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The FORMULA-509 trial randomized patients receiving salvage radiation between 6 months of GnRH agonist plus bicalutamide or 6 months of GnRH agonist plus AAP/Apa. Here we evaluate factors associated with testosterone recovery after trial treatment and the impact of testosterone recovery on patient-reported HRQoL. Testosterone was evaluated prior to treatment, at 3 months, at 6 months (end of systemic treatment), and at least every six months after treatment. Validated Expanded Prostate Cancer Index Composite (EPIC)-26 questionnaire was administered at baseline, end of treatment, and 1 year after completion of treatment. A change of 4 or more was considered a clinically meaningful change in the hormonal function domain. Log-rank test compared testosterone recovery between treatment groups. Wilcoxon rank sum and chi-square compared characteristics between those who did and did not recover testosterone. Multivariate logistic regression evaluated factors associated with lack of testosterone recovery. Chi-square evaluated frequency of clinically meaningful change in hormonal function. Three hundred forty-five patients were randomized (172 bicalutamide; 173 AAP/Apa). Median follow-up was 34 (6-53) months. There was no difference in testosterone recovery (>190 ng/dL) between treatment groups (p = 0.10). 52.6% [95% CI = 42.7-58.0] of patients recovered testosterone 6 months after treatment (bicalutamide: 51.2%; AAP/Apa 54.0%); 74.5% [69.8-79.2] 12 months (70.5%; 78.6%); 81.9% [77.7-86.1] 18 months (77.7%; 86.2%); and 88.8% [85.4-92.3] 30 months after treatment (85.8%; 91.9%). On univariate analysis, older age (median 67 vs 63 years; p<0.01), lower baseline testosterone (median 274 vs 379 ng/dL; p<0.01) and higher PSA at enrollment (median 0.3 vs 0.2; p = 0.02) were associated with lack of testosterone recovery 1 year after treatment. Race, Gleason score, and treatment arm were not associated with testosterone recovery. On multivariate analysis, age at enrollment, baseline testosterone, and PSA at enrollment remained significant (all p <0.05). In the subset of patients who completed EPIC-26 1 year after treatment (n = 219), those patients who did not have testosterone recovery were more likely to report a clinically meaningful decline in hormonal function relative to baseline than those who did achieve testosterone recovery, but it was not statistically significant (59% vs. 43% reporting clinically meaningful functional decline, p = 0.06). The addition of AAP/Apa did not lengthen time to testosterone recovery. Older men or those with lower baseline testosterone or higher PSA prior to treatment were less likely to recover testosterone 1 year after treatment. Patients who did not have testosterone recovery at 1 year were more likely to report decline in hormonal function. [ABSTRACT FROM AUTHOR]

The randomized FORMULA-509 trial demonstrated that for patients with a PSA > 0.5 after prostatectomy receiving salvage radiation and 6 months of GnRH Agonist, the addition of abiraterone acetate plus prednisone (AAP) and apalutamide (Apa) improved metastasis-free survival compared to bicalutamide. Here we present the patient-reported health-related quality of life (HRQoL) results through three years. Validated questionnaires were administered at baseline, end of treatment, and 1 and 3 years after completion of treatment. Patients completed Expanded Prostate Cancer Index Composite (EPIC)-26, PROMIS Fatigue, and Saint Louis University Mental Status Exam (SLUMS). EPIC-26 is scored from 0 to 100 with 100 indicating higher function. PROMIS Fatigue is scored using a standardized T score with higher score indicating greater fatigue. SLUMS is scored from 0 to 30 with 27 to 30 interpreted as normal, 21 to 26 as mild neurocognitive disorder and 20 or less as dementia. Scores between treatment arms were compared using the t-test. Results were interpreted using established thresholds for clinically meaningful differences (4-6 for EPIC-26 hormonal domain, 5-10 for PROMIS Fatigue). Three hundred forty-five patients were randomized (172 bicalutamide and 173 AAP/Apa). Completion rates at baseline, end of treatment, 1 year, and 3 years, were 96%, 80%, 70%, and 57% for EPIC-26; 95%, 79%, 67%, and 57% for PROMIS Fatigue; and 96%, 80%, 70%, and 34% for SLUMS. From baseline to end of treatment, both arms demonstrated clinically meaningful declines in EPIC-26 hormonal domain (median change -15 bicalutamide; -15 AAP/Apa) and increase in PROMIS Fatigue (median change 6 bicalutamide; 7.4 AAP/Apa). From end of treatment to 1 year after treatment patient-reported HRQoL improved to near baseline for both EPIC-26 hormonal function (bicalutamide median score baseline = 95, end = 75, 1 year = 90; AAP/Apa baseline = 95, end = 75, 1 year = 90) and fatigue (bicalutamide median score baseline = 43.1, end = 48.6, 1 year = 46.0; AAP/Apa baseline = 43.1, end = 51.0, 1 year = 46.0) with further improvement in EPIC-26 hormonal function at 3 years (bicalutamide = 95.0; AAP/Apa = 95.0) and stable fatigue at 3 years (bicalutamide = 46.0; AAP/Apa = 46.0). The cMedian SLUMS score was within normal range at baseline (27 bicalutamide; 27 AAP/Apa), end of treatment (28, 28) and 1 (27, 27) and 3 (27, 27) years after treatment. There was no difference in patient-reported hormonal function, fatigue, or mental status between treatment arms, at end of treatment (P = 0.40; P = 0.78; and P = 0.41, respectively), 1 year after treatment (P = 0.78; P = 0.89; and P = 0.76), and 3 years after treatment (P = 0.45; P = 0.95; and P = 0.86). The addition of AAP/Apa improved oncologic outcomes without causing a detectable difference in patient-reported hormonal function, fatigue, or mental status compared to bicalutamide through three years after treatment. [ABSTRACT FROM AUTHOR]