Impact of Persistent Hypogonadism on Overall Survival after Androgen Deprivation Therapy in Localized Prostate Cancer Patients: Long-Term Prospective Data

Purpose The impact of persistent hypogonadism post-androgen deprivation therapy (ADT) on overall survival (OS) of patients with prostate cancer (PCa) is poorly documented. We compared OS between patients who recovered testosterone and those who did not after ADT. Methods and Materials Patients with PCa with intermediate- or high-risk disease were treated with ADT for 6, 18, or 36 months plus radiation therapy in 2 randomized trials. We compared OS between patients who recovered testosterone to a normal level to those who did not, using the log rank test. Multivariable Cox analysis to predict OS included recovered testosterone, age, Zubrod performance, comorbidities, baseline prostate specific antigen, Gleason score, stage, and ADT duration. To avoid immortal time bias, we performed a landmark analysis for each cohort. Results The median follow-up was 16.6 years. Patients not recovering testosterone to a normal level were older, with more associated medical comorbidities. All the results are reported respectively for the 6-, 18-, and 36-month ADT cohorts. Testosterone recovery rates, to normal level, were 76.7%, 58.6%, and 45.3% with a median time to testosterone recovery of 1.64, 3, and 5 years, respectively. The 10-year OS rates were significantly higher in patients recovering testosterone: 77% versus 61%, P < .001; 73% versus 51%, P < .001; and 78% versus 62%, P < .001. However, multivariable analyses with landmark time points failed to show testosterone recovery as an independent predictor. The study is limited by its post hoc analysis. Conclusions In patients with PCa, our study shows that persistent hypogonadism post-ADT is associated with worse survival, particularly in older patients with medical conditions.