Abstract C032: Increased allostatic load is associated with castrate-resistance and de novo metastatic disease in prostate cancer

Abstract

Abstract Introduction: Allostatic load (AL) is a composite measure of chronic stress including cardiovascular, immune, and metabolic biomarkers. AL has previously been associated with health disparities in cardiovascular disease, metabolic syndrome, and certain malignancies. However, there are no prior publications to the best of our knowledge evaluating the association of AL and clinical outcomes in patients with advanced prostate cancer (PCa). Methods: We identified 139 subjects with metastatic or biochemically recurrent (BCR) PCa treated at the University of Illinois Hospital and Health Sciences System between January 2015 and May 2022. Subjects were assigned AL scores based on retrospective assessment of 9 biomarkers (systolic and diastolic blood pressure, heart rate, alkaline phosphatase, albumin, creatinine, body mass index, glucose, white blood cell count) collected at the time of diagnosis of advanced disease. Subjects were assigned a total AL score whereby each of the individual 9 biomarkers were given a value of 0 or 1 if threshold value was met. Results: Of the 139 subjects, the median age at PCa diagnosis was 63. The majority were African American (65.4%), 14.4% were Hispanic or Latino, 12.2% were white and non-Hispanic or Latino, and race/ethnicity was other or unknown for 7.9%. A majority (62.6%) had localized or regional nodal disease at diagnosis but later developed metastases or BCR, while 37.4% had de novo metastatic disease. Those with de novo metastatic disease had a higher mean AL score compared to those who had localized or regional nodal disease at diagnosis (2.62 vs. 2.08, p=0.03). Nearly all of the subjects (98.6%) received androgen deprivation therapy (ADT) while 1.4% had surgical castration. Most (66.2%) had local therapies such as surgery or radiation prior to or in addition to ADT. A minority (39.6%) developed castrate-resistant disease while 60.4% did not. For subjects who developed castrate-resistant disease, median time to castrate-resistance was 31 months. Those who developed castrate-resistant disease had a higher mean AL score compared to those who did not (2.58 vs. 2.08, p=0.03). In the study population, 25.9% had a low sum Gleason score (≤7) at diagnosis, 46.0% had a high sum Gleason score (≥8) at diagnosis, and 28.1% did not have a Gleason score available at diagnosis. Subjects with a high sum Gleason score had higher mean AL compared to those with low sum Gleason scores, though this finding did not reach statistical significance (2.47 vs. 1.94, p=0.06). In our study, 32 out of 139 subjects had at least one biomarker missing from their records and therefore not included in the subject’s AL score. The most common biomarkers missing were albumin and alkaline phosphatase. Discussion: In our pilot, single-institution study, higher AL may be associated with more aggressive phenotypes of PCa including de novo metastatic disease, earlier progression to castrate-resistance, and higher Gleason scores. Prospective studies are needed to further validate the role AL plays in PCa aggressiveness. Citation Format: Michael Weinfeld, Ryan Nguyen, Frank Weinberg, Vijayakrishna Gadi, Natalie Reizine. Increased allostatic load is associated with castrate-resistance and de novo metastatic disease in prostate cancer [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C032.