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Updated: Jul 15, 2026
A New Technique for Treating Low-risk Prostate Cancer—Super Active Surveillance
Published on: November 7, 2025
Testosterone Replacement Therapy in Men With Prostate Cancer on Active Surveillance: A Systematic Review of
Mohammed Aly1, Nadeem Alshunaigat1, Yahia Habana2
1NHS Forth Valley, Larbert, UK.
Background:
Up to 20% of men on active surveillance (AS) for prostate cancer (PCa) have symptomatic hypogonadism; the oncological safety of testosterone replacement therapy (TRT) in this population is uncertain.
Objectives:
To systematically evaluate the oncological safety of TRT in men with histologically confirmed PCa managed by AS.
Materials And Methods:
PubMed, Embase, and CENTRAL were searched up to January 2026 (PRISMA 2020). Eligible studies enrolled men with PCa on AS receiving TRT for ≥ 12 months. Primary outcomes were biopsy progression, treatment conversion, metastasis, and PCa-specific mortality. Risk of bias was assessed using a modified Newcastle-Ottawa Scale.
Results:
Seven observational studies (2011-2025; 295 TRT-treated men; 6826 non-TRT AS comparators; follow-up 2.3-6.1 years) were included. No PCa-specific deaths or metastatic events were reported among TRT recipients. The single controlled biopsy comparison showed comparable Gleason upgrading (10.7% TRT vs. 9.4% comparators; p = 0.732) and no significant difference in biopsy progression (32.1% vs. 44.7%; p = 0.280). The largest population-based study reported lower treatment conversion versus non-TRT AS controls (16.8% vs. 21.9%; adjusted HR 0.66, 95% CI 0.46-0.97), most plausibly reflecting selection bias. PSA remained stable despite two- to threefold testosterone increases and correlated poorly with histological progression.
Discussion:
Short- to intermediate-term observational evidence does not demonstrate increased oncological risk with TRT in the predominantly low-risk populations studied. However, retrospective design, small samples, group imbalance, heterogeneous surveillance, and short follow-up relative to AS natural history substantially limit these findings.
Conclusion:
TRT may be cautiously considered in selected hypogonadal men on AS through shared decision-making; prospective studies with standardised surveillance and extended follow-up are required before broader recommendations.
Insights
Testosterone replacement therapy (TRT) in men with prostate cancer on active surveillance (AS) appears safe in the short term, showing no increased cancer progression. Cautious consideration for selected patients is advised pending further research.
Area of Science:
- Oncology
- Endocrinology
- Urology
Background:
- Symptomatic hypogonadism affects up to 20% of men on active surveillance (AS) for prostate cancer (PCa).
- The oncological safety of testosterone replacement therapy (TRT) in this patient group remains uncertain.
- Evaluating TRT's impact on PCa progression is crucial for managing hypogonadal men on AS.
Purpose of the Study:
- To systematically evaluate the oncological safety of TRT in men with histologically confirmed PCa managed by AS.
- To assess the risk of biopsy progression, treatment conversion, metastasis, and PCa-specific mortality in men receiving TRT while on AS.
- To synthesize current evidence on TRT's oncological outcomes in the context of AS for PCa.
Main Methods:
- Systematic literature search of PubMed, Embase, and CENTRAL up to January 2026.
- Inclusion criteria: men with PCa on AS receiving TRT for ≥ 12 months.
- Primary outcomes: biopsy progression, treatment conversion, metastasis, PCa-specific mortality; risk of bias assessed using a modified Newcastle-Ottawa Scale.
Main Results:
- Seven observational studies (295 TRT users, 6826 non-TRT comparators) were analyzed.
- No PCa-specific deaths or metastases were reported in TRT recipients.
- Comparable Gleason upgrading and no significant difference in biopsy progression between TRT and non-TRT groups; lower treatment conversion in TRT group (potentially due to selection bias).
Conclusions:
- Short- to intermediate-term observational data suggest no increased oncological risk with TRT in predominantly low-risk PCa populations on AS.
- Limitations include retrospective designs, small sample sizes, group imbalances, and heterogeneous surveillance protocols.
- TRT may be cautiously considered for selected hypogonadal men on AS via shared decision-making; prospective studies are needed.
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