A four-kallikrein panel predicts prostate cancer in men with recent screening: data from the European Randomized Study of Screening for Prostate Cancer, Rotterdam.
OBJECTIVE
We have developed a statistical prediction model for prostate cancer based on four kallikrein markers in blood: total, free, and intact prostate-specific antigen (PSA), and kallikrein-related peptidase 2 (hK2). Although this model accurately predicts the result of biopsy in unscreened men, its properties for men with a history of PSA screening have not been fully characterized.


METHODS
A total of 1,501 previously screened men with elevated PSA underwent initial biopsy during rounds 2 and 3 of the European Randomized Study of Screening for Prostate Cancer, Rotterdam, with 388 cancers diagnosed. Biomarker levels were measured in serum samples taken before biopsy. The prediction model developed on the unscreened cohort was then applied and predictions compared with biopsy outcome.


RESULTS
The previously developed four-kallikrein prediction model had much higher predictive accuracy than PSA and age alone (area under the curve of 0.711 versus 0.585, and 0.713 versus 0.557 with and without digital rectal exam, respectively; both P < 0.001). Similar statistically significant enhancements were seen for high-grade cancer. Applying the model with a cutoff of 20% cancer risk as the criterion for biopsy would reduce the biopsy rate by 362 for every 1,000 men with elevated PSA. Although diagnosis would be delayed for 47 cancers, these would be predominately low-stage and low-grade (83% Gleason 6 T(1c)).


CONCLUSIONS
A panel of four kallikreins can help predict the result of initial biopsy in previously screened men with elevated PSA. Use of a statistical model based on the panel would substantially decrease rates of unnecessary biopsy.
Vickers
Andrew J
AJ
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. vickersa@mskcc.org
Cronin
Angel M
AM
Roobol
Monique J
MJ
Savage
Caroline J
CJ
Peltola
Mari
M
Pettersson
Kim
K
Scardino
Peter T
PT
Schröder
Fritz H
FH
Lilja
Hans
H
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D055088:Early Detection of Cancer; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D008297:Male; D015233:Models, Statistical; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D016032:Randomized Controlled Trials as Topic; D012697:Serine Endopeptidases / Q000097:blood; D020840:Tissue Kallikreins / Q000097:blood
D014408:Biomarkers, Tumor; D007610:Kallikreins; D012697:Serine Endopeptidases; D020840:Tissue Kallikreins; D017430:Prostate-Specific Antigen
J Urol. 2008 Apr;179(4):1587-92
18295257
J Clin Oncol. 2008 Feb 20;26(6):835-41
18281654
J Clin Invest. 2006 Jan;116(1):271-84
16395409
Anal Chem. 2006 Nov 15;78(22):7809-15
17105175
Prostate Cancer Prostatic Dis. 2004;7(2):132-7
15007379
JAMA. 2005 Jul 6;294(1):66-70
15998892
Clin Chem. 2004 Jun;50(6):1017-25
15054080
Urology. 2008 Jun;71(6):1016-9
18358515
Int J Cancer. 2007 Nov 15;121(10):2212-7
17657743
J Urol. 2006 Jan;175(1):104-7
16406882
Clin Chem. 2006 Feb;52(2):235-9
16384894
Biometrics. 1988 Sep;44(3):837-45
3203132
Eur Urol. 2009 Nov;56(5):753-60
19682790
Cancer. 2010 Jun 1;116(11):2612-20
20336781
N Engl J Med. 2009 Mar 26;360(13):1310-9
19297565
N Engl J Med. 2009 Mar 26;360(13):1320-8
19297566
J Natl Cancer Inst. 2009 Oct 7;101(19):1325-9
19720969
BMC Med. 2008 Jul 08;6:19
18611265
Med Decis Making. 2006 Nov-Dec;26(6):565-74
17099194
Eur Urol. 2010 Feb;57(2):256-66
19913350
J Urol. 2004 Oct;172(4 Pt 1):1297-301
15371827
J Clin Oncol. 2003 Jun 15;21(12):2312-9
12805332
BJU Int. 2003 Dec;92 Suppl 2:48-54
14983955
J Clin Oncol. 2010 May 20;28(15):2493-8
20421547
Eur Urol. 2005 Sep;48(3):386-99; discussion 398-9
15982797