In a Swedish prostate cancer screening trial (STHLM3-MRI) reported in The Lancet Oncology, Nordström et al found that use of the Stockholm3 screening test together with magnetic resonance imaging (MRI)-guided biopsy reduced overdetection of disease while preserving the ability to detect clinically significant cancer. Stockholm3 combines clinical information, protein measurements (including prostate-specific antigen [PSA]), and a genetic score based on single-nucleotide polymorphisms to provide risk prediction.
Study Details
The noninferiority trial included 2,293 men aged 50 to 74 years from Stockholm County with an elevated risk of prostate cancer (out of 49,118 invited to participate between February 2018 and March 2020 and 12,750 who were enrolled and provided blood specimens). Elevated risk was defined as PSA ≥ 3 ng/mL or Stockholm3 score of ≥ 0.11.
The 2,293 men were randomly assigned 2:3 to receive either systematic prostate biopsies (standard group, n = 921) or biparametric MRI followed by MRI-targeted and systematic biopsy in those who were MRI-positive (experimental group, n = 1,372). The primary outcome was detection of clinically significant disease at biopsy defined as a Gleason score of 3 + 4 or higher.
Key Findings
The receiver-operating characteristic area under the curve for detection of clinically significant disease was 0.76 (95% confidence interval [CI] = 0.72–0.80) with Stockholm3 and 0.60 (95% CI = 0.54–0.65) with PSA.
In the experimental group, Stockholm3 score ≥ 0.11 was noninferior to PSA ≥ 3 ng/mL for detection of clinically significant disease (227 vs 192; relative proportion [RP] = 1.18, 95% confidence interval [CI] = 1.09–1.28, P < .0001 for noninferiority) and detected a similar number of low-grade prostate cancers (50 vs 41; RP = 1.22, 95% CI = 0.96–1.55, P = .053 for superiority). Stockhom3 score ≥ 0.11 was associated with performance of more MRIs (RP = 1.10, 95% CI = 1.04–1.17) and biopsies (RP = 1.18, 95% CI = 1.10–1.27).
Use of a Stockholm3 score ≥ 0.15 as a cutoff vs PSA ≥ 3 ng/mL resulted in identical sensitivity in detecting clinically significant disease and was associated with fewer MRIs (RP = 0.64, 95% CI = 0.55–0.82) and fewer biopsies (RP = 0.92, 95% CI = 0.86–1.03).
Compared with PSA ≥ 3 ng/mL and systematic biopsies, Stockholm3 score ≥ 0.11 with MRI-targeted and systematic biopsies was associated with improved detection of clinically significant disease (3.0% vs 2.1%, RP = 1.44, 95% CI = 1.15–1.81), detection of fewer low-grade cancers (0.7% vs 1.4%, RP = 0.46, 95% CI = 0.32–0.66), and led to fewer biopsies (526 vs 853).
Compared with the standard group, fewer patients in the experimental group were prescribed antibiotics for infection (1.8% vs 4.4%, P = .0002) and admitted to the hospital (1.2% vs 3.4%, P = .0003).
The investigators concluded, “The Stockholm3 test can inform risk stratification before MRI and targeted biopsies in prostate cancer screening. Combining the Stockholm3 test with an MRI-targeted biopsy approach for prostate cancer screening decreases overdetection while maintaining the ability to detect clinically significant cancer.”
Tobias Nordström, MD, of the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the Swedish Cancer Society, Swedish Research Council, and Stockholm City Council. For full disclosures of the study authors, visit thelancet.com.
