Testosterone nadir and PSA recurrence-free survival in men with intermediate and high-risk localized prostate cancer undergoing definitive radiotherapy and androgen deprivation therapy.

Abstract

100 Background: There is limited data on the relationship between testosterone level during androgen deprivation and clinical outcomes of localized prostate cancer treated with hormone therapy and radiation therapy (RT). Here we investigate the association between testosterone nadir during androgen deprivation therapy and prostate-specific antigen (PSA) response and survival. Methods: Using a nationwide Veterans Affairs database, we identified 899 patients with intermediate- or high-risk localized prostate adenocarcinoma diagnosed between 2000 and 2015 and treated with gonadotropin-releasing hormone agonists and RT. All patients had total testosterone measurements while receiving hormone therapy and between 6 weeks and 6 months after the start of hormone therapy. Using univariable and multivariable models we examined the effect of testosterone nadir on 3-month post-treatment PSA, PSA recurrence-free survival, and prostate cancer-specific survival. Multivariable models included age at diagnosis, Gleason score, tumor stage, anti-androgen therapy, hormone therapy duration, comorbidity, BMI, and pre-treatment PSA. Results: Of the 899 patients with testosterone data, 481 patients had a testosterone nadir of < 20 ng/dL, 305 had a nadir between 20 and 49 ng/dL, and 113 had a nadir ≥50 ng/dL. Higher testosterone nadir was associated with higher 3-month post-treatment PSA on univariable (Spearman rho = 0.22, p < 0.001, n = 651) and multivariable (ß = 0.03, 95% CI 0.01-0.05, p = 0.004) analysis. In multivariable Cox regression, higher testosterone nadir was associated with an increased risk of PSA recurrence (hazard ratio [HR] 1.43 per 10-fold increase in testosterone nadir, 95% CI 1.07-1.90, p = 0.01, n = 715) but not prostate cancer-specific mortality (HR 1.45, 95% CI 0.87-2.42, p = 0.16, n = 891). Conclusions: Higher nadir testosterone levels in intermediate- or high-risk localized prostate cancer patients undergoing hormone therapy is associated with higher 3-month post-treatment PSA and inferior PSA recurrence-free survival, though there was no significant effect on prostate cancer-specific mortality.