PSYCHOTROPIC DRUGS IN MEN WITH TESTICULAR CANCER

Testicular cancer is a disease of young men, primarily diagnosed in their 20s and early 30s, and is highly curable.

But according to new research, the use of psychotropic and stimulant medications (PSMs) is high in the survivor population. In a cohort of 680 testicular cancer survivors, 12.5% reported using PSMs.^[1]

"Women are more likely to use psychotropic drugs. If you have this many men using them, it is significant," said study author Clair Beard, MD, director of the Testicular Cancer Center at Dana-Farber Cancer Institute in Boston.

Effective treatments, particularly platinum-based chemotherapy regimens, have resulted in testicular cancer becoming one of the great cancer success stories—with a 10-year survival rate topping 95%.

Because testicular cancer survivors tend to be young, it may be perceived—at least by the public—that they pick up life where they left off. This image is best personified by cyclist Lance Armstrong, who was 25 years old when diagnosed with metastatic testicular cancer that spread to his brain, lungs, and abdomen. Yet he sailed through treatment, got back up on his bike, and went on to win the Tour de France seven consecutive times, from 1999 to 2005 (although he was stripped of his victories in 2012 after a protracted doping scandal).

However, the high survival rate of testicular cancer is offset by the emergence of late and long-term morbidities.^[2] The current study found that the use of PSMs highly correlated with men who were dealing with chronic health conditions.

Pills to Cope With Cisplatin Toxicity

The multi-institutional clinical study, which was presented at the 2016 annual meeting of the American Society of Clinical Oncology (ASCO), sought to characterize the prevalence of PSM use and its associations with demographics, health behaviors, and treatment-associated toxicities among men who had been treated for testicular cancer.

The study cohort comprised the first 680 consecutively enrolled survivors, all of whom were younger than 50 years of age at diagnosis, with histologically or serologically confirmed testicular or with either testicular or extragonadal germ cell tumor (GCT).

All men had undergone treatment with cisplatin-based chemotherapy for initial GCT or recurrence that developed while receiving surveillance after orchiectomy. The median time since completing chemotherapy was 48 months. The patients completed a 36-item questionnaire that included validated questions about the presence of comorbidities and prescription drug use.

A total of 85 men reported using PSMs, and 54.2% of this subgroup had been diagnosed before 35 years of age, compared with 72.6% of nonusers of PSMs. PSMs used by 80 of the patients in the study included antidepressants (n = 65 [76.5%]), anxiolytics (n = 23 [27%]), and stimulants (n = 21 [25%]), and 20 of the men (23%) were receiving two or more PSMs.

The use of PSMs was also associated with a variety of chronic health conditions. Compared with nonusers, PSM users were more likely to have tinnitus (49.4% vs 36.4%; P < .04), a combination of tinnitus and peripheral neuropathy (43.5% vs 27.2%; P < .01), cardiovascular disease (26.2% vs 15.6%; P < .02), and greater use of prescription medications for pain control (20% vs 4.7%; P <.01).

Cancer survivors, in general, may experience a wide range of late effects stemming from chemotherapy, radiation, and surgery. Because of the young age at which the vast majority of men with testicular cancer are diagnosed, along with the extremely high cure rate, the burden of these late effects evolve as the men mature. Their young age also means that many survivors will live with these sequelae for many years after completion of treatment.

"The body never clears all of the cisplatin," said Dr Beard. "Twenty years later, we still see inflammatory changes related to cisplatin treatment."

The finding that PSM use is high in testicular cancer survivors correlates with findings from a national survey.^[3] Prescription data for 2001-2006 from the Medical Expenditure Panel Survey showed that 19% of cancer survivors younger than 65 years and 16% of those older had used psychotropic medications.

Dr Beard and her coauthors note that although survivors of testicular cancer are known to be at an increased risk for acute and chronic medical problems, few US or Canadian studies have evaluated barometers of their psychological health.

Psychological and Emotional Distress

When evaluating the use of psychotropic drugs in testicular cancer survivors, the study only looked at the association of PSM use with chronic health conditions. However, Dr Beard noted that many survivors also experience psychological morbidity and impaired health-related quality of life.

"The diagnosis and treatment of testicular cancer is stressful for most men," explained Dr Beard. "Although most recover and go on to function well, there is a small but significant number of men who have enduring psychosocial or sexual problems."

The repercussions of a diagnosis of testicular cancer may be amplified because of the general age of patients. These are young men who are suddenly given a diagnosis of a potentially life-threatening illness, while at the same time involved in such activities as finishing their education, beginning or growing a career, or starting a family.

"The diagnosis can interfere with the natural progression into adulthood," said Dr Beard. "Some patients may have to move back home with their parents and have someone support them, or they may have to leave school. Career plans may also be disrupted.

The interruption of a person's development process can be very detrimental and is poorly studied, she added.

Long-term survivors have been reported to have increased rates of anxiety. In one large cohort, 19% had an anxiety disorder and 10% reported depression at long-term follow-up.^[4] Compared with controls in the general population, the relative risk for an anxiety disorder was 1.5 for testicular cancer survivors.

The risk for an anxiety disorder was associated with young age, peripheral neuropathy, economic problems, alcohol problems, sexual problems, relapse anxiety, and having been treated for mental disorders.

A more recent study found comparably low rates of clinically significant anxiety and depression in long-term survivors of testicular cancer (anxiety in 6.1% and depression in 7.9%), but the association for greater levels of both anxiety and depression were significant in those who had a high number of physical symptoms and who had children.^[5]

"If you have a baseline mental problem, such as anxiety or depression, you are more likely to develop testicular cancer-related distress," said Dr Beard.

Body image, infertility, and sexual dysfunction are also issues. Patients with testicular cancer may have baseline germ cell dysfunction, and some research suggests that about one third of patients have low sperm counts^[6,7] and motility whereas about 1 in 20 have no sperm, she noted.

Fertility is important to most men, and a large majority want to have children. Although sperm banking is an option, it can be difficult to act decisively or think about an imagined fatherhood at the time of diagnosis.

"These are young men and some may still be teenagers," Dr Beard pointed out. "Having a child is not something that they are thinking about, and the subject of sperm banking may not come up or may be embarrassing."

Some men will experience erectile dysfunction, whereas others may have ejaculation problems. Lack of sexual desire can also be a problem; many of these men have low testosterone, especially if both testicles have been removed or if hormone levels do not return to normal after treatment.

"Body image is also affected, and some patients will get a prosthesis so that they look normal," said Dr Beard.

Range of Morbidities After Platinum Chemotherapy

The PSM study is one of a growing number of investigations by the Platinum Study Group, an ongoing multicenter project that includes eight cancer centers in the United States and Canada. The primary focus of the group is to examine genetic variants associated with cisplatin toxicity.^[8,9] But a secondary goal is to establish a clinically well-characterized cohort of patients.

Patients with testicular cancer represent a unique opportunity to study the long-term health outcomes associated with this therapy, given their very high survival rates and the limited number of cisplatin-based regimens used to treat this disease.

A related study by Dr Beard and her colleagues from the Platinum Study Group, also presented at ASCO 2016, looked specifically at the cumulative burden of morbidity among 751 testicular cancer survivors.^[10]All participants had received first-line chemotherapy, and responses to comprehensive health questionnaires and prescription drug use were used to create a cumulative burden of morbidity (CBM) score. The CBM score was calculated according to the number and severity of each outcome, and was rated as low, medium, high or severe.

Nearly 50% of survivors had a CBM score of medium or greater, and 22.8% had a score of high or greater. Only 4% reported no adverse health outcomes, and older age at the time of evaluation was significantly associated with worse CBM score (odds ratio, 1.04; 95% confidence interval, 1.03-1.06; P < .001).

The most recent work from the Platinum Study Group confirmed the association between hearing loss and tinnitus in testicular cancer survivors who received cisplatin therapy.^[11] This is the largest and most comprehensive study of cisplatin-associated ototoxicity in survivors of adult-onset cancer. Nearly one fifth (18%) of patients reported severe to profound hearing loss. Tinnitus that significantly correlated with reduced hearing at each frequency was seen in 40% of the patients (P < .001).

Taken together, the studies of the Platinum Study Group gauge the effect of cumulative morbidities of platinum chemotherapy on the lives of cancer survivors. Particularly concerning are the number and range of morbidities that impair the lives of patients with testicular cancer, who survive the disease but live for decades trying to recover from the cure.

"Future studies should aim for identification of high-risk patients in need of intensified preventive and therapeutic interventions," the Platinum Study Group concluded.