The influence of prostate volume on prostate-specific antigen performance: implications for the prostate cancer prevention trial outcomes.
OBJECTIVE
Although showing a 25% reduction in the biopsy prevalence of cancer compared with placebo in the Prostate Cancer Prevention Trial, finasteride was associated with a higher prevalence of high-grade disease. This observation was driven by "for-cause" biopsies. We sought to understand how volume-dependent changes in prostate-specific antigen test performance characteristics may have contributed.


METHODS
A retrospective review was done on 1,304 men referred for initial biopsy with a prostate-specific antigen between 4 and 10 ng/mL or an abnormal digital rectal examination. Receiver-operator curves and positive predictive values were ascertained for prostate-specific antigen stratified by diagnosis and prostate volume.


RESULTS
The performance of prostate-specific antigen changed for any and high-grade (Gleason, > or =3 + 4) cancer in a volume-specific manner. For any cancer, the area under the curve (AUC) decreased from 0.758 to 0.629 to 0.520 as prostate volume increased (<30, 30-50, >50 cm(3), respectively). For high-grade cancer, a similar trend was shown (AUC, 0.712, 0.639, and 0.497, respectively). The positive predictive value of a prostate-specific antigen of > or =4 ng/mL was also affected by prostate volume. Trends for Gleason < or = 6 decreased as prostate volume increased (positive predictive value for <30 cm(3), 25.0%; positive predictive value for 30-50 cm(3), 23.8%; and positive predictive value for >50 cm(3), 17.3%). A more significant trend was seen for high-grade cancer (positive predictive value for <30 cm(3), 39.0%; positive predictive value for 30-50 cm(3), 22.3%; and positive predictive value for >50 cm(3), 10.7%).


CONCLUSIONS
Decreases in prostate volume over time and the resultant change in prostate-specific antigen performance characteristics may have contributed a bias toward the detection of high-grade disease in the finasteride arm of the Prostate Cancer Prevention Trial.
Elliott
Christopher S
CS
Department of Urology, 300 Pasteur Drive, Stanford University Medical Center, Stanford, California 94305, USA. chrsuz@aol.com
Shinghal
Rajesh
R
Presti
Joseph C
JC
D000368:Aged; D001706:Biopsy / Q000379:methods; D003937:Diagnosis, Differential; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D018120:Finasteride / Q000627:therapeutic use; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods; D011237:Predictive Value of Tests; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000032:analysis*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D012189:Retrospective Studies
D004791:Enzyme Inhibitors; D018120:Finasteride; D017430:Prostate-Specific Antigen