The following abstract is drawn from a recently published paper in Annals of Internal Medicine. We invite you to read the full paper and join the conversation, become a member of the Pathology News community to share your thoughts, ask questions, and engage with others around this work.

Authors: Thorgerdur Palsdottir, PhD, Chiara Micoli, MSc, Martin Eklund, PhD, Henrik Grönberg, MD, PhD, Fredrik Jäderling, MD, PhD, Derya Tilki, MD, Daniel W. Lin, MD, Matthew R. Cooperberg, MD, MPH, Scott E. Eggener, MD, Kevin C. Oeffinger, MD, Tobias Nordström, MD, PhD and Hari T. Vigneswaran, MD

Abstract

Background:
Prostate-specific antigen (PSA) testing to screen for prostate cancer is controversial. An alternative approach, Stockholm3, combines PSA, plasma protein biomarkers, polygenic risk, and clinical factors into a multivariable risk score.

Objective:
To compare detection of clinically significant prostate cancer (csPC) using PSA and Stockholm3 in a population-based screening with short-term follow-up.

Design:
Secondary analysis of the baseline round of the prospective STHLM3-MRI (Prostate Cancer Screening Using a Combination of Risk-Prediction, MRI, and Targeted Prostate Biopsies) randomized screening trial in men aged 50 to 74 years who had PSA and Stockholm3 screening. Men with abnormal screening tests (PSA ≥3 ng/mL or Stockholm3 ≥11) were randomly assigned (2:3) to systematic biopsy or magnetic resonance imaging with systematic and targeted biopsies for lesions with a Prostate Imaging Reporting and Data System score of 3 or greater. Cancer diagnosed within 2 years was identified through linkage to the Swedish National Cancer Register; cancer after a negative baseline test was classified as false negative. (ClinicalTrials.gov: NCT03377881)

Setting:
Stockholm region, Sweden, 2018 to 2020.

Participants:
Men aged 50 to 74 years who had PSA and Stockholm3 screening.

Intervention:
Prostate-specific antigen and Stockholm3 tests at baseline.

Measurements:
Clinically significant prostate cancer (grade group ≥2) within 2 years of baseline.

Results:
Among 12 670 men, 443 (3.5%) were diagnosed with csPC. Decision curve analysis showed higher net benefit for Stockholm3 versus PSA across a range of decision thresholds for biopsy, indicating fewer unnecessary biopsies and fewer missed csPC cases. Stockholm3 (≥11) had a false-negative rate of 10% (43 of 443) and a false-positive rate of 11% (1289 of 12 227), whereas PSA (≥3 ng/mL) had a false-negative rate of 26% (116 of 443) and a false-positive rate of 10% (1203 of 12 227). Correspondingly, sensitivity was 90% (95% CI, 87% to 93%) for Stockholm3 and 74% (CI, 69% to 78%) for PSA, with similar specificity (89% vs. 90%).

Limitations:
Participation was approximately 25% of invited men; follow-up was limited to 2 years; and the cohort was predominantly Swedish or European, which may limit generalizability.

Conclusion:
In this screening cohort with short-term follow-up, Stockholm3 provided greater clinical net benefit than PSA for detecting csPC, driven by fewer false-negative results, although follow-up was limited to 2 years.

Read the full article: Stockholm3–Magnetic Resonance Imaging Population-Based Prostate Cancer Screening Study: Two-Year Follow-up | Annals of Internal Medicine

Thorgerdur Palsdottir, PhD
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (T.P., C.M., M.E., H.T.V.)

Chiara Micoli, MSc
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (T.P., C.M., M.E., H.T.V.)

Martin Eklund, PhD
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (T.P., C.M., M.E., H.T.V.)

Henrik Grönberg, MD, PhD
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, and Department of Surgery, Capio S:t Göran’s Hospital, Stockholm, Sweden (H.G.)

Fredrik Jäderling, MD, PhD
Department of Diagnostic Radiology, Capio S:t Göran‘s Hospital, and Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden (F.J.)

Derya Tilki, MD
Martini-Klinik Prostate Cancer Center and Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; and Department of Urology, Koc University Hospital, Istanbul, Türkiye (D.T.)

Daniel W. Lin, MD
Department of Urology, University of Washington Medical Center and Fred Hutchinson Cancer Center, Seattle, Washington (D.W.L.)

Matthew R. Cooperberg, MD, MPH
Department of Urology, University of California, San Francisco, San Francisco, California (M.R.C.)

Scott E. Eggener, MD
Department of Urology, University of California, Los Angeles, Los Angeles, California (S.E.E.)

Kevin C. Oeffinger, MD
Department of Medicine, Duke University Medical Center, Durham, North Carolina (K.C.O.)

Tobias Nordström, MD, PhD
Department of Medical Epidemiology and Biostatistics and Department of Clinical Sciences at Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden (T.N.).

Hari T. Vigneswaran, MD
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (T.P., C.M., M.E., H.T.V.)