In this paper, we report ongoing investigations concerning the increased number of high-grade (Gleason grade > or = 7) prostate cancer, despite a reduction in all prostate cancer, found on the finasteride arm of the Prostate Cancer Prevention Trial (PCPT). There was a statistically significant 24.8% reduction in prostate cancer found on biopsy on the finasteride arm compared to placebo, and the reduction was also observed in both groups of end-of-study and for-cause biopsies. However, when the prostate cancers were examined by Gleason score, there was an increased number of high-grade prostate cancers found on the finasteride arm than on the placebo arm. This observation was emphasized in the editorial to the first publication of PCPT results and has dampened enthusiasm for recommendation of finasteride for chemoprevention. So, what are the potential reasons for increased grade on the finasteride arm? The number of high-grade cancers that are detected following a PSA prompt is directly proportional to the sensitivity of PSA for high-grade disease times the actual but unknown number of high-grade disease cases. So the higher the sensitivity the more likely one is to detect more of the existing high-grade cases irrespective of the true number of cases, i.e., there is an ascertainment bias. We are currently performing a quantitative investigation of whether or not this ascertainment bias could explain the higher number of high-grade disease cases observed on the finasteride arm.