Low Testosterone Linked to Higher-Grade Progression in Prostate Cancer Under Active Surveillance: Study
USA: A retrospective cohort study has found that low testosterone levels in patients with prostate cancer undergoing active surveillance were associated with a significantly higher risk of extreme disease progression to grade group 3 or higher. However, low testosterone was not significantly linked to moderate progression to grade group 2 disease. The findings suggest that incorporating testosterone levels into prognostic models may help improve patient selection and monitoring strategies.
The study, published in The Journal of Urology, was conducted by Tarek Lawen from the Department of Urology at The University of Texas MD Anderson Cancer Center and colleagues. Active surveillance is commonly used to manage men with localized prostate cancer, especially those with low-risk disease. However, predicting which patients may experience disease progression during surveillance remains a clinical challenge.
To explore whether testosterone levels could help predict disease progression, the researchers conducted a retrospective cohort study involving 924 men enrolled in an active surveillance program between 2001 and 2024. Among patients who did not experience progression, the median follow-up duration was 46.1 months. Baseline serum testosterone levels were measured and categorized as low when they were ≤300 ng/dL, in line with guideline recommendations.
The primary outcomes were progression detected on biopsy to grade group 2 disease or more severe progression to grade group 3 or higher. The researchers used multivariable Cox proportional hazards models to examine the association between testosterone levels and disease progression while adjusting for factors such as age, prostate-specific antigen (PSA) density, and biopsy tumor volume. Additional variables, including body mass index, smoking status, and ethnicity, were also considered.
The study led to the following findings:
- The mean age of the participants was 63.6 years.
- The average prostate-specific antigen density was 0.13 ng/mL².
- The mean baseline testosterone level was 394 ng/dL.
- Approximately 29.4% of the men had testosterone levels of 300 ng/dL or lower.
- Men with low testosterone levels had a significantly higher risk of progression to grade group 3 or higher disease.
- Low testosterone levels were not significantly associated with progression to grade group 2 disease.
- The findings remained consistent even when different testosterone cut-off values and additional potential confounding factors were taken into account.
The researchers noted that baseline testosterone measurement may offer useful prognostic information when assessing men for active surveillance. Patients with low testosterone levels may require closer monitoring or earlier consideration of definitive treatment.
However, the study had some limitations. It was conducted in a single cohort and included patients treated before the widespread adoption of MRI-based risk stratification, which may have influenced the accuracy of initial tumor grading. Additionally, testosterone measurements were not always obtained under standardized conditions.
Overall, the findings suggest that low testosterone may be associated with a greater risk of aggressive disease progression among men undergoing active surveillance for prostate cancer. Further prospective studies are needed to confirm these observations and better understand the relationship between testosterone levels and prostate cancer progression.
Reference:
Lawen T, Garcia RS, Smith MT, Pyo J, Higgason NM, Robert MJM, et al. Low Testosterone Levels and Grade Group Progression Among Localized Prostate Cancer Patients on Active Surveillance: A Retrospective Cohort Study. Journal of Urology [Internet]. [cited 2026 Mar 13];0(0). Available from: https://doi.org/10.1097/JU.0000000000004986
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