Stockholm3 in a Multiethnic Cohort for Prostate Cancer Detection (SEPTA): A Prospective Multicentered Trial

Area of Science:

• Urology
• Oncology
• Biomarker Discovery

Background:

• Prostate cancer (PCa) disproportionately affects Asian, Black, and Hispanic men, who are often underrepresented in clinical trials.
• Limited validation of novel PCa biomarkers in diverse patient cohorts hinders equitable advancements in diagnosis.

Purpose of the Study:

• To evaluate the efficacy of the Stockholm3 risk score in improving prostate cancer detection within a diverse patient population.
• To assess if Stockholm3 offers noninferior sensitivity and superior specificity for detecting clinically significant PCa (csPC) compared to Prostate-Specific Antigen (PSA).

Main Methods:

• An observational, prospective, multicentered clinical trial involving 2,129 men suspected of having PCa who underwent prostate biopsy.
• The Stockholm3 risk score, incorporating PSA, kallikrein, GDF15, PSP94, genetic risk, and clinical factors, was measured before biopsy.
• Primary endpoints focused on noninferior sensitivity and superior specificity in detecting ISUP Grade ≥2 cancer (csPC).

Main Results:

• Stockholm3 demonstrated noninferior sensitivity (0.95) and nearly threefold higher specificity (2.91) for detecting csPC compared to PSA (PSA ≥4 ng/mL).
• These findings were consistent across racial and ethnic subgroups, showing noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70).
• Utilizing Stockholm3 could reduce unnecessary benign or low-grade (ISUP 1) prostate biopsies by 45% overall and 42-52% across different racial and ethnic groups.

Conclusions:

• The Stockholm3 risk score effectively reduces unnecessary prostate biopsies in diverse populations.
• Stockholm3 maintains comparable sensitivity to PSA for detecting csPC while significantly improving specificity.
• This biomarker holds promise for more accurate and efficient prostate cancer diagnosis across diverse patient groups.