PROSTATE cancer (PCa) continues to be a significant health concern, particularly given the disparities observed in clinical trial representation. Men of Asian, Black, and Hispanic backgrounds have historically been underrepresented in PCa research, leading to limited validation of novel biomarkers across diverse cohorts. The Stockholm3 risk score, a comprehensive biomarker-based tool, was developed to address these gaps by assessing multiple genetic and clinical parameters. This study aimed to evaluate whether Stockholm3 could enhance prostate cancer detection in diverse populations.
The observational, prospective multicenter trial spanned 17 clinical sites from 2019–2023, supplemented by participants recruited from 2008–2020 in urology clinics. Men with suspected PCa underwent prostate biopsy, and prior to biopsy, blood samples were collected to measure the Stockholm3 risk score. Key parameters included prostate-specific antigen (PSA), free PSA, KLK2, GDF15, PSP94, genetic risk factors (single-nucleotide polymorphisms), age, family history, and previous negative biopsies. The primary endpoint focused on detecting International Society of Urological Pathology (ISUP) Grade ≥2 cancer, considered clinically significant PCa (csPC). The study aimed to demonstrate non-inferior sensitivity using Stockholm3 compared to PSA (noninferiority margin of 0.8 lower bound for the 95% CI), as well as superior specificity by reducing benign and low-grade cancer biopsies.
Results from the 2,129 participants (including Asian, Black, Hispanic, and White men) revealed that Stockholm3 demonstrated non-inferior sensitivity (relative sensitivity: 0.95 [95% CI, 0.92 to 0.99]) compared to PSA ≥4 ng/mL and significantly improved specificity (relative specificity: 2.91 [95% CI, 2.63 to 3.22]). These findings were consistent across racial and ethnic subgroups, with sensitivity ranging from 0.91 to 0.98 and specificity increasing from 2.51 to 4.70. Importantly, the use of Stockholm3 reduced unnecessary biopsies for benign or low-grade cancers by 45% overall, with reductions of 42–52% observed across different racial and ethnic groups.
This study suggests that Stockholm3 demonstrates significant potential to enhance prostate cancer detection in diverse populations while maintaining similar sensitivity to PSA. The reduction in unnecessary biopsies, particularly among Asian, Black, and Hispanic men, highlights the value of incorporating biomarker-based approaches to improve prostate cancer screening and reduce health disparities. Further prospective studies are needed to refine these tools and evaluate their long-term impact on patient outcomes.
Katie Wright, EMJ
Reference
Vigneswaran HT et al. Stockholm3 in a multiethnic cohort for prostate cancer detection (SEPTA): a prospective multicentered trial. J Clin Oncol. 2024;42(32):3806-16.
