Testosterone Replacement Therapy in Men with Untreated or Treated Prostate Cancer: Do We Have Enough Evidences?

Abstract

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.

Krüppel-like factor 8 promotes aerobic glycolysis in prostate cancer cells by regulating AKT/mTOR signaling pathway

“…In recent years, the morbidity of PCa has increased [17]. In 2018, approximately 1,300,000 PCa cases were newly reported worldwide, accounting for 13.5% of the morbidity of malignant tumors in males, and approximately 360,000 deaths occurred, accounting for 6.7% of cancer mortality for male patients [18]. Patients are often in an advanced stage of PCa when they are diagnosed due to the lack of significant early symptoms [6].…”

Androgens, aging, and prostate health

“…To summarize, in hypogonadal men on AS for low stage/grade PC, the current body of evidence supporting TRT is restricted to a few small, retrospective observational studies. Taken together, these studies are not conclusive regarding the safe use of TRT in hypogonadal men on AS, as some studies reported high progression rates for patients on TRT during AS [ 147 ]. Prospective randomized clinical trials in this field are needed.…”

“…Also, for radiotherapy, the sparse data available does not show that the use of TRT increase the risk of worsen PC severity. In a recent systematic review of available literature [ 147 ], eight out of nine included studies showed that TRT-treated patients with PC treated by radiation therapy did not have an increased risk for disease progression. However, the overall quality of available evidence is poor and prospective controlled studies are lacking.…”

“…In the same systematic review, seven out of nine included studies indicated that TRT appears to be harmful for patients with advanced PC, although the quality of the included studies was poor [ 147 ]. Thus, despite the non-conclusive nature of the evidence, TRT should not be recommended for this patient group.…”

Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism

“…A recent systematic review of 36 studies, including 2459 testosterone‐treated patients found that testosterone treatment is not associated with increased risk of disease progression in prostate cancer 136 . The quality of studies included was poor though, with no level 1 evidence.…”