Cardiovascular Risk Assessment in Patients With Kidney Cancer

Corresponding Author

Cardiovascular disease (CVD) is the leading cause of death in the United States and a major source of morbidity and mortality in patients with cancer.1, 2, 3 CVD and many cancers share common risk factors such as smoking, obesity, and older age; as a result, patients with cancer have a higher prevalence of comorbid CVD at the time of cancer diagnosis.⁴ In addition to shared risk factors, the inflammatory state of cancer and cardiovascular (CV) effects of cancer therapy together contribute to the higher burden of CV morbidity and mortality in cancer survivors compared with age- and sex-matched controls without cancer across multiple cancer types,³ including renal cell carcinoma (RCC).^3,5 Age, smoking, obesity, hypertension, and chronic inflammation are known risk factors for both RCC and CVD. Although hypertension can often be a presenting feature of RCC, patients can also develop hypertension after undergoing nephrectomy or as a secondary result of systemic therapy. Many patients with RCC develop chronic kidney disease (CKD) early in their treatment course, caused by nephrectomy or tumor-associated renal dysfunction, and this is an independent risk factor for CVD, with a growing list of therapies that improve cardiac and renal outcomes as well as implications for tolerability and efficacy of CV therapies.⁶ Molecularly targeted antiangiogenic therapies and immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of RCC in the last 2 decades, with significant improvements in clinical outcomes for patients with localized as well as advanced RCC (aRCC).^7,8 The CV toxicities of contemporary ICIs and antiangiogenic agents used in the treatment armamentarium of RCC are well described.^9,10 As patients live longer in the setting of localized disease with use of adjuvant ICI therapy, or experience durable responses in the setting of aRCC, they remain at risk for CVD, secondary to factors beyond treatment-related toxicities.

In this issue of JACC: CardioOncology, Deng et al¹¹ analyze patterns of CVD and mortality in patients with RCC diagnosed between 2004 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database.¹¹ The authors demonstrate that CVD overtakes RCC as a competing cause of death across different stages of cancer and survivorship. Crossover time, defined as the time point at which CV and RCC death rate intersect, occurs earlier in older adults (≥75 years of age), patients with tumor size <4 cm, and non-Hispanic Black patients, among other clinical and sociodemographic associations evaluated by the authors. The results suggest that CV death becomes dominant over RCC death during survivorship, especially so for patients with stage 1 RCC. Deng et al¹¹ have added to our knowledge of CV outcomes in RCC by highlighting the importance of risk stratification and competing risks in this patient population.

Recognition that patients with RCC are at higher risk for CV death underscores the need for developing risk-prediction models and prevention strategies. To improve CV outcomes in any population, several important steps are required: accurate CV risk prediction; risk-informed optimization of primary and secondary CV prevention strategies; and shared decision making, accounting for competing risks and patient preferences. Risk-prediction models developed in the general population have been shown to perform worse in survivors of cancer than in matched controls without cancer.¹² Although the present study by Deng et al¹¹ lacks data on comorbidities, physical functioning, frailty assessment, or subsequent therapies, future research including these variables are necessary to develop risk-prediction models for CVD in survivors of RCC. Additional studies are also needed to determine if some primary-prevention models can be updated to provide accurate predictions in cancer populations, if new models specific to cancer survivors are needed, or if some patients with cancer are at such high risk that they should be considered as having a CVD risk equivalent. Although the authors analyzed outcomes in patients diagnosed with RCC between 2004 and 2019, it would also be important to evaluate patients at intermediate-to-high or high risk of recurrence following nephrectomy treated with adjuvant pembrolizumab since its regulatory approval in 2021, to characterize the impact of improved overall survival on the crossover time caused by CV mortality.

The 2025 National Comprehensive Cancer Network (NCCN) Survivorship Guidelines recommend assessment of CV risk factors throughout the survivorship continuum and a personalized approach accounting for traditional risk factors and cardiotoxic cancer treatments.¹³ Clinic visits for RCC follow-up represent an opportunity to streamline not only oncologic surveillance but also CV care. Survivorship visits can potentially be leveraged to improve adherence to primary care, cardiology, or cardio-oncology–driven strategies for CV health using integrated care models. This approach could enhance adherence to primary and secondary prevention efforts such as Life’s Essential 8, statins or other lipid-lowering treatment, optimal blood pressure control, and consideration of incretin mimetics or sodium-glucose cotransporter 2 inhibitors, as indicated.^14,15 The recently completed CARISMA (Cancer Therapy Risk-Reduction With Intensive Systolic BP Management) trial (NCT04467021) tested the feasibility and tolerability of intensive blood pressure control in patients with RCC receiving tyrosine kinase inhibitor (TKI)-based therapy and is an example of cardio-oncology and oncology integration to improve CV primary prevention strategies.

In conclusion, there is a need to improve the recognition of CV risk factors in patients with RCC across the care continuum as the competing risk of CV death overtakes cancer-associated mortality, especially in earlier stages of disease. The optimization of CV care for patients with RCC will require integrated care delivery models with alignment of primary care, urology, oncology, and cardio-oncology teams. Future research should focus on incorporation of these CV risk assessment and mitigation strategies into clinical practice to refine survivorship care.

Funding Support and Author Disclosures

Dr Mittal has played an advisory role for Aveo, Dendreon, Myovant Sciences, AVEO, Janssen, and AstraZeneca; has received research funding from Pfizer; and has received honoraria from Curio Science, IntrinsiQ, Targeted Oncology, Medpage, Targeted Oncology, Aptitude Health, Cardinal Health, and Research to Practice. Dr Upshaw has reported that she has no relationships relevant to the contents of this paper to disclose.