Kallikrein Panel Can Reduce Unnecessary Prostate Biopsies Reducing Unnecessary Biopsy During Prostate Cancer Screening Using a Four-Kallikrein Panel: An Independent Replication

Objective: To independently verify if a panel of 4 kallikreins (total, free, and intact prostate-specific antigen [PSA] and kallikrein-related peptidase 2) can determine who may not need prostate biopsy in the face of an elevated, initial screening PSA. Participants/Methods: 2914 men who underwent their first PSA screening for prostate cancer were evaluated from the European Randomized Study of Screening for Prostate Cancer (ERSPC). Frozen serum was used to measure the kallikreins that were part of the panel. The cohort of patients was divided into separate training and validation sets, and results were analyzed for the ability of the kallikrein panel to predict prostate cancer at the time of biopsy. Results: The kallikrein panel significantly improved the test performance of both a simplified model (age and PSA) and a clinical model (age, PSA, and digital rectal examination) in predicting prostate cancer at the time of biopsy. This was true both in the training and separate validation sets. Among 1000 men with an initial elevated PSA >4.0 ng/mL, the use of the kallikrein panel would reduce the number of biopsies by 513 at the cost of missing 54 of the 177 low-grade cancers and 12 of the 100 high-grade cancers. Conclusions: A panel of kallikreins in combination with patient age and physical exam findings can reduce the number of unnecessary prostate biopsies while still detecting the majority of lowand high-grade cancers. Reviewer's Comments: Because of the known limitations of total PSA as a screening study, a test that could improve its performance characteristics would be very beneficial. This study published by Vickers and colleagues seeks to address this issue using a panel of 4 different kallikreins. It demonstrates that, using this panel, it is possible to dramatically reduce the number of unnecessary biopsies while detecting the majority of cancers, including the majority of high-grade cancers. The study’s strengths are the large number of patients included, the use of completely distinct training and validation patient cohorts, and the careful use of clinical decision analysis to demonstrate the utility of this panel in routine clinical practice. The main limitation of the study is that, at the time the ERSPC study was initiated, the standard biopsy was a sextant biopsy. This has known limitations in prostate cancer detection, and the standard now is a more extended biopsy. It is, therefore, not entirely clear how this test would perform either with the use of an extended biopsy template or if lower PSA threshold <4.0 was used to trigger a biopsy. Despite this limitation, the results presented here are promising, but only time will tell if this panel will become a routine part of clinical practice going forward. (Reviewer-Peter E. Clark, MD).