What are the psychological effects of mesothelioma on patients and their carers? A scoping review

Despite recent advances in research, malignant mesothelioma remains an incurable and devastating disease, typically bringing shock and emotional distress to patients and carers. Little research has addressed the psychological impact on either group. This scoping review examines the current state of evidence on the psychological effects of mesothelioma on patients and carers, and identifies areas for further research.


| INTRODUCTION
Malignant mesothelioma (MM) is an incurable disease usually linked to asbestos exposure. 1 There are two main types: the most common, malignant pleural mesothelioma (MPM), affecting the membrane lining the lungs and chest wall, and peritoneal mesothelioma (PM), affecting the abdominal lining. 2 Symptoms appear after a long latency period (20-50 years), with the disease often progressing very quickly. 3 Mesothelioma is usually diagnosed in older people. 1 Survival rates are poor: for 2014 to 2016 the percentage of patients in England and Wales surviving 1 year post-diagnosis was 38%, and 3 years post-diagnosis was 7%. 1 Within these figures, there is a significant difference in survival times for different subtypes. In mesothelioma's initial stages, symptoms tend to be non-specific, meaning it is often diagnosed at a late stage. 4 However, occasionally, mesothelioma is diagnosed at an asymptomatic stage after an incidental finding. 5 Once disease is advanced, the symptom burden is severe, including breathlessness, chest wall pain, weight loss, sweating and fatigue, with severity increasing and sometimes proving difficult to palliate. 6 Research into the lived experience of mesothelioma patients has been sparse. Cancer patients in general experience psychological distress, including anxiety, depression, existential concerns and posttraumatic stress. [7][8][9] They may also experience posttraumatic growth. 10 Carers of cancer patients in turn are more likely to experience depression, anxiety, hopelessness, isolation, somatic symptoms and financial issues. 11 Mesothelioma, with its high symptom burden, incurability, rarity and asbestos-related causation, has a unique psychosocial impact. 12 Although mesothelioma remains incurable, recent advances in clinical research are providing more treatment options, such as immunotherapy. 13 Further research into the psychological aspects of mesothelioma is required to map any changes that may be occurring alongside the changes in medical treatment and prognosis. This applies to carers as well as patients, as their wellbeing is an important part of the picture. 13,14 However, the experience of carers has not been a particular focus of mesothelioma research to date. 15 Therefore, the aim of this scoping review was to examine the current state of evidence on the psychological effects of mesothelioma on patients and carers, and identify areas for further research. 16

| METHODS
In line with scoping review methodology, the search question was suitably broad, but had clarity regarding the scope of inquiry 17 : what is the current state of the evidence on the psychological effects of mesothelioma on patients and their carers? The population was 'patients and carers', the intervention was 'mesothelioma' (covering all disease types), and the outcome was 'psychological effects' (positive and negative).
A scoping review does not aim to be exhaustive, but to give an initial assessment of the available literature. 18 Therefore, any potentially relevant articles identified from the reference lists of the retrieved articles or from Google Scholar were included, but grey literature was not, nor were attempts made to locate on-going, unpublished research in the field. This decision, made for feasibility reasons, provided a limitation to comprehensiveness.
The review was conducted using the staged method described by Arksey and O'Malley 16 and Levac et al. 17 It was reported following the PRISMA Extension for Scoping Reviews Checklist, 19 with the aim of being systematic, transparent and replicable. 20 A protocol was not registered.
Keywords from published relevant articles were reviewed to inform this process (see Figure 1). Searches took place in May 2019 of these bibliographic databases: PubMed, PsychINFO via OvidSP, CIN-AHL, the Cochrane Library and Web of Science. Search parameters were adjusted to match individual database requirements.
An example search strategy (CINAHL) is given in the Appendix.
The results for each database search were exported into EndNote and duplicates removed. A flowchart of the search strategy is given in Figure 2 For inclusion, articles had to be peer-reviewed research articles (reporting empirical qualitative, quantitative, or mixed methods studies and literature reviews). Other inclusion criteria were: • in English (practical reasons); • involving adult humans (mesothelioma extremely rare in children); • dating from 1981 (seminal Lebovits article published 21 ) to May 2019; • focussing on psychological effects (not physical aspects of symptoms/treatment); • focussing on mesothelioma (mentioned in title or abstract).
Exclusion criteria applied were: • not in English; • not involving adults; • focussing on clinician's perspective, rather than patient's/carer's; • about questionnaire development or focussing primarily on quality of life (QOL) measurement (eg, part of a clinical trial or QOL tool development), as these would not focus on content but on the tool's validity and reliability; • about physical symptoms, treatments or epidemiology; • focussing on intervention development; • conference abstracts, dissertations, editorials, book reviews, individual case reports; • concerning lung and pleural cancers (ie, mixed sample).
A single reviewer (VS) applied the inclusion and exclusion criteria to the retrieved articles after duplicate removal. Titles and abstracts were screened for relevance and irrelevant articles excluded. The remaining articles were obtained in full text and exclusion criteria were applied. Broadly following the team approach recommended to aid rigour, 17 the authors met to discuss eligibility decisions at the beginning of the process. The team also discussed and agreed inclusion/exclusion after the full text studies were obtained. We wanted to understand the range and quality of the existing evidence. While there is debate about quality appraisal in scoping reviews, 20,22,23 we decided to follow a quality appraisal process. The aim was to inform the review by giving an overview of the quality of the existing literature as a whole, including the quality of reporting, but without excluding any of the identified articles. (The authors noted quality appraisal was conducted by Ball et al. 6 ) For our review, after data extraction the articles were critically appraised using CASP checklists. 24 As is recommended to aid rigour, 16 To stay close to the data, VS generated semantic, rather than latent, codes, which stay at the surface of the data, 26 for example, loyalty; stigma; future. Developing the themes was a consciously creative process, requiring reflection and thoughtfulness. 27 Reflexive questions were useful throughout the analysis process, for example, 'Am I making assumptions about loyalty to former employers?' Quirkos enabled codes to be clustered and combined, helping VS identify meaning-  We included this.
The review's findings are presented in two ways: a basic analysis of the characteristics of the included studies, and a report of the themes developed from the data. 16

| Characteristics of the included studies
An overview of the charted characteristics and critical appraisal data for each included article is presented in Supporting Information S1.
The 17 articles comprised 11 qualitative, two quantitative and three literature reviews Moore et al, 29 Bonafede et al, 12 Ball et al 6  Considering the qualitative studies first, four were conducted in the UK, one in Australia, two in Italy, two in Japan, and three in the USA. Nine articles aimed to explore the subjective experience of mesothelioma and identify care and support needs. Two studies explored psychological issues around risk awareness. 21,31 One developed recommendations to improve the diagnosis experience. 32 The majority investigated MPM, while four looked at MPM plus peritoneal. The range of participants was 5 to 112. Eight studies were situated in large teaching hospitals. Two recruited via local specialist nurse referrals, and two via nationwide hospitals, groups and networks. The qualitative studies commonly excluded anyone judged 'not well enough' to participate, or who had a psychiatric diagnosis, or who might experience aggravated emotional distress. Only three included carers and relatives in their design. 30,32,33 In a few articles attention was paid to teasing out patient and carer experiences at different time-points in the disease's course: at diagnosis, 32,34 and in the first 6 months. 30 Kasai and Hino 35 conducted the first longitudinal qualitative study in this field, examining five transition points in disease progression with participants diagnosed 5 to 8 years previously. Whilst the majority of cases of mesothelioma in the literature were men who had been exposed occupationally, the Italian articles 12,15,30 included a higher proportion of females, as they studied people exposed by living in or near National Priority Contamination Sites (rather than occupationally exposed males as is typical).
Of the quantitative studies, one was conducted in the UK (with

| Quality appraisal
The critical appraisal carried out informs the following overview of the field's quality. Of the qualitative articles, three were rated as low risk of bias 28,32,38 ; the rest were rated unclear. Of the quantitative, Henson et al 37 was rated low, and Dooley et al 36 unclear. All three reviews 6,12,29 were rated unclear.
A limitation commonly reported was generalisability: numbers of participants were small, due to mesothelioma's rarity and recruitment difficulties caused by its debilitating nature. The only large-scale study was Henson et al, 37 which added a new dimension to the field by uncovering suicide risk. Kasai and Hino,35 in the only longitudinal study, marked out the illness into five time-periods and provided a useful new framework, but could only follow five participants. All three literature reviews 6,12,29 highlighted the paucity of studies on psychological aspects and lived experiences of mesothelioma patients and carers. They also usefully drew out differences between the experience of mesothelioma patients and those with lung cancer or asbestos-exposed people. The reviews together gave a wider reach across In terms of the standard of reporting, as assessed by the critical appraisal checklists, 24 only four articles could be considered excellent. 28,32,37,38 Amongst the others, there was some lack of transparency regarding reporting of methods. It is possible the journals' limited word counts had an effect. The most noticeable area of omission was detailing the relationship between researcher and participants. There was little critical examination of the researcher's own role, with potential for bias and influence, both in the formulation of questions and in data collection, and there was sometimes lack of clarity around the role of the patient's own medical team. However, more consideration was given to potential bias in the analysis process. In terms of representation, the voices of participants were heard more easily, and showed more range, in some studies than others.
This section has presented the findings relating to the characteristics of the 17 identified articles. Next, this review summarises the findings relating to key themes developed, which captured the range of data in the articles.  (Table 1).

| Themes
Four studies 6,12,15,30 identified the first time-period: pre-diagnosis. For mesothelioma, there is an extra dimension around causality, and the 'Damocles syndrome' (retrospective awareness of personal risk from asbestos exposure was identified as a cause of anxiety and distress. 6,12,15,30 These feelings could also be generated by awareness that the patient's own contact with asbestos may have led to the second-hand exposure of family members, for example, by washing work clothes. 12 Two studies 15,32 highlighted another difficult aspect of this initial period: the long, frustrating journey to a definitive diagnosis.
Diagnosis was a significant time-point in 14 articles, bringing shock, anger, anguish, numbness, anxiety and depression. The fact that the patient's time was now limited brought a terrible certainty.
However, alongside the certainty came distressing uncertainty about disease progression and the future. 6,35 Issues of timing caused distress at diagnosis, for example, the appointment not being long enough; inappropriate levels of information about the illness and compensation. 32,33,40 The initial phase of the illness is critical in terms of suicidality.  After the initial period, the speed and unpredictability of disease progression caused intense anxiety, as three studies showed. 6,12,30 Sometimes, lack of continuity with medical staff left patients unsure about the next treatment steps, with an inability to plan ahead accompanied by distrust of medical interventions and HPCs. 12

| Dealing with difficult feelings
All 17 articles presented difficult feelings and allied coping strategies.
'Difficult feelings' includes negative emotions, and also feelings around identity and states of being (Table 1). These had a range of causes, some described above. Physical symptoms, for example, pain and sweating, were inherently upsetting or frightening, and also frustrating in their impact on independence and social roles. 6,12,34,39 Feeling socially isolated was mentioned in several articles, resulting from depression, apathy and stigma. 15,30,39 The physical burden took its toll on carers, and patients worried about being a burden 6 or agreed to treatment to keep relatives happy ,35 who in turn could feel guilty. 29,33 Distress sometimes resulted from the effect of professionals' activities. It was caused by medical treatments 29,30 ; lack of continuity 6,32 ; feeling abandoned if chemotherapy was not an option 39 ; and feeling like guinea pigs during trials. 15 The anger that was identified was linked to two causes. The first was patients' frustration at not being able to do ordinary activities, with carers also feeling helpless or angry about changes in the patients, such as their sense of identity, willingness to live a normal life, or their irritability. 15,39 Second, complex medico-legal matters led, for some, to feelings of anger and betrayal towards employers. For others, conflicted loyalty towards former employers meant anger was redirected towards families or doctors. 6,12,39 These many difficult feelings led patients and carers to experience a lack of control. This could include feeling powerless over the disease; having to relinquish family responsibilities; fearing total loss of agency at end-of-life; and insecurity about how to live and who could help. 28,34 To cope, they engaged in a wide range of strategies. Avoidance/denial was identified as the main mechanism. 12 Strategies included deciding that statistics do not apply; limiting information 33 ; trying to live normally 6 ; and denying negative emotions. 15 Refusing to talk or think about things was frequently used both by patients and carers. 15,30,39 However, this tended to increase social isolation, brought relationship difficulties, and came at a cost to the individual.
A fighting spirit was identified as helping to protect a sense of control. 33,35 Other factors giving a sense of control were accessing complementary/alternative medicine, support groups, palliative care, physiotherapy and maintaining fulfilling social and family roles. 6,12 Some participants had an accepting attitude, reviewed their lives, mourned their losses and looked for the positive. 15,29,33,35 Patients were more likely to report acceptance than carers. 29 Only the quantitative studies 36 with the difference explained by mesothelioma's incurability, poor prognosis and lack of treatment options.

| Craving good communication
Issues around the sharing of information and positive/negative aspects of communication (Table 1) 15,33 Several studies presented the need of carers and patients for communication with others who had the same experience and understood the nuances of this rare disease. 33,35,39 They valued the emotional support, and some patients found it helped them prepare for dying. 35 For some families, talking to each other about mesothelioma and its effects was extremely difficult, and they wanted to be helped by psychologists to find new ways to communicate. 15 Skilled listeners, for example, psychologists were identified as able to provide valuable emotional support. 15 Hughes and Arber 39 found their participants were grateful for being heard, telling their stories urgently despite becoming very distressed.
They also reported their participants had issues with sex and intimacy, as did Dooley et al, 36  Until relatively recently, researchers did not place emphasis on psychological effects at different stages of the disease, or consider the variety of prognoses, treating the mesothelioma journey as uniform. 29 The general need for more nuance has been recognised and is starting to be addressed, for example, by Ball  Despite the review's search terms allowing for positive effects to be reported, the emphasis in the studies was mostly on the negative.
The most recent article, by Walker et al, 28 was an exception, with its finding that participants frequently expressed hope and optimism. The wider cancer literature includes studies on posttraumatic growth, benefit-finding and hope. 10,[45][46][47] There is therefore scope to explore positive aspects of the mesothelioma experience, which might help counter the hopelessness often transmitted by HCPs.
None of the studies explored the unique experience of carers. If included at all, they were mixed in with patients, so their particular concerns and needs were muted and overlooked. This lack of inclusion may in part be due to lack of recognition by carers themselves, since many relatives, friends or partners of patients might reject the term 'carer' as not applying to them. 48 It may also reflect a lack of recognition by researchers and healthcare systems. 49

| Study limitations
This review was conducted in partial fulfilment of a doctorate. A single researcher carried out the majority of the review using a reflexive process. However, the process and the themes identified were extensively discussed in doctoral supervision with the other authors. Existing studies with psychological effects as secondary outcomes could include valuable relevant information. Our decision not to include these was therefore a limitation. The scope of our search could have been wider (no inclusion of grey literature or attempt to find on-going research). In mitigation, the aim was to be reproducible through transparency in conduct and reporting, with provision of good documentation. 18

| Clinical implications
This review has highlighted the importance of clinical practitioners being aware of the complex psychological impact and sequelae of mesothelioma. The findings indicate currently there is little evidence to inform clinical practice related to the psychological impact of mesothelioma, especially with regard to carers. However, our findings could inform the development of an assessment tool to identify psychological issues and address risk. They could also impress upon HCPs the importance of communication skills training.

| CONCLUSIONS
Though limited, the evidence indicates that mesothelioma, with its high symptom-burden, incurability, rarity and asbestos-related causation, leads to complex and inter-relating psychological effects on patients and carers. These effects are both negative and positive. The sparse literature gives a limited picture and demonstrates an urgent need for more nuanced research. Studies exploring the experiences of specific groups are recommended, such as people exposed in different workplaces. No study has addressed the unique experience of carers, so this is suggested.