Finasteride and high-grade prostate cancer in the prostate cancer prevention trial

M. Scott Lucia, Jonathan I. Epstein, Phyllis J. Goodman, Amy K. Darke, Victor E. Reuter, Francisco Civantos, Catherine M. Tangen, Howard L. Parnes, Scott M. Lippman, Francisco G. La Rosa, Michael W. Kattan, E. David Crawford, Leslie G. Ford, Charles A. Coltman, Ian M. Thompson

Research output: Contribution to journalArticle

191 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1375-1383
Number of pages9
JournalJournal of the National Cancer Institute
Volume99
Issue number18
DOIs
StatePublished - Sep 1 2007

Fingerprint

Finasteride
Prostatic Neoplasms
Placebos
Prostatectomy
Neoplasms
Biopsy
Prostate
Neoplasm Grading
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lucia, M. S., Epstein, J. I., Goodman, P. J., Darke, A. K., Reuter, V. E., Civantos, F., ... Thompson, I. M. (2007). Finasteride and high-grade prostate cancer in the prostate cancer prevention trial. Journal of the National Cancer Institute, 99(18), 1375-1383. https://doi.org/10.1093/jnci/djm117

Finasteride and high-grade prostate cancer in the prostate cancer prevention trial. / Lucia, M. Scott; Epstein, Jonathan I.; Goodman, Phyllis J.; Darke, Amy K.; Reuter, Victor E.; Civantos, Francisco; Tangen, Catherine M.; Parnes, Howard L.; Lippman, Scott M.; La Rosa, Francisco G.; Kattan, Michael W.; Crawford, E. David; Ford, Leslie G.; Coltman, Charles A.; Thompson, Ian M.

In: Journal of the National Cancer Institute, Vol. 99, No. 18, 01.09.2007, p. 1375-1383.

Research output: Contribution to journalArticle

Lucia, MS, Epstein, JI, Goodman, PJ, Darke, AK, Reuter, VE, Civantos, F, Tangen, CM, Parnes, HL, Lippman, SM, La Rosa, FG, Kattan, MW, Crawford, ED, Ford, LG, Coltman, CA & Thompson, IM 2007, 'Finasteride and high-grade prostate cancer in the prostate cancer prevention trial', Journal of the National Cancer Institute, vol. 99, no. 18, pp. 1375-1383. https://doi.org/10.1093/jnci/djm117
Lucia, M. Scott ; Epstein, Jonathan I. ; Goodman, Phyllis J. ; Darke, Amy K. ; Reuter, Victor E. ; Civantos, Francisco ; Tangen, Catherine M. ; Parnes, Howard L. ; Lippman, Scott M. ; La Rosa, Francisco G. ; Kattan, Michael W. ; Crawford, E. David ; Ford, Leslie G. ; Coltman, Charles A. ; Thompson, Ian M. / Finasteride and high-grade prostate cancer in the prostate cancer prevention trial. In: Journal of the National Cancer Institute. 2007 ; Vol. 99, No. 18. pp. 1375-1383.
@article{6f447581843c41e6a3df8fcdc19023d8,
title = "Finasteride and high-grade prostate cancer in the prostate cancer prevention trial",
abstract = "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.",
author = "Lucia, {M. Scott} and Epstein, {Jonathan I.} and Goodman, {Phyllis J.} and Darke, {Amy K.} and Reuter, {Victor E.} and Francisco Civantos and Tangen, {Catherine M.} and Parnes, {Howard L.} and Lippman, {Scott M.} and {La Rosa}, {Francisco G.} and Kattan, {Michael W.} and Crawford, {E. David} and Ford, {Leslie G.} and Coltman, {Charles A.} and Thompson, {Ian M.}",
year = "2007",
month = "9",
day = "1",
doi = "10.1093/jnci/djm117",
language = "English",
volume = "99",
pages = "1375--1383",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "18",

}

TY - JOUR

T1 - Finasteride and high-grade prostate cancer in the prostate cancer prevention trial

AU - Lucia, M. Scott

AU - Epstein, Jonathan I.

AU - Goodman, Phyllis J.

AU - Darke, Amy K.

AU - Reuter, Victor E.

AU - Civantos, Francisco

AU - Tangen, Catherine M.

AU - Parnes, Howard L.

AU - Lippman, Scott M.

AU - La Rosa, Francisco G.

AU - Kattan, Michael W.

AU - Crawford, E. David

AU - Ford, Leslie G.

AU - Coltman, Charles A.

AU - Thompson, Ian M.

PY - 2007/9/1

Y1 - 2007/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34748863567&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34748863567&partnerID=8YFLogxK

U2 - 10.1093/jnci/djm117

DO - 10.1093/jnci/djm117

M3 - Article

C2 - 17848673

AN - SCOPUS:34748863567

VL - 99

SP - 1375

EP - 1383

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 18

ER -