Predictive Value of Four Kallikrein Markers for Pathologically Insignificant Compared With Aggressive Prostate Cancer in Radical Prostatectomy Specimens: Results From the European Randomized Study of Screening for Prostate Cancer Section Rotterdam

• Background: Treatment decisions can be difficult in men with low-risk prostate cancer (PCa). Objective: To evaluate the ability of a panel of four kallikrein markers in blood-total prostate-specific antigen (PSA), free PSA, intact PSA, and kallikrein-related peptidase 2-to distinguish between pathologically insignificant and aggressive disease on pathologic examination of radical prostatectomy (RP) specimens as well as to calculate the number of avoidable surgeries. Design, setting, and participants: The cohort comprised 392 screened men participating in rounds 1 and 2 of the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer. Patients were diagnosed with PCa because of an elevated PSA >= 3.0 ng/ml and were treated with RP between 1994 and 2004. Outcome measurements and statistical analysis: We calculated the accuracy (area under the curve [AUC]) of statistical models to predict pathologically aggressive PCa (pT3-T4, extracapsular extension, tumor volume >0.5 cm(3), or any Gleason grade >= 4) based on clinical predictors (age, stage, PSA, biopsy findings) with and without levels of four kallikrein markers in blood. Results and limitations: A total of 261 patients (67%) had significant disease on pathologic evaluation of the RP specimen. While the clinical model had good accuracy in predicting aggressive disease, reflected in a corrected AUC of 0.81, the four kallikrein markers enhanced the base model, with an AUC of 0.84 (p < 0.0005). The model retained its ability in patients with low-risk and very-low-risk disease and in comparison with the Steyerberg nomogram, a published prediction model. Clinical application of the model incorporating the kallikrein markers would reduce rates of surgery by 135 of 1000 patients overall and 110 of 334 patients with pathologically insignificant disease. A limitation of the present study is that clinicians may be hesitant to make recommendations against active treatment on the basis of a statistical model. Conclusions: Our study provided proof of principle that predictions based on levels of four kallikrein markers in blood distinguish between pathologically insignificant and aggressive disease after RP with good accuracy. In the future, clinical use of the model could potentially reduce rates of immediate unnecessary active treatment. (c) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Urology and Nephrology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Prostate-specific antigen/blood

Prostatic neoplasms

Mass screening

Radical prostatectomy

Kallikrein-related peptidases

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)