Improving prostate cancer detection in veterans through the development of a clinical decision rule for prostate biopsy.
BACKGROUND
We sought to improve prostate cancer (PC) detection through developing a prostate biopsy clinical decision rule (PBCDR), based on an elevated PSA and laboratory biomarkers. This decision rule could be used after initial PC screening, providing the patient and clinician information to consider prior to biopsy.


METHODS
This case-control study evaluated men from the Tampa, Florida, James A. Haley (JH) Veteran's Administration (VA) (N = 1,378), from January 1, 1998, through April 15, 2005. To assess the PBCDR we did all of the following: 1) Identified biomarkers that are related to PC and have the capability of improving the efficiency of PC screening; 2) Developed statistical models to determine which can best predict the probability of PC; 3) Compared each potential model to PSA alone using Receiver Operator Characteristic (ROC) curves, to evaluate for improved overall effectiveness in PC detection and reduction in (negative) biopsies; and 4) Evaluated dose-response relationships between specified lab biomarkers (surrogates for extra-prostatic disease development) and PC progression.


RESULTS
The following biomarkers were related to PC: hemoglobin (HGB) (OR = 1.42 95% CI 1.27, 1.59); red blood cell (RBC) count (OR = 2.52 95% CI 1.67, 3.78); PSA (OR = 1.04 95% CI 1.03, 1.05); and, creatinine (OR = 1.55 95% CI 1.12, 2.15). Comparing all PC stages versus non-cancerous conditions, the ROC curve area under the curve (AUC) enlarged (increasing the probability of correctly classifying PC): PSA (alone) 0.59 (95% CI 0.55, 0.61); PBCDR model 0.68 (95% CI 0.65, 0.71), and the positive predictive value (PPV) increased: PSA 44.7%; PBCDR model 61.8%. Comparing PC (stages II, III, IV) vs. other, the ROC AUC increased: PSA (alone) 0.63 (95% CI 0.58, 0.66); PBCDR model 0.72 (95% CI 0.68, 0.75), and the PPV increased: 20.6% (PSA); PBCDR model 55.3%.


CONCLUSIONS
These results suggest evaluating certain common biomarkers in conjunction with PSA may improve PC prediction prior to biopsy. Moreover, these biomarkers may be more helpful in detecting clinically relevant PC. Follow-up studies should begin with replicating the study on different U.S. VA patients involving multiple practices.
Injury Epidemiology Research Section, Military Performance Division, United States Army Institute of Environmental Medicine, Natick, MA, USA. owen.hill@us.army.mil
Owen T
OT
Hill
Thomas J
TJ
Mason
Skai W
SW
Schwartz
Philip R
PR
Foulis
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D003661:Decision Support Techniques; D055088:Early Detection of Cancer / Q000379:methods*; D004906:Erythrocyte Count; D006454:Hemoglobins; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011237:Predictive Value of Tests; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology*; D012372:ROC Curve; D012189:Retrospective Studies; D014481:United States; D014493:United States Department of Veterans Affairs; D058014:Veterans Health
D006454:Hemoglobins; D003404:Creatinine; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen