Abstract C017: Comparing prostate specific antigen dynamics between Black patients and White patients

Abstract

Abstract Black men have the highest prostate cancer (PCa) mortality across all US population groups. We hypothesize that this may be the result of low participation from black men in clinical trials and socioeconomic facotrs. We use a simple mathematical model to investigate differences in PSA dynamics between black and white men undergoing androgen deprivation therapy (ADT). The model was calibrated to longitudinal PSA data from 57 PCa patients (N = 47 white, N = 10 black) receiving continuous androgen deprivation therapy (ADT). To compensate for the lack of data for black patients, propensity score matching was used to select 15 white patients that were most alike to the 10 black patients based on their Eastern Cooperative Oncology Group (ECOG) score, age, and tumor burden. Using a previously developed model of stem cell, non-stem, and prostate-specific antigen (PSA) dynamics, parameter analysis and leave-one-out process were used to determine which parameters should be uniform among all patients and which should be patient-specific to determine if any parameters showed a significant difference. Each patient’s parameter values were used to see if intermittent ADT (IADT) or adaptive ADT could extend the time to progression and narrow disparity gaps. We then sampled from the parameter distributions to create 50 black and 50 white in-silico patients to simulate continuous and intermittent ADT to further validate our results. The leave-one-out analysis found that a uniform ADT cytotoxicity resulted in the best Akaike Information Criteria score for black and white patients. A nested optimization was subsequently used to determine race-specific uniform cytotoxicity rates, while the remaining patient-specific parameters were determined. Statistical analysis found that black patients had a significantly higher stem cell self-renewal rate than the white patients. We hypothesize that this is primarily responsible for earlier progression in black patients. Simulations of continuous and intermittent ADT for real and in-silico patients showed that IADT and adaptive ADT can extend the time to progression (TTP) for both black and white patients. The TTP was extended by 50% for the black patients, and 25% for the white patients, thus the black patients had a greater benefit. However, the median TTP for black patients on IADT was less than that for white patients on continuous ADT. This suggests that further investigation of different treatments needs to be done to close disparity gaps. Our results show that stem cell self-renewal is driving differences in PSA dynamics between white and black patients. Intermittent Androgen Deprivation Therapy could potentially be a step in addressing the higher stem-cell self-renewal rate in black patients and narrowing the health disparity gap between black and white Pca patients. This valuable information can be used in the future to design race-specific treatment modalities to maximally delay time to progression. Citation Format: Alexandria Johnson, Renee Brady. Comparing prostate specific antigen dynamics between Black patients and White patients [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C017.