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A systematic review examining factors influencing health related quality of life among melanoma cancer survivors

European Journal of Cancer, December 2016, Pages 189 - 198


Eighty percent of melanomas are diagnosed at a localised stage, when they are highly curable. Their survival rate induces long follow-up periods, transforming melanoma into a chronic disease and patients' health-related quality of life (HRQoL). Understanding which patient characteristics are associated with poor HRQoL should allow a more personalised management of their HRQoL. Hence, we propose a systematic review for this purpose.

Systematic literature searches were performed in three different electronic databases: PubMed, Web of Science and the Cochrane Library. Only studies published in English after 2005 until June 2016 and exploring HRQoL over a period of at least one year were considered.

10 articles were identified from seven different studies, representing a total of 4246 patients. All were observational: six were cross-sectional and only one was prospective. Several patient characteristics associated with HRQoL were identified. Women tend to have lower psychological HRQoL than men. Age was generally associated with variations in HRQoL levels, but there was no consistency across studies. Positive associations between marital status or social interactions and psychological subscales were highlighted by a few studies. Finally, the stage related severity of prognosis at initial diagnosis was systematically associated with worse HRQoL levels (either psychological, physical or global).

Several patient characteristics could be identified in melanoma studies that were associated with HRQoL levels. However, these relations were not consistent across studies. Such findings highlight the current lack of empirical data available. Further evidence is needed on HRQoL factors in melanoma survivors.


  • Little is known about quality of life determinants among melanoma survivors.
  • Sex, age, social interactions, melanoma severity and comorbidities have been highlighted as associated with quality of life.
  • However, these findings were highlighted only by limited level of evidence studies and were not consistent across studies.
  • There is a clear need to expand research for enabling better care for melanoma survivors.

Keywords: Quality of life, Survivorship, Melanoma, Systematic review.

1. Introduction

Melanoma is the eighth most common cancer in the developed countries in the world [1] and [2]. About 55,000 deaths in 2012 have been estimated to be caused by melanoma. In European countries, melanoma incidence rose from 6.0 to 11.1 per 100,000 from 2000 to 2012 [3], [4], and [5]. In the same period, mortality rate remained roughly stable, about 2.3 per 100,000, possibly reflecting the effects of early recognition. Primary melanoma treatment has not changed much during this period (surgery—with or without sentinel lymph node resection—still being the primary treatment of most melanomas even if new treatments have been approved for metastatic melanoma recently [6] and [7]). More than 80% of melanomas are actually diagnosed at a localised stage, when they are highly curable [6], [8], and [9]. Such an early diagnosis makes melanoma one of the malignancies with the higher 5-year survival rates: its 5-year relative survival rate is 91%, rising to 98% for patients with localised melanoma [2]. Thus, follow-up periods of medical monitoring can be very long for verifying the absence of disease recurrence, transforming melanoma in a chronic, life-threatening disease [10] and [11]. Appropriated lifestyle practices including strict protection measures against sun and ultra-violet exposure are required, possibly leading to significant repercussions on both personal and social lifestyle [12]. A melanoma diagnosis may then considerably impact patients' lives, especially their health-related quality of life (HRQoL). As HRQoL encompasses all the aspects of quality of life that can be clearly shown to affect health—either physical or mental, it can be ‘affected in a complex way by both the person's physical health, psychological state, personal beliefs, social relationships and their relationship to salient features of their environment’ [13]. Local surgical excision is the treatment of choice for more than 70% of the patients. Thus, the melanoma impact on HRQoL should be mostly determined by the psychological experience of being diagnosed with cancer, the surgery and the remaining scars. The scars may constitute a permanent reminder of the individual's cancer experience. Hence, the psychological issues that face the melanoma survivors should be mostly specific, significantly differing from other types of cancer characterised by long-term side effects of systemic treatment or radiotherapy.

The treatment and management of psychological support and HRQoL remains to be improved for melanoma patients. Even if more than 85% of melanoma patients deem that the medical monitoring during the follow-up was worthwhile, they also indicate that little attention was paid to their well-being during this period [14]. Knowing the determinants of a poor HRQoL among such patients should allow personalising and then improving the HRQoL management by identifying the most vulnerable patients. The objective of this review is to identify, to evaluate and to summarise the possible factors influencing HRQoL among melanoma survivors.

2. Method

We performed the review according to the recommendations of the PRISMA statement for reporting systematic reviews and meta-analyses of studies [15].

2.1. Literature search strategy

To identify studies assessing the determinants of HRQoL among melanoma survivors, systematic searches were performed in January 2016 in three different electronic databases : PubMed, Web of Science and the Cochrane Library. Studies published after January 2005 and in English language journals were considered. The following combinations of MeSH terms and text words were used (melanoma* or ‘skin cancer’) and (‘quality of life’ or ‘patient reported outcome*’ or ‘health-related’) and (survivor* or ‘survival analysis’) not (‘non-melanoma’ or ‘nonmelanoma’ or ‘non melanoma’). Reference lists of included articles were also studied for identifying any other trials. We also spoke to key experts to ensure that all key studies were included.

2.2. Inclusion and exclusion criteria

Studies that met the following criteria were included: (i) subjects with a diagnosis of melanoma, (ii) survivorship after diagnosis longer than 12 months, (iii) HRQoL evaluated using self-assessment questionnaires, (iv) HRQoL analysed as an end-point and explained by patient characteristics and (v) clinical trials or epidemiological studies (prospective observational, cohort, cross-sectional or retrospective). Studies were excluded if (i) it was not a full-text paper (i.e. no literature reviews, protocol publication, abstracts, letters or comments); (ii) study did not explore the HRQoL determinants among melanoma patients or (iii) clinical randomised trials exploring only the impact of the studied treatments without exploring patient characteristics as other covariates; (iv) the studied population was not specifically composed of melanoma patients. No other restriction was used, especially regarding age and gender.

2.3. Data extraction

All results were screened for duplication by author, title, journal and publication date, and then screened for relevance, based on the title and abstract. The full text of all studies considered to be relevant was then reviewed independently by two different co-authors: J.F.H. and M.P. for final assessment. Data were extracted from the included studies to a standard sheet including the first author, the year of publication, the study design, the questionnaires used for assessing HRQoL, the number of patients enrolled, of exclusions for missing data and the proportion of analysed patients, the patient recruitment period, the age restrictions for being eligible, the average age and proportion of females at diagnosis, the average follow-up duration and the list of covariates explored for explaining the HRQoL evolution. Companion papers (i.e. different analyses based on the same study but reported in separate papers) were reported. The first objective of our study was to identify the possible factors influencing the HRQoL evolution among melanoma patients. For each of the considered studies, the list of the covariates significantly associated with a change in HRQoL was reported as well as the direction of the significant associations. Additional data were extracted for identifying the methodological processes used for assessing the associations between studied covariates and HRQoL changes.

If requested data were not available or if further details were needed, the authors of the original studies were contacted via email.

3. Results

The considered search method provided a total of 191 records at first (67 from the Cochrane Library, 36 from PubMed and 122 from Web of Science—34 articles being duplicated). Based on the titles' and abstracts' assessments, 170 studies were excluded because they did not meet the eligibility criteria. After examining the full text articles of the 21 remaining papers, 11 were excluded either because the studied cancers were not specifically melanomas, the HRQoL was not assessed using self-assessment questionnaires, or the determinants of differences in HRQoL were not reported. A final total of 10 articles were eligible and included for analysis, representing 7 different studies. The details of the selection procedure are summarised as a flow chart presented on Fig. 1.

Fig. 1

Fig. 1

Flow chart detailing the selection procedure concerning the articles studied in this systematic review.


Included studies were conducted between 2007 and 2015 (Table 2). All were observational studies, none being a randomised controlled trial. Six of them were cross-sectional, and only one was prospective. All of them were based on self-administered surveys. Ten different questionnaires were used for assessing HRQoL. The characteristics of these questionnaires are presented in Table 1. Nine of the 10 different questionnaires were multidimensional, among which 5 proposed summary scores. More than 50% of the studies used multiple questionnaires for evaluating the HRQoL end-points. The number of questionnaires used for assessing HRQoL ranged from 1 to 4. The most frequently used HRQoL questionnaire was the European Organization or Research and Treatment of Cancer (EORTC) QLQ-C30 [16].

Table 1

Characteristics of the HRQoL questionnaires used in the studies selected for the systematic review.


Instrument Type Goals Domains/subscales
Hornheide Questionnaire 9 items short form (HQ-S) [30] Skin cancer specific Psychosocial distress Eight distress scales
One summary scale
Functional Assessment of Cancer Therapy (FACT-G) [14] Cancer specific Global HRQoL Four HRQoL scales: physical, social, emotional, functional. well-being
One summary scale
FACT–Melanoma (FACT-M) [31] Melanoma specific Global HRQoL Three HRQoL scales: physical, emotional and social well-being.
European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) [32] Cancer specific Global HRQoL Five functional scales: physical, role, cognitive, emotional and social.
Nine symptom scales: fatigue, pain, nausea/vomiting, dyspnoea, appetite loss, insomnia, constipation, diarrhoea.
One scale on the perceived financial impact of the disease.
One global HRQoL scale.
EORTC–Breast cancer module (EORTC QLQ-BR23) [33] Breast cancer specific Global HRQoL Four functional scales: body image, sexual functioning, sexual enjoyment, future perspective
Four symptom scales: systemic therapy side effects, breast symptoms, arm symptoms, upset by hair loss
Palesh ad hoc questionnaire Study specific Global HRQoL Nine scales: vitality, bodily pain, physical functioning, mental health, social functioning, emotional health, body image sexual functioning and melanoma-related symptoms
Mental Health Inventory (MHI) [34] Generic/cancer specific Psychological distress and well-being Six scales: positive affect, emotional ties, life satisfaction, anxiety, depression, loss of emotional control
Two summary scales: psychological distress and psychological well-being
Short Form-36 (SF-36) [35] Generic Global HRQoL Eight scales: physical functioning, vitality, social functioning, general health, bodily pain, physical role, emotional role and mental health
Two summary scales: physical and mental component summary scales (PCS and MCS)
Impact Of Cancer (IOC) [36] Cancer specific Global HRQoL, adjustment to changes Ten scales: health awareness, body changes, positive self-evaluation, negative self-evaluation, positive outlook, negative outlook, life interferences, value of relationships, meaning of cancer, health worry
Adaptation questionnaire [37] Generic Functioning Six scales: physical, social condition, sexual relations, employment, family function, mood.
One general score
Multidimensional Fatigue Inventory (MFI) [38] Generic Fatigue Five scales: general fatigue, physical fatigue, reduced activity, mental fatigue, reduced motivation
Patient Health Questionnaire (PHQ-9) [39] Generic Depression One scale: depression level.

Table 2

Characteristics of the studies selected for the systematic review.


First author Year of Publication Design of study Questionnaire Period range Age at diagnosis for being eligible Average age at diagnosis Percentage of female Sample size Response rate Average follow-up (years) Method for comparing
Fischbeck S. [38]
Beutel M. E. [15]
Cross-sectional QLQ-C30
2000 → 2005 >14 61.8 ± 10.6 51% 1320 52% 8.5 Multivariate logistic modelling the dichotomised HQ-S summary score.
Cromwell K.D. [16] 2015 Prospective FACT-M 2006 → 2012 >18 Not reported (39% under 50) 51% 277 71% 1.2 Multivariate mixed model studying the evolution of the summary scale over time
Palesh O. [19] 2014 Cross-sectional Ad hoc 2012 No restriction 62 ± 13.5 49% 893 20% 6.5 Comparisons repeated for each sub-scale and each covariate
Schubert-Fritschle G. [39]
Schlesinger-Raab A. [20]
Cross-sectional QLQ-C30
2003 → 2004 No restriction 51.3 ± 14.9 53% 1085 61% 2 Multivariate logistic models repeated for each median-dichotomised functioning score
Hamama-Raz Y. [35]
Hamama-Raz Y. [17]
Cross-sectional MHI
2001 → 2002 25–60 48.8 ± 9.2 61% 400 75% 9 Multivariate linear models repeated for psychological well-being and distress scales
Waldmann A. [21] 2011 Cross-sectional QLQ-C30 2002 → 2004 18–85 55 ± 15 54% 762 59% 3.2 Comparisons repeated for each sub-scale and each covariate.
Assessment of differences based on clinical relevance
Holterhues C. [18] 2011 Cross-sectional SF36
1998 → 2007 <85 57 ± 14 62% 699 80% 4.6 Multivariate linear models repeated for PCS, MCS and a higher-order IOC-based scale

The number of melanoma survivors contacted for being included ranged from 277 to 1320, representing a total of 4246 patients. The response rate ranged from 20–80%, allowing a total of 3042 melanoma patients to be analysed. Depending on the studies, the average time of survival before inclusion ranged from 1.2 years to 9 years. The mean age of the melanoma survivors at diagnosis was 55.9 (±13.8). Among them, 54.9% were female. The associations between individual patients' characteristics and HRQoL variations highlighted by each of the considered studies are presented in Table 3. Some studies highlighted an association between gender and HRQoL, showing a lower HRQoL level among women. This association was more frequent for psychological subscales than for physical subscales. Being older was generally associated with better psychological scores and worse global and physical scores. However, this finding was not consistent across studies, since one study reported more psychological distress among older melanoma patients. A few studies reported positive associations between marital status and social interactions on the one hand and psychological sub-scales on the other hand. Comorbidities and worse tumor status were extremely frequently associated with worse HRQoL levels (either psychological, physical or global). An association between more extensive surgical treatment (e.g. including therapeutic lymph node dissection) and HRQoL was less commonly found. A longer survival time since diagnosis seemed to be very modestly associated with HRQoL improvement. No associations between the educational level, the social level, the residential location (urban versus rural) and the HRQoL were reported.

Table 3

Covariates associated with HRQoL variations among melanoma survivors depending on the different studies selected for this systematic review.


First author Scale Gender: female Age: older Marital status Social interaction Comorbidities Extremity affected (lower versus upper) More extensive surgery Worse TNM status (uicc classification) Lymphoedema Extension of time since diagnosis Histology Education Social class Urban/rural destination
Fischbeck S. [38]
Beutel M. E. [15]
HQ-S summary score N fx1 N N N N N N N
Cromwell K.D. [16] FACT-M summary score N fx1 fx1 N
Palesh O. [19] Vitality N N N N
Bodily pain N N N N
Physical functioning N N N N
Mental health N N N N
Social functioning N N N N
Emotional health N N N N
Body image N N N N
Sexual functioning N N N N
Symptoms N fx1 fx2 N
Schubert-Fritschle G. [39] Schlesinger-Raab A. [20] Global QLQ score N fx1 N N fx1 N fx1
Physical functioning N fx1 fx2 N fx1 N W
Role functioning N N N N fx1 fx1 fx1
Emotional functioning fx1 fx2 N fx2 fx1 N fx1
Cognitive functioning N N N N fx1 N N
Social functioning N fx2 N fx2 fx1 N fx1
Body image N fx2 N fx2 fx1 fx1 N
Worry about future N fx2 N N fx1 fx1 N
Hamama-Raz Y. [35]
Hamama-Raz Y. [17]
Psychological well-being N N N N fx1 N
Psychological distress fx1 N fx2 N fx1 N
Waldmann A. [21] Functions N fx1 N N
Symptoms N fx1 N N
Holterhues C. [18] PCS fx1 fx1 N fx1 N fx1 N N
MCS fx1 N fx2 N N N N N
IOC (higher order) fx1 N N fx1 N fx1 fx2 N

N: no association highlighted.

W (in red): significantly associated with poorer quality of life.

B (in green): significantly associated with better quality of life.

Four studies reported comparisons of HRQoL level between melanoma survivors and the general population. These comparisons are summarised in Table 4. HRQoL levels were broadly similar between these two populations. Four studies reported better functioning, physical or global HRQoL dimension levels among melanoma survivors relative to the general population. Two studies reported worse psychological distress or symptoms among melanoma survivors.

Table 4

Main HRQoL differences between melanoma survivors and the general population depending on the different studies selected for the systematic review.


First author Questionnaire Comparison to general population HRQoL subscales worse in melanoma than in general population HRQoL subscales better in melanoma than in general population HRQoL subscales with no differences between melanoma and general population
Fischbeck S. [38]
Beutel M. E. [15]
Yes Depression symptoms' scales Functioning scales Global HRQoL
Cromwell K.D. [16] FACT-M No
Palesh O. [19] Ad hoc No
Schubert-Fritschle G. [39]
Schlesinger-Raab A. [20]
Yes Symptoms' scales Global HRQoL
Hamama-Raz Y. [35]
Hamama-Raz Y. [17]
Waldmann A. [21] QLQ-C30 Yes Global HRQoL Functioning scales symptoms scales
Holterhues C. [18] SF36
Yes Physical Component Summary (PCS) Mental Component Summary (MCS)

The methodology of the studies differed. The number of primary end-points varied depending on the studies. Four studies [17], [18], [19], and [20] focused on analysing only the summary scores instead of analysing all the different sub-scales, avoiding multiplying the statistical tests. For 2 studies [21] and [22], all the sub-scales were separately analysed without carrying out any type I error adjustment. In one study [23], the different sub-scales were aggregated in two different measurement scales: functions and symptoms evaluation, without clearly explaining the aggregation procedure.

The statistical methods varied between studies. In two studies [21] and [23], univariate comparisons were repeated for each sub-scale and each covariate without any type I error adjustment. Multivariate analyses were performed in 4 studies, allowing for taking possible confounders into account and avoiding multiplying the statistical procedures. Finally, the only prospective and longitudinal study [18] was analysed using a multivariate mixed model. Only one study used validated minimal clinically important differences for evaluating the impact of covariates on HRQoL. All the other studies were only based on statistical significance and p-values.

4. Discussion

Despite a deliberately not restrictive choice of selection criteria, the number of studies eligible for being included in the final analysis was very low, reflecting the limited current knowledge concerning factors that are possibly influencing HRQoL in melanoma survivors. Furthermore, the vast majority of these studies were cross-sectional—implying a limited level of evidence. Only one was a longitudinal prospective study. Few factors were found to be associated with differences in HRQoL levels across all the studies, apart from co-morbidity and the severity of the disease. In some studies, gender and age were also associated with HRQoL, even if the impact of age on HRQoL was not consistent across studies. Several explanations can be proposed for both the low number of factors identified and the possible variability of the highlighted effect for some of them. First, none of the studies were powered for detecting effects of covariates on HRQoL, even if such a detection was the main objective of these studies. It cannot be excluded that some factors actually associated with HRQoL variations could not be highlighted because of lack of power. Second, several studies investigated associations by repeating the analyses for each possible covariate and each questionnaire subscale, without any type I error adjustment. In such a situation, characterised by an increase in the false positive rate, some factors actually not associated with HRQoL variations might have been highlighted by mistake. Finally, the considered studies used different questionnaires for assessing HRQoL. The questionnaires were skin cancer specific (as the HQ-S), cancer specific (as the QLQ-C30) or generic (as the PHQ-9) and thus did not focus on the same HRQoL aspects which made it difficult to compare the results between studies [24] and [25].

The effects of the covariates identified as being associated with differences in HRQoL level were difficult to interpret. None of the studies except one, presented the clinical relevance of such effects. In HRQoL research, it is preferable to estimate differences by comparing them to minimal important difference, as the p-value does not give information of the clinical relevance of a HRQoL difference [26] and [27].

The comparison of HRQoL among melanoma survivors and the general population was quit complex to interpret since the HRQoL scores reported by melanoma survivors may be even better than the ones reported by the general population. This result may sound paradoxical but is consistent with other studies investigating different types of cancer showing that patients who survive a cancer usually rate their HRQoL as similar or even better than the general population [28] and [29]. The individual's health status can lead to behavioural, affective and cognitive processes allowing accommodating to illness, having the potential to change his HRQoL standards, values, or conceptualisation. Such a phenomenon, able to influence perceived HRQoL, is referred as ‘response shift’ [30]. It is also possible that the questionnaires used were not sensitive enough to measure HRQoL-related issues between melanoma patients and the general population: the sensitivity of a questionnaire might be different depending on the considered population.

It is important to note the variety of statistics and methodologies employed in the studies. The choice of univariate or multivariate statistics could impact the results, as well as the choice of adjustment variables. In addition, the cross-sectional design of the majority of the studies, with varied response rates, could involve recruitment biases. Future studies should therefore adopt a prospective longitudinal design in order to study the HRQoL evolution among melanoma survivor using multivariate models by considering as possible confounders the covariates already identified as possibly associated with HRQoL variations in the present study.

Our systematic review has some limitations. The first and most important is publication bias. Only published full-text study results were included, not considering short reports, conference presentations or study protocols. A comparison with the database could assist to provide a more comprehensive identification of relevant studies. The restriction of the publication period might also be a limitation. However, analysing a longer period could lead to interpretation problems linked to the developments in the fields of melanoma and HRQoL research.

In conclusion, identifying the determinants of a poor HRQoL among melanoma survivors is of great importance, allowing personalising and improving HRQoL management. Several determinants were identified such as sex, age, marital status or social interactions, initial melanoma severity and comorbidities. However, the findings were highlighted only through a small number of studies, most being cross-sectional with low level of evidence. There is a clear lack of high-level evidence data available in this field and a clear need to expand research for enabling better care for melanoma survivors.

Authors' contributions

JFH, MP, CC and AB conceived and designed this review. JFH and MP collected and assembled the data. All authors analysed and interpreted the data and wrote and gave final approval for the manuscript.

Conflict of interest statement

None declared.


This publication was supported by the EORTC Cancer Research Fund and the University Hospital of Angers.


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a European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium

b Biostatistics and Methodology Department, Angers University Hospital, Angers, France

c Gustave Roussy Cancer Campus Grand Paris, Villejuif, France

d Oncology and Pathology Department, Karolinska Institutet, Stockholm, Sweden

Corresponding author: Biostatistics and Methodology Department, Angers University Hospital, 4 rue Larrey, 49100 Angers, France.

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