A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in G？teborg, Sweden

The study cohort comprised 740 men in G？teborg, Sweden, undergoing biopsy during the first round of the European Randomized study of Screening for Prostate Cancer. We calculated the area-under-the-curve (AUC) for predicting prostate cancer at biopsy. AUCs for a model including age and PSA (the 'laboratory' model) and age, PSA and digital rectal exam (the 'clinical' model) were compared with those for models that also included additional kallikreins.Addition of free and intact PSA and hK2 improved AUC from 0.68 to 0.83 and from 0.72 to 0.84, for the laboratory and clinical models respectively. Using a 20% risk of prostate cancer as the threshold for biopsy would have reduced the number of biopsies by 424 (57%) and missed only 31 out of 152 low-grade and 3 out of 40 high-grade cancers.Multiple kallikrein forms measured in blood can predict the result of biopsy in previously unscreened men with elevated PSA. A multivariable model can determine which men should be advised to undergo biopsy and which might be advised to continue screening, but defer biopsy until there was stronger evidence of malignancy.Prostate specific antigen (PSA) is the only molecular marker routinely used for the early detection of a common cancer. Nonetheless, it remains an imperfect test: although PSA is highly specific to the prostate gland, elevated blood PSA is not specific to cancer as it can be a result of benign conditions such as benign prostatic hypertrophy and prostatitis [1,2]. Accordingly, most men with elevated PSA do not have prostate cancer, with the result that many undergo prostate biopsy unnecessarily. It has been estimated that approximately 1 million biopsies are conducted per year in the USA [3]. As the annual incidence of prostate cancer is 235,000 cases [4], this suggests that, each year, over 750,000 American men are needlessly subjected to prostate biopsy, with attendant pain, inconvenience, financial costs, and risk of infection.Analyzing data from the Prostate Cancer Pre