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Randomized Controlled Trial
. 2024 Apr 1;7(4):e247131.
doi: 10.1001/jamanetworkopen.2024.7131.

Biomarker vs MRI-Enhanced Strategies for Prostate Cancer Screening: The STHLM3-MRI Randomized Clinical Trial

Lars Björnebo  1 , Andrea Discacciati  1 , Ugo Falagario  2   3 , Hari T Vigneswaran  1 , Fredrik Jäderling  2   4 , Henrik Grönberg  1 , Martin Eklund  1 , Tobias Nordström  1   5 , Anna Lantz  1   2
Affiliations
Randomized Controlled Trial

Biomarker vs MRI-Enhanced Strategies for Prostate Cancer Screening: The STHLM3-MRI Randomized Clinical Trial

Lars Björnebo et al. JAMA Netw Open. .

Abstract

Importance: Prostate cancer guidelines often recommend obtaining magnetic resonance imaging (MRI) before a biopsy, yet MRI access is limited. To date, no randomized clinical trial has compared the use of novel biomarkers for risk estimation vs MRI-based diagnostic approaches for prostate cancer screening.

Objective: To evaluate biomarker-based risk estimation (Stockholm3 risk scores or prostate-specific antigen [PSA] levels) with systematic biopsies vs an MRI-enhanced strategy (PSA levels and MRI with systematic and targeted biopsy) for the detection of clinically significant prostate cancer in a screening setting.

Design, setting, and participants: This open-label randomized clinical trial conducted in Stockholm, Sweden, between April 4, 2018, and December 10, 2020, recruited men aged 50 to 74 years with no history of prostate cancer. Participants underwent blood sampling for PSA and Stockholm3 tests to estimate their risk of clinically significant prostate cancer (Gleason score ≥3 + 4). After the blood tests were performed, participants were randomly assigned in a 2:3 ratio to receive a Stockholm3 test with systematic biopsy (biomarker group) or a PSA test followed by MRI with systematic and targeted biopsy (MRI-enhanced group). Data were analyzed from September 1 to November 5, 2023.

Interventions: In the biomarker group, men with a Stockholm3 risk score of 0.15 or higher underwent systematic biopsies. In the MRI-enhanced group, men with a PSA level of 3 ng/mL or higher had an MRI and those with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3 or higher (range: 1-5, with higher scores indicating a higher likelihood of clinically significant prostate cancer) underwent targeted and systematic biopsies.

Main outcomes and measures: Primary outcome was detection of clinically significant prostate cancer (Gleason score ≥3 + 4). Secondary outcomes included detection of clinically insignificant cancer (Gleason score ≤6) and the number of biopsy procedures performed.

Results: Of 12 743 male participants (median [IQR] age, 61 [55-67] years), 5134 were assigned to the biomarker group and 7609 to the MRI-enhanced group. In the biomarker group, 8.0% of men (413) had Stockholm3 risk scores of 0.15 or higher and were referred for systematic biopsies. In the MRI-enhanced group, 12.2% of men (929) had a PSA level of 3 ng/mL or higher and were referred for MRI with biopsies if they had a PI-RADS score of 3 or higher. Detection rates of clinically significant prostate cancer were comparable between the 2 groups: 2.3% in the biomarker group and 2.5% in the MRI-enhanced group (relative proportion, 0.92; 95% CI, 0.73-1.15). More biopsies were performed in the biomarker group than in the MRI-enhanced group (326 of 5134 [6.3%] vs 338 of 7609 [4.4%]; relative proportion, 1.43 [95% CI, 1.23-1.66]), and more indolent prostate cancers were detected (61 [1.2%] vs 41 [0.5%]; relative proportion, 2.21 [95% CI, 1.49-3.27]).

Conclusions and relevance: Findings of this randomized clinical trial indicate that combining a Stockholm3 test with systematic biopsies is comparable with MRI-based screening with PSA levels and systematic and targeted biopsies for detection of clinically significant prostate cancer, but this approach resulted in more biopsies as well as detection of a greater number of indolent cancers. In regions where access to MRI is lacking, the Stockholm3 test can aid in selecting patients for systematic prostate biopsy.

Trial registration: ClinicalTrials.gov Identifier: NCT03377881.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Vigneswaran reported being an employee of A3P Biomedical. Prof Grönberg reported receiving a grant from the Swedish Cancer Foundation during the conduct of the study and grants from Janssen and AstraZeneca outside the submitted work as well as patents pending for prostate cancer diagnostic tests with A3P Biomedical. Prof Eklund reported receiving grants from the Swedish Research Council, the Swedish Cancer Society, and the Swedish Prostate Cancer Society during the conduct of the study and owning stock in A3P Biomedical outside the submitted work as well as patents pending for prostate cancer risk assessment tools with A3P Biomedical. Dr Nordström reported receiving grants from the Swedish Cancer Foundation, the Prostatacancerförbundet, and the Swedish Research Council during the conduct of the study and owning stock in A3P Biomedical outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Trial Flowchart
MRI indicates magnetic resonance imaging; PCa, prostate cancer; PI-RADS, Prostate Imaging–Reporting and Data System; and PSA, prostate-specific antigen. A PI-RADS score of 3 or higher was considered to be a positive MRI result (range: 1-5, with higher scores indicating a higher likelihood of clinically significant prostate cancer). To convert to micrograms per liter, multiply by 1.
Figure 2.
Figure 2.. Screening Tests and Prostate Cancer Outcomes for the Different Diagnostic Strategies per 10 000 Screened Men
Stockholm3 is a blood-based test for estimating the risk of clinically significant cancer. MRI indicates magnetic resonance imaging; PSA, prostate-specific antigen. Error bars indicate the 95% CIs. To convert PSA to micrograms per liter, multiply by 1.
See this image and copyright information in PMC

References

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