Background

In 2018, there was an estimated 18.1 million new cases of cancer worldwide and 9.6 million cancer deaths.1 The frequencies of cancers vary across regions, populations and sexes.1 Fortunately, more than half of people diagnosed with cancer now survive the disease or live with the disease for many years after diagnosis. Many people diagnosed with cancer experience distress because of the physical and physiological consequences of the disease and its treatments, and develop psychological, spiritual, employment and financial forms of distress.2 Distress in cancer can oftentimes go on to become severe and sustained, leading to the development of psychiatric conditions such as depression. Depression is more prevalent in people affected by cancer compared with the general population.3 4 Depression is associated with lower quality of life and may increase mortality in people with cancer5 and patients with depression are less likely to accept and commence systemic cancer therapies.4 One trial of depression treatment in people with cancer showed improved quality of life, but no effect on overall survival.6 Treating depression in people with cancer has been shown to reduce annual healthcare costs by 30% per patient.7 However, almost three-quarters of patients with depression with cancer do not receive appropriate treatment and only 5% have contact with a mental health professional.8

The general prevalence of comorbid depression in cancer is between 10.8%9 and 15%,4 but substantial variation exists depending on diagnostic methods10 (eg, interview, self-report measures), clinical settings (eg, inpatient, outpatient, palliative) and types of cancer.11 To highlight some examples, a meta-analysis found higher rates of depression when using self-report measures in brain cancer (pooled mean 33%), breast cancer (20%) and respiratory tract cancers (21%) compared with diagnostic interviews (brain cancer 28%; breast cancer 11%; respiratory tract cancer 3%).10 The prevalence of any depressive disorder (eg, major, minor and dysthymia) is higher among palliative settings (24.6%) than oncological and haematological settings (20.7%).4

Once a diagnosis of depression is confirmed, the clinician should be able to access evidence-based treatments for depression in that particular cancer.6 12 Growth of psycho-oncology depression research has been rapid, but the generalisability and application of findings and treatments may be limited because of several factors. First, cancer is a single term for a heterogenous collection of diseases involving different organ systems, treatments, side effects and psychological impacts. Second, research across the entire cancer continuum is dominated by particular cancers (eg, breast cancer) and this may limit generalisability.13 14

Data extraction

Studies were identified and exported to data management software (www.covidence.org) from individual electronic databases. After results were collated and duplicates removed, two investigators (BB and SL) independently screened titles and abstracts (figure 1). Disagreements were settled by a third investigator (MM). All eligible papers were retrieved for full-text screening and independently reviewed (BB and SL). Of those that met inclusion criteria, study sample size and participant characteristics, including sex and cancer types, were extracted to a Microsoft Excel spreadsheet for analysis.

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Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses processes for study selection.

Findings

Figure 1 outlines the main results. Four thousand six hundred and twenty-one potential papers were screened, and 173 studies were eligible for inclusion based on title and abstract. After full-text review, 84 studies were included in the final analysis (see online supplementary appendix A). Table 2 shows the main findings of the 84 selected studies. Overall, 6048 depressed participants were included in this review. Controlled trials were the most common study design (45%), and the majority of studies examined psychological treatments for depression (51%).

Supplemental material

[ebmental-2020-300145supp001.pdf]

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Table 2

Characteristics of studies evaluating depression treatments in a cancer population (N=84)

Cancer and tumour types were denoted inconsistently across studies, frequently clustered following unclear methodologies and bespoke cancer terms (eg, ‘aerodigestive’), or not fully detailed and grouped as ‘other’ cancers. Across the 6048 participants, we extracted 54 different labels for types of cancer, some of which overlapped (eg, ‘digestive’ and ‘upper GIT’). These were initially merged into 17 subgroups and later organised according to ICD-11 to make appropriate comparisons. Almost half of all people (49.3%) participating in depression research were identified as having breast cancer (table 1).

According to global estimates, 17 806 354 new cases of cancer were diagnosed in adults aged 20 years and older in 2018. The available individual incidence data for the 36 cancers listed in the GLOBOCAN database accounts for 16 932 314 or 95% of all new cancers in 2018. Table 1 outlines the respective rates of cancer incidence. Figure 2 shows a graphical representation to enable easier appreciation of the relative frequencies. For example, breast cancer research represents a higher relative percentage of total research (49.3% of participants) than its corresponding cancer incidence percentage rate (11.7%) and its corresponding depression in cancer percentage rate (11.8%). Bone and soft-tissue cancers and head and neck cancers were also over-represented in depression research, but only marginally. All other cancers were under-represented when compared with their corresponding cancer incidence percentage rate and comorbid depression percentage rate (figure 2).

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Figure 2

The relative frequency of cancer types represented in depression research (shaded bars) compared with the relative global frequency of these cancers (striped bars) and the relative global frequency of people with these cancers and comorbid depression (white bars). Cancers are ordered from highest to lowest relative frequency in research according to the present systematic review.

Expressing each cancer’s inclusion in depression research as a function of the incidence of cancer-specific depression shows that for every 100 000 people with breast cancer and depression, 714 appear in a study (table 1). This is followed by bone and soft-tissue cancers at 235 participants for every 100 000 cases, and head and neck cancers at 195 participants per 100 000 cases. There was over a 40-fold difference in inclusion rates across cancers. For example, brain cancer had the lowest measured relative representation in depression studies at just 16 participants per 100 000 cases (compared with 714 participants per 100 000 cases of breast cancer with depression).

Conclusions and clinical implications

This paper presents a systematic review of treatment for depression in people with cancer, specifically examining whether certain cancer types dominate this research. It then used data to see whether the pattern within research is reflective of the actual cancer incidence and the relative rate of patients with comorbid depression. We identified 84 relevant studies representing over 6000 participants and looked across many cancer types, revealing several discrepancies. The disparity between cancers is large.

So why are cancers not included in depression research at a level commensurate with the relative frequency of each cancer nor their individual contributions to the population of depressed people with cancer? A systematic review of psychosocial oncology and quality of life research (including depression) found that study participation was not affected by cancer type, patient age and patient sex.18 The same review found that participation was higher in longitudinal studies compared with controlled trials,18 but our review includes an array of study designs and small differences in participation are unlikely to explain the pattern measured here. Factors such as stage at diagnosis or treatment morbidity may be responsible for disparities, but respiratory cancers tend to be late stage with high mortality and are represented in research at a rate nearly commensurate to their overall incidence.

Breast cancer currently dominates this field of psycho-oncology research (both pharmacological and psychological treatments of comorbid depression in cancer). Such is the dominance of breast cancer in this area, no other cancer reaches representativeness and inclusion commensurate with incidence (except perhaps bone and soft-tissue cancer). Factors such as research funding models, advocacy models, public engagement, philanthropic giving and clinician and patient bias, plus the ‘success’ of the breast cancer movement are a likely driver of bias in research on cancer and comorbid depression towards breast cancer. Identifying causal factors for biased research effort detected here is beyond the primary research question of this study and requires a more complex approach.

Generally, in cancer survivorship research, projects on breast cancer dominate the field and in 2011 in the USA there were seven times more projects on breast cancer being conducted than the next best studied cancer, prostate.14 The dominance of breast cancer models and narratives in survivorship research has been referred to as the ‘breast cancerisation’ of the understanding of life with and beyond cancer.13 For those with breast cancer, this bias means that guidelines for the management of depression in cancer are likely based on patients with their cancer and represents an appropriate evidence base for this patient group.

Only two cancers approach relevant parity: head and neck cancer and female genital cancer. Cancers least represented by depression research include digestive cancers, male genital cancers and skin cancer. The most substantial under-representation occurred in digestive cancers, which form 37.7% of people with cancer comorbid with depression but only 11.2% of people in depression studies. The disproportionate attention afforded certain cancers whereby particular cancers receive smaller funding shares and less consideration is well documented.19–21 Only when under-represented patient groups are routinely included and studied in depression research will the evidence base reflect the full distribution of patients in need of treatment.

Last, many cancers were inconsistently reported in psycho-oncology literature. There was limited use of consensus classification systems of neoplasms. As this can lead to difficulties in undertaking systematic reviews in this area, future research should report findings using a recognised system (for example ICD-11). In addition to the correct classification, future research should comment on whether patient and/or cancer factors affected enrolment in studies on treating depression.

This review quantifies the current evidence base for depression treatments in specific cancer populations. Breast cancer accounts for half of all participants with depression. In addition to the impact on psychiatric treatments, the dominance of a particular cancer has the potential to negatively impact the psychological experiences of people with other cancers if their experience does not align.13 Further research is required to investigate the efficacy of depression treatments in other specific cancer populations, particularly digestive (eg, stomach, pancreatic, liver and colorectal) and respiratory cancers (eg, lung), which represent the highest global burden of comorbid disease. This would allow targeted, evidence-based treatments for depression in specific cancer populations.

This study has several limitations. First, our search strategy was limited to MeSH terms which may not have selected relevant papers published in the month prior to the search. However, a search of the grey literature was conducted. Second, because cancer types are inconsistently reported in depression research, assumptions were made when classifying cancer types of participants. For example, when several cancer types were associated with a single number of participants, we divided the participants equally among clustered cancers, such as ‘aerodigestive’ or ‘genitourinary’, which are terms not recognised in the ICD. Finally, level 1 evidence for the prevalence of depression within cancer types was not available for all cancers extracted during our systematic review. For this reason, we limited the comparison between participation in depression research with the incidence of depression to cancer types for which level 1 evidence was available. This is a limitation that will have primarily affected under-represented cancer types. Our estimate of the incidence of depression within each cancer was conducted using the fewest assumptions possible. Ideally, this analysis would have been itemised for each cancer type and used specific prevalence and incidence data. Many reviews of depression in cancer have noted an inability to analyse depression by cancer type because of too few studies and study heterogeneity. This is something that will improve in the future as the number of studies continues to expand.