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Factors influencing prostate cancer mortality

Principal Investigator

Name
David Crawford

Institution
Univeristy of Colorado Health Science Center

Email
david.crawford@uchsc.edu

About this CDAS Project

Study
PLCO (Learn more about this study)

Project ID
2009-0012

Initial CDAS Request Approval
Oct 1, 2009

Title
Factors influencing prostate cancer mortality

Summary
The early results of the prostate component of the PLCO trial showed no mortality benefit due to screening in data on men with 7 years of follow-up. While efforts to reduce prostate cancer (PCa) mortality vis a vis current early detection modalities have shown limited promise in reducing PCa mortality, it is still of great interest to investigate characteristics of men who do die of prostate cancer. The inherent heterogeneity of PCa based upon Gleason grade and clinical stage and the impact of these in determining the risk of PCa mortality among men diagnosed with PCa is well known. However, the impact of comorbidity could be twofold: by limiting PCa mortality among those with indolent tumors and also by promulgating PCa mortality through the decision by more frail individuals to chose a less invasive treatment option which would not otherwise be indicated given the level of aggressiveness of their tumor. Due to the relatively low rate of PCa mortality, roughly 3 per 10000 person years, these are questions which to date remain unanswered because of the inadequacy of available data. In an attempt to further understand the patient profiles underlying death from prostate cancer versus death other causes, we propose to investigate the relationship between high/low Gleason grade, clinical stage, treatment choice and comorbidity upon prostate cancer mortality and non-prostate cancer mortality in the population of men with diagnosed prostate cancers from among both arms of the prostate component of the PLCO trial. We will test for effect modification by screening arm membership, and will adjust analysis for other traditional risk factors such as age, race/ethnicity, index PSA, last screening PSA, smoking, educational level and family history.

Aims

1. To test the association between high versus low Gleason grade and the competing risks of prostate cancer mortality and other cause mortality, adjusted for screening arm, age, race/ethnicity, smoking, PSA, treatment choice and comorbidity. 2. To tabulate mortality rates due to prostate cancer and to other causes by screening arm according to comorbidity, and treatment choice. 3. To establish a basis for possible effect modification of high versus low Gleason grade by the above mentioned factors in a penalized regression approach. This aim is exploratory and to be considered secondarily.

Collaborators

Robert L. Grubb III (Washington University School of Medicine)
Grant Izmirlian (DCP/BRG)
Barnett S. Kramer (Office of Disease Prevention, NIH)
Thomas Riley (Information Management Services)
Timothy R. Church (University of Minnesota School of Public Health)

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