Multicomponent Test Tops PSA for Clinically Significant Prostate Cancers

A multicomponent blood-based biomarker test that combines prostate-specific antigen (PSA) with additional plasma protein biomarkers, a polygenic risk score, and clinical variables identified more clinically significant prostate cancers, while missing fewer cases, compared with standard PSA screening, according to a secondary analysis of a randomized trial.

Among men who had both types of testing, the Stockholm3 test was more sensitive than PSA screening, detecting 90% of clinically significant prostate cancers versus 74%, respectively, while maintaining similar specificity (89% vs 90%), reported Thorgerdur Palsdottir, PhD, of the Karolinska Institutet in Stockholm, and colleagues.

The Stockholm3 test had a false-negative rate of 10% and a false-positive rate of 11%, whereas PSA screening had a false-negative rate of 26% and a false-positive rate of 10%, the authors noted in the Annals of Internal Medicine.

“Stockholm3 provided a favorable balance between identification of clinically actionable cancer and diagnostic work-up across decision thresholds for biopsy compared with PSA,” wrote Palsdottir and colleagues. “These findings support the use of Stockholm3 in the context of a risk-adapted screening approach, enabling more precise identification of men at higher risk for clinically significant disease while reducing unnecessary biopsies.”

Previous results from the STHLM3-MRI trial showed that the strategy of using MRI with targeted and standard biopsy reduced the detection of clinically insignificant cancers as well as unnecessary biopsies. A further analysis showed that combining the Stockholm3 test with an MRI-targeted biopsy approach decreased overdetection, while still detecting clinically significant cancers.

This secondary analysis was designed to compare the detection of clinically significant prostate cancers (grade group 2) using PSA and Stockholm3 with 2-year follow-up.

Between 2018 and 2020, a total of 49,118 men were invited to participate in the original STHLM3-MRI study, of whom 12,670 were included in this analysis. Overall, 12.1% of participants had a PSA level of 3 ng/mL or greater and 13.3% had a Stockholm3 score of 11 or greater at baseline.

Those with these abnormal screening tests were randomly assigned 2:3 to systematic biopsy or MRI with systematic and targeted biopsies for lesions with a Prostate Imaging Reporting and Data System score of 3 or greater.

During the 2-year follow-up, 443 men were diagnosed with clinically significant prostate cancer.

Per 1,000 men screened, the Stockholm3 test detected 31.6 clinically significant prostate cancer cases compared with 25.8 for PSA, with a similar number of false-positive results (101.8 vs 95.0 per 1,000 screened). At the same time, the Stockholm3 test missed fewer clinically significant prostate cancers versus PSA (3.4 vs 9.2 per 1,000 screened).

The authors noted that the implementation of the Stockholm3 test could depend on cost, with the test ranging from $550 to $750 in European markets.

They also acknowledged that the study was limited by a follow-up of just 2 years.

“Further investigation, including longer-term follow-up of survival and cause-specific mortality, will be needed to evaluate the long-term effect and cost-effectiveness of this screening approach,” they wrote. “If confirmed, integrating Stockholm3 into screening pathways may improve the efficiency and clinical utility of prostate cancer screening programs.”