Finasteride and high-grade prostate cancer in the Prostate Cancer Prevention Trial.
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 > or = 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.
Lucia
M Scott
MS
Department of Pathology, University of Colorado Denver and Health Sciences Center, 4200 E Ninth Ave, Box B-216, Denver, CO 80262, USA. scott.lucia@uchsc.edu
Epstein
Jonathan I
JI
Goodman
Phyllis J
PJ
Darke
Amy K
AK
Reuter
Victor E
VE
Civantos
Francisco
F
Tangen
Catherine M
CM
Parnes
Howard L
HL
Lippman
Scott M
SM
La Rosa
Francisco G
FG
Kattan
Michael W
MW
Crawford
E David
ED
Ford
Leslie G
LG
Coltman
Charles A
CA
Thompson
Ian M
IM
D001741:Black or African American / Q000706:statistics & numerical data; D000368:Aged; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D015982:Bias; D001707:Biopsy, Needle; D015986:Confounding Factors, Epidemiologic; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D018120:Finasteride / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control / Q000601:surgery; D012720:Severity of Illness Index; D014481:United States / Q000453:epidemiology; D044465:White People / Q000706:statistics & numerical data
D016588:Anticarcinogenic Agents; D004791:Enzyme Inhibitors; D018120:Finasteride; D017430:Prostate-Specific Antigen