Caregivers of patients with malignant pleural mesothelioma: who provides care, what care do they provide and what burden do they experience?

Malignant pleural mesothelioma (MPM) is a tumour that develops in the mesothelial surfaces of the pleura. It is associated with exposure to asbestos, with asbestos workers and those residing near asbestos manufacturing plants being at increased risk of developing MPM [1‐4]. MPM has a long latency period of around 40 years, patients are often older males with a mean age of approximately 70 years at diagnosis, a median survival time of 8–14 months from diagnosis, and a 5-year survival rate of 10% [5‐9].

MPM is relatively rare with 34,614 new cases reported globally in 2017. Until recently, cases had been rising across most countries; it was only 20–30 years after banning asbestos use that countries like France, Italy, Spain, and the United Kingdom (UK) started to see a decline in cases [10, 11]. Given the long latency, cases are likely to continue to rise in countries slower to enact a complete ban as many countries are yet to reach expected peak death rates [12‐14].

MPM is highly aggressive [15], with a majority of patients presenting with late-stage unresectable disease that responds poorly to treatment [16, 17]. Previously there was little innovation in successful treatment for over a decade and treatment options remained limited for patients with MPM. More recently, nivolumab and ipilimumab immunotherapy has been approved in the United States (US) [18] and is recommended in the European Society for Medical Oncology guidelines [19]. Patients and their caregivers will experience prolonged periods of treatment (many treatment cycles followed by maintenance therapy) and the burden associated with treatment.

MPM is associated with an overall sense of physical debilitation and poor health, depression, anxiety, and cognitive impairment [20]. Given the highly symptomatic and aggressive nature of MPM, many patients require the assistance of caregivers [21]. Caregivers are often spouses, female and over 50 years of age [20, 22]. Due to the rapid progression of MPM and its physical and emotional toll, caregiver burden is likely to be high. However, there are limited data on caregiver burden in MPM and thus it has remained poorly understood.

Caregiver burden has been defined by a multidimensional approach, considering the physical, emotional, psychological, social and financial impacts on caregivers [23, 24]. The limited data on caregiving in MPM has shown that emotional functioning of caregivers is significantly impaired, with caregivers reporting higher levels of personal distress, receiving less support, and feeling less well-informed throughout the process of diagnosis than the patients they care for [20]. In addition, caregivers have poorer physical health than healthy peers and higher rates of depression and intrusive thoughts about death than the patients they care for [25].

In many countries, informal caregiving represents the backbone of the social care delivery system [26], providing an estimated annual economic value of €576 billion in 2016/2017 [27]. Informal caregivers are estimated to make up 10–25% of the total population of caregivers in Europe [28] and provide 80% of long-term care [29]. Therefore, without informal caregivers, societal costs, including health and social care costs would likely be severe. Thus, it is important to understand the burden placed on informal caregivers to ensure they receive the required support. Until recently, support for MPM was based on existing care infrastructures established for lung cancer patients; however, this fails to recognise the different needs in MPM [22]. One study found patients with MPM felt more hopelessness than patients with lung cancer—perhaps owing to fewer successful treatment options in MPM—and many felt anger that their disease resulted from bad workplace practices [30]. Further distress has been linked to delays in MPM diagnoses and uncertain prognoses [22]. These studies highlight how the challenges faced by patients with MPM and their caregivers may differ from patients with lung cancer.

There is a paucity of research on MPM caregiving, with much of the information about caregiver burden being anecdotal [20]. Therefore, there are many gaps in our understanding of caregiver burden in MPM. We aimed to identify the demographic characteristics of caregivers of patients with MPM, the caregiving activities they perform, and which of these were the most troublesome. We also investigated the burden of caregiving, and its impact on the caregivers’ health, work productivity and overall activity. We describe these data stratified by the clinical characteristics of the patients with MPM being cared for to further understand how these characteristics impact the caregiver’s role and associated burden.

This study included data from a sample of caregivers across four European countries. The results provide a greater understanding of who is providing care to patients with MPM, the specific tasks undertaken daily and which tasks caregivers found most troublesome. It also explores caregiver burden and impact on physical and emotional health and impairment of caregiver work and activity.

An MPM diagnosis may require changes in daily activities and work and may result in changed roles within the family unit [40]. Most caregivers in this study lived with and were a family member of the patient (9 in 10) and 7 in 10 were their spouse/partner. This study also found caregivers of patients with MPM engaged in a wide range of daily activities including, supporting patients travelling out of the home, driving to work/hospital/appointments and helping with meals and medication management. Other studies have also shown that caregivers who are family members may be expected to spend a lot of time providing practical support involving such tasks [41].

In addition to various practical tasks, most caregivers in this study reported that they were providing daily emotional support and encouragement to the patient, and this activity was cited as being one of the top three most troublesome caregiving activities. Our findings were similar to a study of caregiving in lung cancer patients where a third of caregivers reported managing patients’ emotions as being one of the most challenging tasks they perform [42], and similar findings have been observed among caregivers of patients with other cancers [43]. The results also indicated potential cultural differences may impact the perception of burden, for example, we found one in three caregivers in France and Italy reported providing emotional support was one of the top three most troublesome tasks compared with two in three in Spain and the UK. This suggests cultural differences may impact perceptions of the burden of specific caregiving tasks. Variations in compensation available to MPM patients across countries may also play a role. For example, comprehensive compensation is available in France and the UK at 4.60 and 1.03 times the median income per year, respectively, [44] but in Spain, many cases may be under-recognised under existing compensation systems [45].

A cancer diagnosis, as well as the subsequent phases of the disease and its treatment, can be a source of intense stress both for the patient and the family as they face the challenge of uncertainty, treatment routines, and the threat of treatment failure [46]. Poor prognosis for patients with MPM and lack of treatment options may cause ever-increasing emotional challenges for the patient; many MPM patients and caregivers indicate their psychosocial care needs are not being met [47]. Harrison et al. showed caregivers receiving a referral to a specialist palliative care team were significantly more satisfied than those that did not, particularly because of the emotional support provided by these services [48]. Further, many patients may experience resentment and blame if their cancer is attributable to their work environment [30]. These factors are likely to cause disappointment and stress for the caregiver [20] as well as requiring them to support the patient through these challenges, likely resulting in stress, negative emotions, and role strain, which contributes to physical and psychological health impairment [46]. Warby et al. reported even in cases where caregivers were satisfied with treatment, they reported needing more communication about available treatments, end-of-life assistance and support after the patient’s death [49].

The level of perceived burden experienced by caregivers of patients with MPM observed in this study was higher than the burden reported for caregivers of advanced non-small cell lung cancer patients [50] and advanced cancer patients in a palliative day care setting [51], but similar to the levels of burden observed for caregivers of cancer patients within six months of diagnosis [52]. Our finding that poor ECOG performance score was a key driver of caregiver burden in MPM is consistent with findings in other cancers [50, 53]. Of note, our study found that caregivers of patients receiving BSC had lower burden than caregivers of patients receiving 1L maintenance and 2L + SACT. These patients may be receiving more external support in a palliative setting which could lead to lower burden on the informal caregiver. Further research should seek to identify optimal times when additional support may be introduced to support both the patient and caregiver to alleviate burden.

An earlier study reported patients with MPM receiving maintenance therapy had better health states and quality of life (QoL) than patients receiving 1L SACT or 2L + SACT [31]. However, we found that the caregivers of patients receiving 1L maintenance were experiencing similar burden to caregivers of patients that had progressed to 2L SACT. This result may reflect patients experiencing ongoing treatment cycles and visits for treatment/ management. This will not only have a psychological effect on the patient and caregiver but also involve more time spent travelling out of the home and driving patients to hospital, both tasks caregivers reported as being among the most troublesome.

Across all subgroups, the levels of burden observed for caregivers of patients with MPM in this study exceeded the threshold for risk of depression identified by Schreiner et al. [36]. Caregivers are at risk for several mental health problems including depression, anxiety, hopelessness, and social isolation [54, 55]. Evidence regarding the potential psychological costs of caregiving and its relationship to caregiver burden has been growing [56]. A recent study found that subjective caregiver burden, as measured by the ZBI, was associated with poorer physical and mental health for caregivers [57]. Studies using other measures of caregiver burden have found a similar positive relationship between increased burden and increased risk of developing anxiety and depression [58]. Emotional concerns were also one of the most identified problems for caregivers in a literature review on the effects of caring for a patient with cancer [59] and declines in psychological wellbeing have been reported for caregivers of lung cancer patients [60, 61]. Caregiver burden is frequently overlooked by physicians and the findings of this study further demonstrate the need for caregiver assessment and intervention [54].

Despite caregivers being essential to the healthcare system, the health of caregivers is not being prioritized. Many caregivers have been described as “hidden patients” [62], susceptible to a variety of stress-related illnesses (including depression) that often go untreated because there is no one to attend to the caregivers’ responsibilities while they recover [63]. Without providing adequate resources in long-term care services, demands on caregivers’ attention and time are likely increased, putting them at risk of developing serious mental and physical health problems. Only a quarter of the caregivers in this study reported that caregiving had not impacted their health. It is important that caregivers are supported in taking care of their own health needs as well as those of the patient they care for. However, for some, this will require them to overcome a culture that encourages caregivers to meet the needs of the patient at the expense of their own [64]. Where systems have been found to be inadequate or not supportive enough of caregivers, levels of anxiety and depression have remained high [65]. Caregivers that have received psychological and social resources reported lower levels of depression than those that have not [66]. In particular, support targeted at specific caregivers’ needs is often the most helpful [67].

In addition to our study providing insights into the burden of caregiving in MPM and the potential impacts to emotional and physical health, we also found that caregivers spent 40% of their daily activities impaired and those that were still working had 12% absenteeism and 25% presenteeism during the past seven days. Family and medical leave policy reform is needed to support caregivers. For example, in the UK, an employer is not legally obligated to pay a caregiver that takes time off to provide care, likely leading to caregivers returning to work before they are ready. There is growing interest from insurers and healthcare systems to understand caregiver burden both for caregivers themselves, the patients and the impact of caregiving on society. Studies such as this are vital across diseases if the required support is to be identified and provided to caregivers and further incorporated into insurer and healthcare system decision making. Importantly, caregiver burden has been found to be associated with factors linked to disease progression such as the ECOG performance score of patients [50] and patient QoL [64], with burden for caregivers increasing as ECOG performance score declines or QoL deteriorates. Recently, the European Medicines Agency and US Food and Drug Administration have approved nivolumab and ipilimumab combination therapy in the 1L setting [68, 69] based on the results of a clinical trial which demonstrated an increased time to QoL deterioration and prolonged survival [70‐73]. Given the relationship between clinical outcomes and caregiver burden, improvements in treatment options for patients with MPM may be expected to lead to improved outcomes for caregivers also. Payers should consider caregiver burden when economically evaluating potential new treatments.

A key strength of this study was the geographical spread of the primary caregivers, which provided a diverse and sizable caregiver population for evaluating the impact of this rare cancer on caregivers of patients in routine clinical care in Europe. As with all point-in-time study designs, the current study provides a snapshot of caregiver status only; therefore, the status of caregivers prior to taking on their caregiving role is unknown.

A limitation of this study was that it relied on the accuracy of recall by caregivers, although the selection of validated instruments that require short recall time was expected to minimise these effects. Caregiver inclusion was based on their willingness to participate, which has an inherent risk of selection bias. However, the demography of the patients with caregivers that did not provide a CSC was similar to that of those who did provide a CSC. Finally, as this study was purely descriptive, differences observed may not be statistically meaningful.

The results of this multi-country, real-world study provide evidence that caring for patients with MPM involves a range of burdensome activities impacting caregivers’ emotional and physical health and their ability to undertake daily activities. Future innovation in the management of MPM will need to ensure improved outcomes for patients are not at the detriment of caregivers, and it is crucial caregivers receive the necessary support to carry out this important role. Interventions that maintain patient ECOG performance score and QoL by delaying disease progression are expected to improve caregiver outcomes. Focussing on maintaining caregiver health alongside the health of patients with MPM will also improve outcomes for caregivers and thus their ability to provide essential care for those with MPM.