Prespecified 4-Kallikrein Marker Model at Age 50 or 60 for Early Detection of Lethal Prostate Cancer in a Large Population Based Cohort of Asymptomatic Men Followed for 20 Years

J Urol. 2020 Aug;204(2):281-288. doi: 10.1097/JU.0000000000001007. Epub 2020 Mar 3.


Purpose: A prespecified statistical model based on 4 kallikrein markers in blood, commercially available as the 4Kscore®, has been shown to accurately detect high grade (greater than Grade Group 2) prostate cancer in men with moderately elevated prostate specific antigen. We assessed whether the model predicted prostate cancer metastasis or death in men not subject to prostate specific antigen screening.

Materials and methods: The cohort includes 43,692 unscreened prostate cancer-free men from a Swedish population based cohort with low rates of prostate specific antigen screening (Västerbotten Intervention Project). Using cryopreserved blood collected at ages 50 and 60 years from men in this cohort we analyzed the association between prostate specific antigen and other kallikrein marker levels in blood and risk of prostate cancer metastasis or death.

Results: There were 308 with metastases and 172 prostate cancer deaths. Baseline prostate specific antigen was strongly associated with 20-year risk of prostate cancer death (c-index at age 50, 0.859, 95% CI 0.799-0.916; age 60, 0.840, 95% CI 0.799-0.878). Men 60 years old with prostate specific antigen below median (less than 1.2 ng/ml) had 0.4% risk of prostate cancer death at 20 years. Among men with moderately elevated prostate specific antigen (2.0 ng/ml or greater) the 4Kscore markedly improved discrimination (c-index 0.767 vs 0.828 and 0.774 vs 0.862 in men age 50 and 60, respectively). Long-term risk of prostate cancer death or metastasis in men with low 4Kscores was very low.

Conclusions: Screening should focus on men in top prostate specific antigen quartile at age 60 years. Men with elevated prostate specific antigen but a low 4Kscore can safely be monitored with repeated blood markers in place of immediate biopsy.

Keywords: early detection of cancer; prostate-specific antigen; prostatic neoplasms.

MeSH terms

  • Adult
  • Biomarkers, Tumor / blood*
  • Early Detection of Cancer*
  • Humans
  • Kallikreins / blood*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / epidemiology
  • Prostatic Secretory Proteins / blood*
  • Sweden / epidemiology


  • Biomarkers, Tumor
  • Prostatic Secretory Proteins
  • beta-microseminoprotein
  • Kallikreins
  • kallikrein 4
  • Prostate-Specific Antigen