Testicular Cancer Awareness Month: A Focus on Implications of Mental Health Among Testicular Cancer Survivors

In 2021, there will be an estimated 9,470 new cases of testicular cancer in the United States with an estimated 440 testis cancer-related deaths.¹ Importantly, the vast majority of men with testis cancer, even in advanced stages, are cured as a result of the success of high dose chemotherapy regimens that are tolerated by this typically young and healthy patient population. Given both the relatively young age at diagnosis and overall high survival rates, there has been a much needed and welcome focus on survivorship for testicular cancer patients.

In addition to concern for long-term treatment toxicity,^2,3 infertility,⁴ secondary malignancy,^5,6 and increased risk of cardiovascular disease,^7,8 testicular cancer survivors are also at increased risk of mental health issues, which has only recently been adequately brought to light, particularly in national guidelines.⁹ Over the last several years, there has been an increase in mental health illness awareness in the general population, based in part to important initiatives from Movember, Suicide Awareness month (September), and the Bell “Let’s Talk” campaign in Canada, to name a few. As part of testicular cancer awareness month, which takes place each year during the month of April, the remainder of this article will discuss implications for mental health illness amongst testicular cancer survivors, including the impact of anxiety and depression, risk of suicidal death, and the emotional burden on testicular cancer survivor caregivers.

Mental Health and Testicular Cancer Survivors

Post-cancer diagnosis risk of mental health illness is well established amongst common cancers, such as prostate, breast, and lung cancer. This has also included several studies assessing the impact of testicular cancer on incidence of mental health post- cancer diagnosis. A recent population-level study published in the Journal of Clinical Oncology evaluated the impact of a testicular cancer diagnosis and treatment on subsequent mental illness and utilization of mental illness healthcare resources.¹⁰ This study included all incident cases of testicular cancer treated with orchiectomy in Ontario, Canada from 2000 to 2010, identified using the Ontario Cancer Registry. Cases were matched to controls in a 1:5 ratio based on age and geography. Additional population-level databases were used to identify mental health service use episodes, which included outpatient use accounting for visits to a general practitioner for a mental health concern or any visit to a psychiatrist. The authors used negative binomial regression modeling was used to estimate the rate of mental health service use in the pretreatment (2 years prior until 1 month before orchiectomy), peri-treatment (1 month before until 1 month after orchiectomy), and post-treatment periods (1 month after orchiectomy until end of follow-up). Rate ratios comparing cases with controls in the peri- and post-treatment periods were adjusted for baseline mental health service use. Overall, there were 2,619 cases of testicular cancer matched to 13,095 controls, for which there was no baseline difference in the rate of mental health service use. Patients with testicular cancer were significantly more likely than controls to have an outpatient visit for a mental health concern in the peri-treatment (adjusted rate ratio [aRR] 2.45, 95% CI 2.06 to 2.92) and post-treatment periods (adjusted RR 1.30, 95% CI 1.12 to 1.52). The difference in mental health service use persisted over a median follow-up of 12 years:

In the post-orchiectomy period, cases with baseline mental health service use were those most likely to use mental health services (adjusted RR 5.64, 95% CI, 4.64 to 6.85). Furthermore, In

the pre-treatment period, cases and controls had comparable use of mental health services for anxiety (61% v 51%) and depression (11% v 7%); controls had substantially more visits for substance-related and addictive disorders (33% v 18%).

Previous work has shown that physical activity has a beneficial influence on an individual’s mental health. To explore this potential effect on testicular cancer patients, Thorsen et al.¹¹ performed a cross-sectional study to estimate the association between the level of self-reported physical activity and the prevalence of depression and anxiety disorder among 1,260 testicular cancer survivors and 20,207 men from the general population. Among testicular cancer survivors, 122 (9.7%) had Hospital Anxiety and Depression Scale (HADS)-defined depression and 254 (20.2%) had HADS-defined anxiety disorder. The vast majority (n=1,090,85.5%) of testicular cancer survivors deemed themselves physically active. The authors found that the prevalence of HADS-defined depression was lower among those who were physically active than in those who were physically inactive (testicular cancer survivors 9% vs 17%, p<0.001; general population 8% vs 15%, p<0.001). Among physically inactive testicular cancer survivors there was a trend towards higher a prevalence of HADS-defined anxiety disorder compared to physically active testicular cancer survivors (p=0.07). Multivariate analysis confirmed the association between physical activity and HADS-defined depression in both the testicular cancer survivors (adjusted OR 0.56, 95% CI 0.31 to 1.02) and the general population (adjusted OR 0.58, 95% CI 0.51 to 0.65), but not the association between physical activity and HADS-defined anxiety disorder.

Work from the British Columbia Cancer Center recently examined the psychosocial needs of patients with germ cell tumors specifically stratifying patients by adolescent and young adults (AYA, age 18-39 years of age), and non-AYA (>39 years of age).¹² Each patient completed a pre-consultation health assessment form, which is a validated screening questionnaire for distress, subclinical/clinical symptoms of depression, and anxiety. Among 349 patients recruited to this study between 2011 and 2015, the patient population was predominantly AYA (n = 227) with a median age of 33 (range 18-83) years. The top three AYA concerns based on survey results were financial, work/school, frustration and anger; additionally, AYA patients more commonly scored positive for symptoms of subclinical/clinical anxiety than non-AYA (39.4% vs. 27.9%, p = 0.028). These results suggest that AYA testicular cancer patients have unique needs and experience more self-reported anxiety symptoms with emotional, informational and practical concerns, than older adults with testicular cancer.

To further assess the prevalence of high-levels of stress among testicular cancer survivors compared to the general population, Kreiberg and colleagues utilized the Danish nationwide cohort of patients.¹³ These authors assessed stress levels stratified by treatment type, including surveillance, chemotherapy (bleomycin, etoposide, and cisplatin (BEP)), or abdominal radiotherapy. In this study, there were 2,252 testicular cancer survivors that filled out the Perceived Stress Scale (PSS) questionnaire between 2014 and 2016, a survey designed to specifically ask questions regarding psychological stress. Results from testicular cancer survivors were compared to a general population sample of 61,927 men without a previous history of cancer. Amongst testicular cancer survivors, there were 1,134 on surveillance, 807 that received BEP chemotherapy, and 311 that underwent radiotherapy. Testicular cancer survivors were more likely to have high levels of stress compared to the reference population with a prevalence ratio of 1.56 (95% CI, 1.40-1.73). Furthermore, testicular cancer survivors undergoing surveillance, BEP and radiotherapy also had higher level of stress compared to the reference population. Longitudinally, testicular cancer survivors had a higher prevalence of stress under the age of 70, however over the age of 70 the general population was more likely to have high stress levels¹³.

Finally, in a systematic review of quantitative observational studies investigating psychological distress among testicular cancer survivors, Ben Smith and colleagues¹⁴ evaluated the prevalence, severity, and correlates of anxiety, depression, fear of cancer recurrence, and distress in testicular cancer survivors. Among 36 studies included in this systematic review, testicular cancer survivors' mean anxiety levels were higher than in the general population, while mean depression and distress were no different. More specifically, clinically significant anxiety (~20%) and to a lesser extent distress (~14%), but not depression, were more prevalent in testicular cancer survivors than the general population. Importantly, nearly 33% of testicular cancer survivors experienced significant fear of cancer recurrence. Factors associated with poorer psychological outcomes included testicular cancer survivors who were single, unemployed/low socio-economic status, suffering from comorbidities, experiencing worse symptoms/side effects, and using passive coping strategies. Based on this comprehensive review, although many testicular cancer survivors may not suffer from significant psychological morbidity, anxiety and fear of cancer recurrence in this population are prevalent.

Suicidal Death Amongst Testicular Cancer Survivors

A cancer diagnosis and the long trajectory of both cancer treatment and recovery can take a toll on patients with cancer and their families. Suicide is the culmination of unmanaged distress and is the 10th leading cause of death in the United States, and risk factors for suicide among cancer patients are similar to those among the general population, including male sex and older age.¹⁵ Using population-level data from the Surveillance, Epidemiology, and End Results (SEER database), Zaorsky et al.¹⁶ assessed the impact of a cancer diagnosis on suicidal death pooling data from 1973 to 2014. For testicular cancer patients, the standardized mortality ratio (SMR) for suicide compared to the general population was 6 when assessing follow-up <1 year after diagnosis. However, with increasing follow-up, unlike the majority of other cancers in this study, the SMR increased for testicular cancer patients with longer follow-up: a SMR of 12 for 1-5 years after diagnosis, and a SMR of 17 for >5 years of follow-up. Data from the Cancer Registry of Norway also has provided some insight into the association of suicidal death and testicular cancer. Looking at individuals diagnosed with cancer before the age of 25 matched to cancer-free individuals, Gunnes et al.¹⁷ found a significantly increased risk of suicidal death for testicular cancer patients (HR 2.9, 95% CI 1.3-6.4). Taken together, testicular cancer patients at the population-level appear to be at increased risk of suicide, perhaps for years after their initial diagnosis.

The Emotional Burden on Testicular Cancer Survivor Caregivers

Not unlike other malignancies, the role of family/spousal support is crucial for testicular cancer survivors. In a study of 129 testicular cancer survivors, Tuinman et al.¹⁸ explored self-esteem, social support, and mental health in three groups of survivors of testicular cancer, including single patients, those with the same partner as at diagnosis (relationship during testicular cancer), and those with a partner they met after completion of treatment (relationship after testicular cancer). The authors used the Social Support List, the Rosenberg self-esteem scale, and the subscale mental health of the RAND-36 to characterize the role of social support on mental health outcomes. While levels of social support were equal amongst all three groups, satisfaction with support was not: testicular cancer survivors with a relationship during cancer diagnosis were most satisfied with support, and had the highest self-esteem and mental health. Survivors with a relationship after testicular cancer reported the next best levels of functioning but had the same mental health issues as single patients. Furthermore, single patients and survivors with a relationship established after testicular cancer had a lower mental health than a reference group of men. The difference in self-esteem between single patients and survivors of testicular cancer with a relationship during testicular cancer appeared most distinct and was clinically relevant. As such, this study concluded that being single at diagnosis appears to cause vulnerability that remains when survivors do develop a relationship after treatment is completed.

Given the excellent survivability of testicular cancer, it is important for physicians and patients/caregivers to align with goals during survivorship care plans. To assess this alignment of expectations, De Padova et al.¹⁹ performed a qualitative analysis of 32 patients, 14 caregivers, and 60 providers, basing questions revolving around survivorship and quality of life. Between patients/caregivers and care providers, expectations were most incongruent for the role of primary care physicians in testicular cancer follow-up, which was deemed important/fundamental for 58% of patients/caregivers and 88% of care providers (p = 0.01). When the authors compared patients/caregivers with healthcare providers in their views of the experience of testicular cancer survivorship, there were several discrepancies noted: (i) the fear of recurrence was high/very high for 42% of patients/caregivers and almost unanimous (98%) for healthcare providers (p <0.001), and (ii) psychological distress was considered as highly relevant by 35% of patients/caregivers and 93% of care providers (p <0.001). Importantly, uncertainties about the roles and responsibilities of physicians can lead to deficiencies in care, supporting the need to make survivorship care planning a standard component in testicular cancer management.

The cancer experience has an impact on not only the patient, but also on their relatives (spouses, parents, siblings, etc)/caregivers, who often have to assume a lead role for the duration of and following treatment. This emotional and physical toll is not insignificant for the caregiver and can lead to significant emotional burden. De Padova and colleagues summarize this emotional burden on the caregiver, with contributions from both the testicular cancer patient and outside sources:²⁰

Mental Health Resources

There are many mental health resources available for testicular cancer survivors and their caregivers. The Substance Abuse and Mental Health Services Administration has a National Helpline at 1-800-662-HELP (4357), as well as the National Suicide Prevention Lifeline providing a 24/7 helpline at 1-800-273-TALK (8255) in addition to the following website: www.suicidepreventionlifeline.org. Finally, during the COVID-19 pandemic, Intermountain Healthcare has established the Emotional Health Relief Hotline at 1-833-442-2211, which may be useful resource to patients/caregivers in need.

Conclusions

The survivability of testicular cancer is excellent, thus putting the onus on comprehensive cancer survivorship programs to ensure appropriate long-term outcomes. Testicular cancer patients are at increased risk of mental health issues, including anxiety and depression, compared to similarly aged men in the general population, and may be at increased risk for many years after diagnosis. Additionally, population-level studies suggest that testicular cancer survivors are at increased risk of suicidal death, with increasing incidence with longer follow-up. The burden of illness, treatment and follow-up may also have an effect on patient caregivers, particularly the emotional burden that may accumulate during these challenging times. It is important for healthcare providers to be cognizant of these mental health disparities among testicular cancer survivors, providing appropriate access to psycho-oncology providers as part of a comprehensive survivorship plan for these patients.

Written by: Zachary Klaassen, MD MSc, Medical College of Georgia, Augusta, Georgia, USA

Published Date: April 2021