Grant Number:	3R01CA300353-01A1S1 Interpret this number
Primary Investigator:	Joshu, Corinne
Organization:	Johns Hopkins University
Project Title:	Prostate Cancer Cohort Consortium (PC3): a Collaborative Approach to an Enigmatic Cancer
Fiscal Year:	2026

PROJECT SUMMARY Prostate cancer is a top cause of cancer death, but many more men are diagnosed with it than those who die from it. Accurate at-diagnosis risk stratification among men with prostate cancer, both for cancer death and for cardiovascular disease, has remained imprecise. Prostate cancer does not need to remain enigmatic if tackled in a collaborative fashion. Notably, few studies have investigated differences based on molecular subtypes of prostate cancer so far, and no epidemiology consortium exists that has linked tumor tissue biospecimens. By using molecular tumor subtyping, this project will lay the foundation for precision prevention efforts. This project will establish the new Prostate Cancer Cohort Consortium (PC3) within the NCI Cohort Consortium. We will include ten of the most powerful cancer epidemiology cohorts with long-term outcome data: the NIH-AARP Diet and Health Study (AARP), Agricultural Health Study (AHS), Atherosclerosis Risk in Communities Study (ARIC), Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, Campaign Against Cancer and Heart Disease (CLUE), Health Professionals Follow-up Study (HPFS), Kings County, WA (KCWA) study, Physicians’ Health Study (PHS), Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), and Southern Community Cohort Study (SCCS). With 72,494 prostate cancer cases and 8,160 prostate cancer deaths, PC3 data will have unprecedented precision, specifically for high-risk groups of Black men, older men, and men with high comorbidity. We will establish data sharing, create central analytical datasets and open-source R packages, and pool tumor biorepositories. In Aim 1, we will evaluate the potential for precision prevention informed by tumor subtype to improve outcomes after cancer diagnosis. We hypothesize that ETS fusions, enhanced by PTEN loss, are particularly sensitive to the hormonal effects of adiposity and physical activity in their progression to fatal outcomes. In Aim 2, we will improve risk stratification for post-diagnosis prostate cancer survival. We will identify the best- performing existing prognostic tool for death from prostate cancer, integrate information about the patient into a novel risk classifier to improve prediction, and use counterfactual prediction approaches to create models that are informative under different treatment patterns. In Aim 3, we will recalibrate risk prediction for cardiovascular events among men with prostate cancer to account for their competing risk of cancer death. The impact of this project will be establishing a novel consortium, PC3, that closes the gap between prostate cancer and other cancer types. PC3 will represent the first U.S. population-based comparative validation of at-diagnosis risk classifiers for the two most common outcomes, cancer death and cardiovascular events. The project will be the steppingstone for future research based on PC3 infrastructure created that can leverage the molecular subtyping data, harmonized data sets, and software created for additional research.





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