PATIENTS under active surveillance for prostate cancer with low testosterone levels are more likely to experience progression to grade group 3 or higher disease, a 2026 retrospective cohort study has found.
Active Surveillance
Active surveillance has become a widely accepted management strategy for patients with low-risk prostate cancer.
Identifying those most at risk of disease progression remains difficult, authors reported.
Previous research has evidenced that testosterone levels may be implicated in prostate cancer biology.
However, the role of testosterone levels in predicting disease progression during active surveillance is not well established, researchers noted.
Low Testosterone and Extreme Cancer Progression
They analysed nearly 1,000 men enrolled in an active surveillance programme between 2001 and 2024, with a median follow-up of nearly 4 years among those who did not progress.
The threshold for low testosterone was any result of less than 300 ng/dL, based on guideline recommendations.
Authors analysed patient progression to grade group 2 or ‘extreme’ progression to grade group 3 or higher disease.
Patients with baseline testosterone levels below 300 ng/dL were at greater risk of progression to grade group 3 or higher disease: ‘extreme’ progression.
Researchers did not, however, report an association between low testosterone and moderate cancer progression (grade group 2).
Limits of Analysis
The study only analysed a single cohort before MRI-based risk stratification, meaning that initial assessment of disease severity may have lacked precision.
Researchers also acknowledged that blood collection was not uniformly completed in the early morning, nor repeated upon hypogonadal level detection, as recommended by current guidelines.
They had no data regarding 5-alpha reductase inhibitor use – a drug that blocks 5-alpha reductase, preventing the conversion of testosterone into dihydrotestosterone.
Authors also defined ‘extreme’ progression as anything from grade group 3 or higher, rather than analysing grades 3–5 individually.
Minimal racial and ethnic variability limited any assessment of potential confounders, researchers reported.
Implications for Prostate Cancer Treatment
Findings suggest that low testosterone at the outset of active surveillance may serve as a prognostic marker for progression to more aggressive disease.
It follows that baseline testosterone measurement may provide valuable prognostic information in prostate cancer counselling for patients considering active surveillance.
Men with low testosterone may benefit from closer monitoring or earlier consideration of definitive treatment, authors concluded.
Reference
Lawen 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;DOI:10.1097/JU.0000000000004986.
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