The Need to Know in Cardio-Oncology

First Author

Testicular cancer (TC) is the most common cancer in men between 14 and 44 years old, with the predominance of cases in Western countries. The incidence of TC is <1 affected individual per 100,000 men in large areas of Africa and Asia, but it is as high as 9.9 affected per 100,000 men in Norway. Approximately 70% of men have stage 1 disease at diagnosis. While geographic variation exists, for stage 1 disease the overall 5-year survival rate is ∼95%, and the cancer-specific survival rate at 15 years is >99%.¹ Even with advanced stage 2 and 3 disease, there is a high chance of cure with multimodality therapy. Given these impressive survival rates, determining how to optimize the cardiovascular care of TC survivors is an area of interest in the field of cardio-oncology.

In this issue of JACC: Case Reports, Ghods et al² describe the case of a 42-year-old man with a prior history of recurrent and refractory TC who presented with angina and progressive dyspnea and who was found to have a large mass in the left atrium. At the time of presentation, his medical history included craniotomy for cerebral lesion resection complicated by right-sided paresis, pulmonary metastatic disease, and prior intracranial hemorrhage. Given the size of the left atrial mass, risk of embolization, and symptoms, he underwent urgent cardiac surgery. The left atrial mass was ultimately diagnosed as a pulmonary metastatic lesion extending into the left atrium through the left superior pulmonary vein.

A key feature of this case was the decision to proceed to surgery despite known pulmonary and cerebral metastases, and it highlights the need for case-by-case decision-making in cardio-oncology regarding aggressive interventions. For this patient, knowing the pathology of the mass was important for ongoing treatment; assuming the mass is a thrombus and simply treating with anticoagulation could have been risky given the patient's history of intracranial hemorrhage, and it likely would not have provided any benefit in an attempt to be conservative. At the same time, placing this patient on cardiopulmonary bypass was not without risk. In addition, tumor biology would suggest that systemic therapy may be adequate to treat a germ cell tumor, but the history of previous lines of adequate therapy, and growth despite 2 curative-intent regimens, suggested a chemoresistant biology unlikely to respond quickly to therapy. The need for case-by-case invasive/interventional consideration extends to approaching bypass surgeries, structural heart disease, and coronary interventions in the cardio-oncology population. The presence of metastatic disease is no longer a blanket pretext to take procedures off the table, and broader considerations of life expectancy in an era of improved treatments, functional status, bleeding risks, and trajectory of cancer care need to be carefully weighed when making these decisions.

Cardio-oncology, a field focused on the management of cardiac disease in cancer patients, has increasingly become focused on longitudinal outcomes; as cancer care has iteratively improved, so have survival rates. Cisplatin-based chemotherapy (CBCT), used in the treatment of metastatic TC, is not associated with acute cardiotoxicity but is associated with long-term cardiovascular (CV) morbidity and mortality. Within the first year of CBCT, there is an increased risk of vascular toxicity, which can present as vascular or arterial thromboembolism, stroke, or myocardial infarction.³ Using the Danish Testicular Cancer database, Lauritsen et al⁴ found that although the risk of CV disease at 1 year after bleomycin-etoposide-cisplatin decreased to normal levels, after 10 years, the risk of myocardial infarction (HR: 1.2, 95% CI: 1.0-2.0) and CV death (HR: 1.6, 95% CI: 1.0-2.0) increased. A long-term study of Norwegian TC survivors exposed to CBCT found that compared with noncancer controls, these individuals had higher rates of diastolic dysfunction, coronary disease, and metabolic syndrome.⁵ The increase in metabolic syndrome, comprised of hypertension, hyperlipidemia, insulin resistance, and abdominal/visceral adiposity, is found in 13% to 39% of TC survivors, depending on the study, and is thought to be driven by cisplatin exposure and hypogonadism. The increased CV risk is hypothesized to be secondary to the platinum therapy in the context of these hormonal alterations and is in some cases coupled with vascular changes from radiation (Figure 1).

Figure 1.

Cardiovascular Risk Associated With Testicular Cancer Treatment

Simplified version of management of testicular germ cell tumors by stage. ∗In some cases. CBCT = cisplatin-based chemotherapy.

Current TC cardiac survivorship care thus focuses on traditional cardiac risk-factor modification, without tailored prevention or management strategies. Long-term studies on the impact of risk-adapted CV care to prevent major adverse cardiac events in TC survivors are needed, but until then the truly optimal CV care of this population is unknown.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.