Results from the PRIMA Trial: Comparison of the STHLM3 Test and Prostate-specific Antigen in General Practice for Detection of Prostate Cancer in a Biopsy-naive Population

Background: Current management of prostate cancer (PC) lacks biomarker tests and diagnostic procedures that can accurately distinguish clinically significant and clinically insignificant PCs at an early stage of the disease.Objective: To compare the Stockholm 3 (STHLM3) test and prostate-specific antigen (PSA) as entry tests for magnetic resonance imaging (MRI) in a prospective study of PC diagnosis in general practice.Design, setting, and participants: Participants were biopsy-na & iuml;ve men aged 50-69 yr who had a PSA test in general practice. Participants with PSA 1-10 ng/ml also had an STHLM3 test and were referred for MRI if the STHLM3(11) test was positive (risk >= 11%) and/or PSA >= 3 ng/ml, and to targeted MRI-guided biopsy (MRGB) if their Prostate Imaging-Reporting and Data System (PI-RADS) score was >= 3.Outcome measurements and statistical analysis: The primary outcome was the number of International Society of Urological Pathology grade group >= 2 (GG >= 2) cases detected with a positive STHLM3(11) test versus PSA >= 3 ng/ml. Post hoc analysis was performed using a higher STHLM3 test cutoff (risk >= 15%; positive STHLM3(15) test).Results and limitations: Between January 2018 and December 2021, we recruited 1905 men. The STHLM3 test was performed in 1134 participants. Of these, 437 underwent MRI and 117 underwent MRGB, which detected 38 (32.5%) GG >= 2 and 52 (44.4%) with GG 1 cases. In comparison to PSA >= 3 ng/ml, a positive STHLM3(11) test increased detection of GG >= 2 from 30 to 37 cases (23.3%, 95% confidence interval [CI] 5.6-52.2%) and detection of GG 1 from 37 to 50 cases (35.1%, 95%CI 11.6-66.7%). STHLM3(15) positivity did not differ from PSA >= 3 ng/ml regarding detection of GG >= 2 PC (30 vs 32; 6.6%, 95% CI -8.1% to 25.9%), GG 1 PC (37 vs 37; 0.0%, 95% CI -19.6% to 25.0%), or MRGB use (88 vs 83; -5.7%, 95% CI -17.9% to 7.4%), but reduced MRI scans from 320 to 236 (-26.2%, 95% CI -33.1% to -18.9%).Conclusions: The STHLM3(11) test improved sensitivity but not specificity for detection of GG >= 2 PC in the clinical setting of nonsystematic PC testing in general practice. Further studies are needed to validate a possible benefit of using a higher cutoff for STHLM3 positivity as an entry test for MRI.

Automated summary

This study compared the effectiveness of the STHLM3 and PSA tests as entry tests for PC diagnosis. The results showed that the STHLM3(11) test improved sensitivity for detecting GG≥2 PC but did not improve specificity. Further research is needed to validate the potential benefits of using a higher cutoff for STHLM3 positivity as an entry test for MRI.