Prolonged hormonal therapy and external beam radiation independently increase the risk of Persistent Hypogonadism in men treated with prostate brachytherapy

Purpose: To identify variables that predict persistent hypogonadism and castration in patients with prostate cancer (PCa) treated with brachytherapy (BT). Materials and Methods: A retrospective analysis was performed on 1,053 patients receiving BT ± external beam radiation therapy (EBRT) ± hormone therapy (HT) for NCCN low, intermediate, or high-risk PCa between 1990 and 2011. Patients were categorized as not receiving HT (n = 438, 41.6%), ≤6 months (n = 317, 31.1%) or > 6 months (n = 298, 28.3%) of HT. 572 (54.3%) received BT alone, and 481 had combination therapy. The five- and 10-year freedom from persistent hypogonadism (T < 280 ng/dL) and castration (T < 50 ng/dL) for each group was evaluated with Kaplan-Meier estimates. Multivariable cox proportional hazards models were used to compare the risk of persistent hypogonadism and castration at a median followup of 6.5 years (posttreatment to final T) (IQR: 4.3–9.1 years; range: 1.0–19.2 years). Results: The 5-year freedom from hypogonadism rates were 92.4%, 88.9%, and 87.0% for patients with no HT, ≤ 6 months and >6 months of HT, respectively (10-year rates: 66.7%, 55.3%, 40.5%); p < 0.01. The 5-year freedom from castration rates were 99.2%, 98.0%, and 98.4%, respectively (10-year rates: 97.9%, 95.5%, 90.9%); p = 0.078. Number of months of HT (HR = 1.04, p = 0.030) and BT with EBRT vs. BT alone (HR = 1.56, p = 0.010) significantly increased the risk of persistent hypogonadism. Number of months of HT was the only variable which increased the risk of persistent castration (HR = 1.09, p = 0.014). Conclusions: The addition of EBRT to BT is an independent risk factor for persistent hypogonadism. Prolonged HT additionally increases the risk of persistent hypogonadism and castration.