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

A systematic review of 4067 screened studies identified 19 studies evaluating TRT in prostate cancer patients, comprising five in active surveillance, 10 post-radical prostatectomy, and six post-radiotherapy.

• Searches were conducted in Medline, EMBASE, PubMed, and Scopus following PRISMA guidelines.
• Studies were included if they assessed progression and biochemical recurrence in men with prostate cancer and testosterone deficiency receiving TRT.
• 4067 studies were identified in total, of which 19 met inclusion criteria.
• Pooled meta-analysis was not valid due to insufficient number of comparative studies and significant clinical and methodological heterogeneity.

Progression rates on active surveillance in TRT-exposed men ranged from 0% to 32% and did not differ significantly from non-exposed controls on retrospective comparison.

• Five studies assessed TRT in men on active surveillance.
• Follow-up in active surveillance studies was as long as 70 months.
• Progression rates did not differ significantly from non-exposed controls on retrospective comparison.
• The wide range of progression rates (0% to 32%) reflects the significant clinical and methodological heterogeneity across studies.

Biochemical recurrence rates in TRT-exposed cohorts were low following definitive treatment, ranging from 0% to 7% post-radical prostatectomy and 0% to 6% post-radiotherapy.

• Ten studies assessed TRT in men post-radical prostatectomy and six assessed TRT post-radiotherapy.
• Post-radiotherapy studies included patients who had received androgen deprivation therapy (±ADT).
• Follow-up for biochemical recurrence assessment was up to 60 months.
• Low biochemical recurrence rates were observed across both post-radical prostatectomy and post-radiotherapy cohorts.

The overall certainty of TRT oncological safety is limited by lack of long-term, prospective, controlled comparative data and lack of assessment of survival outcomes.

• No randomised controlled trial data were available to inform safe management of testosterone deficiency in prostate cancer.
• Survival outcomes were not assessed in the included studies.
• Significant clinical and methodological heterogeneity across studies precluded pooled meta-analysis.
• The authors note that diligent patient selection and monitoring are required until randomised controlled trial data are available.

The authors conclude that retrospective evidence supports cautious use of TRT in men with low-to-intermediate-risk disease on active surveillance and favourable localised disease post-radical prostatectomy or post-radiotherapy with appropriate PSA responses.

• Appropriate prostate-specific antigen responses were cited as a requirement for cautious TRT use.
• Diligent patient selection and monitoring were identified as requirements in the absence of randomised controlled trial data.
• Testosterone deficiency was noted to rise in prevalence with age and may be treatment-related in prostate cancer, contributing to poor health outcomes.
• The recommendation applies to patients with favourable localised disease following definitive treatment.