A panel of kallikrein marker predicts prostate cancer in a large, population-based cohort followed for 15 years without screening.
Vickers AJ., Gupta A., Savage CJ., Pettersson K., Dahlin A., Bjartell A., Manjer J., Scardino PT., Ulmert D., Lilja H.
BACKGROUND: Prostate-specific antigen (PSA) has modest specificity for prostate cancer. A panel of four kallikrein markers (total PSA, free PSA, intact PSA, and kallikrein-related peptidase 2) is a highly accurate predictor of biopsy outcome. The clinical significance of biopsy-detectable cancers in men classified as low-risk by this panel remains unclear. METHODS: The Malmö Diet and Cancer study is a population-based cohort of 11,063 Swedish men aged 45 to 73 providing a blood sample at baseline during 1991-1996. The Swedish Cancer Registry was used to identify 943 men diagnosed with prostate cancer by December 31, 2006. PSA testing was low. We assessed the predictive accuracy of our published statistical model to predict subsequent prostate cancer diagnosis in men with a total PSA level of 3.0 ng/mL or more at baseline. RESULTS: Compared with total PSA and age, the full kallikrein panel enhanced the predictive accuracy for clinically diagnosed prostate cancer (concordance index 0.65 vs. 0.75; P < 0.001). For every 1,000 men with a total PSA level of 3 ng/mL or more at baseline, the model would classify as high-risk 131 of 152 (86%) of the cancer cases diagnosed clinically within 5 years; 421 men would be classified as low-risk by the panel and recommended against biopsy. Of these, only 2 would be diagnosed with advanced prostate cancer (clinical T3-T4 or metastases) within 5 years. CONCLUSIONS: Men with a PSA level of 3 ng/mL or more but defined as low-risk by the panel of four kallikrein markers are unlikely to develop incurable prostate cancer. IMPACT: Use of the panel to determine referral to biopsy could substantially reduce the number of unnecessary prostate biopsies.