Detection of High Grade Prostate Cancer among PLCO Participants Using a Prespecified 4-Kallikrein Marker Panel

Abstract

Purpose To assess the performance of a four-kallikrein panel, with and without microseminoprotein-beta (MSP), to predict high-grade (Gleason 7+, Gleason Grade Group 2+) prostate cancer (PCa) on biopsy in a multiethnic cohort from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. Materials and Methods Levels of free, intact, total prostate-specific antigen (PSA), human kallikrein-2, and MSP were measured blinded to outcome in cryo-preserved serum from men in the intervention arm of PLCO. Marker levels from 946 men, of whom 100 were African-American, were incorporated into a prespecified statistical model to predict high-grade PCa on biopsy. Results The detection of high-grade PCa (n=94, 10%) was enhanced by the four-kallikrein panel with an AUC of 0.79 compared to 0.73 for the Prostate Cancer Prevention Trial (PCPT) risk calculator (increase of 0.060; 95% C.I. 0.032, 0.088; p<0.01). Additionally, the AUC increased from 0.79 to 0.81 when MSP was added to the four-kallikrein panel. In African-American men, the four-kallikrein panel model also enhanced high-grade PCa detection over PSA (AUC 0.80 versus 0.67). As an illustration of clinical implications, use of one cut-point for biopsy (6% risk of high-grade PCa) with the four-kallikrein panel model would have eliminated unnecessary biopsies in 42% (397/946) of our cohort while detecting 88% (83/94) of highgrade PCa. Conclusions In a multiethnic United States population, the four-kallikrein panel demonstrates improved risk discrimination for high-grade PCa over conventional clinical variables (age, PSA, digital rectal examination) as well as the PCPT risk calculator.

A Four-kallikrein Panel and β-Microseminoprotein in Predicting High-grade Prostate Cancer on Biopsy: An Independent Replication from the Finnish Section of the European Randomized Study of Screening for Prostate Cancer

“…Cryopreserved sample aliquots (serum or plasma) were shipped to the Wallenberg Research Laboratories at Lund University (Malmö, Sweden) for assay of the four kallikrein markers and MSP during 2014-2015. The analyses for total and free PSA [18], intact PSA [19], hK2 [20], and MSP [21] were previously reported [22,23]. [26].…”

Improving the evaluation and diagnosis of clinically significant prostate cancer in 2017

“…Using a cut-off of 6% risk of high-grade disease to determine biopsy kept the detection of high-grade disease by 88% and reduced unnecessary biopsies by 42%. [26]…”

Value of a Statistical Model Based on Four Kallikrein Markers in Blood, Commercially Available as 4Kscore, in All Reasonable Prostate Biopsy Subgroups

“…Only data from completely independent validation studies were included, involving 8396 biopsies from eight cohorts. The PLCO study [4] was excluded because of the unusual sampling design; the Rotterdam Repeat Biopsy [5] cohort had an insufficient number of events. The base model consisted of age, total PSA, and digital rectal examination (DRE) result, if available.…”