Integration of serum androgens and Sex Hormone-Binding Globulin for optimized early detection of aggressive prostate cancer

BackgroundAggressive prostate cancer (PC) represents a significant health concern worldwide. Conventional initial screening methods, primarily based on prostate-specific antigen (PSA) levels, lack specificity, leading to a high rate of unnecessary biopsies and an urgent need for more accurate diagnostic tools. This study addresses the gap by exploring the potential of integrating clinical and routine blood laboratory parameters including a comprehensive hormone assessment to enhance the non-invasive prediction of aggressive PC. MethodsIn a pilot study of 578 patients who were scheduled for a prostate biopsy due to suspicion of PC, we analyzed an extensive panel of 28 laboratory values alongside data on family history, diet, and lifestyle. A logistic regression classifier was developed, and model performance was evaluated using repeated k-fold cross-validation on the complete dataset (n=282). Participants were histologically categorized into three risk groups: healthy, moderate PC (ISUP 1-2 PC), and aggressive PC (ISUP 3-5 PC). ResultsSignificant associations were found between PC aggressiveness and lower levels of androstenedione, Dehydroepiandrosterone-Sulfate (DHEA-S) and free PSA percentage, as well as higher levels of Sex Hormone Binding Globulin (SHBG). The integration of these serum markers with clinical parameters into a new multi-stage risk classifier for PC prediction significantly improved the predictive accuracy. The risk model outperformed PSA-only methods, demonstrating higher sensitivity and specificity in predicting aggressive PC. ConclusionsIncorporating serum markers DHEA-S, androstenedione, and SHBG into a novel risk classifier can improve early detection of aggressive PC. These widely available and cost-effective blood biomarkers could reduce reliance on invasive prostate biopsies and expensive magnetic resonance imaging by providing a more targeted approach to non-invasive prediction of aggressive PC following PSA testing. Our pilot study lays the groundwork for larger-scale research to further explore the integration of androgens and SHBG in future risk stratification models for improved clinical decision making.