsAbstract
IMPORTANCE: In men with recurrent prostate cancer, addition of long-term antiandrogen therapy to salvage radiotherapy (SRT) was associated with overall survival (OS) in the NRG/RTOG 9601 study. However, hormone therapy has associated morbidity, and there are no validated predictive biomarkers to identify which patients derive most benefit from treatment.
OBJECTIVE: To examine the role of pre-SRT prostate-specific antigen (PSA) levels to personalize hormone therapy use with SRT.
INTERVENTIONS: Men were randomized to SRT plus high-dose nonsteroidal antiandrogen (bicalutamide, 150 mg/d) or placebo for 2 years.
DESIGN, SETTING, AND PARTICIPANTS: In this secondary analysis of the multicenter RTOG 9601 double-blind, placebo-controlled randomized clinical trial conducted from 1998 to 2003 by a multinational cooperative group, men with a positive surgical margin or pathologic T3 disease after radical prostatectomy with pre-SRT PSA of 0.2 to 4.0 ng/mL were included. Analysis was performed between March 4, 2019, and December 20, 2019.
MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival (OS). Secondary end points included distant metastasis (DM), other-cause mortality (OCM), and grades 3 to 5 cardiac and neurologic toxic effects. Subgroup analyses were performed using the protocol-specified PSA stratification variable (1.5 ng/mL) and additional PSA cut points, including test for interaction. Competing risk analyses were performed for DM and other-cause mortality (OCM).
RESULTS: Overall, 760 men with PSA elevation after radical prostatectomy for prostate cancer were included. The median (range) age of particpants was 65 (40-83) years. Antiandrogen assignment was associated with an OS benefit in the PSA stratum greater than 1.5 ng/mL (n = 118) with a 25% 12-year absolute benefit (hazard ratio [HR], 0.45; 95% CI, 0.25-0.81), but not in the PSA of 1.5 ng/mL or less stratum (n = 642) (1% 12-year absolute difference; HR, 0.87; 95% CI, 0.66-1.16). In a subanalysis of men with PSA of 0.61 to 1.5 (n = 253), there was an OS benefit associated with antiandrogen assignment (HR, 0.61; 95% CI, 0.39-0.94). In those receiving early SRT (PSA ≤0.6 ng/mL, n = 389), there was no improvement in OS (HR, 1.16; 95% CI, 0.79-1.70), an increased OCM hazard (subdistribution HR, 1.94; 95% CI, 1.17-3.20; P = .01), and an increased odds of late grades 3 to 5 cardiac and neurologic toxic effects (odds ratio, 3.57; 95% CI, 1.09-15.97; P = .05).
CONCLUSIONS AND RELEVANCE: These results suggest that pre-SRT PSA level may be a prognostic biomarker for outcomes of antiandrogen treatment with SRT. In patients receiving late SRT (PSA >0.6 ng/mL, hormone therapy was associated with improved outcomes. In men receiving early SRT (PSA ≤0.6 ng/mL), long-term antiandrogen treatment was not associated with improved OS. Future randomized clinical trials are needed to determine hormonal therapy benefit in this population.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00002874.
Author List
Dess RT, Sun Y, Jackson WC, Jairath NK, Kishan AU, Wallington DG, Mahal BA, Stish BJ, Zumsteg ZS, Den RB, Hall WA, Gharzai LA, Jaworski EM, Reichert ZR, Morgan TM, Mehra R, Schaeffer EM, Sartor O, Nguyen PL, Lee WR, Rosenthal SA, Michalski JM, Schipper MJ, Dignam JJ, Pisansky TM, Zietman AL, Sandler HM, Efstathiou JA, Feng FY, Shipley WU, Spratt DEAuthor
William Adrian Hall MD Professor in the Radiation Oncology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Aged, 80 and over
Androgen Antagonists
Double-Blind Method
Humans
Male
Middle Aged
Prostate-Specific Antigen
Prostatectomy
Prostatic Neoplasms
Salvage Therapy
Treatment Outcome
