AT ASCO 2017

CHICAGO (FRONTLINE MEDICAL NEWS) – Hypogonadism may compromise the long-term health outlook for many younger men who have been successfully treated for testicular cancer, according to an analysis conducted by the Platinum Study Group.

“Today, 95% of all testicular cancer patients are cured of their disease thanks to cisplatin-based chemotherapy. Nowadays, testicular cancer survivors can expect to live for over 40 years from the time of their diagnosis,” lead investigator Mohammad Issam Abu Zaid, MBBS , said in a press briefing at the annual meeting of the American Society of Clinical Oncology. “However, they are at risk of other health problems that may be related to their cancer treatment, including late complications from chemotherapy.”

The analysis of almost 500 younger testicular cancer survivors who had received cisplatin-based chemotherapy found that nearly 4 in 10 had hypogonadism. Compared with unaffected peers, men in this group were up to four times more likely to be taking medication for a variety of chronic conditions: dyslipidemia, hypertension, diabetes, erectile dysfunction, and anxiety or depression.

“Testicular cancer survivors, especially those treated with chemotherapy, are at increased risk for hypogonadism, a problem that can be associated with predisposing factors for heart disease,” summarized Dr. Abu Zaid, of Indiana University in Indianapolis. “Mitigating approaches are the usual weight control, exercise, and monitoring of blood pressure and cholesterol levels.”

“We will never omit cisplatin from the treatment regimen to prevent complications, but recognizing and treating symptomatic hypogonadism can improve quality of life and lessen adverse health outcomes, especially those related to the metabolic syndrome and resulting in diabetes, hyperlipidemia, and early cardiac problems,” he asserted.

Expert perspective

“This is an important study, and it sends a loud message to those of us who take care of testis cancer patients, my area of expertise. … We need to watch for hypogonadism, and we need to ask survivors about it. We need to examine them thinking about it, and, in patients who we are worried [they] might have hypogonadism, we need to do blood tests for testosterone and other hormone levels,” commented ASCO Expert Timothy D. Gilligan, MD, MSc , of the Cleveland Clinic in Ohio. “These are young patients, they have many years of life, so it’s many decades of suffering from consequences of this if it’s undetected.”

The findings were not surprising based on his personal experience and on evidence from the prostate cancer field showing the adverse metabolic effects of withdrawing testosterone, he said. Although the prevalence of hypogonadism found in the study was higher than that found in other studies, given the large size of the cohort, it should be taken seriously. Additionally, even if the true prevalence is somewhat lower, the absolute number of survivors affected would be substantial.

“We need to be cautious though and make sure people don’t misunderstand and think that this means we should test testosterone levels in all patients, which is a risky thing to do because the definition of normal testosterone is very fuzzy,” Dr. Gilligan stressed. “There is a wide range of normal, and what’s normal for me may not be the same as what’s normal for another man. So, looking for symptoms is really what guides this work, and, when there are symptoms, then testing is important.”

Study details

The Platinum Study is a large, ongoing, multicenter North American–based cohort study of testicular cancer survivors who received cisplatin as part of their chemotherapy.

Dr. Abu Zaid and his colleagues analyzed data from 491 participants who were aged 50 years or younger at diagnosis. All completed questionnaires addressing comorbidities, medications, and health behaviors; underwent physical examination; had measurement of testosterone levels; and had a genetic analysis.

The men were by and large young at the time of evaluation, with a mean age of just 38 years, he reported in the press briefing and a poster session at the meeting.

Overall, 38.5% had hypogonadism, defined in the study as a serum testosterone level of 3 ng/mL or lower or as use of testosterone replacement therapy.

In a multivariate analysis, survivors’ odds of hypogonadism increased with age (odds ratio, 1.41 per 10-year increment; P = .007) and were higher for those having a body mass index of 25 kg/m2 or greater, vs. lower (OR, 2.22; P = .003). On the other hand, there was a trend whereby survivors who engaged in any vigorous-intensity physical activity, vs. none, were less likely to have hypogonadism (OR, 0.64; P = .06).

The odds rose with number of risk alleles in the sex hormone–binding globulin gene, but findings were not significant, Dr. Abu Zaid said. They were also statistically indistinguishable across groups differing with respect to the chemotherapy regimen received and socioeconomic factors.

Compared with counterparts having normal testosterone levels, survivors having hypogonadism were up to four times more likely to be taking medication to treat dyslipidemia (20.1% vs. 6.0%; P less than .001), hypertension (18.5% vs. 10.6%; P = .013), erectile dysfunction (19.6% vs. 11.9%; P = .018), diabetes (5.8% vs. 2.6%; P = .067), and anxiety or depression (14.8% vs. 9.3%; P = .060).

Testicular cancer survivors should not universally have testosterone testing, agreed Dr. Abu Zaid. Such a practice might lead to overtreatment, and, in older men at least, use of testosterone itself has been linked to elevated cardiovascular risk.

“You really want to treat somebody who has symptoms related to hypogonadism: constant fatigue, night sweats, and depressed mood and some other symptoms that are well known to the clinician,” he maintained. “At the moment, we have no studies done looking at testosterone replacement in young men. I would hypothesize that we actually help them by giving them testosterone, and that’s what I tell my patients.”