Psychological Responses and Coping Strategies Among Patients with Malignant Melanoma a Systematic Review of the Literature

EVIDENCE-BASED DERMATOLOGY: STUDY

SECTION EDITOR: MICHAEL BIGBY, MD; ASSISTANT SECTION EDITORS: OLIVIER CHOSIDOW, MD, PhD; ROBERT P. DELLAVALLE, MD, PhD, MSPH; URBÀ GONZA´ LEZ, MD, PhD; CATALIN M. POPESCU, MD, PhD; ABRAR A. QURESHI, MD, MPH; HYWEL WILLIAMS, MSc, PhD, FRCP Psychological Responses and Coping Strategies Among Patients With Malignant Melanoma A Systematic Review of the Literature

Nadine A. Kasparian, BA(Psych, Hons I), PhD; Jordana K. McLoone, BPsych(Hons I), PhD; Phyllis N. Butow, MPH, PhD

Objective: To conduct a systematic review of the lit- Data Synthesis: Approximately 30% of patients with erature to identify the prevalence of, and demonstrated melanoma reported clinically relevant levels of psycho- risk factors for, psychological distress among individu- logical distress, as measured by a range of validated scales, als affected by, or at high risk of developing, melanoma. with symptoms of anxiety more prevalent than depres- For a substantial subset of patients, the diagnosis and/or sion. A number of empirically demonstrated risk factors treatment of cutaneous malignant melanoma may cause for distress were identified, including female sex, younger significant psychological distress. age, lower education, visibility of affected body site, lack of social support, and negative appraisal of melanoma. Data Sources: Using the MEDLINE, PsycINFO, and CINAHL databases, published studies (1988 to March 2008) Conclusions: Routine psychological screening of pa- of individuals affected by melanoma were included if they tients with melanoma is widely recommended as stan- examined the demographic, clinical, psychological, and/or dard practice; however, standard screening measures may social correlates of emotional distress. have limited sensitivity and specificity as demonstrated by the wide range of results reported in this review. De- Study Selection: Searches were restricted to publications in English and were supplemented by citation lists velopment of a brief screening tool that incorporates in retrieved articles and contact with researchers. empirically supported risk factors is recommended to improve the timely identification and support of those Data Extraction: A total of 356 articles were critically patients most susceptible to adverse psychological appraised by 2 reviewers to assess eligibility and clinical outcomes. evidence level. A total of 44 studies met the inclusion criteria. Arch Dermatol. 2009;145(12):1415-1427

ESPITE CONTINUED and finances.1,2 The distress evoked by such progress in the medical changes may have wide-ranging implica- Author Affiliations: School of management of many tions. Psychological distress has been as- Women’s and Children’s Health malignant diseases, the sociated with patient delay in seeking (Dr Kasparian) and Prince of diagnosis of cancer, in- Wales Clinical School medical advice for melanoma, decreased cluding melanoma, remains a difficult (Dr McLoone), Faculty of D adherence to treatment regimes, in- Medicine, University of New event in the lives of many patients and their creased rates of melanoma recurrence and South Wales, Kensington, New families. Clinical impressions and re- mortality, lower quality of life (QOL), in- South Wales, Australia; search findings suggest that a diagnosis of creased medical costs, and reduced en- Department of Medical gagement in posttreatment skin cancer Oncology, Prince of Wales screening and preventive behaviors.3-5 Hospital, Randwick, New South For editorial comment Thus, understanding the prevalence and Wales (Drs Kasparian and see page 1439 correlates of psychological distress and de- McLoone); and Centre for veloping interventions to reduce distress Medical Psychology and Evidence-Based melanoma has the potential to change all remain critical research and clinical Decision-Making, School of aspects of an individual’s daily living from endeavors. Psychology, University of self-identity, body image, and perceived According to the Surveillance, Epide- Sydney, Sydney, New South well-being, to family roles and relation- miology, and End Results (SEER)6 data Wales (Dr Butow). ships, career opportunities, friendships, from 1995 to 2001, 83% of melanoma cases

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©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 Table 1. Literature Search Exclusion Criteria and Number of Published Studies Excluded According to Each Criterion

Studies Meeting Exclusion Criteria Exclusion Criteria, No. Other primary cancer site (eg, breast cancer, lymphoma, retinoblastoma, endobronchial metastases), or no differentiation 12 between a mix of cancers Other primary condition (eg, cardiovascular disease, diabetes mellitus, asthma, osteoporosis, endometriosis, pigmented lesion) 19 Assessment of measures, diagnostic tools, or theoretical models 12 Epidemiological (or survival) study 71 Medical treatment trial (drug, radiation, or surgery) 66 Molecular genetics or biological study 28 Case study 16 Review 20 Editorial comments, letters, discussions, or conferences abstracts 7 Clinical guidelines or recommendations 6 No assessment of psychological factors 29 Sample population Ͻ18 y 1 Animal studya 6 Other (eg, dissertation thesis) 20 Total number of studies excluded 313 Studies remaining 43 Additional studies identified via publication reference lists 1 Total number of studies included in systematic review 44

a Although “human” was included as an original search limit, some animal studies circumvented this because reference was made to the human implicationsof the study.

in the United States are diagnosed while the cancer is still tients with melanoma. The findings of the review were confined to the primary site, yielding good prognoses.7 This, then used to develop a series of evidence-based clinical coupled with the often healthy outward appearance of pa- recommendations for the supportive care of patients with tients with early-stage melanoma, may contribute to the malignant melanoma. Ways in which the empirical lit- prevailing belief that such patients have little or nothing erature may be used to inform the development of a brief, to worry about.8-10 Despite a good prognosis, however, pa- tailored screening tool for the identification of patients tients with early-stage melanoma deal with both the im- with melanoma who are most susceptible to adverse psy- mediate stress of being diagnosed with a possibly life- chological outcomes, as well as the cost-effective design threatening disease as well as the threat of recurrence or and implementation of appropriate psychological inter- systemic spread, which is greatest during the first 2 years ventions in this setting, are also discussed. after diagnosis but may occur within 10 years of diagnosis. Several studies have also found evidence to suggest that some patients with melanoma experience an underlying METHODS fear of disfigurement caused by cancer surgery, and that the visibility of treatment-related scarring may form a con- Three strategies were used to conduct the literature search. First, stant reminder of the individual’s cancer experience,8 ir- the electronic databases MEDLINE, MEDLINE In-Process, Psy- respective of the body site affected.3,8,11 Disfiguration of cINFO, and CINAHL were searched from January 1988 to March bodily appearance may threaten patients’ self-esteem and 2008 using the keyword “melanoma” in combination with each self-confidence,4,12 particularly in younger adult age groups, of the following terms: depression, anxiety, adjustment, psy- among whom melanoma is the most common malignant chological adjustment, distress, psychological distress, worry, disease.5 Thus, seemingly high-functioning patients with cope, and coping. We agreed on the inclusion and exclusion criteria before commencement of the review (Table 1). Stud- early-stage melanoma may be overlooked by family, friends, ies were considered eligible for inclusion in the review if they and health care professionals in terms of social and psy- were published in a peer-reviewed journal or were otherwise chological support, potentially exacerbating feelings of anxi- in the public domain in a peer-acceptable format. Multiple ar- ety and/or depression.10 ticles that seemed to describe overlapping patient populations Synthesizing previous research findings, the aims of were grouped together and, where necessary, only the data from the present review were 4-fold: (1) to systematically re- the largest study population or the most recent article in these view the body of literature on the prevalence of psycho- groups were reviewed. Second, the resulting list of publica- logical distress among individuals affected by mela- tions was then screened for nonresearch articles, duplicates, noma; (2) to compare these findings with the limited and irrelevant references such as single case reports, letters, com- number of studies assessing psychological distress among mentaries, or conference abstracts. Third, the reference lists of all publications identified were examined for relevant articles individuals at increased risk of developing melanoma due not captured by the initial literature search. to strong family history; (3) to identify the demo- This review is concerned with the psychological responses graphic, clinical, psychological, and/or social predictors of patients with melanoma, and the term “melanoma-specific of distress in these populations; and (4) to examine the distress” will be used hereinafter to denote emotional distress various coping strategies commonly adopted by pa- specific to some aspect of an individual’s melanoma diagnosis

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©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 and/or treatment. This form of distress is typically assessed via ticular symptoms that are unique to each disorder. Anxi- administration of the Impact of Events Scale (IES), a validated ety is characterized by symptoms of excessive, perva- 15-item measure of intrusion and avoidance responses in re- sive, and uncontrollable worry, whereas depression is lation to a specific stressor, in this case melanoma. Where ref- typified by symptoms of low mood and diminished in- erence is not made to melanoma-specific distress, the emo- terest or pleasure in most activities.20 Gibertini et al19 re- tional responses described should be considered generalized. A wide range of scales have been used to measure psychologi- ported that approximately 1 in 5 patients newly diag- cal distress, and in some instances clinical cutoff scores are pro- nosed as having nonmetastatic melanoma have some form 16 vided for these scales (eg, the Hospital Anxiety and Depres- of treatable depression, whereas Sigurdardo´ttir et al re- sion Scale [HADS], Brief Symptom Inventory, Beck Depression ported that approximately 1 in 4 patients with mela- Inventory). These cutoff scores allow clinicians and research- noma beginning chemotherapy report clinically rel- ers to identify patients recently experiencing psychological symp- evant levels of anxiety. Anxiety seems to be more prevalent toms of a severity that may warrant clinical intervention; for than depression, with studies reporting the percentage example, a potential diagnosis of clinical depression. Despite of participants within the clinical range on the HADS to differences between scales in terms of item wording and re- be around 23% and 11% for anxiety and depression, sponse format, clinical cutoff scores are typically considered respectively.17,21-24 comparable across scales. There is, however, substantial variability between studies in regard to the prevalence of reported anxiety and RESULTS depression. Among patients with nonmetastatic melanoma, the proportion of participants scoring within the The initial search yielded 569 articles. After deletion of clinical range for anxiety on the HADS has been re- duplicates (n=213), the exclusion of 313 articles accord- ported to range from 18% to 44%.18,24,25 Similarly, the per- ing to our predefined criteria (Table 1), and the inclu- vasiveness of clinically relevant depressive symptoms sion of 1 article identified by citation within the refer- among patients with early-stage melanoma is reported ence list of a selected publication, 44 articles were to be 6% to 28%.24-26 Only 3 studies16,17,24 have reported identified for review. These articles were examined and the prevalence of clinically relevant levels of anxiety and their results tabulated. In accordance with the National depression in patients with metastatic disease or more Health and Medical Research Council (NHMRC) of Aus- aggressive tumors (thickness Ͼ0.8 mm). These studies tralia evidence rating system,13 most relevant articles pro- also report wide variation, with the prevalence of anxi- vided level IVa evidence; that is, evidence obtained from ety ranging from 13% to 28%, and the prevalence of de- descriptive studies of patient behaviors, knowledge, and/or pression ranging from 4% to 19%.16,17,24 Wide variation attitudes. The remaining articles provided level III evi- in the prevalence of clinically relevant distress among pa- dence; that is, evidence obtained from well-designed con- tients with melanoma may reflect important differences trolled trials without randomization, well-designed co- between study samples in terms of time since diagnosis hort or case-control studies, or multiple time series with and/or treatment, involvement in clinical trials, and/or or without an intervention. cultural attitudes or beliefs. Limitations such as retro- spective study design, lack of control or comparison PREVALENCE OF PSYCHOLOGICAL groups, failure to adjust for disease severity, reliance on DISTRESS AMONG PATIENTS WITH single assessments of psychosocial status, and small MALIGNANT MELANOMA sample sizes also impede the generalization of findings.

Although a small number of studies document general emo- POSTTRAUMATIC STRESS AS A FRAMEWORK tional well-being and resilience among persons diag- FOR UNDERSTANDING PSYCHOLOGICAL nosed as having melanoma,10,14-17 a much larger number DISTRESS IN THIS SETTING of studies have identified a considerable proportion of patients who experience elevated levels of psychological Other researchers have assessed the psychological im- distress around the time of melanoma diagnosis and treat- pact of melanoma from a posttraumatic stress (PTS) re- ment. These studies indicate that, on average, approxi- sponse framework. From this perspective, 2 key symp- mately 30% of all patients with melanoma report levels of tom clusters are considered critical to understanding psychological distress indicative of the need for clinical in- psychological responses to melanoma diagnosis and/or tervention, as measured by a range of validated scales.1,18,19 treatment. These are (1) intrusion, defined as disturb- In comparison with other cancers, the proportion of pa- ing, persistent, and unwanted images, thoughts, and feel- tients with melanoma who report clinically relevant lev- ings, often accompanied by autonomic arousal, hyper- els of distress is equivalent to that identified in patients vigilance, and marked anxiety; and (2) avoidance, marked with breast and colon cancer and demonstrably higher than by ignoring the implications of threat, forgetting impor- the prevalence of distress found among patients with gy- tant problems, and experiencing emotional numbing.27 necological and prostate cancer.1 Advocates of this perspective argue that the assessment The prevalence of anxiety and depression in patients of PTS provides valuable clinical information concern- with melanoma is often reported in the literature con- ing psychological adjustment in patients with cancer, sur- currently because these internalizing states share simi- vivors, and their immediate family.28 lar features of negative affect, emotional distress, and sig- Kelly et al21 were one of the first groups to examine nificant interference in daily life. However, anxiety and PTS responses in a cross-sectional study of 95 patients depression may be differentiated by the presence of par- with stage I to stage IV melanoma. Using the IES to quan-

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©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 tify levels of intrusive and avoidant symptoms related to viduals from p16-Leiden families who had chosen to de- melanoma diagnosis, this study identified patients with cline genetic testing for melanoma risk, and, in agree- stage III disease (ie, nodal metastasis) as having signifi- ment with the findings reported by Kasparian et al,30 these cantly greater stress symptoms compared with patients researchers found that only a small proportion (7.6%) with stage I disease, with a trend in the same direction of participants reported elevated levels of anxiety. It is compared with patients with stage II or stage IV disease possible, however, that the factors associated with the de- (ie, distant metastasis).21 A similar result was also found cline of genetic testing may also be related to the low lev- when participants with nonmetastatic melanoma were els of reported anxiety. classified according to tumor thickness, suggesting an association between PTS and prognostic indication.21 These DEMOGRAPHIC, CLINICAL, AND findings were not replicated using the HADS, leading the PSYCHOSOCIAL PREDICTORS OF DISTRESS authors of that study to suggest, similarly to Brandberg et al,24 that IES symptoms may be more sensitive indi- Over the past 20 years, very few studies have used mul- cators of the differing psychological concerns emerging tivariate analysis to elucidate the factors contributing to across the spectrum of melanoma progression. higher levels of psychological distress in the population As noted, anxiety symptoms also seem to be more fre- of patients with melanoma. In total, only 5 of the 44 ar- quently reported by individuals affected by melanoma com- ticles included for review provided explanatory analysis pared to those with depressive symptoms.17,24 Further- of the variance in distress. As shown in Table 2, this more, Baughan et al29 found that 54% of patients with limited literature has identified a variety of measurable, melanoma attending a routine follow-up appointment at and in some cases relatively stable, variables that may be a pigmented lesion clinic reported some degree of anxi- predictive of psychological distress in individuals af- ety prior to their consultation, with 17% of these patients fected by melanoma. also reporting physical symptoms of anxiety such as di- arrhea, nausea, and sleeplessness. These data lend addi- Demographic Factors tional support for the specific assessment of PTS, as linked to the spectrum of anxiety disorders, in analyses of the psy- Several studies have found that women,* those younger chological impact of melanoma, and highlight the need in age,11,22 and those who are unmarried,38,39 with fewer for melanoma-related concerns to be examined as signifi- children,38,39 or with lower levels of education14 are more cant dimensions of psychological morbidity. likely to report symptoms of psychological distress. Fur- thermore, 2 studies have identified an association be- PSYCHOLOGICAL DISTRESS AMONG tween unemployment and increased psychological INDIVIDUALS WITH A STRONG FAMILY distress.8,38 HISTORY OF MELANOMA Clinical Factors To our knowledge, since 1988, only 2 studies30,31 have spe- cifically investigated psychological distress among fami- Patients diagnosed as having advanced disease,8,21 a de- lies with an inherited pattern of melanoma (ie, multiple terioration of physical condition,39 or with tumors lo- melanoma cases in the family and a family-specific mu- cated on visible parts of the body, such as the face or tation in the CDKN2A gene). Recently, Kasparian et al30 hands,8 have been found to report higher levels of psy- examined psychological outcomes in this context and found chological distress. In several studies, stage of cancer at that among individuals unaffected by melanoma but at high diagnosis and time since diagnosis were not found to be risk of developing the disease due to family history, only significant predictors of general distress,21,33,38 but there 1% of participants exhibited clinically relevant levels of are some data to dispute this, particularly in terms of de- melanoma-specific distress. Surprisingly, this study found pression24 and melanoma-specific distress.21 This find- no evidence of clinically relevant melanoma-specific dis- ing is surprising given the substantial differences in treat- tress among high-risk individuals with a previous diag- ment and prognosis between early- and late-stage nosis of melanoma. Similarly low levels of depressive symp- melanoma; however, it does support the importance of toms were reported by those with, and those without, a subjective appraisal in psychological adjustment to dis- personal history of melanoma, whereas levels of anxiety ease. For example, compared with those who experi- were comparable with population norms, with 5% of pre- ence low levels of distress, individuals who report high viously affected participants and 15% of unaffected par- distress levels have also been found to report signifi- ticipants reporting anxiety potentially warranting clini- cantly worse evaluations of current and future personal cal intervention. Thus, overall the level of reported distress health, higher ratings of pain intensity, decreased en- in this familial melanoma cohort was relatively low, even ergy ratings, and greater interference from physical and after notification of the presence of a family-specific mu- emotional problems on social activities.18 tation in the CDKN2A gene which, in Australia, confers an estimated lifetime melanoma risk of 91%.31 Psychological and Social Factors To date, and to our knowledge, the only other published study to shed light on the psychological experi- In terms of psychosocial predictors of distress, ences of individuals with a strong family history of mela- Hamama-Raz and Solomon38 and Hamama-Raz et al39 noma was that conducted by Riedijk et al.32 This study examined psychological distress among high-risk indi- *References 8, 10, 11, 15, 17, 22, 40, 43, 44.

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©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 Table 2. Studies Examining Factors Associated With Psychological Distress Among Individuals Affected by Malignant Melanoma

NHMRC Participants Predictors of Psychological Evidence Time Since Measures of Psychological Distress and/or Coping Rating, Age, Male, Disease Diagnosis, Distress and Descriptive (Based on Multivariate Source Country Level No. Mean, y % Stage Mean, mo Results Analysis) Baider et al,33 1999; Israel IVa 100 50.2 47 I, II 21 Low levels of psychological dis- After controlling for sex, age, Baider et al,15 1997 tress (BSI, POMS) detected. No education, and staging, spiritu- significant differences between ality accounted for 8% of the patients with stage I disease vs variance in total mood distur- those with stage II disease. bance. Women reported greater dis- After controlling for sex, age, tress compared with men (IES, education, and staging, spiritu- POMS). ality accounted for 20% of the Spirituality (SBI-54) was nega- variance in active-cognitive tively correlated with anxiety coping style. (BSI), depression (BSI, POMS), total mood disturbance (POMS), anger, and confusion (POMS). Spirituality (SBI-54) was positively correlated with active- cognitive coping style (DWI-CI). Bergenmar et al,22 Sweden IVa 437 NR 53 I, II Within 3 mo Percentage reporting clinically NR 2004 of surgery relevant distress levels: 21% (anxiety, HADS-A); 6% (depression, HADS-D). Presence of clinically relevant anxiety associated with younger age, ulceration, greater mitotic index, higher Clarke level. Presence of clinically relevant depression associated with younger age, greater tumor thickness. Brandberg et al,24 Sweden IVa 273 NR 50 DNS Stage I: 3 mo No differences in anxiety (HADS-A) NR 1992 (unaffected) after according to disease stage; I, IV surgery 19% of total sample reported Stage IV: 2 mo clinically relevant anxiety levels. Low levels of depression (HADS-D) in all groups; 8% of total sample reported clinically relevant depression levels. Clinical cases of depression greatest in patients with stage IV disease (19%), followed by those with stage I disease (6%), then those with DNS (3%). Brandberg et al,17 Sweden III 144 NR NR I 3 mo after wide At 13-mo follow-up, 24% of wom- NR 1995 excision en and 13% of men reported clinically relevant levels of anxiety (HADS-A); 15% of women and 4% of men reported clinically relevant levels of depression (HADS-D). Greater anxiety was associated with female sex. Brown et al,34 2000; Australia III 110 55 68 IV 6 Cognitive appraisal of threat (SQ Ability to minimize the impact of Brown et al,35 44 54 57 IV 11.6 subscale) did not change over cancer associated with fewer 2000 the last year of life. concerns about the disease, Increased use of a more active increased tiredness, greater or problem-focused coping use of distraction, and lower style (COPE) over time. level of active coping. Minimizing the impact of cancer Anger associated with male on daily living (PAC) became sex, lower level of tiredness, increasingly difficult, and con- greater perceived indepen- cerns regarding family were dence, and greater concerns more important than concerns about the disease. for one’s own disease or inde- pendence (SQ subscale). Changes in psychological adjustment (PAC) were associated with changes in physical well- being over time (N=44).

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reported that a lower appraisal of melanoma as threat- was the use of more active coping styles.33 A recent ening and a confident appraisal of one’s subjective abil- study of high-risk individuals by Kasparian et al30 found ity to cope with the situation were predictive of reduced that believing that melanoma has important implica- psychological distress. Religious beliefs were also pre- tions for one’s family and a tendency to monitor or dictive of lowered levels of anxiety and depression, as search for risk-relevant information were predictive of

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NHMRC Participants Predictors of Psychological Evidence Time Since Measures of Psychological Distress and/or Coping Rating, Age, Male, Disease Diagnosis, Distress and Descriptive (Based on Multivariate Source Country Level No. Mean, y % Stage Mean, mo Results Analysis) Brown et al,36 2000 Australia III 426 53 61 I, II 4.5 After controlling for prognostic NR factors, those who perceived the aim of treatment as cure, who did not use avoidance coping (COPE), or who were concerned about their disease (SQ subscale) experienced longer periods without relapse. Shorter survival duration was associated with a positive mood, use of avoidance coping (COPE), greater concern about the impact of the disease on family, and lower disease concern (SQ subscale). Butow et al,37 1999 Australia III 125 55 62 IV 8 After controlling for demographic NR and prognostic factors, psychological predictors of overall disease survival were perception of treatment as cure, minimization of the impact of cancer (PAC), greater anger (PAC), and lower perceived effort to cope (PACIS). Those who were married and who reported an overall better QOL (GLQ-8) also survived longer. Gibertini et al,19 1992 United IVa 75 52.6 67 I-IV Presenting for Clinically relevant levels of NR States 81%, Stage treatment depression (IDD) in 18% of I-II sample, with 8% meeting criteria for major depression. 25% of participants reported feeling “stressed” on a daily basis (GARS) due to sickness, lifestyle change, or interpersonal problems. Recurrence of disease associated with biological, but not psychological, variables. Hamama-Raz and Israel IVa 300 48.8 39 I, II 108 Mean distress scores (MHI) were Increased distress associated Solomon,38 2006; comparable with norms for the with being single (vs married), Hamama-Raz Israeli population. earlier stage of illness at et al,39 2007 In terms of correlational diagnosis, anxious attachment findings related to attachment style, lower hardiness, greater style, secure and perceived threat, and lower dismissive-avoidant attachment subjective ability to cope. styles associated with lower Final model accounted for distress. 38% of variance in distress. Holland et al,10 1999 United IVa 117 53 48 I, II 24 Negative correlations between After accounting for age, sex, States III, IV 67 distress (GSI) and social education, and staging, adding support (ISEL), QOL (MOS). spirituality to the regression Positive correlations between model indicated a statistically distress (GSI) and avoidant significant increment in coping style (DWI-CI). predicting use of Patients with advanced disease active-cognitive coping style stage used significantly more among patients with social support and melanoma. active-cognitive coping strategies (DWI-CI) than those with early-stage disease. No correlation between distress (GSI) and spirituality (SBI-54).

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melanoma-specific distress. Of particular concern is the COPING STRATEGIES AND RESPONSES potential for a downward spiraling link between psychological symptoms and QOL. Lehto et al,40 for The ways in which patients cope with melanoma may have example, reported the presence of psychological and a profound influence on their immediate and long-term depressive symptoms as key predictors of poor QOL. psychological, social, and physical health.45 In a key ar- Furthermore, a substantial decrease in an individual’s ticle describing 10 strategies to promote psychological physical QOL has been shown to be another important adjustment to melanoma, Kneier4 defined coping as the correlate of psychological distress.10,18 attitudes, beliefs, and behaviors that have an adaptive pur-

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NHMRC Participants Predictors of Psychological Evidence Time Since Measures of Psychological Distress and/or Coping Rating, Age, Male, Disease Diagnosis, Distress and Descriptive (Based on Multivariate Source Country Level No. Mean, y % Stage Mean, mo Results Analysis) Kasparian et al,30 2008 Australia IVa 121 48 48 Strong family Overall, remarkably low levels of Variables associated with history of distress were identified. melanoma-specific distress: melanoma No affected patients and only 1% personal history of melanoma, and of unaffected patients reported greater concern about family- clinically relevant levels of implications of melanoma for specific melanoma-specific distress family, information-seeking CDKN2A (IES). coping style (MBSS). mutation; 5% of affected patients and 15% Variables associated with 31% of unaffected patients reported anxiety: greater perceived family melanoma- clinically relevant levels of implications of melanoma risk, affected, anxiety (HADS-A). greater perceived importance of 69% No affected patients and only 1% sun exposure as a cause of unaffected of unaffected patients reported melanoma, absence of children. clinically relevant levels of Information-seeking coping depression (HADS-D). style moderated the relationship between endorsement of a genetic model of melanoma and anxiety. Kelly et al,21 1995 Australia IVa 95 47.9 53 I-IV Stage I: 15.9 Patients with stage III disease NR Stage II: 15.5 reported greater levels of Stage III: 42.1 intrusion (IES-I) and avoidance Stage IV: 70.2 (IES-A) compared with those with stage I disease. No differences in depression (HADS-D) or anxiety (HADS-A) according to disease stage. Lehto et al,40 2005 Finland IVa 72 55 50 I-III 3.5 Female patients reported Variables associated with 97%, depression (DEPS) more often psychological symptoms: use Stage I than males. of behavioral escape-avoidance No difference between patients coping and lower social with melanoma vs those with support. breast cancer in level of reported Variables associated with psychological or physical depressive symptoms: use of symptoms (RSCL). behavioral escape-avoidance or The most frequently used coping cognitive escape-avoidance style was seeking social support coping styles, chronic strain, (WOC). and greater number of negative Patients with melanoma life events. (particularly those undergoing surgery only) reported receiving less social support (SFSS) vs those with breast cancer. Lichtenthal,12 2005 United IVa 48 40.1 31 DNS 9 Concern about bodily appearance NR States (unaffected) (MBA) was positively correlated 0-III with perceived stress (PSS) and fatigue (FSI). Reimer et al,41 2003 Germany IVa 93 61 47 66 36% of patients with CM reported NR potentially clinically relevant levels of distress (SCL-90-R), compared with 16% of healthy controls. Global QOL (SF-36) among patients with CM assessed as poor over the long term. 1 In 3 long-term survivors of CM may require psychosocial counseling, particularly for issues relating to anxiety and/or dissatisfaction with support.

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pose when one is faced with a threatening situation. or passive) stance, and maintaining self-esteem are among Viewed from this perspective, coping may be conceptu- the most useful strategies an individual affected by mela- alized as a primary mediator of the impact of stressful noma can implement to cope with the varied aspects of events on outcomes.46 The aims of coping, according to their diagnosis and/or treatment. Kneier,4 are to safeguard and protect the emotional state of the individual and to allow for psychological adjust- STYLES OF COPING ment to aversive conditions. Kneier4 posited that facing the reality of one’s illness, maintaining hope and opti- Three general theoretical coping styles, among those that mism, expressing one’s emotions, seeking support from have been identified in the psycho-oncology literature, others, adopting a participatory (as opposed to avoidant are (1) active-behavioral coping, which refers to overt be-

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NHMRC Participants Predictors of Psychological Evidence Time Since Measures of Psychological Distress and/or Coping Rating, Age, Male, Disease Diagnosis, Distress and Descriptive (Based on Multivariate Source Country Level No. Mean, y % Stage Mean, mo Results Analysis) Riedijk et al, 200532 Netherlands IVa 66 40 52 p16-Leiden NR Low mean anxiety (HADS-A) NR families; scores, with only 8% reporting 17% clinically relevant anxiety levels. affected, All participants in this study had 83% declined genetic testing for unaffected. melanoma risk. Söllner et al,8 1998 Austria IVa 215 48 47 Stage I, 69% 39 Of the total sample, 30% reported 65% of variance in interest in Stage II, 31% moderate, and 14% reported support from oncologist Stage III, 5% high distress (HQ) levels. predicted by feeling Stage IV, 4% Severe distress associated with insufficiently informed about depressive coping style melanoma and fears regarding (FQCI-SF) and greater reliance tumor progression. on spirituality. 74% of variance in interest in Tumor on visible body sites (eg, support from psychologist face, hands) associated with predicted by higher depressive greater emotional disturbance, coping style, poor prognosis, as well as employment and and low social support. financial problems. Middle-aged patients expressed greatest fear of metastasis. 65% of moderately distressed, and 83% of highly distressed, patients interested in receiving professional emotional support, mostly from treating oncologist. Söllner et al,42 1999 Austria, IVa 358 NR 43 I-IV Patients expressed limited Variables associated with greater Germany satisfaction with perceived perceived emotional support: support. shorter time since diagnosis, Cluster analyses yielded 4 less depressive coping, and coping-support patterns. High greater active coping. social support (SOZU-K22), Model accounted for 6% of combined with active coping or variance in perceived emotional stoicism (FQCI-SF), was support. associated with good adjustment (HQ). Low perceived support reported by those living alone or those exhibiting depressive coping (FQCI-SF) behavior was associated with poor adjustment. Trask et al,18 2001 United IVa 178 52.2 47 0-III Presenting for Low levels of mean distress (BSI) NR States treatment identified. However, 29% of sample reported clinically relevant distress levels. Increased distress (BSI) correlated with more negative evaluations of current and future health, higher ratings of pain intensity (SF-36), decreased energy ratings (SF-36), greater interference from physical and emotional problems on normal social activities (SF-36), maladaptive coping strategies (WOC), and higher levels of trait anxiety (STAI).

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havioral attempts to deal directly with cancer and its ef- In contrast, positive correlations have been demon- fects, such as relying on others for support; (2) active- strated between avoidance coping methods and anxiety, cognitive coping, which includes one’s attitudes, beliefs, depression, confusion, and total mood disturbance in pa- and thoughts about cancer; and (3) avoidance coping, tients with early-stage melanoma.9 which refers to attempts to actively avoid the problem or indirectly reduce emotional tension through the use SOCIAL SUPPORT of distraction. Overall, studies suggest that patients who use active (problem-focused) coping strategies demon- In numerous studies of patients with cancer, social sup- strate better adjustment to melanoma than those who use port (eg, sharing thoughts, emotions, and concerns passive or avoidant coping styles.9,10,15,18,40 By and large, with others) has been associated with enhanced QOL patients who have used active-behavioral methods of cop- and better disease outcome47,48 and is generally thought ing have reported higher levels of self-esteem and vigor, to play a critical role in the psychological adjustment of fewer physical symptoms, and less anger and fatigue.9,45 patients, including those with melanoma.2,49 Söllner et

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Abbreviations: BDI, Beck Depression Inventory; BSI, Brief Symptom Inventory (subscale of the Global Severity Index); CM, choroidal melanoma; COPE, self-report adaptation of the General Coping Strategies Scale; DEPS, Depression Scale; DNS, Dysplastic Nevus Syndrome; DWI-CI, Dealing With Illness Inventory-Coping Inventory; FQCI-SF, Freiburg Questionnaire for Coping with Illness-Short Form; FSI, Fatigue Symptom Inventory; GARS, Global Assessment of Recent Stress Scale; GLQ-8, Quality of life measure; GSI, Global Severity Index; HADS, Hospital Anxiety and Depression Scale; HQ, Hornheide Questionnaire; IDD, Inventory to Diagnose Depression; IES, Impact of Events Scale; ISEL, Interpersonal Support Evaluation List; MBA, Measure of Body Apperception; MBSS, Miller Behavioural Style Scale; MHI, Mental Health Inventory; MOS, Medical Outcomes Scale; NHMRC, National Health and Medical Research Council; NR, not reported; PAC, Psychological Adjustment to Cancer scale; PACIS, Perceived Ability to Cope with Illness Scale; POMS, Profile of Mood States; PSS, Perceived Stress Scale; QOL, quality of life; RSCL, Rotterdam Symptom Check List; SBI-54, Systems of Belief Inventory; SCL-90-R, Symptom Checklist 90-R; SF-36, Medical Outcome 36-Item Short Form Health Survey; SFSS, Structural-Functional Social Support Scale; SOZU-K22, Short Version of the Social Support Questionnaire; SQ subscale, cognitive appraisal subscale of the Stress Questionnaire; STAI, State-Trait Anxiety Inventory; WOC, Ways of Coping questionnaire.

al42 argue that social support and coping are strongly ROLE OF SPIRITUAL AND RELIGIOUS BELIEFS interdependent. Examining the combined effects of coping behaviors and perceived social support in a Seeking to explore the extent to which personal spiri- homogenous sample of patients with melanoma, Söllner tual and/or religious belief systems might be associated et al42 found that different coping-support patterns cor- with levels of distress and ways of coping with malig- related with adjustment to melanoma. A high level of nant melanoma, Holland et al10 found that while scores social support combined with active coping or stoicism on the Systems of Belief Inventory (SBI)51 did not corre- was associated with good adjustment, whereas low late with distress, greater reliance on spiritual or reli- social support combined with depressive coping was gious beliefs was associated with active-cognitive coping. associated with poor adjustment. Given the cross- This association between religious beliefs and active- sectional nature of this study, however, causality cannot cognitive coping style was also reported by Baider et al,15 be inferred from these results. as well as significant negative correlations between spiri- In a prospective study of 53 patients with metastatic tuality and anxiety, depression, anger, and confusion. melanoma and renal cell cancer, Devine et al50 found that Fawzy et al9 defined this coping style as an individual’s greater social support and fewer intrusive and avoidant acceptance of his or her illness and the patient’s attempt thoughts before treatment predicted better psychologi- to view its effects in a positive, meaningful manner.9 cal adjustment 1 month after treatment.50 Moreover, the effect of social support on adjustment was mediated, at COPING WITH ADVANCED, least in part, by fewer intrusive and avoidant thoughts INCURABLE MELANOMA before treatment. Devine et al50 accounted for these findings by suggesting that social support may facilitate the In a longitudinal study on coping with metastatic mela- cognitive processing of a traumatic event, allowing pa- noma during the last year of life, Brown et al34 found that tients to ascribe meaning to the threat and assimilate the as terminally ill patients moved closer to death, the use of cancer experience into their views of the self and the active coping strategies increased, even though the pa- world. In contrast, Baider et al15 did not find an associa- tients also experienced increasing levels of tiredness and tion between melanoma-related distress and degree of per- deterioration in mood and daily functioning ability.34 These ceived social support. In contrast again, Holland et al10 patients were found to increasingly use strategies such as reported a significant negative association between so- information seeking, meditation, and social support. Is- cial support and psychological distress. sues of enhanced self-care and family support are promi-

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©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 Table 3. Summary of the Evidence and Quality of Evidence-Based Recommendations for Clinical Practice

Grade of Quality Recommendationa of Evidencea Evidence Summary Recommendation Sources 1 B Approximately 30% of all patients Screening for symptoms of Bergenmar et al,22 Bonevski et al,52 with melanoma report psychological distress in patients Brandberg et al,17,23-25 Reimer et psychological distress levels with melanoma should be routinely al,41 Söllner et al,53 Trask et al,18 indicative of the need for clinical implemented in clinical practice. Zabora et al1 intervention. However, the Referring patients who have risk psychosocial needs of patients factors to specialized psychological with melanoma frequently go services minimizes the likelihood of undetected and unmet. their developing significant distress. 1 B Demographic factors associated Clinicians need to consider the Baider et al,15 Bergenmar et al,22 with adverse psychological increased risk status associated Brandberg et al,17 Hamama-Raz et outcomes in patients with with particular demographic al,39 Holland et al,10 Lehto et al,40 melanoma include: female sex, factors. These factors may Missiha et al,11 Söllner et al,8 younger age, absence of a spouse influence susceptibility to distress Trask and Griffith,43 Vurnek et al44 or partner, lower education, and irrespective of patients’ medical economic adversity. status or prognosis. The treatment team also needs to be aware that the psychosocial needs of men and women may vary both in extent and how they are expressed. Successful strategies for meeting psychosocial support needs may therefore differ for men and women. 2A B The association between clinical Access to psychological support Baider et al,33 Brandberg et al,24 factors (eg, disease stage and should not be limited to patients Hamama-Raz et al,38,39 Kelly et tumor thickness) and with poor prognosis. Specialized al,21 Söllner et al8 psychological distress is unclear. supportive care should be made There is some evidence to available to those experiencing suggest that patients with greater emotional distress and/or physical deterioration or tumors tumor-related difficulties. on visible parts of the body experience greater distress. 1 B Patients with melanoma who form It is essential to ascertain the extent of Baider et al,15 Devine et al,50 Fawzy positive or meaningful appraisals support available to the patient, to et al,54,55 Hamama-Raz et al,38 of their cancer experience, have recommend additional support as Holland et al,10 Kasparian et al,30 an active-cognitive coping style, required, and to provide Lehto et al,40 Söllner et al,42,56 and/or greater social support are information about where support is Trask et al18 more likely to demonstrate available. A range of therapies, healthy psychological adjustment. including cognitive behavioral therapy, are efficacious in reducing symptoms of psychological distress

a According to the Archives of Dermatology criteria for assessing the quality of the evidence to support recommendations.57 Criteria for grade of recommendation: (1) strong recommendation: high-quality, patient-oriented evidence; (2A) weak recommendation: limited-quality, patient-oriented evidence; and (2B) weak recommendation: low-quality evidence. Criteria for assessing the quality of the evidence: (A) systematic review/meta-analysis, randomized controlled trials with consistent findings, or all-or-none observational study; (B) systematic review/meta-analysis of lower-quality clinical trials or studies with limitations and inconsistent findings, lower-quality clinical trial, cohort study, or case-control study; and (C) consensus guidelines, usual practice, expert opinion, or case series.

nent concerns for patients with advanced melanoma. Hol- lished in English from January 1988 through March 2008. land et al10 also found that those with advanced disease This review demonstrated that not all patients with mela- used more active coping styles as well as more social sup- noma exhibit clinically relevant levels of psychological port than patients with early-stage disease. distress or need intensive psychological support. In- This suggests that patients’ coping styles vary over the deed, many patients with melanoma adjust and cope well. course of their illness, possibly in response to changing Yet, approximately one-third of individuals experience psychosocial and physical demands.34 A summary of the substantial difficulty adjusting to, or coping with, the di- reviewed literature and a series of evidence-based clini- agnosis and/or treatment of malignant melanoma, and cal recommendations for the supportive care of patients the symptoms of psychological distress may have wide- with malignant melanoma are presented in Table 3. reaching implications for these patients and their families. A number of empirically demonstrated risk factors COMMENT for psychological distress were identified from the available literature, including demographic factors such as fe- Conducting a systematic search of the literature on psy- male sex, younger age, absence of a spouse or partner, chological morbidity among individuals affected by ma- and lower levels of education; clinical factors such as lignant melanoma, we identified 44 original studies pub- greater physical deterioration or visibility of affected body

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©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 site; and psychosocial factors, such as negative cogni- distress at baseline, participants reported significantly tive appraisals of melanoma and lack of social support. lower levels of distress compared with controls at inter- In addition, this review found evidence for a positive as- vention completion. The intervention implemented by sociation between active-cognitive coping styles and Fawzy et al9 consisted of 4 key components: (1) health healthy emotional adjustment to melanoma. Further- education specific to melanoma, its treatment, recur- more, patients who report depressive symptoms also show rence reduction, and nutrition; (2) stress management; greater interest in receiving mental health support in ad- (3) coping and problem-solving techniques; and (4) psy- dition to standard medical care.8 The review did, how- chological support. Six months after intervention, group ever, reveal a lack of prospective studies in this area of differences were even more pronounced, with the inter- research. It is also clear from this review that most stud- vention group, on average, demonstrating lower levels ies assessing psychological responses to malignant mela- of depression, confusion, fatigue, and total mood distur- noma are purely descriptive in nature. Clearly, there is a bance, as well as higher levels of vigor.9 Beneficial ef- need for more rigorously designed studies that are ad- fects of the intervention on immune function were also equately equipped to reliably elucidate the factors con- demonstrated, including an increase in certain types of tributing to psychological morbidity among patients with natural killer (NK) cells and an increase in the tumor- melanoma. fighting potential of NK cells.61 At the 5-year follow-up, A recent, landmark Institute of Medicine report com- these researchers were able to show that these psycho- missioned by the National Institutes of Health58 has sug- logical and biological changes were, in turn, associated gested that some of the most basic psychological and so- with superior recurrence and survival rates.62 cial issues affecting patients with cancer are not being As evidence for the clinical effectiveness of such psy- adequately addressed in the clinical setting. In response chological programs continues to grow, studies evaluat- to this, it is argued that psychosocial care is essential as ing the fiscal cost associated with provision of support- the standard of care for all patients with cancer.58 Rou- ive care interventions are also necessary to allow for tine psychological screening of patients with melanoma adequate allocation of limited resources. For example, is widely recommended as standard practice in many Bares et al64 have recently provided evidence for the cost- countries, including Australia, the United States, and the effectiveness of cognitive behavioral therapy for pa- United Kingdom59; however, standard psychological tients with heterogeneous melanomas compared with screening measures may have limited sensitivity and speci- standard care. Also, although this review did not yield ficity as demonstrated by the wide range of results re- any studies on the effectiveness of pharmacotherapy with ported herein. The development of a brief screening tool patients with melanoma, numerous studies with other that incorporates empirically supported risk factors as patients with cancer have demonstrated the efficacy of a identified by the literature is recommended to improve combination of supportive psychotherapy, cognitive be- the timely identification and support of those patients with havioral techniques, and pharmacotherapy in the treat- melanoma who are most susceptible to adverse psycho- ment of anxiety and depression.65,66 Published data of this logical outcomes. There is also some evidence to sup- sort are needed for melanoma. Furthermore, as our knowl- port the clinical evaluation of PTS responses among pa- edge of the genetics of melanoma continues to evolve, tients with melanoma, and this may be achieved in a research efforts aimed at understanding the experiences timely, reliable, and cost-effective manner via the ad- and needs of individuals with an inherited pattern of mela- ministration of validated and situation-specific assess- noma are required. ment tools, such as the revised IES.60 Patients identified From his extensive work on the psychological expe- as vulnerable should be referred to psychosocial health riences of patients with cancer, Spiegel67 has argued that professionals who can gauge the patients’ cognitive ap- all patients who show emotional distress, receive low lev- praisals of melanoma, as well as their capacity to cope els of social support, and/or experience tumor-related dif- emotionally with this disease and its treatment. Future ficulties in various aspects of daily life should be offered studies focusing on the routine assessment of psycho- psychological support, irrespective of whether they meet logical distress responses among patients with mela- the criteria for psychiatric disorder. Accurate detection noma in the clinical setting, and the implications such of distress, or identification of those most vulnerable to assessments have on appropriately targeting the provi- developing negative psychological symptoms, can en- sion of psychological services, are needed. able health professionals to initiate early intervention, tai- In terms of appropriate and effective psychological in- lor assistance to meet individual needs, and effectively terventions, clinical practice guidelines for the manage- target limited health care resources to reduce patient suf- ment of melanoma consistently recommend that struc- fering.10,11,45 The clinical care of patients with severe or tured psychosocial interventions and psycho-education life-threatening conditions such as melanoma also poses be made available to all patients.59 Fawzy45 and Fawzy et special burdens for clinicians. Recognition and under- al9,54,61,62 and Boesen et al63 have demonstrated that struc- standing of the emotional issues for health professionals tured interventions offering psycho-educational sup- will allow strategies to be developed to address these con- port can reduce distress and mood disturbances and lead cerns; a process likely to lead to improved therapeutic to greater use of active coping strategies among individu- relationships and enhanced professional satisfaction.13 als affected by melanoma. In a series of seminal articles evaluating the short- and long-term outcomes of a 6-week Accepted for Publication: June 15, 2009. structured psycho-educational group intervention, Fawzy Correspondence: Nadine A. Kasparian, BA (Psych, Hons et al9,62 reported that, despite moderate to high levels of I), PhD, Psychosocial Research Group, Dickinson Build-

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©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 ing Level 3, Prince of Wales Hospital, High Street, Rand- 13. National Breast Cancer Centre and National Cancer Control Initiative. Clinical Prac- wick, NSW 2031 Australia ([email protected] tice Guidelines for the Psychosocial Care Of Adults With Cancer. Camperdown NSW, Australia: National Breast Cancer Centre; 2003. .au). 14. Cassileth BR, Lusk EJ, Tenaglia AN. A psychological comparison of patients with Author Contributions: Dr Kasparian had full access to malignant melanoma and other dermatologic disorders. J Am Acad Dermatol. all of the reviewed articles and takes responsibility for 1982;7(6):742-746. the integrity and accuracy of the reported findings. Drs 15. Baider L, Perry S, Sison A, et al. The role of psychological variables in a group of Kasparian and McLoone share first authorship on this ar- melanoma patients: an Israeli sample. Psychosomatics. 1997;38(1):45-53. 16. Sigurdardo´ttir V, Bolund C, Brandberg Y, Sullivan M. The impact of generalized ticle. All authors were involved in the formulation of the malignant melanoma on quality of life evaluated by the EORTC questionnaire research question and the identification of specific in- technique. Qual Life Res. 1993;2(3):193-203. clusion and exclusion criteria for this review. Drs Kaspar- 17. Brandberg Y, Mansson-Brahme E, Ringborg U, Sjoden P. Psychological reac- ian and McLoone conducted the literature search, re- tions in patients with malignant melanoma. Eur J Cancer. 1995;31A(2):157- 162. viewed all articles, tabulated all relevant articles, and 18. Trask PC, Paterson AG, Hayasaka S, Dunn RL, Riba M, Johnson T. Psychosocial assessed each article to determine evidence rating level. characteristics of individuals with non-stage IV melanoma. J Clin Oncol. 2001; Dr Kasparian produced the first draft of the manuscript 19(11):2844-2850. and incorporated the contributions of Dr McLoone and 19. Gibertini M, Reintgen DS, Baile WF. Psychosocial aspects of melanoma. Ann Plast Dr Butow in subsequent drafts. Study concept and de- Surg. 1992;28(1):17-21. 20. American Psychiatric Association. Diagnostic and Statistical Manual of Mental sign: Kasparian and Butow. Acquisition of data: Kaspar- Disorders. 4th ed. Washington, DC: American Psychiatric Association; 2000. ian and McLoone. Analysis and interpretation of data: 21. Kelly B, Raphael B, Smithers M, et al. Psychological responses to malignant mela- Kasparian, McLoone, and Butow. Drafting of the manu- noma: an investigation of traumatic stress reactions to life-threatening illness. script: Kasparian, McLoone, and Butow. Critical revision Gen Hosp Psychiatry. 1995;17(2):126-134. of the manuscript for important intellectual content: Kaspar- 22. Bergenmar M, Nilsson B, Hansson J, Brandberg Y. Anxiety and depressive symptoms measured by the Hospital Anxiety and Depression Scale as predictors of ian, McLoone, and Butow. Obtained funding: Kasparian. time to recurrence in localized cutaneous melanoma. Acta Oncol. 2004;43(2): Administrative, technical, and material support: McLoone. 161-168. Study supervision: Kasparian and Butow. 23. Brandberg Y, Bergenmar M, Michelson H, Mansson-Brahme E, Sjoden PO. Financial Disclosure: None reported. Six-month follow-up of effects of an information programme for patients with Funding/Support: Dr Kasparian is supported by a Post- malignant melanoma. Patient Educ Couns. 1996;28(2):201-208. 24. Brandberg Y, Bolund C, Sigurdardo´ttir V, Sjoden P-O, Sullivan M. Anxiety and doctoral Clinical Research Fellowship from the Na- depressive symptoms at different stages of malignant melanoma. Psycho-oncology. tional Health and Medical Research Council of Austra- 1992;1(2):71-78. lia (NHMRC ID 510399). 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