Experts in Singapore and Malaysia Issue Consensus on Heart Risks of Prostate Cancer Therapy

Prostate cancer is the fourth most common cancer in men worldwide, with more than 1.4 million new cases and nearly 400,000 deaths recorded in 2022, and the number of cases is expected to more than double by 2040. The therapies that keep advanced disease in check, however, carry a hidden toll on the heart and metabolism. Androgen deprivation therapy, or ADT, and androgen receptor-targeted treatments remain central to the management of advanced prostate cancer, but they are associated with significant cardiovascular and metabolic risks, including increased risks of diabetes and cardiovascular disease. Now, a multidisciplinary panel of 12 clinicians from Malaysia and Singapore has produced a set of evidence-based consensus recommendations for assessing, monitoring and managing those risks, published in Frontiers in Oncology.

The panel, which included one cardiologist, two onco-cardiologists, five urologists, two clinical oncologists, one radiation oncologist and one medical oncologist, was assembled from tertiary academic institutions across both public and private healthcare sectors. Eligibility required more than 10 years of relevant clinical or academic experience, active involvement in clinical practice, research or guideline development, and evidence of peer-reviewed publications or recognised leadership in metastatic prostate cancer. Using a modified Delphi method with two voting rounds, the experts drafted 13 statements informed by a targeted PubMed literature search covering randomised controlled trials, systematic reviews and meta-analyses from the past decade. A statement was accepted if at least 75 percent of panellists chose ‘accept completely’ or ‘accept with minor reservation’. Twelve of the 13 statements achieved consensus; one was rejected.

The regional context shaped the recommendations. In Singapore, prostate cancer is the most diagnosed cancer in males, accounting for 17.4 percent of male cancers from 2018 to 2022, and patients are frequently diagnosed at more advanced stages than in Western cohorts, with correspondingly high ADT use. A real-world study of ADT in Asian patients, the READT study, which included Singapore and Malaysian centres, reported that metabolic complications, including weight gain, hyperglycaemia and dyslipidaemia, were highly prevalent within the first year of ADT. In Malaysia, where lifetime risk of prostate cancer varies across ethnic groups, from 1 in 72 among Chinese to 1 in 117 among Malays, considerable heterogeneity in healthcare access between urban and rural settings means that cardiology referral pathways recommended by international guidelines may not be uniformly achievable, prompting the panel to favour a pragmatic, tiered approach.

The first focus area concerns what should happen before treatment begins. The panel unanimously agreed that a baseline evaluation of lifestyle risk factors and comorbid conditions is essential for every patient with prostate cancer prior to starting ADT or androgen receptor-targeted therapy. Smoking, for example, has been linked to a nearly fivefold increase in the likelihood of coronary heart disease and is also associated with an elevated risk of high-grade prostate cancer. Early detection of comorbidities such as hypertension and diabetes offers opportunities to optimise a patient’s cardiovascular profile before therapy, and in line with a Journal of the American College of Cardiology: CardioOncology consensus, the panel recommended measuring and managing blood pressure, lipids and haemoglobin A1c before ADT initiation. A second unanimous statement endorsed a simplified cardiovascular disease risk assessment checklist for all patients, categorising them as high, intermediate or low risk based on clinical history and key factors including diabetes, smoking, hypercholesterolaemia and hypertension. The checklist is favoured over complex tools for its ease of use in busy clinics, and the panel suggested it be pre-filled or completed by nursing staff to reduce clinician burden.

During treatment, the panel agreed unanimously that treatment plans should include strategies to mitigate associated comorbidities, and that a structured management protocol tailored to cardiovascular risk categories could be implemented to optimise care. The evidence base for concern is substantial. In a full cohort study of 1,244 prostate cancer patients who received ADT and 1,806 non-users, ADT use was associated with a higher heart failure incidence rate, 4.00 versus 1.89 per 100 person-years, corresponding to a hazard ratio of 1.72. A propensity score-matched analysis of 1,088 ADT users and 1,088 non-users found an even higher adjusted hazard ratio of 1.92. Patients treated with abiraterone showed significantly elevated risks of major composite adverse events, including diabetes, hypertension, congestive heart failure, dysrhythmia and coronary artery disease, with a hazard ratio of 1.77, and of minor composite adverse events, with a hazard ratio of 1.24. Enzalutamide has been associated with increased risks of acute myocardial infarction, coronary artery disease and high-grade hypertension, while abiraterone and apalutamide have been linked to higher incidence of angina pectoris and myocardial infarction.

One of the most technically nuanced recommendations addresses drug selection in patients with significant pre-existing cardiovascular disease. For these patients, the panel agreed that gonadotropin-releasing hormone, or GnRH, antagonists can be considered over GnRH agonists and surgical castration. The evidence is mixed but leans toward antagonists. The PRONOUNCE trial, which randomised 545 prostate cancer patients with pre-existing cardiovascular disease to degarelix or leuprolide, did not demonstrate a significant difference in major adverse cardiovascular events at 12 months, though it was limited by early termination and lower-than-expected event rates. Conversely, the HERO trial comparing relugolix with leuprolide in 934 patients demonstrated a significant 54 percent reduction in major adverse cardiovascular events with relugolix. Systematic reviews and meta-analyses add weight: in a cohort of 499 GnRH antagonist users and 15,127 agonist users, antagonist use was linked to a 33 percent lower risk of major adverse cardiovascular events and an 84 percent lower risk of composite cardiovascular events. A pooled analysis found lower event rates, 2.9 percent versus 4.8 percent, and reduced odds of all-cause mortality with antagonists, and meta-analyses of degarelix showed a significant reduction in major adverse cardiovascular events. The higher cardiac risk with agonists may be attributable to their potential to trigger atherosclerotic plaque instability and rupture, possibly mediated by a compensatory increase in follicle-stimulating hormone. Reflecting this evidence, the 2022 European Society of Cardiology guidelines recommend considering GnRH antagonists for patients with symptomatic coronary artery disease who require ADT, and at the Advanced Prostate Cancer Consensus Conference, 71 percent of experts favoured antagonists for patients with advanced prostate cancer and a recent history of major cardiovascular events. Surgical castration, though effective, is infrequently used because it is irreversible and carries psychological burden.

Follow-up care forms the third focus area. The panel unanimously agreed that cardiometabolic parameters should be monitored after initiation of therapy, and that monitoring frequency should be individualised. The metabolic shifts are measurable: ADT has been shown to increase fasting glucose by 4.8 percent, haemoglobin A1c by 2.7 percent, triglycerides by up to 20.6 percent and body weight by 1.09 kilograms. Androgen receptor-targeted therapies are associated with higher risks of hypertension, ischaemic heart disease and arrhythmia. Regular monitoring of blood pressure, body mass index, haemoglobin A1c or fasting blood sugar and lipid levels is therefore recommended. Because evidence from an Asian-focused prospective registry study indicates that the first year of ADT is a critical period for metabolic changes, the panel suggested assessments at 6 and 12 months in the first year, then every 3 months for high-risk or poorly controlled patients and every 6 to 12 months for those at low risk or well controlled. However, the panel acknowledged that a uniform schedule may not suit all patients and that there is a lack of evidence from controlled trials on optimal timing.

Lifestyle counselling also earned unanimous endorsement. Evidence shows that 62 percent of coronary events can be prevented through adherence to healthy behaviours, including maintaining a healthy body mass index, smoking cessation, regular physical activity, moderate alcohol intake and a balanced diet. To structure these interventions, the panel endorsed integrating the modified ABCDE Cardio-Oncology framework into routine care: A for assessing cardiovascular risk, B for blood pressure control below 140/90 mmHg, C for cholesterol management and cigarette cessation, D for diabetes screening, diet and weight management, and E for exercise. Real-world evidence supports the approach, with smoking cessation and adherence to a healthy lifestyle linked to significant reductions in cardiovascular events. The panel further agreed unanimously that an integrated care model involving various specialties is preferred, noting that strong expert consensus endorses collaborative care among urologists, oncologists, cardiologists, endocrinologists and primary care physicians to enable comprehensive, coordinated management, especially given the need to balance cancer control with cardiovascular safety.

Not every proposal survived the vote. The panel rejected, with agreement of only 41.7 percent, a statement recommending a baseline electrocardiogram for all prostate cancer patients before initiating therapy. The reasoning was pragmatic: there is a lack of strong evidence that ECGs improve cardiovascular risk stratification in asymptomatic individuals, ECG machines may not be readily available in non-cardiology departments such as urology or oncology, and the logistical burden combined with limited expertise in interpretation among non-cardiology specialists could introduce delays or misinterpretation. The panel also noted that routine ECG screening could detract from the primary objective of initiating timely cancer therapy, especially in patients without cardiovascular symptoms or high-risk characteristics. ECGs may still be appropriate for selected high-risk or symptomatic patients, and the panel separately endorsed referring symptomatic patients or those at high cardiovascular risk for appropriate care, whether that means a cardiologist, a cardio-oncology clinic or, in resource-limited areas, a general physician trained in cardiovascular conditions. In most cases, the panel stressed, referral should not delay the commencement of ADT.

The authors acknowledge limitations. The panel did not include primary care physicians, endocrinologists or nurses, and broader stakeholder collaboration may help refine the recommendations in future. Because the guidance rests on expert consensus and available evidence rather than long-term outcome data, real-world studies will be essential to optimise implementation across diverse healthcare environments. The panel also emphasised that institutions should adapt the structured management protocol to their specific clinical settings, patient demographics and available resources, and that shared decision-making deserves active promotion, particularly in Malaysia, where patients may expect a more paternalistic role from their healthcare providers. The consensus document, its authors write, is intended to support individualised care that balances oncological efficacy with cardiovascular safety, offering clinicians in the region and beyond a practical, risk-adapted framework for a growing patient population.

Subject of Research: Expert consensus recommendations for managing cardiometabolic risk in prostate cancer patients receiving androgen deprivation therapy or androgen receptor-targeted therapy

Article Title: Management of cardiometabolic risk in prostate cancer: expert consensus from Singapore and Malaysia

Article References: Chen, K., Chiong, E., Kanesvaran, R., Koo, C. C. Y., Lo, W. H. L., Loch, A., Malek, R., Ng, C. T., Saad, M., Thiagarajan, M., Ong, T. A., & Tuan, J. K. L. (2026). Management of cardiometabolic risk in prostate cancer: expert consensus from Singapore and Malaysia. Frontiers in Oncology, 16, Article 1781791. https://doi.org/10.3389/fonc.2026.1781791

Image Credits: AI Generated

DOI: 10.3389/fonc.2026.1781791

Keywords: prostate cancer, androgen deprivation therapy, androgen receptor-targeted therapy, cardiometabolic risk, cardiovascular disease, consensus recommendations, modified Delphi method, Singapore, Malaysia, cardio-oncology, GnRH antagonists, lifestyle modification