Low Testosterone Levels and Grade Group Progression Among Localized Prostate Cancer Patients on Active Surveillance: A Retrospective Cohort Study

PURPOSE: Active surveillance (AS) is an increasingly used strategy for managing localized prostate cancer, yet reliable biomarkers for predicting disease progression remain limited. Low testosterone has been associated with aggressive prostate cancer features at diagnosis, but its role in Grade Group (GG) progression during AS remains unclear. Our objective was to evaluate the association between baseline serum testosterone levels and GG progression in men undergoing AS for localized prostate cancer. MATERIALS AND METHODS: We conducted a retrospective cohort study of 924 men enrolled in an AS program between 2005 and 2024, with a median follow-up of 46.1 months among those who did not progress. Serum testosterone levels were categorized as low if they met a threshold of ≤ 300 ng/dL based on guideline recommendations. Primary outcomes were biopsy progression to GG2 or "extreme" progression to GG3 or higher disease. Multivariable Cox proportional hazards models were used to assess associations between testosterone levels and progression, adjusting for age, PSA density, and biopsy tumor volume. Potential clinically significant confounding by BMI, smoking status, and ethnicity was also considered. RESULTS: = .13). Findings were consistent when employing alternative cut points for testosterone and when considering other potential confounders. CONCLUSIONS: These findings suggest that while low testosterone is not clearly associated with moderate progression (GG2), it may increase the risk of higher-grade "extreme" progression to GG3 or higher. Future studies should focus on prospective validation of our findings to elucidate the biological relationship between androgens and prostate cancer progression.