Introduction: Obesity and type II diabetes mellitus (T2DM) have been associated with adverse prostate cancer (PrCa) outcomes in several studies; however, results have been inconsistent. We examined the independent and combined effects of body mass index (BMI)/obesity and T2DM in relation to the National Comprehensive Cancer Network (NCCN) PrCa risk groups in a large, racially-diverse patient population from an urban medical center. Methods: We abstracted demographic, clinical and pathological data, as well as BMI/obesity and T2DM status at time of PrCa diagnosis from all patients, who underwent radical prostatectomy for their cancer at our academic institution from 2005 through 2019. Patients were classified into three NCCN PCa risk groups: low, intermediate and high risk based on their pathological Gleason score, tumor stage and diagnostic serum PSA. Multinomial logistic regression models were used to examine associations of obesity (BMI>30kg/m2) and T2DM with risks of intermediate and high risk PCa (comparison group were men with low risk disease). We examined both independent and combined effects of obesity and T2DM in multivariate models adjusted for age and race/ethnicity (main effect models were also adjusted for BMI or T2DM). Results: A total 1,366 PrCa patients with an average age of 60±6.9 years old with complete data were included in this analysis. The majority of patients were African-American (37.2%) or Hispanic (31.5%). The prevalence of obesity and T2DM were 29.4% and 28% respectively in this cohort, with African-Americans having the highest prevalence of both obesity (38.1%) and T2DM (43.6%) compared to other races/ethnicities. A large proportion of patients had NCCN intermediate (64%) or high-risk (14%) disease. In multivariate analyses, obesity was associated with 2.23 increased odds of high-risk PCa (95%CI: 1.26-3.93), while T2DM was associated with OR=1.53 (95%CI: 1.08-2.17) of intermediate risk PCa. Interaction analysis showed that obese patients with T2DM had increased risks of both intermediate (OR=1.99; 95%CI 1.16-3.41) and high-risk PCa (OR=2.28; 95%CI 1.14-4.53) when compared to lean men without T2DM.

Discussion: In this multiracial population, both obesity and T2DM were independently associated with high risk PrCa. Moreover, there was an additive effect of obesity and T2DM in the odds of developing both intermediate and high risk PrCa. Potential biological pathways of insulin signaling and inflammatory factors arising from adipokines could be involved in promoting more aggressive PrCa phenotypes. Larger cohort studies are needed to better elucidate the mechanisms between T2DM, obesity, and PrCa tumor pathology.

Citation Format: Michelle Toker, Denzel Zhu, William Shyr, Ethan Fram, Kara L. Watts, Ilir Agalliu. Association of obesity and diabetes with prostate cancer risk group in a multiethnic population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB087.