Projecting prostate cancer mortality in the PCPT and REDUCE chemoprevention trials.
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.
Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA. pp4f@nih.gov
Paul F
PF
Pinsky
Amanda
A
Black
Robert
R
Grubb
E David
ED
Crawford
Gerald
G
Andriole
Ian
I
Thompson
Howard
H
Parnes
D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001378:Azasteroids / Q000627:therapeutic use*; D002277:Carcinoma / Q000175:diagnosis / Q000453:epidemiology / Q000401:mortality* / Q000517:prevention & control*; D018890:Chemoprevention / Q000379:methods; D000068538:Dutasteride; D005544:Forecasting; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D015995:Prevalence; D011379:Prognosis; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000453:epidemiology; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000401:mortality* / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D015996:Survival Rate / Q000639:trends
D058891:5-alpha Reductase Inhibitors; D018931:Antineoplastic Agents, Hormonal; D001378:Azasteroids; D000068538:Dutasteride