EURURO Vol. 72 No. 3

Prostate Cancer

Evaluating the Four Kallikrein Panel of the 4Kscore for Prediction

of High-grade Prostate Cancer in Men in the Canary Prostate

Active Surveillance Study

Daniel W. Lin

a , b , c , * ,

Lisa F. Newcomb

a , b ,

Marshall D. Brown

a ,

Daniel D. Sjoberg

d ,

Yan Dong

e ,

James D. Brooks

f ,

Peter R. Carroll

g ,

Matthew Cooperberg

g ,

Atreya Dash

c ,

William J. Ellis

b ,

Michael Fabrizio

h ,

Martin E. Gleave

i ,

Todd M. Morgan

j ,

Peter S. Nelson

a ,

Ian M. Thompson

k ,

Andrew A. Wagner

l ,

Yingye Zheng

a ,

for the Canary Prostate Active Surveillance Study Investigators

Fred Hutchinson Cancer Research Center, Seattle, WA, USA;

University of Washington, Seattle, WA, USA;

Veterans Affairs Puget Sound Health Care

System, Seattle, WA, USA;

Memorial Sloan-Kettering Cancer Center, New York, NY, USA;

OPKO Labs, Nashville, TN, USA;

Stanford University, Stanford, CA,

USA;

University of California at San Francisco, San Francisco, CA, USA;

Eastern Virginia Medical School, Norfolk, VA, USA;

University of British Columbia,

Vancouver, Canada;

University of Michigan, Ann Arbor, MI, USA;

University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA;

Beth

Israel Deaconess Medical Center, Boston, MA, USA

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 4 4 8 – 4 5 4

available at

www.scienced irect.com

journal homepage:

www.europeanurology.com

Article info

Article history:

Accepted November 11, 2016

Associate Editor:

Giacomo Novara

Keywords:

Prostatic neoplasms

Prospective studies

Active surveillance

Biomarker

Kallikrein

Abstract

Background:

Diagnosis of Gleason 6 prostate cancer can leave uncertainty about the

presence of undetected aggressive disease.

Objective:

To evaluate the utility of a four kallikrein (4K) panel in predicting the

presence of high-grade cancer in men on active surveillance.

Design, setting, and participants:

Plasma collected before the first and subsequent

surveillance biopsies was assessed for 718 men prospectively enrolled in the multi-

institutional Canary PASS trial. Biopsy data were split 2:1 into training and test sets. We

developed statistical models that included clinical information and either the 4Kpanel or

serum prostate-specific antigen (PSA).

Outcome measurements and statistical analysis:

The endpoint was reclassification to

Gleason 7. We used receiver operating characteristic (ROC) curve analyses and area

under the curve (AUC) to assess discriminatory capacity, and decision curve analysis

(DCA) to report clinical net benefit.

Results and limitations:

Significant predictors for reclassification were 4Kpanel (odds

ratio [OR] 1.54, 95% confidence interval [CI] 1.31–1.81) or PSA (OR 2.11, 95% CI 1.53–

2.91),

20% cores positive (OR 2.10, 95% CI 1.33–3.32), two or more prior negative

biopsies (OR 0.19, 95% CI 0.04–0.85), prostate volume (OR 0.47, 95% CI 0.31–0.70), and

body mass index (OR 1.09, 95% CI 1.04–1.14). ROC curve analysis comparing 4K and base

models indicated that the 4Kpanel improved accuracy for predicting reclassification

(AUC 0.78 vs 0.74) at the first surveillance biopsy. Both models performed comparably

for prediction of reclassification at subsequent biopsies (AUC 0.75 vs 0.76). In DCA, both

models showed higher net benefit compared to biopsy-all and biopsy-none strategies.

Limitations include the single cohort nature of the study and the small numbers; results

should be validated in another cohort before clinical use.

* Corresponding author. Department of Urology, University of Washington, 1959 NE Pacific Street,

Box 356510, Seattle, WA 98195, USA. Tel. +1 206 2210797; Fax: +1 206 5433272.

E-mail address:

dlin@uw.edu

(D.W. Lin).

http://dx.doi.org/10.1016/j.eururo.2016.11.017

0302-2838/