Properties of the 4-Kallikrein Panel Outside the Diagnostic Gray Zone: Meta-Analysis of Patients with Positive Digital Rectal Examination or Prostate Specific Antigen 10 ng/ml and Above.
The 4-kallikrein panel, commercially available as the 4Kscore™, is a reflex test for prostate cancer early detection that has been extensively validated in multiple international cohorts. It has been suggested that use of such reflex tests be limited to those with prostate specific antigen less than 10 ng/ml and negative digital rectal examination. We aimed to determine the value of the panel in men outside this "diagnostic gray zone."



We performed an individual patient data meta-analysis using data from prior studies on the 4-kallikrein panel. We calculated the properties of the panel for predicting high grade (Gleason 7+) cancer in a subgroup of men with either positive digital rectal examination or prostate specific antigen 10 to 25 ng/ml.



A total 2,891 men from 8 cohorts were included. An important proportion of patients, including 32% in the United States validation study, had prostate specific antigen 10 to 25 ng/ml or a positive digital rectal examination. For men with prostate specific antigen 10 to 25 ng/ml the fixed-effects estimate for the discrimination of the kallikrein model was 0.84 vs 0.69 for the base model (difference 0.128, 95% CI 0.098-0.159). In the positive digital rectal examination group discrimination was 0.82 vs 0.72 (difference 0.092, 95% CI 0.069-0.115). Decision analysis showed a clinical net benefit for use of the panel in this subgroup with a reduction in biopsy rates of about 20% and only a small number of high grade cancers missed, or fewer than 3% of those not biopsied.



The use of the kallikrein panel in men with a positive digital rectal examination or prostate specific antigen 10 to 25 ng/ml is justified.
New York, New York; Lille, France. Electronic address: vickersa@mskcc.org.
Andrew
A
Vickers
New York, New York.
Emily A
EA
Vertosick
New York, New York.
Daniel D
DD
Sjoberg
Rotterdam, The Netherlands.
Monique J
MJ
Roobol
Oxford, United Kingdom.
Freddie
F
Hamdy
Oxford, United Kingdom.
David
D
Neal
Lund, Sweden.
Anders
A
Bjartell
Göteborg, Sweden.
Jonas
J
Hugosson
Bristol, United Kingdom.
Jenny L
JL
Donovan
Lille, France.
Arnauld
A
Villers
Andover Urology, Andover, Massachusetts.
Stephen
S
Zappala
New York, New York.
Hans
H
Lilja
D051517:Digital Rectal Examination; D055088:Early Detection of Cancer; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D008297:Male; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism
D007610:Kallikreins; C120801:kallikrein 4; D017430:Prostate-Specific Antigen
digital rectal examination; early detection of cancer; kallikreins; prostate-specific antigen; prostatic neoplasms
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