Subcastrate Testosterone Nadir and Clinical Outcomes in Intermediate- or High-Risk Localized Prostate Cancer

It is unclear if additional serum testosterone suppression below the castrate threshold of 50 ng/dL improves clinical outcomes in patients with localized prostate cancer undergoing definitive therapy.

We examined the association of subcastrate testosterone nadir with prostate-specific antigen (PSA) response and long-term clinical outcomes in 764 U.S. veterans with intermediate- or high-risk localized prostate cancer treated with androgen deprivation therapy and definitive radiation therapy from 2000 to 2015. Patients were categorized into testosterone nadir groups based on the minimum testosterone measurement during continuous gonadotropic-releasing hormone agonist therapy (<20 ng/dL vs 20-49 ng/dL). Outcomes included PSA response (3-month post-radiation therapy PSA and 2-year PSA nadir; multivariable linear regression) and long-term clinical outcomes (biochemical recurrence, metastasis, and prostate cancer-specific mortality; Fine-Gray competing risk regression).

A testosterone nadir of 20 to 49 ng/dL was associated with higher 3-month post-radiation therapy PSA compared to <20 ng/dL (ß = 0.16, 95% confidence interval [CI], 0.06-0.26, P = .001) and higher 2-year PSA nadir (ß = 0.12, 95% CI, 0.04-0.21, P = .005). Compared to the <20-ng/dL group, the 20 to 49-ng/dL group showed higher 10-year biochemical recurrence rates (28.1% vs 18.3%) and metastasis rates (12.9% vs 7.8%) persisting on multivariable analyses (biochemical recurrence: sub-distribution hazard ratio [SDHR], 1.62 for 20-49 ng/dL, 95% CI, 1.07-2.45, P = .02; metastasis: SDHR, 2.19, 95% CI, 1.21-3.94, P = .009). There was a trend toward inferior prostate cancer-specific mortality for the 20 to 49-ng/dL group (SDHR, 1.95, 95% CI, 0.90-4.22, P = .09).

Additional serum testosterone suppression below 50 ng/dL was associated with improved PSA responses and lower rates of biochemical recurrence and metastasis in this cohort of patients with localized prostate cancer.