Testosterone replacement therapy in men on active surveillance for prostate cancer.

Background: While the use of testosterone replacement therapy (TRT) in men undergoing active surveillance (AS) for prostate cancer (PCa) has been historically contraindicated, recent studies have contributed to a paradigm shift to this approach.

Aim: To examine the impact of testosterone on prostate-specific antigen (PSA) levels and prostate biopsy progression in men with low testosterone on AS for PCa.

Methods: A retrospective single-center analysis was conducted on men undergoing AS for PCa who subsequently underwent TRT. Men previously treated for PCa were excluded. PSA and testosterone levels were recorded at regular intervals one year before and after the initiation of testosterone. ANOVA was used to analyze variance in PSA and testosterone levels, and paired t-tests and linear regression analysis were performed. Baseline and surveillance biopsies were documented.

Outcomes: The primary outcomes were changes in PSA levels and biopsy progression following initiation of testosterone therapy.

Results: Forty-three men met the inclusion criteria. Median (IQR) testosterone level before testosterone therapy was 272 (221.5-333.5) ng/dL and 578.5 (354.5-846.5) ng/dL after therapy (P < 0.01). No significant variation in mean PSA levels was observed (P = 0.87). Baseline biopsies were available for 27 patients, showing Gleason 3 + 3 = 6 in no more than three cores. Fifteen (55.6%) patients had one or more surveillance biopsies after starting testosterone therapy. Of these, 12 (80.0%) had no disease progression in biopsies over a mean of 44.3 months on testosterone. Three patients (20.0%) had a Gleason score 7 on biopsy after a mean of 79.5 months on testosterone therapy. No patients developed metastatic disease.

Clinical implications: Testosterone therapy did not result in statistically significant changes in PSA levels in men with low testosterone on AS. Pathology changes were inconclusive, but the available data showed no apparent increase in PCa progression or disease worsening in the cohort.

Strengths and limitations: The study's strengths include a longitudinal follow-up design and use of multiple statistical analyses. Limitations include the retrospective design, small sample size which may limit generalizability, and lack of control group.

Conclusion: No significant change in PSA level was observed after initiating testosterone therapy, despite an increase in testosterone levels. Despite limited biopsy data, our findings suggest similar rates of disease progression compared to the general AS population.