Benign prostatic hyperplasia (BPH) is prevalent in older men. 5-α-reductase inhibitors (5-ARIs) such as finasteride are a common treatment for the urinary symptoms of BPH [1]. These drugs treat BPH, and improve symptoms, by shrinking enlarged prostate tissue [2]. A reduction in prostate size is accompanied by decreased levels of prostate-specific antigen (PSA) in blood; something which has consequences for prostate cancer screening [3].

Many studies have investigated the effect of finasteride on total PSA and have consistently found that after 6–12 mo on finasteride, total PSA is approximately halved [4], [5], [6]. Based on these findings, it is recommended that PSA levels be doubled in men on finasteride to determine whether further work-up is required. This means that, for instance, while a man with a PSA of 2.1 ng/ml would normally be told to return for a repeat PSA within a year or two, if that man was taking a 5-ARI, his PSA would be calculated as 4.2 ng/ml and he would be referred for further evaluation to determine whether a biopsy would be indicated.

Because PSA alone has poor specificity for clinically relevant prostate cancer, guidelines recommend a secondary risk assessment—a reflex marker or magnetic resonance imaging study—to determine eligibility for biopsy [7]. However, several of the secondary marker tests, the 4Kscore being one example, include total PSA, free PSA, intact PSA, and human kallikrein 2 (hK2). Because the effects of 5-ARIs on these other kallikrein levels are unknown, 5-ARI use is a contraindication for marker tests based on kallikreins.

Here we use data from the Prostate Cancer Prevention Trial (PCPT) to first investigate changes in kallikrein marker levels associated with the use of finasteride. Subsequently, we assess whether this information can be used to adjust marker levels so that the 4K model can be used in men on finasteride to aid in biopsy decision-making.