MEN with low baseline testosterone undergoing active surveillance (AS) for localised prostate cancer may face a greater risk of developing higher-grade disease, according to a new retrospective cohort study.
Researchers evaluated 924 men enrolled in an AS programme between 2005 and 2024 to determine whether baseline serum testosterone levels were associated with Grade Group (GG) progression. While previous studies have linked low testosterone to aggressive prostate cancer at diagnosis, its impact during surveillance has remained uncertain.
Participants had a mean age of 63.6 years, with an average baseline testosterone level of 394 ng/dL. Approximately 29% of patients had testosterone levels ≤300 ng/dL, the threshold used to define low testosterone based on current guideline recommendations. Median follow-up among men who did not progress was 46.1 months.
Low Testosterone Linked to GG3 Progression
The primary outcomes were progression to GG2 disease and “extreme” progression to GG3 or higher. After adjusting for age, PSA density, and biopsy tumour volume, investigators found that low testosterone was significantly associated with an increased risk of progression to GG3 or higher disease. Men with testosterone levels ≤300 ng/dL had a 61% higher risk of extreme progression compared with those with higher testosterone levels.
In contrast, low testosterone was not significantly associated with progression to GG2 disease. Researchers noted that findings remained consistent when alternative testosterone cut-offs and additional confounding factors, including BMI, smoking status, and ethnicity, were considered.
Low Testosterone May Worsen Prostate Cancer
The authors suggested these findings may indicate a specific relationship between low testosterone and biologically aggressive disease progression, rather than more moderate tumour changes observed during AS. They also highlighted the need for prospective studies to validate the results and further explore the biological mechanisms linking androgen levels and prostate cancer progression.
As active surveillance becomes increasingly common in the management of localised prostate cancer, identifying biomarkers that can better predict disease progression remains a key clinical priority. The researchers propose that baseline testosterone assessment could potentially help identify patients at greater risk of developing higher-grade disease during surveillance.
Reference
Lawan T et al. Low Testosterone Levels and Grade Group Progression Among Localized Prostate Cancer Patients on Active Surveillance: A Retrospective Cohort Study. J Urol. 2026;215(6):679-87.
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