Testosterone replacement therapy in men with untreated or treated prostate cancer: Do we have enough evidences?

Purpose: To investigate the oncologic safety of testosterone replacement therapy (TRT) in men with untreated or treated prostate cancer. Materials and Methods: We systematically searched PubMed, Embase, and Cochrane library database from January 1941 to March 2019. Results: In total, 36 articles met the eligibility criteria for this systematic review. They included a total of 2,459 TRT-treated patients, with a median of 20 patients per study (range: 1-1,142). Except for four studies, all were single-armed studies with poor quality scores (median MINOR, 9 of 24). Of the 36 studies, prostate cancer was managed through active surveillance (AS), in 5 studies; radical prostatectomy, in 11 studies; radiation therapy, in 5 studies; multiple intervention modalities, in 5 studies; and systemic therapy, in 9 studies. In comparison with TRT-treated and untreated patients, the pooled risk ratio (RR) was not significantly higher than one in comparisons of risk for disease progression (pooled RR, 0.83; 95% confidence interval, 0.57-1.21). The results of systematic review implied that TRT might be harmful in men with advanced disease (progression rate: 38.5%-100.0%), who undergo AS (15.4%-57.1%), and who successfully treated but having high-risk disease (0.0%-50.0%). Conclusions: Compared to TRT-untreated patients, TRT-treated patients may not have increased risks for disease progression in prostate cancer. However, the quality of currently available evidence is extremely poor. TRT may be harmful in men with advanced disease burden, in those with untreated prostate cancer undergoing AS, and in those with successfully treated prostate cancer but having high-risk disease.