Testicular cancer is associated with an excellent prognosis, but survivors face a worrisome risk of developing certain metabolic effects, such as hypertension, that are tied to platinum-based chemotherapy, according to new findings.
In the study, 1 in 5 testicular cancer survivors who were treated with this chemotherapy developed metabolic syndrome, which is associated with the risk of developing cardiovascular disease and type 2 diabetes, explained lead author Mohammad Issam Abu Zaid, MBBS, of Indiana University School of Medicine in Indianapolis.
Dr Zaid presented the results of his study here at the Cancer Survivorship Symposium (CSS) Advancing Care and Research.
"There is a high prevalence of metabolic syndrome in testicular cancer survivors treated with modern day chemotherapy, and the onset is at a relatively young age and appears shortly after the completion of treatment," Dr Zaid said.
Testicular cancer is highly curable, with a 10-year survival of more than 95%. Treatment is homogeneous, consisting primarily of platinum-based chemotherapy. The possibility of long-term survival is excellent, but survivors are at risk for late effects, including cardiovascular disease.
Dr Zaid explained that several European studies have shown that survivors have an increased risk of up to sevenfold for developing cardiovascular disease.
"But these studies also show a wide variation in the development of metabolic syndrome in this population, ranging from 13% to 39%," he pointed out.
One European study recently reported that the prevalence metabolic syndrome was higher among testicular cancer survivors who were homozygous for a single nucleotide polymorphism (SNP), rs523349 (V89L), in 5-α-reductase gene (SRD5A2). That study found reported the prevalence of metabolic syndrome to be 67% in survivors with low testosterone levels who carried the variant genotype.
Higher Rates of Hypertension, Troublesome HDL and Triglycerides
Given the conflicting evidence from the European studies regarding the prevalence of metabolic syndrome and the lack of any data for North American survivors, Dr Zaid and his colleagues evaluated the incidence of metabolic syndrome and its associated risk factors among survivors who were enrolled in the Platinum Study, an ongoing multicenter study that is being conducted in eight centers in the United States and Canada.
The study included 486 testicular cancer survivors (median age at evaluation, 38 years). All of the participants were younger than 50 years at diagnosis and had been treated with first-line chemotherapy.
All participants underwent physical examinations and completed questionnaires regarding comorbidities and health behaviors. Lipid, testosterone, and serum soluble cell adhesion molecule–1 (sICAM-1) levels were measured. Genotyping was performed for the SNP rs523349 (V89L), which had been associated with metabolic syndrome in another study.
The authors defined metabolic syndrome as the presence of three or more of the following symptoms: hypertension, waist circumference ≥102 cm, triglyceride level ≥150 mg/dL, high-density lipoprotein (HDL) level ≤40 mg/dL, and diabetes.
Participants in the National Health and Nutrition Examination Survey were used as a control group and were matched with respect to age, race, and educational status.
"Overall prevalence of metabolic syndrome was similar between survivors and controls," said Dr Zaid, "but there were differences in the individual components."
Survivors were more likely to be hypertensive (43% vs 31%; P < 0.01), and the prevalence of low HDL was lower among survivors (24% vs 35%; P < .01). Survivors also had higher triglyceride levels or were taking cholesterol medication (40.1% vs 35.8%). However, the survivors did not have a higher degree of abdominal obesity (28% vs 40%; P < .01), which is another indication of metabolic syndrome.
Low serum testosterone level and age were significantly associated with metabolic syndrome. "Low testosterone level was associated with a twofold increased risk as compared with higher levels," said Dr Zaid. "The risk also increased with increasing levels for sICAM, up to 3.6-fold."
The variant rs523349 was not associated with metabolic syndrome. Among survivors with metabolic syndrome, there was no difference in the percentages of wild type or variant, and it did not make a difference whether the participants had low or high testosterone levels.
Thus, he explained, "we do not validate those findings."
Dr Zaid concluded that, on the basis of these findings, providers should screen testicular cancer survivors for metabolic syndrome and should adequately treat hypogonadism, hypertension, and hyperlipidemia. They should also encourage a healthy lifestyle.
"It is possible that chemotherapy predisposes to cardiovascular disease through mechanisms other than metabolic syndrome, such as through direct vascular damage," he added. "Whether the high prevalence of metabolic syndrome will translate to future cardiovascular events to the same extent or higher in the general population needs further study — which is a major aim of the platinum study."
Close Surveillance, Education Needed
Approached by Medscape Medical News for an independent comment, ASCO expert Charles J. Ryan, MD, reiterated that testicular cancer survivors require lifelong follow-up, for a variety of reasons.
"In particular, it is important for their primary care physicians to be aware of these late metabolic effects and for the patients themselves to be especially attentive to issues of weight and blood pressure control, both of which can be impacted by the prior chemotherapy," said Dr Ryan, who is also professor of clinical medicine and urology and the clinical program leader for genitourinary medical oncology at the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco.
"Prior studies have suggested that platinum exposure may in fact be the metabolic insult," Dr Ryan explained. "Platinum has late effects that other chemotherapy agents may not."
That said, testicular cancer survivors are at greater risk for having low testosterone levels, and assessment of testosterone level should be included in the routine monitoring of these patients.
Testicular cancer is associated with a very high survival rate, and because it occurs primarily in young men, the long survival time allows for the development of late effects. Many of these patients may be lost to follow-up as they move on with their life. Therefore, Dr Ryan emphasized, it is very important that treating physicians be attentive to the fact that the decisions they make now will have ramifications for up to 40 to 50 years post therapy.
"It is particularly important to not use chemotherapy in situations where it can be avoided and to counsel the patient up front about the need for lifelong monitoring and attentiveness to these details," he said.
"When faced with an immediate cancer challenge, discussions about late effects are necessary, but may not sink in," Dr Ryan added. "Upon completion of chemotherapy, in my practice, I have a conversation with the patient that I call 'your life after chemotherapy,' where we talk about these issues. I think it is more likely to sink in when we have this conversation for the second time."
Ideally, patients would have access to trained and dedicated cancer survivorship programs so that problems can be tracked, screened for, and responded to in an appropriate and personalized manner.
The study was funded by the National Cancer Institute. Dr Zaid has disclosed no relevant financial relationships. Several coauthors have disclosed relationships with industry.
Cancer Survivorship Symposium (CSS) Advancing Care and Research. Abstract 102, presented January 27, 2017
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