Detection of High Grade Prostate Cancer among PLCO Participants Using a Prespecified 4-Kallikrein Marker Panel.
We assessed the performance of a 4-kallikrein panel with and without microseminoprotein-β to predict high grade (Gleason 7+/Gleason Grade Group 2+) prostate cancer on biopsy in a multiethnic cohort from PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial).



Levels of free, intact, total prostate specific antigen, human kallikrein-2 and microseminoprotein-β were measured while blinded to outcomes in cryopreserved serum from men in the intervention arm of PLCO. Marker levels of 946 men, of whom 100 were African American, were incorporated into a prespecified statistical model to predict high grade prostate cancer on biopsy.



The detection of high grade prostate cancer in 94 men (10%) was enhanced by the 4-kallikrein panel with an AUC of 0.79 compared to 0.73 for PCPTRC (Prostate Cancer Prevention Trial Risk Calculator), representing a 0.060 increase (95% CI 0.032-0.088, p <0.01). Additionally, the AUC increased from 0.79 to 0.81 when microseminoprotein-β was added to the 4-kallikrein panel. In African American men, the 4-kallikrein panel model also enhanced high grade prostate cancer detection over that of prostate specific antigen (AUC 0.80 vs 0.67). As an illustration of clinical implications, using 1 cutoff point for biopsy (6% risk of high grade prostate cancer) with the 4-kallikrein panel model would have eliminated unnecessary biopsies in 420 per 1,000 men (42%) while detecting high grade prostate cancer in 83 of 93 (88%).



In a multiethnic United States population, the 4-kallikrein panel demonstrated improved risk discrimination for high grade prostate cancer over conventional clinical variables (age, prostate specific antigen and digital rectal examination) as well as PCPTRC.
Division of Urology, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
Eric H
EH
Kim
Division of Urology, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
Gerald L
GL
Andriole
Division of Urology, Department of Surgery, University of Colorado, Aurora, Colorado.
E David
ED
Crawford
Department of Epidemiology and Biostatistics, Clinical Chemistry Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Daniel D
DD
Sjoberg
Department of Epidemiology and Biostatistics, Clinical Chemistry Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Melissa
M
Assel
Department of Epidemiology and Biostatistics, Clinical Chemistry Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Andrew J
AJ
Vickers
Department of Laboratory Medicine, Urology Service, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Surgery and Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom; Department of Translational Medicine, Lund University, Skåne University Hospital, Malmö, Sweden. Electronic address: liljah@mskcc.org.
Hans
H
Lilja
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001706:Biopsy; D055088:Early Detection of Cancer; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology*; D018570:Risk Assessment
D014408:Biomarkers, Tumor; D007610:Kallikreins
biopsy; kallikreins; mass screening; prostate-specific antigen; prostatic neoplasms