Oncological safety of testosterone replacement therapy in men with localised prostate cancer: a systematic review of observational studies

Objectives To evaluate the oncological safety of testosterone replacement therapy (TRT) in hypogonadal patients with prostate cancer, as testosterone deficiency (TD) rises in prevalence with age and in prostate cancer may be treatment‐related, whilst contributing to poor health outcomes. Patients and Methods Following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, Medline, EMBASE, PubMed, and Scopus were searched. Studies were included assessing progression and biochemical recurrence in men with prostate cancer and TD receiving TRT. Results Searches yielded 4067 studies, of which 19 were included: five in active surveillance, 10 post‐radical prostatectomy (RP), six post‐radiotherapy. Pooled meta‐analysis was not valid due to insufficient number of comparative studies and significant clinical and methodological heterogeneity. Progression rates on active surveillance ranged from 0% to 32% and did not differ significantly to non‐exposed controls on retrospective comparison at follow‐up as long as 70 months. Biochemical recurrence rates in TRT‐exposed cohorts were low post‐definitive treatment ranging from 0% to 7% post‐RP to 0–6% post‐radiotherapy (± androgen deprivation therapy) with up to 60 months of follow‐up. Overall certainty of TRT oncological safety is limited by lack of long‐term, prospective, controlled comparative data and lack of assessment of survival outcomes. Conclusions Retrospective evidence supports cautious use of TRT in low–intermediate‐risk disease on active surveillance and favourable localised disease post‐RP or post‐radiotherapy with appropriate prostate‐specific antigen responses. Diligent patient selection and monitoring are required until randomised controlled trial data are available to inform safe management of TD in prostate cancer.