Received on June 14, 2006
Accepted on November 29, 2006

Cancer Diagnostics

Comparison of Free and Total Forms of Serum Human Kallikrein 2 and Prostate-Specific Antigen for Prediction of Locally Advanced and Recurrent Prostate Cancer

¹ Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, and Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
² Departments of Urology and Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY
³ Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY
⁴ Department of Biotechnology, University of Turku, Turku, Finland
⁵ Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
⁶ Department of Urology, and Clinical Laboratories, Urology and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, and Department of Laboratory Medicine, Division of Clinical Chemistry, Lund University, University Hospital, Malmö, Sweden

^* To whom correspondence should be addressed. E-mail: steuber{at}uke.uni-hamburg.de.

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 10 µg/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, 0.714, 0.762, and 0.763 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 10 µg/L. Independent of tPSA and fPSA, hK2 predicts unfavorable prognosis.