03/11/2025
By Danielle Candelieri
Candidate Name: Danielle Candelieri
Degree: Doctoral
Defense Date: Monday March 24, 2025
Time: 1-2:30 p.m. ET
Location: Health Sciences Hub, Room 342 (HSS 342)
113 Wilder St, Lowell, MA 01854
University of Massachusetts Lowell (South Campus)
Thesis/Dissertation Title: "Epidemiologic, Clinical, and Genetic Insights into Prostate Cancer Outcomes in Veterans"
Committee:
Advisor: Dan Berlowitz, MD, Public Health, Zuckerberg College of Health Sciences, University of Massachusetts Lowell
Committee Members:
JongSoo Lee, Ph.D., Mathematics & Statistics, Kennedy College of Sciences, University of Massachusetts Lowell
Camilla Pimentel, Ph.D., Public Health, Zuckerberg College of Health Sciences, University of Massachusetts Lowell
Craig Teerlink, Ph.D., Epidemiology & Public Health, School of Medicine, University of Utah
Brief Abstract:
Background: Prostate cancer, particularly metastatic castration-resistant prostate cancer (mCRPC), presents significant challenges in terms of disease management and patient outcomes. Limited research on the burden and outcomes of mCRPC, especially among Veterans, has hindered optimal disease management. Additionally, racial disparities in incidence and mortality rates, as well as the genetic underpinnings of treatment responses, further complicate the landscape of mCRPC treatment. This study aims to provide a comprehensive description of mCRPC among Veterans, assess survival outcomes based on race and treatment, and explore the genetic factors influencing prostate cancer risk and treatment response.
Methods: Data from the Veterans Health Administration's Corporate Data Warehouse (CDW) were utilized to identify Veterans with prostate cancer, metastatic prostate cancer, and mCRPC. The study calculated prevalence and age-adjusted incidence rates of mCRPC from 2005-2022 and performed trend analyses. A retrospective observational cohort study assessed survival outcomes based on race and first-line treatment in Veterans diagnosed with mCRPC from January 1, 2011, to March 12, 2024, treated with either abiraterone or enzalutamide. For the genetic analysis, the Million Veteran Program, the nation’s largest biorepository of Veteran data was used. Gene-level tests using SKAT and burden tests were conducted to analyze the risk of rare variants with prostate cancer risk and treatment response.
Results: A total of 44,246 patients with mCRPC were identified within the VA, with increasing prevalence, incidence, and survival rates each year. The highest prevalence was observed in the western United States. Median time to mCRPC from prostate cancer diagnosis was 5.68 years for de novo cases and 10.98 years for those progressing from localized disease. Median overall survival improved from 1.23 years (2005-2011) to 2.17 years (2017-2023). Among 12,355 patients treated for mCRPC, Black Veterans were diagnosed younger and had higher median overall survival compared to White Veterans (36.3 months vs. 31 months). Enzalutamide was associated with higher median overall survival compared to abiraterone (28 months vs. 23.7 months). Gene-level analyses indicated that variants within several genes could serve as potential prognostic markers, influencing prostate cancer risk and treatment outcomes.
Conclusions: This comprehensive study highlights the improving survival and diagnostic methods for Veterans with mCRPC, emphasizing the need for enhanced disease management strategies. Racial disparities in survival outcomes suggest differences in tumor biology and treatment responses. Genetic analyses provide novel insights into the genetic architecture of prostate cancer, suggesting that rare variants may play a role in prostate cancer risk and resistance to androgen-receptor targeted therapies. Future research should focus on pathway analyses to better understand gene interactions and their impact on prostate cancer pathophysiology and survival outcomes, ultimately informing risk stratification and therapeutic strategies.