Association of Presalvage Radiotherapy PSA Levels After Prostatectomy With Outcomes of Long-term Antiandrogen Therapy in Men With Prostate Cancer

Abstract

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 PARTICIPANTSIn 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 MEASURESThe 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 Յ0.6 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 RELEVANCEThese 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 Յ0.6 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.

Outcome After 68Ga-PSMA-11 versus Choline PET-Based Salvage Radiotherapy in Patients with Biochemical Recurrence of Prostate Cancer: A Matched-Pair Analysis

“…However, it is worth mentioning that patients with no metastases on PET and favorable accompanying risk factors had high two- and three-year BRFS rates of >74% and >66%, respectively. A risk-adapted treatment approach regarding the initiation of ADT is in line with a secondary analysis of the multicenter Radiation Therapy Oncology Group (RTOG)9601 trial randomizing men to sRT with/without ADT [ 43 ]. In this analysis, pre-sRT PSA level was a prognostic biomarker for outcome after sRT with an overall survival benefit for the combination with ADT limited to patients with late sRT initiation with PSA level >0.6 ng/mL.…”

Simplified Predictive Nomogram for Postprostatectomy Patients Treated with High-dose Salvage Intensity Modulated Radiation Therapy

“…However, none of the clinical factors reached a signi cant level of association with MFS. In comparison, the survival bene t of 24-month bicalutamide from the subgroup analysis from the RTOG 9601 trial was not signi cant in patients with early salvage RT (PSA 0.6 ng/ml) 18 . Both studies emphasized the differential effects of ADT between the subgroups of patients undergoing salvage RT.…”

Simplified Predictive Nomogram for Postprostatectomy Patients Treated with High-dose Salvage Intensity Modulated Radiation Therapy

“…However, none of the clinical factors reached a signi cant level of association with MFS. In comparison, the survival bene t of 24-month bicalutamide from the subgroup analysis from the RTOG 9601 trial was not signi cant in patients with early salvage RT (PSA 0.6 ng/ml) 17 . Both studies emphasized the differential effects of ADT between the subgroups of patients undergoing salvage RT.…”