Konrad Stopsack

M.D., M.P.H.

Harvard T.H. Chan School of Public Health

Research Scientist

PLCO (Learn more about this study)

PLCO-1046

Sep 9, 2022

Prostate Cancer Cohort Consortium (PC3): A collaborative approach to an enigmatic cancer

Prostate cancer is the top cause of cancer death among men in 56 countries. With a 2.1-fold difference in mortality rates between Black and White men, prostate cancer also has the highest racial disparity of any cancer in the U.S. Despite its high burden, the etiology of prostate cancer is an unsolved enigma. Older age, family history of prostate cancer, and African ancestry are the only established risk factors, none of which are modifiable. With the burden of overdiagnosis, post-diagnosis risk stratification for survival is clinically important but has remained imprecise.
Pooled, cohort study-based research on prostate cancer is needed to identify risk factors for development and prognosis of this high-burden cancer. Individual cohort studies have suggested that risk factors for clinically aggressive prostate cancer differ substantially from risk factors for indolent prostate cancer. Purported risk factors for aggressive prostate cancer include smoking, obesity, and use of statins; pooled efforts are needed to provide power to investigate these purported risk factors in relation to specific clinical subtypes. The maturation of prospective cohort studies now allows successfully addressing the major challenges that historically have limited studies of prostate cancer, including its long natural history, etiologic heterogeneity, effects of PSA screening, and limited representation of the racial and ethnic groups most burdened by prostate cancer.
We seek to establish individual-level pooled studies in the new Prostate Cancer Cohort Consortium (PC3) within the NCI Cohort Consortium. By pooling individual-level data from multiple cohort studies, PC3 will be able to address open questions on prostate cancer in diverse populations with unprecedented precision, with explicit consideration of the effects of PSA screening and of potential differences in relative or absolute risk by race.

Aim 1: To investigate emerging risk factors for aggressive prostate cancer, overall and by race. We hypothesize that smoking, early and mid-life adiposity, and statin use cause aggressive prostate cancer, defined by our established PC3 definition, and that these risk factors can be credentialed in pooled analyses that account for confounding/effect modification by PSA screening.

Aim 2: To validate risk stratification tools for post-diagnosis survival, overall and by race. We hypothesize that cohort-based data will elucidate major differences between clinically-used risk classifiers (e.g., DAmico, NCCN) and nomograms (CAPRA, MSK). We will a) Test these tools, developed in hospital-based populations, to identify the best-performing tool in the cohort study setting, b) Integrate epidemiologic risk factors (smoking, adiposity, family history of prostate cancer) with risk classifiers to improve prediction.