Is High-Grade Prostate Cancer Easier to Find in Smaller Prostates Because There Is More High-Grade Disease to Find? – Response
Authors: Joseph Presti
Journal: Clinical Cancer Research (2010)

We appreciate Dr. Walsh's comments about our article and acknowledge that our study provides only one possible explanation for the findings from the Prostate Cancer Prevention Trial. We are also familiar with the literature that he has cited. It is important to emphasize that the difference in the detection of high-grade cancer between finasteride and placebo during the Prostate Cancer Prevention Trial was only seen in the “for cause biopsies,” driven by prostate-specific antigen (PSA) or an abnormal prostate examination. There was no difference in the detection of high-grade cancers at the end of the study biopsy, in which no “trigger” for biopsy was used other than the rules of the protocol. If small prostates are biologically more likely to harbor high-grade disease, why would not the smaller prostates at the end of study in the finasteride arm be more likely to have high-grade disease?

We appreciate his suggestion about analyzing the data from Stanford that was meticulously characterized by John McNeal. These data were recently accepted for presentation at the American Urological Association Meeting in San Francisco this year (1). We identified 1,404 patients from the Stanford Radical Prostatectomy Database with clinical stage T1c ( n = 723) and T2 ( n = 681) disease who underwent surgery and had detailed morphometric mapping by Dr. McNeal. Multivariate linear regression was done to assess for the effects of prostate weight (a surrogate for prostate volume) and PSA, on the volume and percentage of high-grade disease (Gleason grade 4 and 5). Among patients with T1c disease, a multivariate model including PSA and prostate weight showed that only PSA was significantly associated with the volume of high-grade disease ( P = 0.0015). Among patients with T2 disease, a similar multivariate model including PSA and prostate weight showed that only PSA was significantly associated with volume of high-grade disease ( P < 0.0001). There was a significantly greater volume of high-grade disease in the T2 patients compared with T1c patients ( P = 0.026).

As we and others have shown, the performance of PSA is better for the detection of high-grade disease (2). In a radical prostatectomy series in which PSA is the driving force for biopsy (stage T1c), smaller prostates will have a higher PSA density (PSA/prostate weight) and are thus more likely to harbor high-grade disease. In patients with palpable disease (T2) in which PSA is not the only indication for biopsy, the effect of PSA exceeds the effect of prostate size in predicting high-volume and high-grade disease. These data suggest that the association between prostate size and high-grade disease seen in radical prostatectomy series may be related to ascertainment bias rather than cancer biology.

The additional data we present here further supports a PSA performance bias in the observations from Prostate Cancer Prevention Trial.

Disclosure of Potential Conflicts of Interest No potential conflicts of interest were disclosed.