JPOS/JASCC clinical guidelines for psychological distress in adult cancer patients: a summary of recommendations

Abstract

Objectives

This article aims to describe the newly developed Japanese practice guidelines for psychological distress of adult individuals with cancer who have elevated levels of psychological distress.

Methods

We conducted systematic reviews and Delphi consensus rounds to determine the levels of certainty of evidence and strength of recommendation.

Results

In our proposed flow of care, all individuals with cancer should initially be provided with general support, comprising supportive communication, detection of psychological distress, attendance to their needs, and differentiating physical conditions that mimic psychological distress. If a patient still has significant psychological distress despite such support, more specific care for psychological distress should be considered. Collaborative care has strong evidence base and is strongly recommended. Evidence for psychotherapy for psychological distress and fear of cancer recurrence is moderate to strong, however, recommendations for these interventions were weakened because of the heterogeneity of interventions and lack of formal training system. Evidence of pharmacotherapy was weak. Thus, anxiolytics are weakly recommended only for short term and should be accompanied with psychosocial support. Antidepressants are weakly recommended when a patient is diagnosed with depression. Early specialized palliative care, care for caregivers and peer support are not recommended as a sole means to alleviate psychological distress, due to the scarce supporting evidence. Provision of these interventions is not hindered when they aim to improve the outcomes other than psychological distress, such as quality of life, symptom burden and self-efficacy.

Discussion

New practice guidelines for psychological distress of adult individuals with cancer have been developed.

Mini-abstract New practice guidelines for psychological distress of individuals with cancer present recommendations for collaborative care, psychotherapy, pharmacotherapy, early specialized palliative care, care for caregivers and peer support.

Introduction

Psychological distress, which can be defined as “a multifactorial unpleasant experience of psychological, social, spiritual, and/or physical nature that may interfere with one’s ability to cope effectively with cancer, its physical symptoms, and its treatment” [1], is one of the commonest difficulties that individuals with cancer may experience, regardless of the type and stage of their illnesses. Psychological distress presents itself as a spectrum. At one end there are normal, temporal psychological reactions to the changes of an individual’s life which were brought by cancer and cancer treatments. At the other end there are more persisting and disabling psychological syndromes, some of which correspond to clinical diagnosis of mental disorders such as depression and anxiety disorders.

Several clinical guidelines for psychological distress of individuals with cancer have been published worldwide [1–4]. Guidelines should be updated with latest evidence and should be tailored to adapt to the circumstances where they are used, since the available resource for care varies between countries. The Japan Psycho-Oncology Society (JPOS) and the Japanese Association of Supportive Care in Cancer (JASCC) have been collaboratively developing a series of practice guidelines for psychological issues in patients with cancer [5–7]. The supposed users of the guidelines were all healthcare professionals working with individuals with cancer. In this article, we aim to present a summary of the recommendations of the recently published practice guidelines for psychological distress in individuals with cancer [8], referring to its development process and the background evidence.

Methods

The guidelines were developed in accordance with the 2017 and 2020 Medical Information Network Distribution Service system (Minds) [9]. We formed a multidisciplinary guideline development team, consisting of psychiatrists, palliative care physicians, nurses, an oncologist, a pharmacist, a patients advocate, and an ordinary citizen. The scope of the guidelines was reviewed by a panel of three reviewers, consisting of an oncologist, a nurse, and a patient advocate.

We formulated nine clinical questions (CQs) and conducted systematic reviews for each of them using five electronic databases (PubMed, Cochrane Central Resister of Controlled Trial, Cochrane Database of Systematic Reviews, APA Psycinfo and Ichushi-Web). The eligible literature was the following: (i) targeting adult individuals with cancer with significant psychological distress, which was defined as either having been diagnosed with a mental disorder or having scored above the threshold on a standardized evaluation scale for psychological distress, (ii) study designs being either systematic reviews, meta-analyses or randomized controlled trials (RCTs), (iii) addressing relevant care (e.g. antidepressant, psychotherapy, peer support), (iv) published prior to 31st December 2020 and (v) written in English or Japanese. Two members of the team independently reviewed the abstracts as the first-step screening, then, full-texts were reviewed according to the strict eligibility criteria. Additional articles were identified by hand search.

The guideline development team drafted the recommendations based on the results of the systematic reviews. The certainty of evidence and the strength of the recommendations were graded using the grading system developed by the Minds, based on the concept of the Grading of Recommendations Assessment, Development and Evaluation system (Table 1). The Evidence to Decision framework, in consideration of the balance between benefit and harm, value and preference of targeted patients, cost, and clinical applicability were used to determine the recommendations. Two rounds of Delphi consensus meetings to validate the recommendations were conducted. The Delphi team consisted of representatives of 18 relevant societies, including palliative care physicians, pharmacists, oncologists, home care physicians, psychiatrists, nurses, and patient advocates. Each of the Delphi members evaluated the appropriateness for the strength of recommendations, certainty of evidence and recommendation summaries on a nine-point scale (9: most appropriate, 1: least appropriate) for each CQ. The median score of eight or over and the difference between the highest and lowest rating was five or less are considered reached agreement. The guidelines were finalized after the review by a panel of three reviewers, consisting of an oncologist, a nurse and a patient advocate.

Table 1.

Evidence and recommendation levels.

Strength of recommendations
1. Strong	The referenced intervention is strongly recommended to be provided (or not to be provided). Its benefit certainly outweighs its harm or burden.
2. Weak	The referenced intervention is weakly recommended (“proposed”) to be provided (or not to be provided). Its benefit may outweigh its harm or burden in certain circumstances.
Certainty of evidence
A. Strong	The evidence for the referenced intervention is supported by high-quality studies, such as RCTs with concordant results or one or more meta-analysis of RCTs.
B. Moderate	The evidence for the referenced intervention is insufficient, which is partly supported by moderate-quality studies, such as RCTs with inconsistent results, low-quality controlled trials, or high-quality observational trials with consistent results.
C. Weak	The evidence for the referenced intervention is insufficient, which is partly supported by some low-quality studies, such as observational trials with consistent results
D. Very weak	There is scarce evidence for the referenced intervention. For example, there are only observational trials with inconsistent results, case reports, or expert opinions.

RCT: randomized controlled trial

Results

Outline of the guidelines

As described earlier, the levels of psychological distress can be diverse, and in majority cases, psychological distress subsides with minimal support and does not require specific treatments. To cover the whole spectrum of the levels of psychological distress, the guideline development team articulated the recommended flow of care as shown in Fig. 1. All individuals with cancer should initially be provided with general support, which comprises (i) supportive communication, (ii) detection of their psychological distress, (iii) identification of and attendance to their needs, and (iv) differentiating physical conditions that mimic psychological distress. If a patient still has significant psychological distress despite such general support, more specific care for psychological distress should be considered. Significant psychological distress was defined that an individual either has strong feelings of distress or impairment in social, occupational, or other important areas of functioning. We formulated nine CQs covering six areas of care: (i) Pharmacotherapy (CQ1: anxiolytics, CQ2: antidepressants), (ii) Psychotherapy (CQ3), (iii) Multidisciplinary care (CQ4: collaborative care, CQ5: Early specialized palliative care), (iv) Care for caregivers (CQ6), (v) Peer support (CQ7), and (vi) Psychosocial care to alleviate fear of cancer recurrence (FoCR) [CQ8: Psychotherapy, CQ9 (back ground question): other interventions].

Figure 1.

Recommended flow of care: CQ and FoCR.

Recommendation summary

The summary of recommendations is presented in Table 2. The levels of evidence for each intervention were generally weak except for psychotherapy (CQ3 and CQ8) and collaborative care (CQ4). Strong recommendation was granted for collaborative care only.

Table 2.

Summary of recommendations.

Interventions	Recommendation	Certainty of evidence
CQ1: Anxiolytics	2 (weak)	D (very weak)
CQ2: Antidepressants	2 (weak)	C (weak)
CQ3: Psychotherapy	2 (weak)	B (moderate)
CQ4: Collaborative care	1 (strong)	A (strong)
CQ5: Early specialized palliative care	2 (weak, against)	D (very weak)
CQ6: Psychosocial intervention for caregivers (with intention to alleviate psychological distress of a patient)	2 (weak, against)	D (very weak)
CQ7: Peer support	2 (weak, against)	D. (very weak)
CQ8: Psychotherapy for fear of cancer recurrence	2 (weak)	A. (strong)
CQ9: Other psychosocial care for fear of cancer recurrence	N/A (back ground question)	N/A (back ground question)

N/A: not applicable

CQ1: Anxiolytics

“Recommendation: Anxiolytics are weakly recommended to alleviate psychological distress in adult individuals with cancer with elevated psychological distress. When using anxiolytics, psychological and/or psychosocial management should also be provided. Long-term use of anxiolytics should be avoided (Strength of recommendation: 2, Evidence level: D).”

Effectiveness of anxiolytics for anxiety and depression has been established outside cancer settings [10, 11]. There are a few categories of drugs, including benzodiazepines, serotoninergic anxiolytics, and antihistamine hydroxyzine, all which of we included in our systematic review. The use of benzodiazepines, especially for long-term use, has been warned because of its adverse effects such as sedation, amnesia, and cognitive impairment, and risk of abuse or dependence [12–14].

We identified two systematic reviews and two RCTs on this CQ. All the studies were related to benzodiazepines. Salt et al. conducted a systematic review on pharmacotherapy for anxiety in adult patients receiving palliative care and found no study that met the inclusion criteria [15]. Ng et al. [16] conducted a systematic review on pharmacotherapy for depression in cancer patients and found only one RCT that used anxiolytics, which was conducted by Holland et al [17]. In this RCT, alprazolam was compared with progressive muscle relaxation (PMR) in a sample of 174 cancer patients with anxiety or depression. The patients who scored above the cutoff on either COVI Anxiety Scale or Raskin Depression Scale were eligible. The alprazolam group showed significantly greater improvement in anxiety and depression compared to PMR group. In the alprazolam group, adverse effects of drowsiness were observed, which lead to interruption of treatment or dose reduction in some patients. Since PMR is a well-established intervention to improve depressive symptoms of patients with cancer [18], alprazolam was considered efficacious in alleviating elevated level of psychological distress in patients with cancer. Wald et al. conducted a double-blind, placebo-controlled RCT to evaluate the efficacy of alprazolam in a sample of 36 cancer patients who met the DSM-III criteria of general anxiety disorder, panic disorder, or adjustment disorder with anxiety. Both alprazolam and placebo significantly improved the level of anxiety and depression, but there was no significant difference between the groups. Transient drowsiness and fatigue were observed in the alprazolam group [19].

In summary, there was only very weak evidence to support the use of anxiolytics for patients with cancer, with possible harm due to their adverse effects. We took the evidence outside cancer settings into consideration. Finally, we weakly recommended the use of anxiolytics, with a warning for their possible adverse effects, especially for the long-term use.

CQ2: Antidepressants

“Recommendation: Antidepressants are weakly recommended to alleviate psychological distress in adult individuals with cancer with elevated psychological distress, if the patient is diagnosed with major depression (Strength of recommendation: 2, Evidence level: C).”

Antidepressants are one of the standard treatments for depression and anxiety disorders outside cancer settings [20, 21]. We identified two systematic reviews [22, 23] and six RCTs [24–29], which compared antidepressants and placebo. Costa et al. conducted an RCT of 73 women with breast or gynecological cancer who were diagnosed with major depression [24]. The patients were randomly assigned to mianserin or placebo for 4 weeks. Significant improvement was observed in mianserin group on the total score of the 17-item Hamilton Rating Scale for Depression (HAM-D), compared with placebo. Heeringen and Zivkov randomly assigned 55 depressed women with breast cancer (stage I or II) to either mianserin or placebo for 6 weeks [25]. The patients in the mianserin group experienced significantly greater decrease in the score of the 21-item HAM-D, with larger number of treatment responders (more than 50% improvement). Razavi et al. randomly assigned 91 female cancer patients with major depression or adjustment disorder with depressed mood to fluoxetine or placebo for 5 weeks [26]. There was no significant between-group difference in the total score of the Montgomery and Asberg Depression Scale (MADRS) and the Hospital Anxiety and Depression Scale (HADS). Musselman et al. randomly assigned 35 female ambulatory breast cancer patients with major depression or adjustment disorder with depressed mood to three groups (paroxetine, desipramine or placebo) for 6 weeks [27]. There was no significant between-group difference either in the mean changes of the 21-item HAM-D score or in the proportion of treatment responders, who were defined as a total score of 7 or below on the 21-item HAM-D score. Navari et al. randomly assigned 180 mildly depressed women with newly diagnosed breast cancer (stage I or II) to fluoxetine or placebo for 6 months [28]. Depressive symptoms were assessed by the two-question screening. Larger proportion of patients experienced statistically significant increase in quality of life (QOL), which was measured by the Functional Assessment of Cancer Therapy-General in fluoxetine group. Also, the proportion of patients who experienced statistically significant decrease in depression (measured by the Zung Self-rating Depression Scale: SDS) was larger in the fluoxetine group. However, the definition of improvement was not documented, and precise data were not presented. Fisch et al. randomly assigned mildly depressed patients with advanced solid tumor with expected survival between 3 and 24 months to either fluoxetine (n = 83) or placebo (n = 80) for 12 weeks [29]. Although the total score of SDS was lower in fluoxetine group, clinically meaningful difference was not archived.

Ostuzzi et al. conducted a systematic review of studies on antidepressants for the treatment of depression in cancer patients [22]. This systematic review included the six above-mentioned RCTs, two additional RCTs comparing antidepressants with other antidepressants, and two unpublished studies. There was no statistically significant difference between antidepressants and placebo, with a standardized mean difference (SMD) of −0.45 [95% confidence interval (CI) −1.01 to 0.11]. Beevers et al. conducted a systematic review of pharmacological treatments of depression in people with a primary brain tumor, which retrieved no eligible studies [23].

In summary, supportive evidence for the use of antidepressants for psychological distress in cancer patients was limited to patients who are diagnosed with major depression. Therefore, we concluded that antidepressants deserve weak recommendations only for adult cancer patients who are diagnosed with depression.

CQ3: Psychotherapy

“Recommendations: Psychotherapy is weakly recommended to alleviate psychological distress of adult individuals with cancer with elevated psychological distress (Strength of recommendation: 2, Evidence level: B).”

Psychotherapy is an established treatment for depression and anxiety outside cancer settings [20, 21]. We identified 26 RCTs on this CQ. The most common type of cancer among the study participants was breast cancer (11 studies). The participants were at various stages of cancer, with two studies including terminal cancer patients. Cognitive Behavioral Therapy [30–37] and related psychotherapies were the most common type of psychotherapy (17 studies), including five mindfulness-based intervention studies (Mindfulness-based Cancer Recovery [38, 39] and Mindfulness-based Cognitive Therapy [40–42]), Acceptance and Commitment Therapy [43–45], and Behavioral Activation [43, 45]. Other studies included two Supportive Psychotherapy, one Supportive-Expressive Group Therapy, one Narrative Therapy, one Positive Psychotherapy, one Meaning-centered Psychotherapy, one Short-term Psychodynamic Psychotherapy, one Reminiscence Therapy, and one Cancer and Aging: Reflections for Elders (CARE program). Ten studies addressed group therapy, and eight studies addressed telephone or internet-based interventions.

Twenty-one studies evaluated depression as a treatment outcome [30–32, 34–36, 40, 43–56], which was measured with Structured Clinical Interview for DSM-IV, Beck Depression Inventory, Center for Epidemiologic Studies Depression Scale, HAM-D, HADS—Depression subscale (HADS-D), MADRS, SDS, and Patient Health Questionaire-9 (PHQ-9). Among them, 16 studies yielded positive results [30–32, 34, 40, 43, 45–54]. Eleven studies evaluated anxiety [30–32, 35, 40, 43, 44, 46–49, 51–53, 55], which was measured with Clinical Global Impression, Generalized Anxiety Disorder Scale, Hamilton Anxiety Scale, HADS—anxiety subscale, and Zung Self-Rating Anxiety Scale. Among them, 11 studies yielded positive results [31, 35, 40, 43, 46–49, 52, 53, 55]. Nine studies evaluated general psychological distress [38–41, 45, 47, 48, 51, 53], which was measured with HADS total score, Distress Thermometer, and Profile of Mood States. Eight studies yielded positive outcomes [38, 40, 41, 45, 47, 48, 51, 53].

Lack of sufficient qualified therapists downgraded the strength of recommendation, despite the moderate certainty of evidence in psychotherapy. First, clinical psychologists, who are supposed to be main providers of psychotherapy, are understaffed in Japanese cancer settings; only two-thirds of the designated cancer centers and one-third of general hospitals are staffed with full-time psychologists [57]. Second, under the Japanese national health insurance system, psychotherapy is reimbursed only when it is conducted by psychiatrists, and not by psychologists. Third, training system for psychotherapy for patients with cancer has yet been established.

CQ4: Collaborative care

“Recommendations: Collaborative care is strongly recommended to alleviate psychological distress of adult individuals with cancer elevated psychological distress (Strength of recommendation: 1, Evidence level: A).”

Collaborative care interventions are multicomponent strategies characterized by active collaboration between specialist and primary care providers, which is assisted by a case manager, and typically includes measurement-based care. Their effectiveness has been widely known for depression, anxiety, and comorbid physical conditions [58–61]. Also promising results have been shown in oncology settings [62].

We identified seven RCTs [63–69], all of which were compiled in two systematic reviews [70, 71]. We presented a summary of the referenced studies in Table 3. A typical collaborative care program was a manualized care provided by trained nurses, social workers, or clinical psychologists, and included educational sessions, problem-solving psychotherapy and/or behavioral activation, and pharmacotherapy (either medication-adherence support or prescription by primary care physicians or oncologists), under the supervision of psychiatrists. Interventions were provided typically on face-to-face basis, with a few studies using an automated symptom monitoring system through telephone or the internet. Collaborative care consistently showed greater improvement in depression and QOL compared to treatment as usual. The SMDs for the severity of depression comparing collaborative care and the control were −0.58 (95% CI: −0.91 to −0.25, P = .0007), −0.53 (−0.85 to −0.20, P = .001), and −0.49 (−0.81 to −0.16, P = .003) at 3, 6, and 12 months, respectively [70].

Table 3.

Randomized controlled trials of collaborative care.

Author (publication year)	Patients	Intervention	Control	Outcomes	Major findings
Dwight-Johnson M, et al. (2005) [64]	Female, breast or cervical cancer within 3 months of diagnosis. MDD, dysthimic disorder, or persistent depressive symptoms over 1 month	Manualized care provided by social workers who were trained in the care of cancer and depression, with the supervision by psychiatrists. Educational sessions followed by PST (weekly for 8 weeks) or pharmacotherapy by oncologists (consultation for psychiatrist available). 8 months N = 28	TAU N = 27	Depression (PHQ), Emotional wellbeing (FACT) at 4 and 8 months	Greater 50% improvement in depression (P = .03) and better emotional well-being (P = .03) in intervention group. Higher mortality in control group (P = .002).
Strong V, et al. (2008) [67]	Mixed cancer patients with prognosis of at least 6 months. MDD and SCL-20 score > = 1.75	Care provided by nurses under the supervision by psychiatrists (psychoeducation and PST), pharmacotherapy by primary care physicians 3-months intervention with subsequent monthly follow-up N = 101	TAU N = 99	Depression (SCL-20), Anxiety (SCL10), QOL (EORTC-QLQ C30) at 3, 6, 12 months	Lower depression (P = .002), higher 50% improvement (P = .008) in intervention group at 3 months, persistent in 6 and 12 months.
Fann JR, et al. (2009) [68]	Mixed cancer, aged 60 or over. MDD of dysthimic disorder (DSM-IV)	IMPACT intervention: depression management by nurses or clinical psychologists under the supervision by psychiatrists (medical review, psychoeducation, behavioral activation, support for treatment decision-making)) and optional PST and pharmacotherapy 12 months at maximum N = 112	TAU N = 103	Depression (SCL-20), QOL (numeric scale) at 3, 6, 12, 18, 24 months	Better 50% improvement rate in depression (P = .03, P = .03, at 6 and 12 months, respectively), higher remission in depression at 12 months (P = .03), more depression-free days (P < .001) and better QOL (P = .04) in intervention group.
Ell K, et al. (2008) [65]	Hispanic female aged 18 or over. Diagnosis of cancer in over 90 days before. Presence of at least one core depressive symptoms for more than one day in 2 days	Care provided by social workers under the supervision by psychiatrists (weekly PST for 6–12 weeks) and/or pharmacotherapy by psychiatrists 12 month N = 242	TAU N = 230	Depression (PHQ-9), QOL (FACT, SF-12) at 6 and 12 months	Better 50% improvement rate (P = .01), and higher 5-point reduction rate (P = .02) on PHQ-9 at 12 months in intervention group. Better physical, functional and mental wellbeing at 6 months, better physical, social/familial, emotional and functional wellbeing at 12 months.
Kroenke K, et al. (2010) [69]	Mixed cancer Depressive mood or anhedonic, with PHQ-9 of 10 or over	Telephone calls by nurse care managers under supervision by psychiatrists at 1, 4 and 12 weeks, automated monitoring system on telephone or website and prescription-prompts to oncologists N = 154	TAU N = 155	Depression (HSCL-20) at 1, 3, 6 and 12 months	Better improvement in depression throughout 12 months (P = .001) in intervention group
Sharpe M, et al. (2014) [66]	Mixed cancer, aged 18 or over MDD for 4 weeks or over	Manualized care provided by nurses under the supervision by psychiatrists (symptom monitoring, PST and/or behavioral activation), pharmacotherapy by primary care physicians N = 253	TAU N = 247	Depression (SCL-20), QOL (EORTC-QLQ-C30) at 12, 24, 36 and 48 weeks	Better 50% improvement rate in depression at 24 week (P < .0001), better QOL throughout study period (P = <.05), lower depression anxiety, pain and fatigue severity in intervention group (all P < .05).
Walker J, et al. (2014) [63]	Lung cancer with prognosis over 3 months, aged 18 or over, MDD for 4 weeks or over	Manualized are provided by nurses under the supervision by psychiatrists (symptom monitoring, PST and/or behavioral activation), pharmacotherapy by primary care physicians N = 68	TAU N = 74	Depression (SCL-20), QOL (EORTC-QLQ-C30)	Lower depression (P = .0003), higher QOLt (P = .018) in intervention group

DSM: diagnostic and statistical manual by American Psychiatric Association, FACT: Functional Assessment of Cancer Therapy, HSCL: Hopkins symptom checklist, MDD: major depressive disorder, PHQ: Patient Health Questionnaire, PST: problem solving therapy, QOL: Quality of life, SF: Short form QOL instrument, TAU: treatment as usual

Although collaborative care is not common in Japanese oncology practice, we considered that it is implementable with the currently available human resource in Japanese medical settings. For example, almost all the designated cancer centers in Japan are staffed with certified nurse specialists and/or clinical psychologists. They have the potential to serve as case managers, under supervision by psychiatrists (either full-time or part-time) in the collaborative care model. Therefore, in the current guidelines, we decided to strongly recommend collaborative care.

CQ5: Early specialized palliative care

“Recommendations: Early specialized palliative care (ESPC) is recommended for all the adult individuals with cancer with an aim to reduce their symptom burden and to increase their QOL, however, for cancer patients with elevated psychological distress, ESPC alone is not recommended as a sole means to alleviate their psychological distress due to lack of relevant evidence. Other interventions with stronger recommendations should be provided along with ESPC (Strength of recommendation: 2, Evidence level: D).”

Vast evidence supports the benefit of ESPC in improving the QOL of patients with cancer. A recent practice guideline on palliative care states that “Oncology clinicians should refer patients with advanced solid tumors and hematologic malignancies to specialized interdisciplinary palliative care teams that provide outpatient and inpatient care beginning early in the course of the disease, alongside active treatment of their cancer” [72]. In the current CQ, we defined ESPC as “providing comprehensive care (care for physical, psychological, social, and existential distress) through specialized palliative care services from an early stage to patients with incurable (advanced or recurrent) cancer”. We examined the effectiveness of ESPC to alleviate psychological distress in cancer patients with elevated psychological distress.

Our systematic literature search retrieved only one study by Woo et al. [73]. In this study, cancer patients with elevated pain or depression were eligible; however, only minority (27%) of the sample were enrolled in the study because of depression. Therefore, we excluded this study, resulting in no eligible study for the CQ.

We conducted a supplemental literature review to collect RCTs, which did not include the level of psychological distress as patients’ eligibility. Twenty RCTs were found, 16 of which contained depression as an outcome. Only three studies of them showed statistically significant improvement compared to control arms [74–76]. Twelve studies contained anxiety as an outcome, of which only one study showed statistically significant improvement [76]. Three studies contained psychological distress as an outcome, of which no study showed statistically significant improvement in the intervention group. In one study, the control group outperformed the interventional arm with trend-level significance [77].

We concluded that there is no sufficient evidence to support the ESPC to alleviate psychological distress of patients with elevated psychological distress, thus we determined not to recommend ESPC as a sole approach for this purpose. However, we emphasize that this recommendation does not preclude the provision of ESPC for other purposes, such as improving QOL, alleviating symptoms, and supporting decision-making in cancer treatment.

CQ6: Psychosocial interventions for the caregivers

“Recommendations: Psychosocial interventions for caregivers alone (either an intervention involving both patients and caregivers or an intervention involving caregivers only) are not recommended to alleviate psychological distress of adult individuals with cancer with elevated psychological distress. Other interventions with stronger recommendations should be provided along with psychosocial interventions for caregivers. Provision of psychosocial interventions for caregivers is not precluded when they are intended to improve outcomes in caregivers, such as to alleviate their psychological distress, to increase their QOL, and to improve family relationship (Strength of recommendation: 2, Evidence level: D).”

In the current CQ, we examined whether psychosocial interventions for the caregivers of cancer patients are effective in alleviating the level of psychological distress of patients themselves. This question was articulated since interventions for family caregivers have been known to alleviate the level of patients’ psychological symptoms in general psychiatric settings [78].

We found one RCT by Manne et al. [79]. In this three-arm study, Intimacy-enhancing Therapy (an intervention to raise mutual understanding and emotional intimacy between a couple), General-Health-and-Wellness intervention (an intervention to promote healthy lifestyle), and usual care were compared in 237 patients with localized prostate cancer who scored 16 or higher on the Impact of Events Scale (IES) and their partners who scored 17 or higher on the IES. The measured outcomes were general psychological adjustment (Mental Health Inventory-38: MHI-38) and depression (PHQ-9). After the intervention, the total scores of MHI-38 and PHQ-9 improved in all three groups, but there were no descriptions on between-group differences. We found no RCT on interventions for caregivers that involved caregivers only pertaining to this CQ.

We concluded that there is no supporting evidence for psychosocial interventions for the caregivers of cancer patients to alleviate psychological distress of patients themselves, thus we determined not to recommend the intervention as a sole approach for this purpose. However, provision of psychosocial interventions for caregivers is not precluded when they are intended to improve outcomes in caregivers, such as to alleviate their psychological distress, to increase their QOL, and to improve family relationship.

CQ7: Peer support

“Peer support alone is not recommended to alleviate psychological distress of adult individuals with cancer with elevated psychological distress. Other interventions with stronger recommendations should be provided along with peer support. Provision of peer support is not precluded when it is intended to improve other outcomes such as self-efficacy and adaptation to cancer (Strength of recommendation: 2, Evidence level: D).”

Peer support groups are voluntary associations of individuals with the same disease or condition arranged at various local or regional levels of organization. These groups meet to share their experience and concerns, and to support each other in coping with illness. Information and support provided by peers (cancer survivors) based on their own experience could be helpful for patients, especially those who are at an earlier stage of treatment or recovery [80, 81].

In the current systematic review, we defined peer support as an intervention in which (i) cancer survivors (“peers”) are the main actors, (ii) health professionals do not meet patients directly, and (iii) mutual interaction of cancer patients is the main intervention. The method of interaction can be diverse (e.g. face-to-face, telephone, e-mail, or video conference). We identified a single RCT by Lee et al. [82]. In this RCT, newly diagnosed stage I–III breast cancer patients with the total score of HADS of eight or over were randomized to peer support (n = 64) or to usual care (n = 65). A trained “peer-support partner” provided weekly emotional support (face-to-face or by telephone) to patients for 6 weeks. The program was designed to improve self-efficacy, and it did improve self-efficacy compared with the control group. However, no significant between-group difference was observed in depression or anxiety [83, 84].

We conducted a supplemental literature review to collect RCTs that did not include the level of psychological distress as patients’ eligibility. We found twelve RCTs. Among these RCTs, two trials conducted subgroup analyses for samples with elevated psychological distress, but the results of these subgroup analyses were inconsistent [85, 86]. In the remaining 10 studies, 10 studies evaluated depression, of which only two studies showed significant improvement [85, 86]. In one study, the control group showed greater improvement than the intervention group [87]. The remaining seven studies yielded no between-group difference. Three studies evaluated anxiety [88–90], of which only one study demonstrated significant reduction in anxiety [88]. Three studies evaluated general psychological distress [84, 87, 91], of which one study demonstrated significant between-group difference, where the intervention group experienced worsening of symptoms [91].

In summary, we found no solid evidence to support the benefits of peer support interventions for alleviating psychological distress in cancer patients, especially for those with elevated psychological distress. However, it is noted that the aims of peer support are not limited to improving psychological distress. It can be provided to improve participants’ self-efficacy, health-related behaviors (e.g. physical activity, dietary habits, medication, and treatment adherence), social support, coping, and QOL [92, 93]. Our recommendation would not preclude provision of peer support for such purposes.

CQ8: Psychotherapy for fear of cancer recurrence

“Recommendation: Psychotherapy for the fear of cancer recurrence is weakly recommend for adult individuals with cancer with the fear of cancer recurrence (Strength of recommendation: 2, Evidence level: A).”

FoCR is excessive worry on the progression or recurrence of one’s cancer, to an extent that it impedes one’s daily functioning. Many rating scales to measure the level of FoCR have been developed, however, there has been no established threshold to define clinically significant FoCR. Therefore, we did not include a threshold as an eligibility for our systematic review.

A preliminary search identified a systematic review conducted by Tauber et al. [94]. We adopted the same search strategy as Tauber’s and collected the RCTs that were reported after their work (published between July 2018 and December 2020). We integrated newly obtained literature with the literature in Tauber’s review to conduct a new systematic review.

A total of 35 studies, including 14 studies which is additional to Taubers’ review [40, 41, 44, 95–104], were identified. A meta-analysis of controlled studies demonstrated that the effect size for psychotherapies for FoCR was moderate (SMD –0.53 [95% CI –0.78, –0.28]). However, heterogeneity was as high as 88%, which corresponded to the moderate risk. Most studies involved patients with breast cancer. Most-commonly used interventions were Cognitive Behavioral Therapy [47, 95–97, 99, 105–109], mindfulness-based interventions [40, 41, 100, 101, 110–116], and Acceptance and Commitment Therapy [44, 102, 117, 118]. A notable intervention that specifically targeted FoCR was the Conquer Fear, a five-session program based on metacognition models such as the Common-Sense Model and the Self-Regulatory Executive Function Model [117, 118]. Its effectiveness persisted for more than 6 months post-intervention.

Two studies had been conducted in Japan. Park et al. conducted an RCT, which compared an 8-week Mindfulness-based Cognitive Therapy intervention and the wait-list control in 74 patients with breast cancer. Statistically significant reduction in FoCR was observed in the intervention group, and its effectiveness persisted for 4 weeks after the intervention [40]. Akechi et al. compared problem solving therapy which comprised four face-to-face and telephone sessions tailored to the needs of breast cancer patients (N = 31) with the wait-list control (N = 28). The study did not yield significant between-group difference [95].

Considering the high heterogeneity of the studies, and the lack of therapists who were expertise in each psychotherapy, we concluded that psychotherapy should be weakly recommended for FoCR. This high heterogeneity might be due to variations in underlying models, techniques, and intervention durations, necessitating further investigation into the differential effects of various intervention methods.

CQ9: Non-psychological interventions for fear of cancer recurrence

We searched interventions other than psychological therapy that targeted FoCR. We used the same search terms as other CQs (such as “pharmacotherapy”, “collaborative care”, “early palliative care”, and “peer support”) substituting the outcomes with FoCR. We articulated this issue as a background question, since the type of interventions were supposed to be diverse.

The following three studies were found. Crane-Okada et al. conducted an RCT on mindfulness-based movement [119]. This study involved older breast cancer patients who engaged in a mindfulness-based movement program with weekly 2-hour sessions over 12 weeks. The program significantly reduced FoCR compared to the control group, with its effects lasting up to 18 weeks post-intervention. Damude et al. conducted an RCT to reduce the frequency of medical follow-up [120]. This study was a non-inferiority trial in melanoma patients where traditional quarterly follow-ups were compared with fewer follow-up visits (1–3 times per year). No significant between-group difference was found, indicating that reduced follow-up does not worsen FoCR. Another study by Sheppard et al. tested reduction of frequency of medical follow-ups [121]. This RCT involved breast cancer patients, comparing no regular follow-up visits with monthly visits. No significant difference in FoCR was observed, suggesting that reduced follow-up frequency does not exacerbate FoCR.

Discussion

In the current article, we presented an overview of a newly-developed practice guidelines for psychological distress of individuals with cancer. Every individual should first be provided with “general” supportive care by primary health professionals, which includes supportive communication, attention to their needs, differentiation of medical conditions that mimic psychological symptoms, and monitoring for serious psychological distress that requires further specialized care. For those with elevated psychological distress despite such care, evidence-based interventions that are more specific to psychological distress should be provided. Collaborative care was the only intervention that was granted with strong recommendation due to its solid supporting evidence. Evidence for psychotherapies for psychological distress and for FoCR was also solid; however, due to the high heterogeneity of referenced studies and lack of qualified therapists, recommendations for psychotherapy were weakened. Evidence for pharmacotherapy (anxiolytics and antidepressants) was weak for psychological distress of patients with cancer, despite its established evidence outside cancer settings. Thus, its indication should be considered elaborately referring to patient conditions. We barely found supporting evidence for ESPC, psychological interventions targeting caregivers, and peer support in alleviating psychological distress of cancer patients with elevated psychological distress. Therefore, these interventions should not be provided as a sole means to alleviate psychological distress, despite that we do not preclude these interventions to be provided as to improve other relevant outcomes.

Our next steps include implementing the recommended flow of patient care and recommended interventions. Implementing care delivery based on collaborative care models and establishing a training system for evidence-based psychotherapies for individuals with cancer are urgently needed.

Some of the areas that the current guideline is yet to cover include the following. First, we didn’t collect evidence for the interventions targeting individuals whose psychological distress level is below thresholds. Second, choice of appropriate interventions that suit each of the individuals depending on his/her physical condition, cancer treatment status and characteristics of psychological distress is needed. These issues are potential candidates for future CQs.

We believe that our newly developed guidelines will contribute to the dissemination of evidence-based care and management of psychological distress of adult individuals with cancer in Japan.

Author contributions

Conceptualization: all authors. Drafting recommendations: all authors. Systematic review (ES, SA, MK, AK, AK, KI, YI, HO, YY, TB, YO, AA, YU, YM, KA, MO, KH, KM, ET). Drafting manuscript (DF, ES, SA, MK, AK, AK, KI, YI, HO, YY, TB, YO, AA, YU, YM, KA, MO, KH, KM, ET). All authors reviewed and approved the manuscript.

Conflict of interest statement

None.

Funding

The guideline development was partly supported by the Grant-in-aid by the Ministry of Health Labor and Welfare Japan (Grant number: 202208011C).

Data availability

Not applicable.