Asian, Black, and Hispanic men are underrepresented in prostate cancer (PCa) clinical trials. Few novel prostate cancer biomarkers have been validated in diverse cohorts. We aimed to determine if Stockholm3 can improve prostate cancer detection in a diverse cohort.
An observational prospective multicentered (17 sites) clinical trial (2019-2023), supplemented by prospectively recruited participants (2008-2020) in a urology clinic setting included men with suspicion of PCa and underwent prostate biopsy. Before biopsy, sample was collected for measurement of the Stockholm3 risk score. Parameters include prostate-specific antigen (PSA), free PSA, KLK2, GDF15, PSP94, germline risk (single-nucleotide polymorphisms), age, family history, and previous negative biopsy. The primary endpoint was detection of International Society of Urological Pathology (ISUP) Grade ≥2 cancer (clinically significant PCa, csPC). The two primary aims were to (1) demonstrate noninferior sensitivity (0.8 lower bound 95% CI noninferiority margin) in detecting csPC using Stockholm3 compared with PSA (relative sensitivity) and (2) demonstrate superior specificity by reducing biopsies with benign results or low-grade cancers (relative specificity).
A total of 2,129 biopsied participants were included: Asian (16%, 350), Black or African American (Black; 24%, 505), Hispanic or Latino and White (Hispanic; 14%, 305), and non-Hispanic or non-Latino and White (White; 46%, 969). Overall, Stockholm3 showed noninferior sensitivity compared with PSA ≥4 ng/mL (relative sensitivity: 0.95 [95% CI, 0.92 to 0.99]) and nearly three times higher specificity (relative specificity: 2.91 [95% CI, 2.63 to 3.22]). Results were consistent across racial and ethnic subgroups: noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70). Compared with PSA, Stockholm3 could reduce benign and ISUP 1 biopsies by 45% overall and between 42% and 52% across racial and ethnic subgroups.
In a substantially diverse population, Stockholm3 significantly reduces unnecessary prostate biopsies while maintaining a similar sensitivity to PSA in detecting csPC.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2024 Jul 22 [Epub ahead of print]
Hari T Vigneswaran, Martin Eklund, Andrea Discacciati, Tobias Nordström, Rebecca A Hubbard, Nathan Perlis, Michael R Abern, Daniel M Moreira, Scott Eggener, Paul Yonover, Alexander K Chow, Kara Watts, Michael A Liss, Gregory R Thoreson, Andre L Abreu, Geoffrey A Sonn, Thorgerdur Palsdottir, Anna Plym, Fredrik Wiklund, Henrik Grönberg, Adam B Murphy, SEPTA STHLM3 Study Group
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Department of Biostatistics, Epidemiology & Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Department of Surgery, University of Toronto, University Health Network, Toronto, Canada., Department of Urology, University of Illinois at Chicago, Chicago, IL., Department of Surgery, University of Chicago, Chicago, IL., Uropartners, LLC, Westchester, IL., Department of Urology, Rush University Medical Center, Chicago, IL., Department of Urology, Montefiore Medical Center, Bronx, NY., Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX., Urology Clinics of North Texas, Dallas, TX., Institute of Urology, University of Southern California Keck School of Medicine Los Angeles, CA., Department of Urology, Stanford University School of Medicine, Palo Alto, CA., Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL.