Psychosocial well-being and mental adjustment of patients with stage III melanoma in the re-entry phase: a scoping review : Journal of Psychosocial Oncology Research and Practice

Secondary Logo

Journal Logo

Review

Psychosocial well-being and mental adjustment of patients with stage III melanoma in the re-entry phase: a scoping review

Visser, Annaa; Post, Lennekeb,c,*; Dekker, Joostd; Konings, Inge R.e

Author Information
Journal of Psychosocial Oncology Research and Practice 4(4):, October-December 2022. | DOI: 10.1097/OR9.0000000000000089

Abstract

1. Introduction

The incidence rate of melanoma has increased over the last two decades.[1] Melanoma has traditionally been regarded as an inevitably fatal disease when diagnosed at a late stage. However, options for adjuvant treatment have improved considerably since 2010,[2] leading to major improvements in overall survival[3] and prolonged progression-free survival of patients with metastatic disease (stage IV).[4] In recent years, patients with regional nodal metastases (stage III) have also become eligible for adjuvant therapy, resulting in an increase of relative disease-free survival rates from 18–38%[5] to 50%.[6] The increasing incidence of stage III melanoma, together with prolonged survival,[7,8] has resulted in an expanding group of stage III melanoma survivors. While research has understandably focused on improving treatment options and survival rates, the patient recovery process has received less attention. In the initial period immediately after cancer treatment, psychosocial problems are common.[9–11] The phase in which patients are considered cured, receive follow-up care, and have to resume normal life is referred to as the “re-entry phase”.[12] This transition from active treatment to medical surveillance may involve the loss of sources of security and control. The long-term effects of treatment may require a patient to adapt to a change or decline in physical abilities that affects daily life.[13] At home, patients have to resume their former roles, while the physical and psychological effects of diagnosis and treatment may still be present.[12] Because the duration of this transitional phase is different for each patient, there is no stark cutoff between the re-entry phase and the survivor phase. Following Stanton,[12] the re-entry phase in this article is defined as the first 18 months after completion of treatment. Patients with cancer in general face emotional, physical, social, practical, and existential challenges during the re-entry phase,[12] while less is known about the specific challenges faced by patients with stage III melanoma. These patients find themselves in a particularly difficult position after treatment: The risk of relapse within 5 years is still relatively high, with the highest risk in the first 18 months after initial treatment.[14,15] Furthermore, adjuvant therapy is demanding, making the subsequent resumption of daily life especially challenging. To support these patients, we need to better understand the psychosocial impact of stage III melanoma and its treatment on patients in the re-entry phase. We chose to conduct a scoping rather than a systematic review to initially summarize the existing evidence and identify knowledge gaps[16] concerning psychosocial well-being and the mental adjustment of patients with stage III melanoma in the re-entry phase.

2. Methods

This scoping review was conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist.[17] The protocol was registered prospectively with the Open Science Framework on the 15th of December 2020 (https://osf.io/xtn45/). The search strategy focused on melanoma in relation to psychosocial well-being and mental adjustment to the re-entry phase. Psychosocial well-being was broadly defined,[18–21] encompassing emotional health, concerning one's feelings (emotional resilience, happiness, and satisfaction); psychological health, concerning one's functioning (autonomy, mastery, and personal growth); social health, concerning engagement with one's environment (meaningful and positive relations with others and valued social contributions); and existential health, concerning one's outlook on life and death (feelings of comfort regarding mortality and suffering, satisfaction in life, hope, meaning, and purpose). Related constructs concerning mental adjustment to the re-entry phase such as coping, post-traumatic growth, resilience after cancer, and meaning-making (a psychological process in which a patient with cancer tries to appraise the impact of the cancer on their life and understanding of the world[22]) were also included. Specific details of the search strategy are shown in Appendix 1 (https://links.lww.com/OR9/A38). PubMed (MEDLINE) and CINAHL databases were searched systematically in March 2022. All included studies were checked for additional studies that were eligible for inclusion (snowballing method). If a systematic review was included, all the articles covered were separately reviewed to determine whether they met our inclusion criteria. Studies were included if they were available in full text and published in English after 2000. This period was chosen because adjuvant therapy to prolong recurrence-free survival only became available in the last two decades. The required research subjects were patients with stage III cutaneous melanoma after curative treatment, minimally consisting of complete surgical resection. We aimed to study patients in the re-entry phase, defined as the point from completion of treatment (surgical treatment and when applicable, adjuvant treatment) up to 18 months in remission. We included studies in the separate category “re-entry fading into early survivorship” if it was not possible to distinguish between patients within or beyond 18-month completion of treatment or in cases where the exact time since treatment was unclear (eg, when only time since diagnosis was given). Outcome measures, assessed using either qualitative or quantitative methods, were taken into account when they concerned psychosocial well-being or mental adjustment. Studies were excluded when the patient population included ocular, mucosal, or unresectable melanoma; when (some) patients were still receiving treatment during the study; when the melanoma stage was not reported; or when no separate subgroup analysis of melanoma stages was available. Articles were selected for full-text review based on the title and abstract by one reviewer (AV). Obtained articles were screened by reading the full text to determine whether they met the eligibility criteria (AV). During the screening process, doubts about eligibility were discussed and resolved together with a second reviewer (LP). A data charting form was developed by two reviewers (AV, LP) to determine which variables to extract. Data on citation details, population characteristics, and results for psychosocial well-being were then abstracted. Three articles were first screened by two reviewers (AV, LP) to become familiar with the data, followed by refinement of the data charting form. The data from all remaining articles were then charted by one reviewer (AV), with the second reviewer (LP) consulted only when uncertainty existed concerning the data. The Mixed Methods Appraisal Tool was used to assess quality of the literature. This tool was designed to assess the quality of qualitative, quantitative, descriptive, and mixed method design studies.[23] The first five articles were independently screened and discussed by two reviewers (AV, LP) to reach consensus and become familiar with the appraisal tool. The remaining articles were screened by a single reviewer (AV), with uncertainties discussed with the second reviewer (LP). The results are presented in a narrative format. The extracted data are presented in Tables 2–4.

3. Results

3.1. Study characteristics

The literature search produced 2,182 results (see Fig. 1). After removal of duplicates, 1,877 were assessed for eligibility by screening the title and abstract, resulting in the exclusion of 1,736 articles. Full-text screening identified 17 eligible articles. The references therein were screened for additional eligible studies, but no additional records were added. Seven articles were systematic reviews and were excluded after screening their included studies for eligibility. Finally, nine studies were included for analysis.[24–32]

F1
Figure 1.:
Flow diagram of selection process.

The results of the critical appraisal can be found in Appendix 3 (https://links.lww.com/OR9/A38). According to the Mixed Methods Appraisal Tool, the qualitative studies met all five core quality criteria. The randomized controlled trials (RCTs) and cross-sectional studies generally met three to five core quality criteria. An exception was the study by Bottomley et al,[26] which met only two of five core quality criteria. This was partly due to loss of follow-up and a low compliance rate as a consequence of adverse events related to the treatment used.

Characteristics of each source of evidence are presented in Table 1. Two of the included studies were qualitative in study design,[31,32] while the others had quantitative outcomes. The latter included four RCTs[24–27] and three cross-sectional descriptive studies.[28–30] In four of the included studies,[28,29,31,32] the re-entry phase was not differentiated from early survivorship. These studies reported on re-entry fading into early survivorship, with some patients in the re-entry phase, while others were in early survivorship. These studies are presented separately in Table 1 and below.

Table 1 - Characteristics of included studies.
Studies including re-entry phase
Year of publication 2005 2009 2021 2017 2016
First author Boesen Bottomley Bottomley Coens Rogers
Country of origin Denmark Belgium, European Organization for Research and Treatment for Cancer (EORTC) headquarters Belgium, EORTC headquarters Belgium, EORTC headquarters United Kingdom
Study design and intervention when applicable RCT; 6 weekly 2 hr of psychoeducation vs observation [40] RCT; PEGylated interferon alpha-2b (PEG-IFN-α-2b) for 5 yrs vs observation RCT RCT; ipilimumab up to a maximum of 3 yrs vs placebo Cross-sectional descriptive study
Time after diagnosis/end of treatment Between 3 and 12 weeks after surgical resection Maximum of 70 days after surgical resection Follow‐up up to 84 weeks after start of adjuvant treatment (which lasted approximately 1 year) Maximum of 12 weeks after regional lymphadenectomy 3–6 months after diagnosis
Sample size Intervention: 112 participants, observation: 129 participants PEG-IFN-α-2b: 590 participants, observation: 593 participants Pembrolizumab: 514 participants, placebo: 505 participants Ipilimumab: 475 participants, placebo: 476 participants 2,088 participants
Diagnosis Melanoma of T1-4, N1a-2a, M0 Stage III melanoma Stage IIIA, IIIB, or IIIC melanoma [without in-transit metastases] Stage III melanoma Stage I–IV melanoma (13% stage III and 0.5% stage IV)
Age Mean or median age not available (range 18–70 yrs) Median: 50 yrs (range 18–70 yrs) Pembrolizumab: median 54 yrs (range 19–88 yrs), placebo median: 54 yrs (range 19–83 yrs) Ipilimumab: mean 51 yrs (range 20–84 yrs), placebo: mean 52 yrs (range 18–78 yrs) Mean: 55 yrs (SD 13.6 yrs)
Sex Intervention group: 61% female, 39% male, observation group: 64% female, 36% male 41.9% female, 58.1% male Pembrolizumab: 37% female, 63% male. Placebo: 39.8% female, 60.2% male 38% female, 62% male 43% female, 57% male
Type of primary treatment Surgery with complete excision Surgery with complete excision and regional lymphadenectomy Surgical resection with no further specifics Surgery with complete excision and regional lymphadenectomy Surgical resection with no further specifics
Type of adjuvant therapy Not mentioned; however, immunotherapy was an exclusion criterion PEG-IFN-α-2b, in observation group: no adjuvant treatment Pembrolizumab (200 mg every 3 weeks for a total of 18 doses about 1 year), in placebo group: no adjuvant treatment Ipilimumab 10 mg/kg every 3 weeks for 4 doses, then every 3 months for up to 3 years, in placebo group: no adjuvant treatment 4.5% of the patients with stage III reported that they had received adjuvant therapy, in which type was not mentioned
Studies including re-entry phase fading into early survivorship phase
Year of publication 2011 2014 2014 2015
First author Holterhues Molassiotis Tan Stamataki
Country of origin Netherlands United Kingdom Australia United Kingdom
Study design Cross-sectional descriptive study Cross-sectional descriptive study Qualitative study using semistructured interviews Qualitative study using semistructured interviews
Time after diagnosis/end of treatment Mean 4.6 yrs after diagnosis (SD 2.6 yrs, range 0.5–10 yrs) Mean 24 months after diagnosis (diagnosed at least 3 months and no more than 5 yrs previously) Mean 1.7 yrs after diagnosis (range 0.6–3.1 yrs) Recruited approximately 3 months after end of treatment (diagnosed at least 3 months and no more than 5 yrs previously)
Sample size 562 participants 455 participants 19 participants 15 participants
Diagnosis Stage III melanoma Stage I–III melanoma Stage III melanoma Stage I–III melanoma, among which 53.3% stage III
Age Mean: 57.2 yrs (SD 14 yrs) Mean: 60 yrs (range 20–90 yrs, SD 13.5 yrs) Mean 57.8 yrs, (SD 14.1 yrs, range 30–82 yrs) Mean 52 yrs (range 27–78 yrs)
Sex 62% female, 38% male 54% female, 46% male 52.6% female, 47.4% male 53.3% female, 46.7% male
Type of primary treatment 99% surgery with complete excision, 20% sentinel node procedure, 5% lymphadenectomy Surgery with complete excision Surgery with complete excision and lymphadenectomy Surgery with no further specifics
Type of adjuvant treatment 0.5% systemic therapy and 0.5% radiotherapy, 5% other Not mentioned 15.8% immunotherapy, 10.5% radiotherapy 5.3% chemotherapy, 68.4% no adjuvant treatment Not mentioned

Sample size ranged from 15 to 19 participants in the qualitative studies and from 241 patients to 2,088 patients in quantitative studies. When reported, the mean age of included patients ranged from 51–60 years. Five studies included more female patients, and three studies included more male patients. All included patients had undergone surgery; in four studies (some), patients had undergone a (regional) lymphadenectomy.

Three of the included RCTs investigated adjuvant therapy, of which only one investigated the effect of adjuvant treatment during re-entry. Apart from these clinical trials, use of adjuvant treatment in studies was low. Rogers et al,[30] Holterhues et al,[28] and Tan et al[32] reported use of adjuvant therapy in 4.5%, 6%, and 31.6% of patients, respectively. No comparison was performed between those patients who had received adjuvant therapy and those who had not. Methods used to measure patient's experiences comprised various questionnaires, and four studies used questionnaires that measured (health-related) quality of life or health status. Of these questionnaires, only subscales that were relevant to the psychosocial impact of cancer (IOC) were used (in this case, emotional and social well-being). Other studies used questionnaires covering unmet needs, mood disturbance, the IOC on well-being and adjustment to changes, coping strategies, or melanoma-related worry. Two studies used semistructured interviews. Details of the measurements are shown in Appendix 2 (https://links.lww.com/OR9/A38). Data extracted from the included studies are shown in Tables 2–4, and the results are summarized in two categories: psychosocial well-being and mental adjustment to the re-entry phase (see below).

Table 2 - Results for psychosocial well-being for studies including the re-entry phase.
Studies including the re-entry phase
Study Boesen et al [24] Bottomley et al [26] Bottomley 2021 [25] Coens et al [27] Rogers et al [30]
Time points at which the data were collected At baseline and 6 months and 12 months after surgery At baseline and 3 months and 12 months after start treatment At baseline and at week 12, 24, 36, and 48 (during treatment) and at week 60, 72, 84, 96, and 108 (after treatment) At baseline and at weeks 4, 7, 10, 24, 36, 48, and 60 after starting treatment One time research: 3–6 months after diagnosis
Methods POMS EORTC QLQ-C30 EORTC QLQ-C30 EORTC QLQ-C30 Melanoma-related worry
Results and conclusion for psychosocial well-being At baseline: no significant differences between the group who received psychoeducation, and the control group were found on the variables of the POMS-scores. Baseline TMD scores on the POMS scale were low. Mean scores: anger 5.6 (range 0–48), confusion 1.8 (range 0–28), depression 5.2 (range 0–60), fatigue 5.1 (range 0–28), anxiety 4.2 (range 0–36) and vigor 15.9 (range 0–32), total mood disturbance: 6.1 (range −32 to 200) At baseline: social and emotional functioning: no significant or clinically relevant differences were found between normative population and study groups At baseline: The mean scores for the subscales were comparable between pembrolizumab and the placebo group. Total score of both study groups (range 0–100): emotional functioning pembrolizumab mean: 82.83 (SD: 19.12) and placebo: mean 81.90 (SD: 18.97). Social functioning: 84.97 (SD: 21.54) and placebo: mean 84.56 (SD: 21.98). At week 60, 72, 84, and 96 (=8, 20, 32 and 44 weeks after treatment), the mean scores for the subscales were lower for the pembrolizumab group, however not statistically significant and clinically relevant. Social functioning pembrolizumab mean: 86.4 (SD: 20.8), placebo mean: 89.3 (SD: 18.2), means difference: −2.9. Emotional functioning pembrolizumab mean: 82.9 (SD: 18.7), placebo: 84.7 (SD: 18.0). Difference in means: −1.7. At baseline: The mean scores for the subscales were comparable between ipilimumab and the placebo group. Total score of both study groups (range 0–100): emotional functioning mean: 81.94 (SD: 18.06), social functioning mean: 87.73 (SD: 19.96) 63% in the stage III and IV group was confident, 43% was worried about the future (P < .0001). Patients with stage III and IV were more likely to be worried than patients in the reference group (stages I/II). Univariable and multivariable analyses (adjusted for age, sex, and disease stage) showed that the patients who reported the following variables were more likely to be worried (significant positive odds ratio): -receiving no or poor support from the melanoma health care team -being told about the diagnosis unsympathetically -not knowing enough about melanoma -having financial hardship -having experienced over three negative life events in the last 5 years compared with none/one negative life events -having experienced previous depression/anxiety

Table 3 - Results for psychosocial well-being for studies including the re-entry fading into early survivorship phase.
Studies including re-entry phase fading into early survivorship phase
Study Holterhues et al [28] Molassiotis et al [29] Tan et al[32] Stamataki et al [31]
Time points at which the data were collected One time research: mean 4.6 yrs after diagnosis (SD 2.6 yrs) One time research: mean 2.0 yrs after diagnosis One time research: mean 1.7 yrs after diagnosis One time research: recruited approximately 3 months after end of treatment (diagnosed at least 3 months and no more than 5 yrs previously)
Methods SF-36, IOC SCNS-SF34, fact-M Qualitative semistructured interview with questions about the experience and impact of having melanoma Qualitative semistructured interview with questions to reflect about the experience with a melanoma diagnosis and the impact on their physical and psychosocial well-being
Results and conclusion for psychosocial well-being The mental component of the SF-36 did not significantly differ between tumor stage (III vs I). Higher melanoma stage (III vs I) was associated with a higher-order negative IOC score. For the higher-order positive IOC score, there was no difference between tumor stages. The highest mean score on a subscale (regarding stage I–IV melanoma) was seen on the subscale spiritual/existential: positive outlook: 3.1 (range 0–5) FACT-M: Emotional well-being was lower in those with lymph node involvement (LNI) compared with those without LNI (P < .05); between functional and social well-being, there was no significant difference. Of patients with stage III melanoma, 65.2% had no need frequency and 34.8% had some need frequency. This was significantly higher (P < .05) compared with stage I and II (22.2% and 24.6%, respectively, had some needs). Patients with LNI reported more of the following unmet needs: -worry that the results of the treatment are beyond your control (P < .001) -fears about the cancer spreading (P < .01) -lack of energy/tiredness (P < .01) -uncertainty about the future, more information about the risk of the recurrence of melanoma (P < .05) -concerns about the worries of those close to you (P < .05) -learning to feel in control of your situation (P < .05) -feeling sad/down, anxiety (P < .05) Impact of survivorship reported: -some (25–50%): frequent fears of recurrence and never feeling completely free of the disease -a few (1–25%): having sense of abandonment by the treating team after treatment and perceived lack of adequate follow-up care and support impact throughout disease journey ongoing into re-entry/survivorship reported: -most (75–100%): emotional distress, including feelings of anger and frustration (lack of sun-safe behavior before diagnosis, limitation during treatment recovery; inconsiderate treatment by others; perceived lack of appreciation of difficulties by others; disruption to patients life; uncertainty faced into survivorship) -anxiety and fear (because of prognostic uncertainty, lack of control over the disease and worries about how the patient's family would cope if they died) -feelings of depression, hopelessness, grief -feelings of guilt and regret regarding their history of unsafe sun exposure -some (25–50%): disfigurement as a result of treatment-related scarring, lymphedema and/or hair loss. Disfigurement led to negative body image, unhelpful comments from others, feeling uncomfortable wearing revealing clothing, psychological distress, and restriction in social and vocational roles -some (25–50%): sense of injustice regarding illness, resulting in feelings of anger and/or depression Patients reported: -uncertainty for the future -feelings of anxiety -feelings of helplessness and frustration because of only being able to be reactive to the disease (looking out for new moles and lumps) instead of, in their view, being proactive (being given treatment to reduce the risk of recurrence) -not being able to take control contributed to being “over vigilant” (eg, checking their body every day) -over anxious that any new change could be a sign of recurrence lack of emotional support from the health care system added on the concerns, anxiety, and feelings of helplessness regarding their future -fear of the sun which leads to being concerned about living their everyday lives not being able to discuss their fears regarding their melanoma diagnosis with partners because it could affect their relationship or because being afraid to over burden their partner -anxiety and uncertainty for the future increased by the lack of understanding the information about the prognosis/disease stage/previous treatment decisions

Table 4 - Results for mental adjustment to the re-entry phase.
Mental adjustment to the re-entry phase
Study Boesen et al [24] Tan et al[32] Stamataki et al [31]
Method used to assess patients' experience Dealing With illness Inventory-Revised (DWI-R) Qualitative interview semistructured interview Qualitative interview semistructured interview
Time points at which the data were collected Baseline and 6 months and 12 months after surgery One time research: mean 1.7 yrs after diagnosis One time research: recruited approximately 3 months after end of treatment (diagnosed at least 3 months and no more than 5 yrs previously)
Results and conclusion for mental adjustment to the re-entry phase At baseline: both intervention and observation group scored highest on cognitive coping (mean: 51.7), followed by behavioral coping (mean: 45.9) and as last avoidance (mean: 28.8). At 6 and 12 months: The control group scores decreased most for the cognitive method with −3.4 after 6 months and −3.71 after 12 months. At 6 months, the intervention group used significantly more active behavioral coping and active cognitive coping than the control group; at 12 months, there was no significant difference anymore. For avoidance coping, no differences were observed. On the TMD scale, significantly larger average decrease was seen in the intervention group compared with the control group at first follow-up (P < .04). The difference between the groups was mainly caused by differences on the subscales for vigor (P < .003) and fatigue (P < .04), respectively. After 12 months, no differences in TMD were observed Reported coping/adjustment strategies patients used throughout the disease journey: -most (75–99%) receiving support from friends and family -most (75–99%) receiving professional support from doctors, nurses, psychologists and participation in clinical trials -most (75–99%) using helpful thinking strategies, including adopting an optimistic and hopeful mindset, being rational and rejecting worry, “living for the moment” and making downward social comparisons -some (25–50%): concealing psychological distress and “putting on a brave face” around others -a few (1–25%) redirecting attention away from thoughts and worries about the disease, including focusing attention on calming activities such as meditation and relaxation techniques, visiting quiet and peaceful areas, exercise, yoga, gardening, and hobbies. -A few (1–25%) religious beliefs and practices (comfort from the belief that one's future is determined by God; emotional strength from prayer; support from church community). -Reported coping/adjustment strategies patients used during extended survivorship: -many (50–75%) finding a positive meaning for the disease, these included being more appreciative of family and life in general, leading a healthier and more fulfilling lifestyle, “putting things in perspective” and worrying less about everyday stresses, learning how to accept help from others, and strengthening relationships with others. -Raising awareness of melanoma, promote sun-safe behavior; helping others affected by the disease -many (50–75%) putting the disease behind them, moving on with their lives and returning to a sense of normality during the survivorship phase (affirming life) -a few (1–25%) acceptance of own mortality throughout the disease journey -a few (1–25%) relying on religious beliefs and practices (comfort from the belief that one's future is determined by God; emotional strength from prayer; support from church community) Finding a positive meaning: -more appreciation for employment-positive influence on the relationship with partner

3.2. Psychosocial well-being

Social and emotional functioning of patients with stage III melanoma at the start of the re-entry phase was comparable with the general, noncancer population.[26] In addition, patients with stage III melanoma had low scores on the mood disturbance scale.[24] Nevertheless, at the beginning of the re-entry phase, 43% of patients admitted to being worried about the future. Studies that compared stage III with stage I/II patients found that patients with stage III melanoma were more likely to be worried than patients with stage I/II melanoma.[30] One RCT compared the effects of adjuvant therapy with a placebo on the re-entry phase and found that the emotional and social functioning of patients did not differ between the pembrolizumab and placebo groups.[25]

The studies reporting on the re-entry fading into early survivorship phase found that 75–100% of patients with stage III melanoma reported emotional distress, including feelings of anger, anxiety, depression, and grief.[31,32] Of patients with stage III melanoma who reported unmet needs, about a quarter said this concerned anxiety, feeling down and depressed, and concerns about the worries of relatives and friends.[29] Lack of emotional support or appreciation of difficulties by others, lack of information, or not being able to understand the information increased emotional distress.[31,32] Some patients reported feeling abandoned after treatment and desired more support.[32]

Studies of the re-entry fading into early survivorship phase that compared the psychosocial IOC in patients with stage III melanoma versus stage I/II melanoma found similar outcomes for mental health and social well-being.[28,29] However, patients with stage III melanoma had significantly lower scores on emotional well-being[29] and had a higher negative IOC score compared with patients with stage I/II melanoma; they experienced more life interference, a negative self-evaluation, and a negative outlook.[28]

Almost half of all patients with stage III melanoma worried about the future with respect to melanoma, experienced frequent fears of recurrence, and felt they were never really free of the disease.[32] Feelings of guilt and regret were reported regarding previous unsafe sun exposure.[32] Other existential concerns mentioned were lack of control over the disease, preoccupation with the disease, and hopelessness.[32] Of the patients with stage III melanoma who reported having unmet needs, help was most often requested for existential concerns such as worry that treatment results are beyond one's control, fears about the cancer spreading, uncertainty about the future, and learning how to feel in control of the situation.[29] Existential concerns caused emotional distress, such as anxiety and fear, and affected daily life and social relations.[31,32]

3.3. Mental adjustment to the re-entry phase

Patients reported several coping styles to deal with the impact on their psychosocial well-being. To adjust to the re-entry phase, patients mostly used cognitive coping, followed by behavioral coping and avoidant coping.[18] Patients who had received psychoeducation aimed at coping in the re-entry phase showed greater use of cognitive and behavioral coping compared with the control group and subsequently had less mood disturbance.[18]

Studies that reported on the re-entry fading into early survivorship phase and used standardized questionnaires found that patients with stage III melanoma consistently used active cognitive coping and active behavioral coping as their main coping strategies.[18] Behavioral coping included seeking support from friends, family, or professionals, and cognitive coping consisted of helpful thinking strategies or trusting in one's belief in God. Patients gave examples of how they had adopted an optimistic mindset or tried to think rationally. The phrase “living for the moment” was also mentioned, as well as making downward social comparisons. Some patients also used avoidant strategies[31,32] or concealed psychological distress by “putting on a brave face” around others.[32] Qualitative studies reported that patients also made use of meaning-making, which can be considered another type of coping. Patients found a positive meaning for the disease and noticed being more appreciative of family, work, or life in general or leading a healthier and more fulfilling lifestyle.[31,32] The disease “put things in perspective” strengthened relationships with others, taught them how to accept help from others, and made them worry less about everyday stressors.[32] Some patients mentioned trying to raise awareness of melanoma and promote sun-safe behavior.[32] Some patients also mentioned they had put the disease behind them, moved on with their lives, and returned to a sense of normality during the early survivorship phase. Up to a quarter of the patients also mentioned that they had accepted their own mortality.[32]

4. Discussion

This scoping review identified several gaps in knowledge and found that the overall level of evidence concerning the psychosocial well-being of patients with stage III melanoma in the re-entry phase is limited. The results concerning emotional, psychological, and social health were inconclusive, with a number of studies finding no differences in social and emotional functioning compared with the general population,[26] as well as a stable mood at the start of the re-entry phase.[24,26] Other studies reported that patients in the re-entry survivorship phase experienced emotional distress and impairment in mental health, including feelings of anxiety and depression.[29–32] To optimize supportive measures, better evidence on the emotional, psychological, and social health of patients with stage III melanoma is needed.

Regarding existential health, the results indicated that patients with stage III melanoma face existential concerns in the re-entry fading into early survivorship phase,[29,30] which resulted in a variety of negative emotions.[31,32] Existential concerns were more often voiced by patients with stage III melanoma compared with patients with stage I/II melanoma.[29,30] This may relate to the fact that patients with stage III compared with stage I/II melanoma face a worse prognosis (5-year survival rates of 65.5% for stage III and 98.7% for stage I/II, respectively),[33] and while new adjuvant therapies have reduced the chance of recurrence, the cancer nevertheless recurs in 50% of patients with stage III melanoma.[6] Patients with stage III melanoma therefore have specifically recognizable concerns about an uncertain future and fear of recurrence.

In both the re-entry and early survivorship phases, patients with stage III melanoma primarily dealt with uncertainties by using active cognitive and behavioral coping, together with meaning-making.[24,32] Studies have shown that meaning-making can help when dealing with the demands of the re-entry phase.[31,32] Meaning-making is initiated when patients are confronted with a severe stressor, in this case the experience of cancer, which leads to a violation of one's global meaning (ie, fundamental beliefs, goals, and attitudes). To reduce this violation, patients try to adjust the meaning of the cancer or the purpose of life to make sense of the situation. Earlier research demonstrated that meaning-making leads to a better adjustment to cancer.[34] This review found that patients with stage III melanoma face existential concerns in the re-entry phase and use meaning-making as a coping mechanism after their treatment has finished.[32] To help patients in the re-entry phase, it might be beneficial to address these existential concerns and support the meaning-making process. This could be helpful in restoring a person's general sense that their life has order and purpose, a concept that is positively linked to well-being and provides the motivation for patients with cancer to reengage in life.[22] Earlier research in cancer survivors showed that high levels of existential well-being were associated with less emotional distress.[35] However, more research is clearly needed to properly understand the relationship between emotional distress, existential concerns, and meaning-making of patients with stage III melanoma in the re-entry phase.

4.1. Impact of adjuvant therapy

Despite a higher intensity of systemic treatment[36] and the risk of (long-lasting) side effects of immunotherapy,[37] patients who received immunotherapy showed no negative effect of adjuvant therapy on psychosocial well-being in the re-entry phase.[25] However, this study examined social and emotional factors only and failed to consider other domains such as existential health. It is also noteworthy that only one study to date has included patients in the re-entry phase after use of adjuvant therapy. This could be due either to the fact that use of adjuvant therapies has become common only in the last few years or because the importance of the effect of adjuvant therapy on quality of life and psychosocial well-being after treatment has not yet been recognized.[26,27]

4.2. Limitations

Four of the included studies did not clearly distinguish between patients in the re-entry phase (less than 18 months after completion of treatment) and patients in early survivorship (more than 18 months after completion of treatment). To make the results as transparent as possible, the results of studies on the re-entry phase and results of studies including the re-entry phase fading into survivorship were presented separately.

A possible additional limitation was that articles were reviewed by only one reviewer, although eligibility was discussed with a second reviewer.

4.3. Implications for the future

Patients with stage III melanoma reported concerns characteristic of the re-entry phase,[12] for example, uncertainty about the future, not feeling in control, and perceived lack of adequate follow-up care and support.[31,32] Although patients reported challenges typically experienced during the re-entry phase, it is interesting to note that this phase was not recognized as a separate phase of survivorship in the studies included in this scoping review. We propose further study of the specific problems faced by patients in the re-entry phase.

The data included in this scoping review have certain limitations. Most of the initially identified studies were excluded because a separate analysis for patients with stage III melanoma was not performed. Only one of the included studies determined the effect of adjuvant therapy on the re-entry phase. This further underlines the need for more research specifically on the re-entry phase as experienced by patients with stage III melanoma and the impact of adjuvant therapy on psychosocial well-being in the re-entry phase.

Although data are limited, our review shows that while patients may have good functioning scores, there are indications that they have existential concerns. This supports our view that the re-entry phase for this patient group should not be overlooked by clinicians. Providing support related to existential concerns and meaning-making could be especially helpful. We are therefore currently developing a practical tool to help patients to set meaningful goals for the re-entry phase to motivate them to reengage with life after cancer. We hope this will help patients to find meaningful engagement and a coherent identity that integrates their precancer and postcancer lives, as well as helping them cope with the existential challenges that arise after cancer.[22,38,39]

5. Conclusion

Patients with stage III melanoma represent an expanding group because of both the increasing incidence and the success of newly available adjuvant treatments. During the re-entry phase, patients have to resume their lives after intense treatment, while there is still a high risk of tumor recurrence. The psychosocial status of patients in this phase is still poorly understood. Regarding existential health, this review found that existential concerns are common among patients with stage III melanoma in the re-entry phase. Besides behavioral and cognitive coping, meaning-making is frequently used to deal with and make sense of the situation. It may therefore be helpful to provide support aimed at existential concerns and meaning-making, such as by developing a practical tool to help set meaningful goals for the re-entry phase. More research is needed to effectively evaluate the psychosocial well-being of patients with stage III melanoma in the re-entry phase, the impact of adjuvant therapy, and the relationship between emotional distress, existential concerns, and meaning-making.

Conflicts of interest

The authors declare no conflicts of interest.

Source of funding

This work was supported by Novartis Pharma BV with an unrestricted grant.

Availability of data and material

The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

All authors above declare that other than the grant from Novartis, they did not receive additional payments or support and do not have financial relationships with entities.

Authors' contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Anna Visser and Lenneke Post. The first draft of the manuscript was written by Anna Visser, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

References

[1]. Glazer AM, Winkelmann RR, Farberg AS, Rigel DS. Analysis of trends in US melanoma incidence and mortality. JAMA Dermatol 2017;153(2):225–226.
[2]. Napolitano S, Brancaccio G, Argenziano G, et al. It is finally time for adjuvant therapy in melanoma. Cancer Treat Rev 2018;69:101–111.
[3]. Han D, van Akkooi ACJ, Straker RJ, et al. Current management of melanoma patients with nodal metastases. Clin Exp Metastasis. 2022;39(1):181–199.
[4]. Rogiers A, Boekhout A, Schwarze JK, Awada G, Blank CU, Neyns B. Long-term survival, quality of life, and psychosocial outcomes in advanced melanoma patients treated with immune checkpoint inhibitors. J Oncol 2019;2019:5269062.
[5]. Dummer R, Hauschild A, Santinami M, et al. Five-year analysis of adjuvant dabrafenib plus trametinib in stage III melanoma. N Engl J Med 2020;383(12):1139–1148.
[6]. Michielin O, van Akkooi ACJ, Ascierto PA, Dummer R, Keilholz U. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2019;30(12):1884–1901.
[7]. Leeneman B, Schreuder K, Uyl-de Groot CA, et al. Stage-specific trends in incidence and survival of cutaneous melanoma in The Netherlands (2003–2018): a nationwide population-based study. Eur J Cancer 2021;154:111–119.
[8]. Tarhini A, Ghate S, Ionescu-Ittu R, et al. Stage III melanoma incidence and impact of transitioning to the 8th AJCC staging system: a US population-based study. Future Oncol 2019;15(4):359–370.
[9]. Allen JD, Savadatti S, Gurmankin Levy A. The transition from breast cancer ‘patient’ to ‘survivor’. Psychooncology 2009;18(1):71–78.
[10]. Henselmans I, Helgeson VS, Seltman H, de Vries J, Sanderman R, Ranchor AV. Identification and prediction of distress trajectories in the first year after a breast cancer diagnosis. Health Psychol 2010;29(2):160–168.
[11]. Willems RA, Bolman CAW, Mesters I, Kanera IM, Beaulen AAJM, Lechner L. Cancer survivors in the first year after treatment: the prevalence and correlates of unmet needs in different domains. Psychooncology 2016;25(1):51–7.
[12]. Stanton AL. What happens now? Psychosocial care for cancer survivors after medical treatment completion. J Clin Oncol 2012;30(11):1215–20.
[13]. Holland JC, Reznik I. Pathways for psychosocial care of cancer survivors. Cancer 2005;104(S11):2624–37.
[14]. Bhave P, Pallan L, Long GV, et al. Melanoma recurrence patterns and management after adjuvant targeted therapy: a multicentre analysis. Br J Cancer 2021;124(3):574–580.
[15]. Lo V, Francescutti V, McWhirter E, Farrokhyar F, Lee LM. Recurrent disease in patients with stage III melanoma in the era of adjuvant immune and targeted therapy. Wolters Kluwer Health; 2021.
[16]. Munn Z, Peters MDJ, Stern C, Tufanaru C, McArthur A, Aromataris E. Systematic review or scoping review? Guidance for authors when choosing between a systematic or scoping review approach. BMC Med Res Methodol 2018;18(1):143.
[17]. Tricco AC, Lillie E, Zarin W, et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med 2018;169(7):467–473.
[18]. Eiroa-Orosa FJ. Understanding psychosocial wellbeing in the context of complex and multidimensional problems. Multidisciplinary Digital Publishing Institute; 2020:5937.
[19]. Larson JS. The World Health Organization's definition of health: social versus spiritual health. Soc Indicat Res 1996;38(2):181–192.
[20]. Ryff CD. Well-being with soul: Science in pursuit of human potential. Perspect Psychol Sci 2018;13(2):242–248.
[21]. Ryff CD, Keyes CLM. The structure of psychological well-being revisited. J Pers Soc Psycholo 1995;69(4):719–27.
[22]. Lee V. The existential plight of cancer: meaning making as a concrete approach to the intangible search for meaning. Support Care Cancer 2008;16(7):779–785.
[23]. Hong QN, Pluye P, Fàbregues S, et al. Mixed methods appraisal tool (MMAT), version 2018. Registration of copyright; 2018;1148552.
[24]. Boesen EH, Ross L, Frederiksen K, et al. Psychoeducational intervention for patients with cutaneous malignant melanoma: a replication study. J Clin Oncol 2005;23(6):1270–1277.
[25]. Bottomley A, Coens C, Mierzynska J, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol 2021;22(5):655–664.
[26]. Bottomley A, Coens C, Suciu S, et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma: a phase III randomized controlled trial of health-related quality of life and symptoms by the European Organisation for Research and Treatment of Cancer Melanoma Group. J Clin Oncol 2009;27(18):2916–2923.
[27]. Coens C, Suciu S, Chiarion-Sileni V, et al. Health-related quality of life with adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): secondary outcomes of a multinational, randomised, double-blind, phase 3 trial. Lancet Oncol 2017;18(3):393–403.
[28]. Holterhues C, Cornish D, van de Poll-Franse LV, et al. Impact of melanoma on patients' lives among 562 survivors: a Dutch population-based study. Arch Dermatol 2011;147(2):177–85.
[29]. Molassiotis A, Brunton L, Hodgetts J, et al. Prevalence and correlates of unmet supportive care needs in patients with resected invasive cutaneous melanoma. Ann Oncol 2014;25(10):2052–2058.
[30]. Rogers Z, Elliott F, Kasparian NA, Bishop DT, Barrett JH, Newton-Bishop J. Psychosocial, clinical and demographic features related to worry in patients with melanoma. Melanoma Res 2016;26(5):497–504.
[31]. Stamataki Z, Brunton L, Lorigan P, Green AC, Newton-Bishop J, Molassiotis A. Assessing the impact of diagnosis and the related supportive care needs in patients with cutaneous melanoma. Support Care Cancer 2015;23(3):779–789.
[32]. Tan JD, Butow PN, Boyle FM, Saw RP, O'Reilly AJ. A qualitative assessment of psychosocial impact, coping and adjustment in high-risk melanoma patients and caregivers. Melanoma Res 2014;24(3):252–60.
[33]. Howlader N NA, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA. SEER cancer statistics review 1975–2018; 2021. Accessed 26th of May 2021 https://seer.cancer.gov/csr/1975_2018/.
[34]. Park CL, Edmondson D, Fenster JR, Blank TO. Meaning making and psychological adjustment following cancer: the mediating roles of growth, life meaning, and restored just-world beliefs. J Consult Clin Psychol 2008;76(5):863–875.
[35]. Laubmeier KK, Zakowski SG, Bair JP. The role of spirituality in the psychological adjustment to cancer: a test of the transactional model of stress and coping. Int J Behav Med 2004;11(1):48–55.
[36]. Engel J, Schlesinger-Raab A, Emeny R, Hölzel D, Schubert-Fritschle G. Quality of life in women with localised breast cancer or malignant melanoma 2 years after initial treatment: a comparison. Int J Behav Med 2014;21(3):478–486. doi: 10.1007/s12529-013-9334-x.
[37]. Ghisoni E, Wicky AM, Latifyan S, et al. Long-lasting, irreversible and late-onset immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs): a real-world data analysis. J Clin Oncol 2020;38(15_suppl):e15095.
[38]. Pool G. Psychological interventions in cancer. Psychologie en Gezondheid 2009;37(5):276–287.
[39]. Vehling S, Philipp R. Existential distress and meaning-focused interventions in cancer survivorship. Curr Opin Support Palliat Care 2018;12(1):46–51.
[40]. Fawzy FI, Fawzy NW, Hyun CS, et al. Malignant melanoma. Effects of an early structured psychiatric intervention, coping, and affective state on recurrence and survival 6 years later. Arch Gen Psychiatry 1993;50(9):681–9.
Keywords:

cancer survivors; stage III melanoma; re-entry phase; psychosocial well-being; existential concerns; mental adjustment; coping; meaning-making

Supplemental Digital Content

Copyright © 2022 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the International Psycho-Oncology Society.