Abstract Body (Do not enter title and authors here): Background and Aim: For metastatic castrate-resistant prostate cancer (mCRPC), the European Association of Urology recommends multiple therapies as first-line. However, these recommendations do not account for additional cardiotoxicity of the therapies for prior stages of the disease, such as the metastatic hormone-sensitive prostate cancer (mHSPC) stage. We seek to adjudicate the cardiotoxicities of first-line mCRPC therapies assuming history of mHSPC treatment based on the five International Cardio-Oncology Society (IC-OS) cardiotoxicity domains: heart failure, myocarditis, vascular toxicity, hypertension, and arrhythmias.

Methods: Ovid Medline, Elsevier Embase, and the Cochrane Library were searched for randomized clinical trials (RCTs) of mCRPC and mHSPC patients from inception until January 2024. Studies reporting at least one first-line therapy and effect size of at least one cardiotoxicity domain were included. Network meta-analyses with indirect treatment comparison with multivariate multi-level analysis were performed for each cardiotoxicity domain to estimate relative risk (RR) with 95% confidence intervals (CI) for mCRPC and mHSPC therapies. A Bayesian model was then constructed using the mHSPC network as a prior for informing the RRs and 95% CIs of mCRPC first-line therapies.

Results: Network meta-analyses of mHSPC treatment cardiotoxicity, mCRPC treatment cardiotoxicity assuming no treatment history, and mCRPC treatment cardiotoxicity assuming prior mHSPC treatment are provided in Images 1-2. We did not find any studies assessing myocarditis. For patients with mHSPC treatment history, olaparib (OLA) plus androgen deprivation therapy (ADT) plus abiraterone with prednisone (AA+P) decreased hypertensive risk relative to ADT+AA+P (RR 0.20, 95% CI 0.16-0.26).

Conclusion: OLA may offer a protective antihypertensive effect when superimposed on ADT+AA+P for mCRPC treatment after prior androgen deprivation from mHSPC therapy.