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Prostate volume may have influenced high-grade disease incidence associated with finasteride
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The incidence of high-grade disease associated with finasteride in the Prostate Cancer Prevention Trial may be explained by the drug’s ability to decrease prostate volume, therefore increasing the performance of PSA detection, according to data from a retrospective review.
“We show that high-grade cancer diagnosis is selectively diagnosed more often in smaller prostates, a known effect of finasteride use,” the researchers wrote. “This finding would, in part, explain the slight increase in high-grade prostate cancer diagnosis in the finasteride arm of the trial and would serve to allay the fear that finasteride, while inhibiting low-grade prostate cancer development, might increase the risk for high-grade cancer.”
Researchers conducted a retrospective review using prospectively collected data for 1,304 men undergoing transrectal ultrasound guided extended prostate biopsy between 1996 and 2006. Men were referred for an initial biopsy and had a PSA between 4 ng/mL and 10 ng/mL or an abnormal digital rectal exam. The researchers determined receiver-operator curves and positive predictive values for PSA stratified by diagnosis and prostate volume.
PSA performance changed in a volume-specific manner for any and high-grade cancer (Gleason ≥3 + 4). The area under the curve decreased as prostate volume increased for any cancer: from 0.758 (volume <30 cm3) to 0.629 (volume 30 cm3 to 50 cm3) to 0.520 (volume >50 cm3). The researchers observed a similar trend for high-grade cancer: AUC 0.712 to 0.639 to 0.497.
Prostate volume also affected the positive predictive value of a PSA of ≥4 ng/mL. As prostate volume increased, trends for Gleason ≤6 decreased (positive predictive value for <30 cm3 =25.0%; for 30 cm3 to 50 cm3 =23.8% and for >50 cm3 =17.3%. The trend was more significant for high-grade disease: positive predictive value for <30 cm3 =39.0%, for 30 cm3 to 50 cm3 =22.3% and for >50 cm3 =10.7%.
“Decreases in prostate volume over time and the resultant change in PSA performance characteristics may have contributed a bias toward the detection of high-grade disease in the finasteride arm of the Prostate Cancer Prevention Trial,” the researchers wrote.
Elliott CS. Clin Cancer Res. 2009;doi:10.1158/1078-0432.CCR-08-2277