Comparison of free and total forms of serum human kallikrein 2 and prostate-specific antigen for prediction of locally advanced and recurrent prostate cancer.
BACKGROUND
We evaluated the association of total and free forms of serum human kallikrein 2 (hK2) and prostate-specific antigen (PSA) with prostate cancers of unfavorable prognosis.


METHODS
We retrospectively measured total PSA (tPSA), free PSA (fPSA), and total hK2 (thK2) in preoperative serum samples from 867 men [and assessed free hK2 (fhK2) measured in 577 of these men] treated with radical prostatectomy for clinically localized prostate cancer. Associations between biomarker concentrations and extracapsular extension, seminal vesicle invasion, and biochemical recurrence (BCR) were evaluated. A subset of patients with PSA < or =10 microg/L, the group most commonly seen in clinical practice in the US, was analyzed.


RESULTS
thK2 was the strongest predictor of extracapsular extension and seminal vesicle invasion (areas under the ROC curve [AUC], 0.662 and 0.719, respectively), followed by tPSA (AUC, 0.654 and 0.663). All biomarkers were significant predictors of BCR. hK2 forms, but not PSA forms, remained highly significant for predicting BCR in the low-PSA group. Combining tPSA, fPSA, and thK2 in a multivariable model improved prediction compared with any biomarker used individually (AUC, 0.711, 0.755, and 0.752 for this combination predicting extracapsular extension, seminal vesicle invasion, and BCR, respectively; P <0.001 for all).


CONCLUSIONS
Increased concentrations of hK2 in the blood are significantly associated with unfavorable features of prostate cancer, and thK2 is predictive of locally advanced and recurrent cancer in patients with PSA < or =10 microg/L. Independent of tPSA and fPSA, hK2 predicts unfavorable prognosis.
Steuber
Thomas
T
Department of Surgery (Urology), Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Vickers
Andrew J
AJ
Serio
Angel M
AM
Vaisanen
Ville
V
Haese
Alexander
A
Pettersson
Kim
K
Eastham
James A
JA
Scardino
Peter T
PT
Huland
Hartwig
H
Lilja
Hans
H
D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D011485:Protein Binding; D012306:Risk; D020840:Tissue Kallikreins / Q000097:blood*
D020840:Tissue Kallikreins; D017430:Prostate-Specific Antigen