Journal of the National Cancer Institute Advance Access originally published online on September 11, 2007
JNCI Journal of the National Cancer Institute 2007 99(18):1375-1383; doi:10.1093/jnci/djm117
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© The Author 2007. Published by Oxford University Press.
ARTICLES |
Finasteride and High-Grade Prostate Cancer in the Prostate Cancer Prevention Trial
Affiliations of authors: University of Colorado Denver and Health Sciences Center, Denver, CO (MSL, FGLR, EDC); Department of Pathology, Johns Hopkins Hospital, Baltimore, MD (JIE); Fred Hutchinson Cancer Research Center, Seattle, WA (PJG, AKD, CMT); Memorial Sloan-Kettering Cancer Center, New York, NY (VER); University of Miami School of Medicine, Miami, FL (FC); National Cancer Institute, Bethesda, MD (HLP, LGF); The University of Texas M. D. Anderson Cancer Center, Houston, TX (SML); Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, OH (MWK); Southwest Oncology Group, San Antonio, TX (CAC); The University of Texas Health Science Center at San Antonio, TX (IMT)
Correspondence to: M. Scott Lucia, MD, Department of Pathology, University of Colorado Denver and Health Sciences Center, 4200 E Ninth Ave, Box B-216, Denver, CO 80262 (e-mail: scott.lucia{at}uchsc.edu).
Background: The Prostate Cancer Prevention Trial (PCPT) reported a decreased incidence of prostate cancer overall but an increase in the incidence of high-grade prostate cancer with finasteride compared with placebo. We assessed whether the increased high-grade prostate cancer associated with finasteride in the PCPT was due to finasteride's potential effects on tumor morphology or prostate size.
Methods: Prostate biopsies with Gleason score 8–10 (n = 90, finasteride; n = 52, placebo) were examined histologically for hormonal effects, and those with Gleason score 7–10 (n = 282, finasteride; n = 244, placebo) were examined for pathologic surrogates of disease extent. Prostate volumes were measured at biopsy. Samples from radical prostatectomies (n = 222, finasteride; n = 306, placebo) were examined for tumor grade and extent, and, where possible, grades at biopsy and prostatectomy were compared between the groups. Logistic regression was used to analyze differences between treatment groups with respect to pathologic criteria. All statistical tests were two-sided.
Results: Degenerative hormonal changes in high-grade biopsies were equivalent between the finasteride and placebo groups, but prostate volumes were lower in the finasteride group (median = 25.1 versus 34.4 cm3, P<.001). Pathologic surrogates for tumor extent were lower with finasteride than with placebo, including mean percentage of positive cores (34% versus 38%, P = .016), mean tumor linear extent (greatest [4.4 versus 4.8 mm, P = .19] and aggregate [7.6 versus 9.2 mm, P = .13]), bilaterality (22.8% versus 30.6%, P = .046), and perineural invasion (14.2% versus 20.3%, P = .07). Among patients who had prostatectomy, the finasteride-associated increase in high-grade disease (Gleason score 
7) at biopsy (42.7% finasteride versus 25.4% placebo, P<.001) was diminished at prostatectomy (46.4% finasteride versus 38.6% placebo, P = .10). Biopsy identified a greater proportion of patients with high-grade disease present at prostatectomy in the finasteride group than in the placebo group (69.7% versus 50.5%, P = .01). The rate of upgrading (from low-grade cancer at biopsy to high-grade cancer at prostatectomy) and pathologic stage at prostatectomy were similar in both groups.
Conclusions: Effects of finasteride on prostate volume and selective inhibition of low-grade cancer, rather than effects on tumor morphology, may have contributed to the increase in high-grade cancers with finasteride in the PCPT. Although induction of high-grade cancer cannot be excluded, the results suggest that high-grade cancer was detected earlier and was less extensive in the finasteride group than in the placebo group.
| CONTEXT AND CAVEATS Prior knowledge Results from the Prostate Cancer Prevention Trial (PCPT) indicated a higher incidence of high-grade prostate cancer among men who were treated with finasteride than men who were treated with placebo. Study design Disease extent in prostate biopsies with high-grade tumors (Gleason score 7–10), prostate gland volume, and tumor grade and extent in radical prostatectomy samples were compared among men who were treated with finasteride and men treated with placebo in the PCPT. Contributions Men who were treated with finasteride had reduced tumor extent in prostate biopsies and lower prostate gland volumes than men who were treated with placebo. The increase in high-grade disease observed at initial diagnostic needle biopsy in the finasteride group compared with the placebo group was less apparent at prostatectomy. In the finasteride group, needle biopsy identified a larger proportion of the men found to have high-grade disease at prostatectomy. Stage at prostactectomy and the proportion of men with prostate cancer that was upgraded from low grade to high grade at prostatectomy were similar in the two groups. Implications The increase in high-grade prostate cancer incidence with finasteride observed in the PCPT may have been due in part to effects of finasteride on prostate gland volume and reduced low-grade cancer rather than to effects on tumor morphology or biology. Limitations Not all men who had biopsies had prostatectomy, and unknown differences among the men who did and did not might have affected the findings in the two groups. This was a multicenter study, and different centers used different methods to prepare prostatectomy samples for analysis, which may have led to variations in the detection of high-grade disease. In addition, long-term outcomes, such as death from prostate cancer or overall survival, were not followed in this study.
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Manuscript received February 17, 2006; revised June 18, 2007; accepted July 20, 2007.
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J Natl Cancer Inst 2007 99: 1355-1356.
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J Natl Cancer Inst 2007 99: 1353.
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