Recommendations of first-line therapies for metastatic hormone-sensitive (mHSPC), nonmetastatic castrate-resistant (M0CRPC), and metastatic castrate-resistant (mCRPC) prostate cancer do not account for cardiotoxicity due to a lack of clear prior evidence. This manuscript assesses cardiotoxicity of these therapies.
We searched Ovid Medline, Elsevier Embase, and the Cochrane Library for randomized clinical trials (RCTs) from database inception to January 14, 2024. Network meta-analyses of first-line mHSPC, M0CRPC, and mCRPC therapies were constructed for the five cardiotoxicity metrics defined by the International Cardio-Oncology Society: heart failure, myocarditis, vascular toxicity, hypertension, and arrhythmias. Additional Bayesian network meta-analyses also accounted for prior treatment history.
Thirteen RCTs (16 292 patients) were included. For mHSPC, androgen deprivation therapy (ADT) plus docetaxel (DTX) plus abiraterone acetate (AA) with prednisone (P) demonstrated a significant increase in hypertension and arrhythmias versus ADT + DTX (risk ratio [RR] 2.85, 95% confidence interval [CI] 1.67-4.89, and RR 2.01, 95% CI 1.17-3.44, respectively); however, no corresponding differences were observed between ADT + DTX plus darolutamide (DAR) and ADT + DTX (RR 1.55, 95% CI 0.73-3.30, and RR 0.94, 95% CI 0.63-1.40, respectively). For mCRPC assuming a history of mHSPC treatment, ADT + AA + P plus olaparib (OLA) demonstrated a statistically significant decrease in hypertension versus ADT + AA + P (RR 0.20, 95% CI 0.16-0.26). M0CRPC results were unremarkable.
For mHSPC, ADT + DTX + DAR demonstrates less cardiotoxicity than ADT + DTX + AA + P due to a lower risk of hypertension and arrhythmias from decreased mineralocorticoid excess. In addition, OLA counterintuitively offers decreased hypertension when superimposed on ADT + AA + P for mCRPC treatment after prior androgen deprivation from mHSPC therapy.
European urology. 2024 Sep 18 [Epub ahead of print]
Moez Karim Aziz, Donald Molony, Dominique Monlezun, Travis Holder, Oliver Brunckhorst, Noel Higgason, Jerry Roland, Resa Magill, Mariya Fatakdawala, Alexander Iacobucci, Neal Mody-Bailey, Chris Owen, Andrew Zarker, Emma Thames, Justin Swaby, Daniel Xiao, Lily Choi, Shubh Desai, Jacob Galan, Brett Deng, Taylor Hartshorne, Alexis Nichols, Allan Zhang, Jared Imber, Jeffrey Song, William Jones, Alexis Rivas, Darren Sanchez, Maya Guhan, Giorgio Gandaglia, Shreyas Ranganath, Jerril Jacob, Skyler Howell, Juan Plana, Roderick van den Bergh, Matthew Roberts, Silke Gillessen Sommer, Jan Oldenburg, Guillaume Ploussard, Derya Tilki, Ivo Schoots, Erik Briers, Johan Stranne, Olivier Rouviere, Inge van Oort, Daniela Oprea-Lager, Maria De Santis, Philip Cornford, European Association of Urology Prostate Cancer Guidelines Panel
Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA; Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA., McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA., Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., MRC Centre for Transplantation, Guy's Hospital Campus, King's College London, King's Health Partners, London, UK., Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA., Department of Internal Medicine, University of Georgia, Augusta, GA, USA., Department of Internal Medicine, University of the Incarnate Word, San Antonio, TX, USA., Department of Urology, San Raffaele Hospital, Milan, Italy., Prostate Cancer Guidelines Panel, European Association of Urology, Arnhem, The Netherlands.