Patients on these therapies have experienced cardiotoxicity, defined in 2021 by the International Cardio-Oncology Society (IC-OS) as any combination of heart failure, myocarditis, vascular toxicity, hypertension, or arrhythmias. Interestingly, a February 2024 study published by Mani, et al confirmed that cardiac disease is the most common non-oncologic cause of death in metastatic prostate cancer patients. Therefore, assessment of cardiotoxicity risk should be paramount when choosing among first-line regimens but is often overlooked due to a paucity of directive evidence.
To delineate this risk, we created a prostate cancer cardiotoxicity map (PROXMAP) as a patient’s prostate cancer progresses from either metastatic hormone-sensitive (mHSPC) or non-metastatic castrate-resistant (M0CRPC) prostate cancer to metastatic castrate-resistant prostate cancer (mCRPC). We reviewed 4846 articles of all study designs across these prostate cancer states; based on pre-determined criteria for risk of bias and constraints of Bayesian network meta-analysis, 13 randomized controlled trials with over 16000 patients were included. Constraints of the analysis acknowledge limitations of primary data, as most of these studies to date exclude patients with preexisting cardiovascular disease to varying extents.
Our results demonstrated two key findings. First, for patients with mHSPC, triple therapy with ADT, docetaxel, and abiraterone was associated with greater hypertension and arrhythmias compared to triple therapy with ADT, docetaxel, and darolutamide. One possible explanation for this finding could be due to mineralocorticoid excess from CYP17 inhibition in the adrenal gland, with the resulting hypokalemia predisposing to arrhythmias. Therefore, our study offers a potential decision point between these first-line triple therapies. Second, the route by which mCRPC arises (mHSPC versus M0CRPC), the speed at which M0CRPC progresses to mCRPC, and the treatments received during mHSPC or M0CRPC can influence the cardiotoxicity observed during mCRPC treatment. More work remains to further delineate the subtleties of these effects, but we are hopeful that future primary study designs can be mindful of these possibilities given the recent cardiotoxicity definition provided by IC-OS. Observing the effects and harms of cancer therapeutics with this framework in a real-world population, which may not be directly representative of the tightly controlled trial populations that led to their indications, can potentially generate real-world evidence incorporable in clinical decision-making and future guidelines.
Ultimately, the selection of a prostate cancer regimen requires partnerships between patients, families, and their care teams to ensure optimal outcomes. Given the complexity of this decision, we expect that urologists, oncologists, cardiologists, and primary care providers will continue to provide valuable input. We hope that our study can meaningfully contribute to this interdisciplinary decision.
Written by:
- Moez Karim Aziz, MD, MS, Department of Cardiology, The University of Texas MD Anderson Cancer Center, McGovern Medical School at The University of Texas Health Science Center at Houston, Department of Internal Medicine, Baylor College of Medicine, Houston, TX
- Donald Molony, MD, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX
- Dominique Monlezun, MD, PhD, Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX
- Syed Wamique Yusuf, MBBS, Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX
- Cezar Iliescu, MD, Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX
- Steven Canfield, MD, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX