Projecting prostate cancer mortality in the PCPT and REDUCE chemoprevention trials

Paul F. Pinsky, Amanda Black, Robert Grubb, E. David Crawford, Gerald Andriole, Ian Thompson, Howard Parnes

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background. Two recent chemoprevention trials demonstrated significant reductions in overall prostate cancer incidence. However, a possible increase in high-grade disease has raised concerns that the harms of the drugs, including mortality because of high-grade disease, may outweigh the benefits. The authors attempted to estimate the effect of these drugs on prostate cancer mortality to be able to better evaluate the cost-benefit tradeoff. Methods. The authors analyzed prostate cancer incidence in the Prostate Cancer Prevention Trial (PCPT) and Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which evaluated finasteride and the related compound dutasteride, respectively (both vs placebo). They used 13-year prostate cancer survival data from the Prostate, Lung, Colorectal and Ovarian (PLCO) trial to project prostate cancer mortality from incidence patterns; survival rates were applied to incident cancers according to prognostic strata, which were defined by Gleason score, prostate-specific antigen level, and clinical stage. For PCPT, the analysis was performed using both original trial results and previously published adjusted analyses that attempted to account for artifacts related to the drugs' effect on prostate volume. Results. For the PCPT trial, the estimated relative risk (RR) for prostate cancer mortality was 1.02 (95% confidence interval [95% CI], 0.85-1.23) using the original trial results and 0.87 (95% CI, 0.72-1.06) and 0.91 (95% CI, 0.76-1.09) based on the adjusted PCPT analyses. For the REDUCE trial, the RR for prostate cancer mortality was 0.93 (95% CI, 0.80-1.08). Conclusions. Projecting a mortality outcome of the PCPT and REDUCE trials as an approach to weighing benefits versus harms suggests at most a small increase in prostate cancer mortality in the treatment arms, and possibly a modest decrease. Cancer 2013.

Original languageEnglish (US)
Pages (from-to)593-601
Number of pages9
JournalCancer
Volume119
Issue number3
DOIs
StatePublished - Feb 1 2013

Fingerprint

Chemoprevention
Prostatic Neoplasms
Mortality
Confidence Intervals
Dutasteride
Prostate
Incidence
Pharmaceutical Preparations
Finasteride
Neoplasm Grading
Prostate-Specific Antigen
Artifacts
Cost-Benefit Analysis

Keywords

  • chemoprevention trial
  • dutasteride
  • finasteride
  • Gleason score
  • mortality
  • prostate cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pinsky, P. F., Black, A., Grubb, R., Crawford, E. D., Andriole, G., Thompson, I., & Parnes, H. (2013). Projecting prostate cancer mortality in the PCPT and REDUCE chemoprevention trials. Cancer, 119(3), 593-601. https://doi.org/10.1002/cncr.27774

Projecting prostate cancer mortality in the PCPT and REDUCE chemoprevention trials. / Pinsky, Paul F.; Black, Amanda; Grubb, Robert; Crawford, E. David; Andriole, Gerald; Thompson, Ian; Parnes, Howard.

In: Cancer, Vol. 119, No. 3, 01.02.2013, p. 593-601.

Research output: Contribution to journalArticle

Pinsky, PF, Black, A, Grubb, R, Crawford, ED, Andriole, G, Thompson, I & Parnes, H 2013, 'Projecting prostate cancer mortality in the PCPT and REDUCE chemoprevention trials', Cancer, vol. 119, no. 3, pp. 593-601. https://doi.org/10.1002/cncr.27774
Pinsky PF, Black A, Grubb R, Crawford ED, Andriole G, Thompson I et al. Projecting prostate cancer mortality in the PCPT and REDUCE chemoprevention trials. Cancer. 2013 Feb 1;119(3):593-601. https://doi.org/10.1002/cncr.27774
Pinsky, Paul F. ; Black, Amanda ; Grubb, Robert ; Crawford, E. David ; Andriole, Gerald ; Thompson, Ian ; Parnes, Howard. / Projecting prostate cancer mortality in the PCPT and REDUCE chemoprevention trials. In: Cancer. 2013 ; Vol. 119, No. 3. pp. 593-601.
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abstract = "Background. Two recent chemoprevention trials demonstrated significant reductions in overall prostate cancer incidence. However, a possible increase in high-grade disease has raised concerns that the harms of the drugs, including mortality because of high-grade disease, may outweigh the benefits. The authors attempted to estimate the effect of these drugs on prostate cancer mortality to be able to better evaluate the cost-benefit tradeoff. Methods. The authors analyzed prostate cancer incidence in the Prostate Cancer Prevention Trial (PCPT) and Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which evaluated finasteride and the related compound dutasteride, respectively (both vs placebo). They used 13-year prostate cancer survival data from the Prostate, Lung, Colorectal and Ovarian (PLCO) trial to project prostate cancer mortality from incidence patterns; survival rates were applied to incident cancers according to prognostic strata, which were defined by Gleason score, prostate-specific antigen level, and clinical stage. For PCPT, the analysis was performed using both original trial results and previously published adjusted analyses that attempted to account for artifacts related to the drugs' effect on prostate volume. Results. For the PCPT trial, the estimated relative risk (RR) for prostate cancer mortality was 1.02 (95{\%} confidence interval [95{\%} CI], 0.85-1.23) using the original trial results and 0.87 (95{\%} CI, 0.72-1.06) and 0.91 (95{\%} CI, 0.76-1.09) based on the adjusted PCPT analyses. For the REDUCE trial, the RR for prostate cancer mortality was 0.93 (95{\%} CI, 0.80-1.08). Conclusions. Projecting a mortality outcome of the PCPT and REDUCE trials as an approach to weighing benefits versus harms suggests at most a small increase in prostate cancer mortality in the treatment arms, and possibly a modest decrease. Cancer 2013.",
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N2 - Background. Two recent chemoprevention trials demonstrated significant reductions in overall prostate cancer incidence. However, a possible increase in high-grade disease has raised concerns that the harms of the drugs, including mortality because of high-grade disease, may outweigh the benefits. The authors attempted to estimate the effect of these drugs on prostate cancer mortality to be able to better evaluate the cost-benefit tradeoff. Methods. The authors analyzed prostate cancer incidence in the Prostate Cancer Prevention Trial (PCPT) and Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which evaluated finasteride and the related compound dutasteride, respectively (both vs placebo). They used 13-year prostate cancer survival data from the Prostate, Lung, Colorectal and Ovarian (PLCO) trial to project prostate cancer mortality from incidence patterns; survival rates were applied to incident cancers according to prognostic strata, which were defined by Gleason score, prostate-specific antigen level, and clinical stage. For PCPT, the analysis was performed using both original trial results and previously published adjusted analyses that attempted to account for artifacts related to the drugs' effect on prostate volume. Results. For the PCPT trial, the estimated relative risk (RR) for prostate cancer mortality was 1.02 (95% confidence interval [95% CI], 0.85-1.23) using the original trial results and 0.87 (95% CI, 0.72-1.06) and 0.91 (95% CI, 0.76-1.09) based on the adjusted PCPT analyses. For the REDUCE trial, the RR for prostate cancer mortality was 0.93 (95% CI, 0.80-1.08). Conclusions. Projecting a mortality outcome of the PCPT and REDUCE trials as an approach to weighing benefits versus harms suggests at most a small increase in prostate cancer mortality in the treatment arms, and possibly a modest decrease. Cancer 2013.

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