The Stockholm3 blood-test predicts clinically-significant cancer on biopsy: independent validation in a multi-center community cohort

Background Several blood-based tests have been suggested to improve prostate cancer testing. The Stockholm3 test has been shown to reduce the number of prostate biopsies, to decrease detection of low-grade cancer and to maintain the detection rate of ISUP Gleason Group (GG) >= 2 cancer in a screening-by-invitation setting. We aimed to validate the performance of the Stockholm3 test in an independent, clinical practice cohort. Methods The study-population consisted of 533 men in ages 45-75 without previous diagnosis of prostate cancer scheduled for prostate biopsy at any of three centers in Norway and Sweden. Blood samples for Stockholm3 analysis were drawn prior to systematic prostate biopsies. Clinically significant prostate cancer was defined as any finding of ISUP Grade Group (GG) 2 or higher. We calculated area under the curve (AUC) for predicting prostate cancer at biopsy and calculated. Models including PSA and PSA-density (PSA/prostate volume) were compared to a model including also clinical information,protein levels and single nucleotide polymorphisms (SNP). Results 263 of 533 (49%) participants were diagnosed with prostate cancer. 162 men had prostate cancer with GG >= 2. The Stockholm3 test discriminated better for GG >= 2 prostate cancer than PSA in combination with PSA-density AUC 8.9 (95%CI 82.7-89.2) and AUC 74.8 (95% CI 70.3-79.3). Using a Stockholm3 cut-off of 10% risk of GG >= 2 cancer, 38% of the biopsy procedures were saved, however delaying diagnosis for 6% (n = 10) of men with GG >= 2 cancer. Using PSA-density 0.1 as cut-off for biopsy saved 35% of biopsies, delaying diagnosis for 16% (n = 26) of men with GG >= 2 cancer. Conclusion A prediction model including clinical information, protein levels and SNPs was independently validated in a clinical practice cohort and reduces the number of un-necessary biopsies while delaying diagnosis for a limited number of men.