SUN-129 - Treatment-Specific Prognostic Value of Serum Testosterone in Metastatic Castration-Resistant Prostate Cancer : A Stratified Meta-Analysis

Background
Androgen signaling is central to prostate cancer progression, making serum testosterone (ST) a potential prognostic biomarker in advanced disease. While higher ST has been associated with improved survival in metastatic castration-resistant prostate cancer (mCRPC), prior pooled analyses show marked heterogeneity, possibly due to differences in treatment mechanisms. Modern mCRPC therapy combines androgen deprivation therapy (ADT) with either androgen receptor-targeted agents (ARTA) or taxane chemotherapy (CTx), which act through different mechanisms and may modify the prognostic relevance of ST. We therefore conducted a treatment-stratified meta-analysis to evaluate the prognostic impact of baseline ST on survival across these therapeutic contexts.

Methods:
This meta-analysis followed PRISMA guidelines. PubMed, Embase, and Cochrane Library were searched for studies evaluating ST as a prognostic factor in mCRPC. Eligible studies reported multivariable-adjusted hazard ratios (aHRs) for overall survival (OS) and/or progression-free survival (PFS) in patients receiving ADT, with ST measured before or during treatment. ST was analyzed as a categorical variable as defined by primary study authors. Risk of bias was assessed using the Newcastle–Ottawa Scale. aHRs were pooled using a random-effects model in Review Manager v5.4.1. Heterogeneity was assessed using Chi² and I² statistics.

Results
Eleven studies were included. Among the ARTA-treated patients, higher ST levels were significantly associated with improved OS (HR 0.59, 95% CI 0.46-0.75; p < 0.0001), with low heterogeneity (I² = 17%), and PFS (HR 0.41, 95% CI 0.32-0.53; p < 0.00001), with no observed heterogeneity.
In contrast, no statistically significant associations were observed in CTx treated patients for either OS (HR 0.87, 95% CI 0.42-1.82; p = 0.71), with high heterogeneity (I² = 89%), or PFS (HR 1.78, 95% CI 0.83-3.84; p = 0.14), with moderate heterogeneity (I² = 58%).
In pooled analyses across all treatment groups, higher ST levels were associated with improved OS (HR 0.69, 95% CI 0.49-0.97; p = 0.03) and PFS (HR 0.57, 95% CI 0.36-0.89; p = 0.01), however, both analyses demonstrated high heterogeneity (OS: I² = 82%; PFS: I² = 74%). Subgroup analyses indicated that these overall effects were primarily driven by the ARTA-treated cohorts. A significant difference in the prognostic effect of ST on PFS was observed between treatment classes (p = 0.0004).

Conclusion:

This meta-analysis demonstrates that the prognostic significance of ST in mCRPC patients is treatment-dependent. Higher ST levels are associated with improved survival outcomes in ARTA-treated patients, whereas no significant associations are observed in CTx-treated patients. These findings support repositioning ST from a general prognostic marker to a treatment-specific biomarker in mCRPC.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*