Testicular cancer survivors may be at increased risk for cardiovascular disease

Mohammad Abu Zaid

Testicular cancer survivors who underwent chemotherapy demonstrated increased risk for high blood pressure, high cholesterol and obesity, according to results of The Platinum Study.

The study, funded by NCI, is the largest to examine the rates of metabolic abnormalities among testicular cancer survivors who received prior platinum-based chemotherapy and the only such study to use patients from North America.

“The North American population is generally more ethnically and genetically diverse compared to Europeans, making it interesting to examine the similarities and differences in potential genetic risk factors for metabolic syndrome,” Mohammad Abu Zaid, MD, assistant professor of medicine at Indiana University School of Medicine and Indiana University Melvin and Bren Simon Cancer Center, said in a press release.

The study included 486 testicular cancer survivors (median age, 38.1 years). Researchers defined metabolic syndrome as three or more of the following conditions: hypertension, abdominal obesity, hypertriglyceridemia, diabetes and decreased levels of high-density lipoprotein.

Results showed testicular cancer survivors were more likely than those without cancer to have hypertension (43.2% vs. 30.7%; P < .001). However, cancer survivors were less likely to have lower levels of HDL (23.7% vs. 34.8%; P < .001) or abdominal obesity (28.2% vs. 40.1%; P < .001).

“We found that one in 10 testicular cancer survivors aged younger than 30 years had metabolic syndrome, and that increased to more than one-third of patients aged older than 50 years,” Abu Zaid said. “However, some of the genetic changes that reportedly play a large role in increasing the risk for metabolic syndrome among Europeans were not factors for our patients.”

HemOnc Today spoke with Abu Zaid about the study, the clinical implications of the findings and plans for subsequent research.

Question: How did the study come about?

Answer: During the early 1970s, testicular cancer was an incurable disease, with a 95% chance for mortality within 1 year from diagnosis. Since cisplatin was discovered, nearly 95% of these patients have been cured. Testicular cancer is probably one of the only cancer types that, once it spreads to other parts of the body, can be cured. Survivors can now be expected to live for many years. We see these patients now in clinic and they still have issues as it relates to their cancer diagnosis and treatment, such as neuropathy, hearing loss or cardiovascular/metabolic issues. For this reason, we have been very interested to study what medical problems and complications can happen with cisplatin-based chemotherapy. The physician who discovered the cure for testicular cancer — Lawrence Einhorn, MD — has been pioneering this survivorship research along with Lois Travis, MD.

Q: How did you conduct this study?

A: The Platinum Study is an ongoing multicenter study that includes eight of the larger centers that treat patients with testicular cancer. We collected patient blood samples and asked them questions about their health, examined genetics and studied the complications that can happen over time. For this specific study, we focused on the metabolic complications, including high blood pressure, high triglycerides and obesity. We also wanted to see if there were any genetic variants that can predict the development of the metabolic syndrome.

Q: What did the results show?

A: At a very young age, survivors had a very high prevalence of high blood pressure. Many of them (75%) were overweight or obese. We also found that total cholesterol was elevated among survivors compared with healthy controls. As survivors aged, these risks increased. We also found that low testosterone and inflammation had a big part to play in the risk; however, it was not completely explained by genetic variants among these patients.

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Q: What are the clinical implications of the findings?

A: Survivors of testicular cancer, as well as other cancer types, can be at risk for other complications related to treatment once they are cured from their malignancies. The clinical implications of this is to first alert survivors to this probability so that they maintain a healthy lifestyle and weight, as well as avoid smoking and high-fat diets. For health care providers, implications are to be able to help them be more aware and screen survivors for these problems in addition to screening for cancer recurrence.

Q: Are there plans for subsequent research?

A: Absolutely. The Platinum Study is a longitudinal study with the plan of following these patients for many years. So far, the study included patients treated with chemotherapy only. It would be of significant interest to see how survivors who were cured with surgery only and did not receive chemotherapy fared, and whether they, too, are at risk for metabolic problems. Ultimately, we want to see if there is anything we can do to prevent these complications or keep these complications from getting worse.

Q: Is there anything else that you would like to mention?

A: We know a lot about how cardiovascular disease develops in the general population and among the elderly, and there are a lot of different guidelines available on metabolic syndrome. However, what we found in this study is that these metabolic abnormalities may not be exactly the same in the cancer population as they are in the general population. Without studying these factors in cancer survivors, we will never know how these differences happen and this can have important clinical implications. Trying to understand this will require in-depth study and long-term follow-up. – by Jennifer R. Southall

Reference:

Zaid MA, et al. J Natl Compr Canc Netw. 2018;doi:10.6004/jnccn.2017.7046.

For more information:

Mohammad Abu Zaid, MD, can be reached at Indiana University, Melvin and Bren Simon Cancer Center, 535 Barnhill Drive, RT433, Indianapolis, IN 46202; email: mabuzaid@iu.edu.

Disclosure: Abu Zaid reports no relevant financial disclosures.