Pathologic characteristics of cancers detected in the Prostate Cancer Prevention Trial

Implications for prostate cancer detection and chemoprevention

M. Scott Lucia, Amy K. Darke, Phyllis J. Goodman, Francisco G. La Rosa, Howard L. Parnes, Leslie G. Ford, Charles A. Coltman, Ian M. Thompson

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

The Prostate Cancer Prevention Trial (PCPT) showed a risk of prostate cancer at prostate-specific antigen (PSA) <4.0 ng/mL and that prostate cancer risk is reduced by finasteride. A major concern about early detection by PSA and prevention by finasteride is that they may involve biologically inconsequential tumors. We reviewed the pathologic characteristics of prostate biopsies from men in the placebo and finasteride groups of the PCPT. We examined tumor pathology characteristics stratified by level of PSA for men in the placebo group who underwent radical prostatectomy. Seventy-five percent of all cancers and 62% of Gleason score ≤6 cancers in the PCPT met the biopsy criteria for clinically significant tumors. Surrogate measures for tumor volume (number of cores positive, percent cores positive, linear extent, and bilaterality) and risk of perineural invasion were lower in men who received finasteride. The PSA-associated risks of insignificant cancer were 51.7% (PSA, 0-1.0 ng/mL), 33.7% (1.1-2.5 ng/mL), 17.8% (2.6-4.0 ng/mL), and 11.7% (4.1-10 ng/mL). Conversely, the risks of high-grade (Gleason score ≥7) tumors for the same PSA strata were 15.6%, 37.9%, 49.1%, and 52.4%, respectively. These data highlight the dilemma of PSA when used for screening: Lower cutoff levels increase detection of insignificant disease, but cure is more likely, whereas higher cutoff levels make detection of significant cancer more likely, but cure is less likely. Therefore, the effectiveness of finasteride in preventing prostate cancer, including Gleason score ≤6 cancer, with meaningful rates of significant disease in the PCPT suggests that cutoff values for PSA screening should be individualized and that men undergoing screening should be informed of the opportunity to reduce their risk of disease with finasteride.

Original languageEnglish (US)
Pages (from-to)167-173
Number of pages7
JournalCancer Prevention Research
Volume1
Issue number3
DOIs
StatePublished - Aug 2008

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Chemoprevention
Prostate-Specific Antigen
Finasteride
Prostatic Neoplasms
Neoplasms
Neoplasm Grading
Placebos
Biopsy
Prostatectomy
Tumor Burden
Prostate
Pathology

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Pathologic characteristics of cancers detected in the Prostate Cancer Prevention Trial : Implications for prostate cancer detection and chemoprevention. / Lucia, M. Scott; Darke, Amy K.; Goodman, Phyllis J.; La Rosa, Francisco G.; Parnes, Howard L.; Ford, Leslie G.; Coltman, Charles A.; Thompson, Ian M.

In: Cancer Prevention Research, Vol. 1, No. 3, 08.2008, p. 167-173.

Research output: Contribution to journalArticle

Lucia, M. Scott ; Darke, Amy K. ; Goodman, Phyllis J. ; La Rosa, Francisco G. ; Parnes, Howard L. ; Ford, Leslie G. ; Coltman, Charles A. ; Thompson, Ian M. / Pathologic characteristics of cancers detected in the Prostate Cancer Prevention Trial : Implications for prostate cancer detection and chemoprevention. In: Cancer Prevention Research. 2008 ; Vol. 1, No. 3. pp. 167-173.
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abstract = "The Prostate Cancer Prevention Trial (PCPT) showed a risk of prostate cancer at prostate-specific antigen (PSA) <4.0 ng/mL and that prostate cancer risk is reduced by finasteride. A major concern about early detection by PSA and prevention by finasteride is that they may involve biologically inconsequential tumors. We reviewed the pathologic characteristics of prostate biopsies from men in the placebo and finasteride groups of the PCPT. We examined tumor pathology characteristics stratified by level of PSA for men in the placebo group who underwent radical prostatectomy. Seventy-five percent of all cancers and 62{\%} of Gleason score ≤6 cancers in the PCPT met the biopsy criteria for clinically significant tumors. Surrogate measures for tumor volume (number of cores positive, percent cores positive, linear extent, and bilaterality) and risk of perineural invasion were lower in men who received finasteride. The PSA-associated risks of insignificant cancer were 51.7{\%} (PSA, 0-1.0 ng/mL), 33.7{\%} (1.1-2.5 ng/mL), 17.8{\%} (2.6-4.0 ng/mL), and 11.7{\%} (4.1-10 ng/mL). Conversely, the risks of high-grade (Gleason score ≥7) tumors for the same PSA strata were 15.6{\%}, 37.9{\%}, 49.1{\%}, and 52.4{\%}, respectively. These data highlight the dilemma of PSA when used for screening: Lower cutoff levels increase detection of insignificant disease, but cure is more likely, whereas higher cutoff levels make detection of significant cancer more likely, but cure is less likely. Therefore, the effectiveness of finasteride in preventing prostate cancer, including Gleason score ≤6 cancer, with meaningful rates of significant disease in the PCPT suggests that cutoff values for PSA screening should be individualized and that men undergoing screening should be informed of the opportunity to reduce their risk of disease with finasteride.",
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