Abstract 4141498: Coronary Atherosclerosis and Prostate Cancer: The Impact of Androgen Deprivation Therapy

Background: Men with prostate cancer (PC) who receive androgen-deprivation therapy (ADT), targeting the gonadotropin releasing hormone (GNRH) axis, are at higher risk of cardiovascular disease (CVD). However, the pathophysiology behind ADT cardiotoxicity is unclear. Hypothesis: We hypothesize that ADT is associated with accelerated atherosclerosis due to GNRH-mediated inflammatory cascade. Aims: To prospectively evaluate coronary plaque progression, using coronary computed tomography angiography (CCTA), in a cohort of PC men treated with versus without ADT. Methods: Sixty-eight men with localized PC receiving radiation (XRT) alone (n=17) or XRT+ADT (n=51) were prospectively enrolled. Patients underwent CCTA, as per clinical protocols , at baseline and 12-month follow-up. Plaque quantification was conducted, blinded to therapy and time-point, using semi-automated software (Coronary analysis research prototype, Siemens Healthineers, Forchheim, Germany), with assessment of total plaque volume (TPV) and plaque volume by subtype (calcified, CPV, high-density non-calcified, HD, low-density non-calcified, LD) on a per-patient basis. CAD-RADS was also evaluated. Results: At baseline, median (IQR) TPV, CPV, HD, LD (mm 3 ) and CAD-RADS among patients who received XRT alone versus XRT+ADT were 341.1 (118.5-778.2) vs 717.3 (207-1158.9), 22.2 (4.9-131.9) vs 74.3 (21.3-205.8), 306.6 (102.1-593.6) vs 585.8 (175-895.2), 14 (2.3-47) vs 22.6 (6.2-50.4), 1 (1-2) vs 2 (2-3), respectively. At 12-month follow-up, TPV, CPV, HD, LD, and CAD-RADS between XRT alone versus XRT+ADT were 410.1 (177-941) vs 904.6 (283.7-1402), 21 (12.1-195.1) vs 102.6 (30.5-259.4), 372.6 (157.6-721.6) vs 686.1 (242.7-1062.7), 11.7 (5.6-69.8) vs 34 (10.4-62.1), 2 (1-2) vs 3 (2-3). A statistically significant difference between baseline and follow-up was noted among patients treated with XRT+ADT for TPV, CPV, LD (p<0.001), and HD (p=0.006). A significant difference in CAD-RADS grade was noted in both cohorts (p=0.025 for XRT and p<0.001 for the XRT +ADT). There was no significant difference in any plaque volume between baseline and follow-up in the XRT alone cohort. Conclusion: Addition of ADT to XRT for localized PC treatment was associated with a significant progression of TPV, CPV, HD, LD, and CAD-RADS grade over a 12-month period. Insights on ADT cardiotoxicity may lead to enhanced cardioprotective strategies tailored to patients with PC undergoing combined therapy, potentially improving cardiac outcomes.