Nº de DOI: 10.34896/RSI.2026.79.98.002
AUTHORS
- José Vicente Cargua Pintag. General Practitioner with a Master’s Degree in Healthcare Quality Management and Auditing. Affiliated with the Ecuadorian Armed Forces. Graduate of Universidad Nacional de Chimborazo. Based in Riobamba, Ecuador. https://orcid.org/0009-0003-2616-3473
- Eliana Jazmin Tobar Pozo. General Practitioner. Affiliated with Private Clinics in Ecuador. Graduate of Pontificia Universidad Católica del Ecuador. Based in Ibarra, Ecuador. https://orcid.org/0009-0001-3553-9300
- Miriam Elizabeth Litardo Chamba. General Practitioner. Affiliated with Integraldial Hemodialysis Center. Graduate of Universidad de Guayaquil. Based in Guayaquil, Ecuador. https://orcid.org/0009-0007-2012-9572
- Miguel Angel Tito Borja. General Surgeon with a Master’s Degree in Healthcare Management and Administration and a Specialty in General Surgery. Affiliated with Private Clinics in Ecuador. Graduate of Universidad de Las Américas. Based in Quito, Ecuador. https://orcid.org/0009-0006-8003-4199
- Mishell Dayanara Vargas Saltos. General Practitioner. Affiliated with Hospital General San Francisco IESS. Graduate of Universidad Central del Ecuador. Based in Quito, Ecuador. https://orcid.org/0009-0000-0985-7498
ABSTRACT
Across studies, roughly one third of patients in hospital-based oncology settings met criteria for some form of mood, anxiety or adjustment disorder. Major depression in routine clinic screening ranged from 5.6% to 13.1% according to tumour site, whereas symptom-based estimates were considerably higher, at approximately 28% for depression and 35% for anxiety in a large outpatient cohort. Tumour site (with lung, brain, pancreatic and head and neck cancers frequently showing a high burden), younger age, female sex, social deprivation and somatic symptom burden were repeatedly associated with distress, although the direction of some associations, particularly age, differed between studies. Anxiety and depression showed independent and additive associations with poorer mental-health QoL and greater somatic symptom burden. In pooled analyses, depression and anxiety were associated with higher cancer-specific and all-cause mortality, with relative risks of approximately 1.2 to 1.3. Most patients with major depression received no potentially effective treatment, yet integrated collaborative care and psychological interventions improved outcomes.
Routine screening with validated instruments, followed by stepped, evidence-based care, should be embedded in oncology pathways. The main limitations of the evidence are heterogeneity of measurement, the predominance of cross-sectional designs, and the small number of studies that examine anxiety as a distinct outcome.
KEY WORDS
Anxiety, depression, neoplasms, quality of life, psycho-oncology, risk factors, systematic review.
RESUMEN
En diversos estudios, aproximadamente un tercio de los pacientes atendidos en servicios de oncología hospitalaria cumplían los criterios para algún tipo de trastorno del estado de ánimo, de ansiedad o de adaptación. La prevalencia de depresión mayor detectada mediante cribado clínico rutinario osciló entre el 5,6 % y el 13,1 % según la localización del tumor; por el contrario, las estimaciones basadas en síntomas fueron considerablemente más elevadas, situándose en torno al 28 % para la depresión y al 35 % para la ansiedad en una amplia cohorte de pacientes ambulatorios. La localización del tumor (observándose una elevada carga sintomática frecuentemente en cánceres de pulmón, cerebro, páncreas y cabeza y cuello), la edad más joven, el sexo femenino, la privación social y la carga de síntomas somáticos se asociaron reiteradamente con el malestar emocional, si bien la dirección de algunas asociaciones —en particular la relativa a la edad— varió entre los estudios. La ansiedad y la depresión mostraron asociaciones independientes y aditivas con una peor calidad de vida relacionada con la salud mental y una mayor carga de síntomas somáticos. En los análisis combinados, la depresión y la ansiedad se asociaron a una mayor mortalidad específica por cáncer y por todas las causas, con riesgos relativos de aproximadamente 1,2 a 1,3. La mayoría de los pacientes con depresión mayor no recibió ningún tratamiento potencialmente eficaz; no obstante, los modelos de atención colaborativa integrada y las intervenciones psicológicas mejoraron los resultados.
El cribado sistemático mediante instrumentos validados, seguido de una atención escalonada basada en la evidencia, debería integrarse en las vías asistenciales oncológicas. Las principales limitaciones de la evidencia disponible son la heterogeneidad en las mediciones, el predominio de diseños transversales y el escaso número de estudios que analizan la ansiedad como un desenlace diferenciado.
PALABRAS CLAVE
Ansiedad, depresión, neoplasias, calidad de vida, psicooncología, factores de riesgo, revisión sistemática.
INTRODUCTION
Anxiety and depression are among the most frequent psychological complications of cancer, yet they remain under-recognised and under-treated. This review aimed to synthesise current evidence on the prevalence of anxiety and depression in adults with cancer, the clinical, demographic and psychosocial factors associated with them, and their impact on quality of life (QoL) and clinical outcomes. A structured review guided by the PRISMA 2020 statement was carried out. The evidence base comprised 20 peer-reviewed journal articles with verified digital object identifiers, including large interview-based and questionnaire-based epidemiological studies, meta-analyses of cohort studies, a randomised effectiveness trial, narrative and mechanistic reviews, and a clinical practice guideline. Findings were synthesised narratively because of marked heterogeneity in instruments, cut-offs, settings and cancer types.
OBJECTIVE
The general objective of this review was to synthesise the evidence on anxiety and depression in adult patients with cancer, with particular attention to associated factors and to the impact on quality of life. The specific objectives were:
- To describe the prevalence of anxiety and depression in patients with cancer, and how it varies by instrument, setting and tumour site.
- To identify the demographic, clinical, social and psychological factors associated with anxiety and depression.
- To examine the association of anxiety and depression with quality of life, symptom burden and clinical outcomes, including mortality.
- To summarise what is known about the recognition and treatment of anxiety and depression, and to identify gaps in the evidence.
METHODOLOGY
Design and reporting framework:
This article is a structured systematic review reported in accordance with the PRISMA 2020 statement, which provides a 27-item checklist and flow-diagram conventions for reporting systematic reviews11. Because the primary studies differed substantially in design, instruments, populations and outcome definitions, a narrative synthesis was planned in preference to a pooled quantitative analysis. Where a source was itself a meta-analysis, its pooled estimates are reported as published and are not re-analysed.
Review questions and eligibility criteria:
The review questions were framed using a population, exposure, comparator and outcome structure. The population was adults (aged 18 years or older) with a diagnosis of any solid or haematological cancer, at any stage and in any treatment setting, including survivors. The exposures were anxiety and depression, defined either as symptoms measured with validated self-report scales or as diagnoses established by structured clinical interview. The comparators, where available, were patients without anxiety or depression or the general population. The outcomes were (a) prevalence; (b) associated sociodemographic, clinical and psychosocial factors; (c) quality of life and symptom burden; (d) cancer-related outcomes, including recurrence and mortality; and (e) recognition, treatment and response to interventions.
Sources were eligible if they were full-length articles published in peer-reviewed scientific journals, were written in English, reported primary data or a systematic or structured synthesis of primary data (or were an evidence-based clinical practice guideline published in a journal), and had a digital object identifier (DOI) that could be verified. Conference abstracts, theses, books, news items, websites, preprints and non-journal reports were excluded. Studies confined to children, and studies in which anxiety or depression was not measured separately from other forms of distress, were not treated as principal evidence for the review questions.
Information sources and identification of evidence:
Evidence was identified through targeted searching of the published biomedical and psychological literature using combinations of terms for cancer (neoplasms, cancer, oncology), for anxiety and depression (anxiety, depression, depressive symptoms, mood disorders, psychological distress), and for the outcomes of interest (prevalence, risk factors, associated factors, quality of life, mortality, treatment, guideline). Priority was given to the types of evidence that offer the most reliable basis for answering the review questions: large multicentre epidemiological studies using representative sampling; meta-analyses and systematic reviews; randomised trials of treatment; mechanistic reviews; and clinical practice guidelines. The reference lists of retrieved articles were examined to identify additional relevant sources.
Selection and verification of sources:
The titles and abstracts of retrieved records were screened against the eligibility criteria, and the full text or the complete bibliographic record of potentially eligible articles was examined. For every source retained, the authors, title, journal, year, volume, pages and DOI were checked against at least one independent bibliographic record, such as the publisher page, an institutional repository or a literature database. Sources whose DOI or bibliographic details could not be confirmed were not retained. Twenty journal articles were retained, of which 17 provided data or conclusions for the review questions and three provided methodological frameworks or measurement instruments: the PRISMA 2020 statement, the Hospital Anxiety and Depression Scale and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 3011,12,13.
Data extraction and outcome definitions:
From each source the following information was extracted: first author and year; design; setting; sample size and population; instruments used to measure anxiety, depression and quality of life; principal quantitative findings, including prevalence estimates, odds ratios and relative risks with 95% confidence intervals where reported; and any reported associated factors.
The sources used three broad approaches to define anxiety and depression. The first was structured diagnostic interview, which yields diagnoses according to formal classification systems; the large meta-analysis of interview-based studies relied on this approach, as did the German four-week prevalence study, which administered a standardised diagnostic interview to patients who screened positive on the Patient Health Questionnaire-91,5. The second was symptom screening by self-report. The Hospital Anxiety and Depression Scale (HADS) is a 14-item instrument, with seven anxiety items and seven depression items scored from 0 to 3, designed to detect clinically significant anxiety and depression in medical patients while avoiding reliance on somatic symptoms12. The Patient Health Questionnaire-9 (PHQ-9), with a threshold of 10 or more, and the Generalised Anxiety Disorder 7-item scale (GAD-7) were also used in several studies4,16. The third approach drew on routinely collected clinic screening data6. Quality of life was assessed mainly with the EORTC QLQ-C30, which comprises five functional scales, three symptom scales and a global health status scale and was validated in an international study of patients with lung cancer, or with other health-related quality-of-life measures13.
Appraisal and synthesis:
The methodological quality of each source was appraised qualitatively, taking into account the representativeness of the sample, the response rate, the validity of the instruments, the handling of confounders, the length of follow-up for prognostic questions, and, for meta-analyses, the search strategy and the heterogeneity of included studies. No numerical quality score was assigned, and no source was excluded on the basis of the appraisal alone; the appraisal informed the weight given to each source and the certainty with which conclusions are stated.
Results were grouped according to the review questions and summarised narratively. Prevalence estimates were compared descriptively, with attention to the instrument and threshold used. Associations with demographic and clinical factors were summarised by direction and consistency across sources. Findings on quality of life and mortality were summarised separately because they rest on different study designs. Because the sources were heterogeneous, formal assessment of publication bias and pooled meta-analysis were not undertaken. The review was not prospectively registered, screening and extraction were not performed in duplicate, and the search was targeted rather than exhaustive; these limitations are considered in the Discussion.
RESULTS
Characteristics of the evidence base:
The 17 sources that contributed data or conclusions to the review questions are summarised in Table 1. They comprise large meta-analyses of prevalence and prognosis in mixed cancer populations1,8,9,17, one meta-analysis of prognosis in breast cancer, five large cross-sectional or epidemiological studies4,5,6,14,15,18, a smaller cross-sectional study including three measures of distress, a cross-sectional analysis of quality of life16,7, a randomised effectiveness trial, a mechanistic review, an evidence review of systematic reviews, a clinical reviewand a clinical practice guideline2,3,10,19,20. Sample sizes ranged from several hundred to more than two and a half million participants in the pooled cohort analysis.
Prevalence of anxiety and depression:
The prevalence of anxiety and depression depended strongly on how it was measured. In the meta-analysis of interview-based studies, some combination of mood disorders was present in 29.0% of patients in palliative-care settings and 38.2% of patients in oncological and haematological settings, and the difference between settings was not significant for depression and anxiety1. In palliative-care settings, adjustment disorder alone was present in 15.4% of patients and anxiety disorders in 9.8%; in oncological and haematological settings, adjustment disorder was present in 19.4%, anxiety in 10.3% and dysthymia in 2.7%1. The authors concluded that depression is not inevitable, with only about one in six patients having depression alone in the first five years after diagnosis, but that the combined burden of mood disorders is substantial.
A similar picture emerged from the German multicentre study that used a standardised diagnostic interview. The four-week prevalence of any mental disorder was 31.8% (95% CI 29.8 to 33.8), comprising anxiety disorders in 11.5%, adjustment disorders in 11.1% and mood disorders in 6.5% of patients5. By contrast, when depressive symptoms were measured with the PHQ-9 using a threshold of 10 or more, 24% of patients (about one in four) were classified as depressed, and the odds of being depressed were 5.4 times higher (95% CI 4.6 to 6.2) than in the general population sample4. In a Scottish programme of routine screening in cancer clinics, major depression was identified in 7.5% of 21,151 patients overall6.
Symptom-based estimates from self-report scales were higher still. In an Austrian outpatient cohort of 7,509 patients assessed with the HADS, 35.2% showed symptoms of anxiety and 27.9% showed symptoms of depression, and about one in six patients had a very likely psychiatric condition15. Among 10,153 consecutive patients assessed shortly after diagnosis in a Canadian cancer centre, approximately 19% met diagnostic criteria for an anxiety disorder and nearly 13% for clinical depression, with a further 22.6% and 16.5% showing sub-threshold symptoms of anxiety and depression, respectively14. A cross-sectional study in Jordan that used the HADS, PHQ-9 and GAD-7 in inpatients and outpatients likewise concluded that depression and anxiety are a substantial problem and that enhanced clinical monitoring and treatment are required16.
Taken together, these studies indicate that the prevalence of clinically diagnosable depression is typically in the range of about 5% to 15%, that anxiety disorders are of similar magnitude, that adjustment disorders are at least as frequent as either, and that between one quarter and one third of patients report clinically relevant symptoms of anxiety or depression on screening instruments. The evidence review by Niedzwiedz and colleagues similarly noted that estimates vary with the treatment setting, the type of cancer and the time since diagnosis, and that depression and anxiety are often more prevalent than in the general population3.
Variation by cancer type:
Tumour site was among the most consistently reported correlates of distress, although the ranking differed according to the outcome measured. In the Scottish routine-screening data, the prevalence of major depression was highest in lung cancer (13.1%, 95% CI 11.9 to 14.2), followed by gynaecological cancer (10.9%), breast cancer (9.3%), colorectal cancer (7.0%) and genitourinary cancer (5.6%)6. In the German PHQ-9 data, patients with pancreatic, thyroid and brain tumours had the highest mean depressive symptom scores, whereas patients with prostate cancer and malignant melanoma had the lowest4. In the Austrian outpatient cohort, the prevalence of both anxiety and depression was significantly higher in patients with lung and brain cancer than in other patients, and breast cancer patients showed the lowest depression rates15.
The four-week prevalence of any diagnosed mental disorder in the German interview study followed a different pattern: it was highest in breast cancer (41.6%) and head and neck cancer (40.8%) and lowest in pancreatic cancer (20.3%) and stomach or oesophageal cancer (21.2%)5. This apparent paradox, in which patients with more treatable tumours had more diagnosable disorders than those with a poor prognosis, probably reflects the inclusion of anxiety and adjustment disorders, and differences between symptom scales and diagnoses. It underscores that the burden is not confined to patients with a grave prognosis, and that cancers with high survival, such as breast cancer, are associated with substantial psychological morbidity.
Factors associated with anxiety and depression:
The evidence indicates that anxiety and depression arise from the interaction of individual, psychological, social and contextual factors together with characteristics of the cancer and its treatment3. The factors most consistently reported are summarised below.
Age: The relationship with age was not uniform. Among consecutive patients assessed shortly after diagnosis, those younger than 50 years generally showed higher rates of both anxiety and depression than older patients, although the difference was small in poor-prognosis cancers14. In the Scottish data, major depression was more likely in younger patients within each cancer group6. By contrast, in the Austrian HADS cohort elderly patients more often showed signs of depression15. These discordant findings probably reflect differences in instruments, in the cancer types included and in the stage of illness at assessment, and they indicate that neither young nor old patients can be assumed to be at low risk.
Sex: Women were more frequently affected by symptoms of anxiety and depression in the Austrian cohort, and in the Scottish data a diagnosis of major depression was more likely in women with lung cancer and colorectal cancer6,15. In the Canadian study, the size of the sex difference varied by tumour type and was especially pronounced in some cancers14. Because several cancers occur only or predominantly in one sex, sex and tumour site are partly confounded, and analyses that adjust for both are preferable15.
Cancer type and stage:
Lung, brain, pancreatic, head and neck and gynaecological cancers were repeatedly associated with a high burden of distress, whereas prostate cancer and melanoma were associated with a lower burden of depressive symptoms4,5,6,15. Disease stage appears to matter less than might be expected: in the meta-analysis of interview-based studies the difference between palliative and non-palliative settings was not significant for depression and anxiety, suggesting that the importance of stage and setting may have been overemphasised1.
Social deprivation and context:
In Scottish cancer clinics, major depression was more likely among patients with worse social deprivation scores, in addition to those who were younger6. This finding is consistent with the broader conclusion that social and contextual factors contribute to the development of depression and anxiety in people with cancer3.
Somatic symptom burden and pain:
In patients selected for pain and/or depression, anxiety and depression were each associated with greater disability and somatic symptom severity7. Mechanistic work further links depression in cancer with fatigue, cognitive dysfunction and sleep disturbance, symptoms that are also treatment targets19. Measurement is complicated because somatic symptoms such as fatigue and poor sleep may result from cancer or its treatment as well as from mood disorder, which is one reason why the HADS was designed to rely on non-somatic items12.
Psychological and treatment-related factors:
The evidence review by Niedzwiedz and colleagues identified psychological factors, characteristics of the cancer and aspects of the treatment received as contributors to anxiety and depression, and drew attention to the long-term and late effects of treatment as an area requiring urgent research3. The clinical review by Pitman and colleagues similarly emphasised the importance of careful clinical assessment of anxiety and depression in patients with cancer2.
Impact on quality of life:
The clearest quantitative evidence on quality of life comes from a cross-sectional analysis of 397 patients with cancer who screened positive for pain and/or depression, of whom 135 had comorbid anxiety and depression, 174 had depression without anxiety and 88 had neither7. When modelled separately, anxiety and depression were each associated with all domains of health-related quality of life examined. When modelled together, anxiety and depression had independent and additive effects on the mental-health domains of quality of life and on somatic symptom burden, while depression had a more pervasive association with the other domains7. In other words, anxiety adds to the burden of depression rather than merely accompanying it, and patients with both conditions are the most impaired.
This finding is important for the way quality of life is measured. The EORTC QLQ-C30, the most widely used cancer-specific instrument, includes functional scales for physical, role, cognitive, emotional and social functioning, symptom scales for fatigue, pain, and nausea and vomiting, and a global health status scale13. Emotional functioning is therefore an explicit component of cancer quality of life, and changes in anxiety and depression should be expected to alter scores on this and related scales. The evidence review of Niedzwiedz and colleagues likewise notes that depression and anxiety may hinder cancer treatment and recovery as well as quality of life and survival3.
Impact on clinical outcomes:
Several meta-analyses examined whether anxiety and depression predict cancer outcomes. The earliest, which pooled 26 studies including 9,417 patients, found that depression predicted mortality but that there was no clear association with disease progression, although only three studies were available for the progression analysis8. Depressive symptoms were associated with an increase in mortality of up to 25%, and a diagnosis of major or minor depression with a 39% higher risk, although the authors cautioned that the absolute increase in risk was small8. A separate meta-analysis also reported an association between depression and higher cancer mortality, in patients with cancer and in community cohorts followed for cancer deaths17.
The largest synthesis to date included 51 cohort studies with 2,611,907 participants and a mean follow-up of 10.3 years9. Depression and anxiety were associated with a significantly increased risk of cancer incidence (adjusted relative risk 1.13, 95% CI 1.06 to 1.19), cancer-specific mortality (1.21, 1.16 to 1.26) and all-cause mortality in patients with cancer (1.24, 1.13 to 1.35). Subgroup analyses showed that clinically diagnosed depression and anxiety were related to higher incidence, poorer survival and higher cancer-specific mortality, whereas psychological distress measured by symptom scales was related to higher cancer-specific mortality and poorer survival but not to increased incidence9.
In breast cancer, a meta-analysis of 17 studies with 282,203 patients found that depression was associated with recurrence (relative risk 1.24, 95% CI 1.07 to 1.43), all-cause mortality (1.30, 1.23 to 1.36) and cancer-specific mortality (1.29, 1.11 to 1.49). The comorbidity of depression and anxiety was associated with all-cause mortality (1.34, 1.24 to 1.45) and cancer-specific mortality (1.45, 1.11 to 1.90), while anxiety alone was not related to cancer-specific mortality18. This pattern suggests that the combination of anxiety and depression carries greater prognostic weight than either condition alone.
A mechanistic review proposed that shared biobehavioural pathways may link depression to cancer progression. Psychosocial stressors in cancer were described as promoting inflammation and oxidative and nitrosative stress, decreasing immunosurveillance, and producing dysfunctional activation of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis. Depression was also linked to non-adherence to treatment19. These mechanisms remain hypotheses supported mainly by indirect evidence and should not be interpreted as proof of causation.
Recognition, treatment and response to interventions:
The Scottish analysis demonstrated a large treatment gap: of 1,538 patients with depression and complete patient-reported treatment data, 1,130 (73%) were not receiving potentially effective treatment6. Recognition and delivery of care are therefore the first problems. The SMaRT Oncology-2 randomised effectiveness trial assigned 253 patients with cancer and major depression to an integrated collaborative care programme and 247 to usual care provided by primary care physicians. The integrated programme was more effective than usual care in alleviating depressive symptoms and improving quality of life20.
The updated guideline of the American Society of Clinical Oncology is based on a systematic review of evidence published between 2013 and 2021. It concluded that psychological, educational and psychosocial interventions improved depression and anxiety, whereas evidence for pharmacological management was inconsistent10. It recommends that all patients with cancer be offered education about depression and anxiety. For moderate symptoms of anxiety, clinicians should offer cognitive behavioural therapy, behavioural activation, structured physical activity, acceptance and commitment therapy, or psychosocial interventions. For severe symptoms of depression or anxiety, clinicians should offer cognitive therapy, behavioural activation, cognitive behavioural therapy, mindfulness-based stress reduction or interpersonal therapy. A pharmacological regimen may be offered when patients lack access to first-line treatment, prefer pharmacotherapy, have responded well to it in the past, or have not improved after first-line psychological or behavioural management10.
DISCUSSION
This review brings together evidence from large epidemiological studies, meta-analyses, a randomised trial and a clinical guideline to describe the burden of anxiety and depression in adults with cancer. Three principal findings emerge. First, the burden is substantial but depends on how it is measured: roughly 30% to 40% of patients in hospital settings have some form of mood, anxiety or adjustment disorder on interview, about one in four report clinically relevant depressive symptoms on a screening questionnaire, and symptom-based anxiety is even more common1,4,5,15. Second, the burden is not evenly distributed: it is associated with tumour site, age, sex, social deprivation and somatic symptom burden, although the strength and even the direction of some associations vary3,4,6,14,15. Third, anxiety and depression are associated with worse quality of life and with worse survival, and yet most patients with major depression do not receive effective treatment6,7,8,9,18.
The difference between interview-defined and questionnaire-defined prevalence is a central methodological issue. Diagnostic interviews apply formal thresholds for severity, duration and functional impairment, and therefore identify a smaller group of patients than screening scales, which capture symptoms of varying severity and which may be elevated in patients who are adjusting normally to a serious illness. The meta-analysis of interview-based studies concluded that depression and anxiety are less common than previously thought [1], and the German interview study found that anxiety and adjustment disorders were more frequent than mood disorders1,5. At the same time, symptom-based estimates remain clinically relevant: sub-threshold symptoms were numerous in the Canadian cohort14.
The heterogeneity also reflects differences in sampling. Studies of consecutive patients shortly after diagnosis, outpatient cohorts, inpatient samples and palliative-care populations are not directly comparable3. The finding that population-based comparison data reveal a more than fivefold increase in the odds of depression is valuable because it addresses whether the prevalence in patients merely reflects the background prevalence of mood disorders. It does not: patients with cancer are at substantially higher risk4. For service planning, it is prudent to anticipate that approximately one patient in three will experience a clinically significant psychological problem during the course of care, while recognising that fewer will meet criteria for major depression at any one time.
The inconsistent findings for age deserve comment. Younger patients may face disruption to employment, fertility, parenting and financial stability, which could explain the higher rates of anxiety and depression observed in some studies6,14. Older patients, however, may have more comorbidity, functional limitation and social isolation, which could explain the higher depression scores in the Austrian cohort15. These explanations are plausible but were not tested directly in the included studies. A reasonable interpretation is that risk is shaped by the interaction of age with tumour type, treatment and social circumstances rather than by age alone.
Sex differences are consistent with those in the general population, in which women are more frequently diagnosed with depression and anxiety, but the cancer-specific modifiers deserve further study14,15. The association with social deprivation highlights that psychological outcomes in oncology are partly determined by social determinants of health, and implies that screening and referral pathways must be designed so as not to disadvantage patients who have fewer resources3,6. The finding that tumour site matters is clinically useful but should not be used to exclude any group from screening, since the German diagnostic data showed that about one in five patients had a diagnosable disorder even in the cancers with the lowest prevalence5.
The lack of a significant difference between palliative and non-palliative settings in the meta-analysis of interview studies challenges the assumption that psychological morbidity is determined mainly by prognosis1. It is more compatible with a model in which the experience of diagnosis, treatment burden, symptom control, uncertainty and social support are the principal determinants, and in which the late effects of treatment continue to affect survivors long after treatment ends3.
The relationships between psychological distress and cancer are likely to be bidirectional. Cancer and its treatment cause pain, fatigue, sleep disruption and functional loss, which in turn can precipitate or maintain depression and anxiety. Conversely, depression and anxiety may amplify the perception of symptoms, reduce engagement with health care, impair adherence and promote unhealthy behaviours such as inactivity and poor diet3,19. Biological hypotheses propose that inflammation, oxidative and nitrosative stress, altered immune surveillance and dysregulation of the autonomic and hypothalamic-pituitary-adrenal systems provide additional links between depression and tumour progression19. The meta-analytic findings are consistent with such hypotheses, but they are also compatible with confounding by disease severity, because patients with more advanced disease have higher mortality and may also be more depressed. The earliest meta-analysis did not find a clear link with progression, and its authors cautioned that the absolute increase in mortality risk is small8. The more recent and larger meta-analyses found modest but consistent associations, with relative risks of about 1.2 to 1.39,18. These findings justify treating depression and anxiety as clinically important in their own right and as plausible modifiers of outcome, but they do not show that treating them will prolong survival.
The analysis of Brown and colleagues illustrates why anxiety should be assessed alongside depression7. Much of the earlier literature focused on depression, and anxiety was either not measured or treated as a secondary feature. The demonstration that anxiety has independent and additive associations with mental-health quality of life, and that patients with both conditions carry the greatest burden, means that interventions targeting depression alone may leave a substantial source of impairment untreated. The finding that depression had a more pervasive association with other domains suggests that depression may be the more important target when functional recovery is the goal7. A caveat is that the study sample was selected for pain and/or depression, so the magnitudes of association cannot be generalised to all patients with cancer, and the cross-sectional design does not permit causal inference.
From the perspective of measurement, the EORTC QLQ-C30 and the HADS capture overlapping but distinct constructs12,13. Emotional functioning on the QLQ-C30 will be lower in patients with anxiety and depression, but a quality-of-life profile does not identify who requires treatment. A screening instrument with validated thresholds is therefore needed in addition to quality-of-life measurement, and the results of each should be interpreted in light of the other.
Several practical implications follow. First, the treatment gap is large. If 73% of patients with major depression in specialist cancer clinics are not receiving potentially effective treatment [6], the main limitation is not the absence of effective treatments but failure of recognition and delivery. The guideline recommendation that all patients be offered education and that symptoms be assessed with validated measures is a necessary foundation [10]. Second, interventions should be matched to severity: education and psychosocial support for all, structured psychological or behavioural therapy for moderate symptoms, and more intensive psychological treatment, with pharmacotherapy in defined circumstances, for severe symptoms10. Third, integrated models of care appear to work: the SMaRT Oncology-2 trial showed that a collaborative care programme produced better outcomes than usual care20. Fourth, clinicians should be aware that the evidence for pharmacological treatment is more limited than that for psychological interventions, which is why current guidance reserves medication for particular circumstances10.
Assessment should also look beyond mood symptoms. Because pain and other somatic symptoms co-occur with anxiety and depression, a comprehensive assessment of symptom burden is needed7,19. Services should also consider the particular needs of younger patients, patients experiencing social deprivation, and patients with the tumour types associated with higher distress, without limiting screening to these groups4,6,14,15.
The strengths of this review include the use of a recognised reporting framework, the emphasis on large, representative studies and meta-analyses, the inclusion of evidence on both anxiety and depression, the coverage of quality of life as well as survival, and the verification of every bibliographic detail and DOI11. The sources include samples from several countries and health systems, which supports the generalisability of the main conclusions.
Several limitations should be acknowledged. The review was not prospectively registered, and the search was targeted rather than exhaustive; relevant studies may therefore have been missed. Screening and extraction were not carried out in duplicate. The sources used different instruments, thresholds and time frames, which precluded a quantitative synthesis of prevalence, so the ranges reported here are descriptive. Most of the evidence on associated factors is cross-sectional, so the direction of association between, for example, symptom burden and depression cannot be determined. The prognostic meta-analyses are subject to residual confounding and to reverse causation, because cancer progression may itself cause depression8,9. Evidence from low- and middle-income countries is limited in the included sources, apart from the Jordanian study, which constrains generalisation to those settings16. Finally, many studies relied on the HADS or PHQ-9, which are screening tools and do not provide diagnoses12.
DIRECTIONS FOR FUTURE RESEARCH:
Future research should prioritise prospective cohort studies that follow patients from diagnosis through treatment and survivorship using both symptom scales and diagnostic interviews, so that trajectories and temporal relationships can be defined. Anxiety deserves study as a distinct outcome rather than as an adjunct to depression, since evidence on its separate effects on quality of life and survival is limited7,18. Trials of collaborative care models should be extended to more diverse settings and to patients with a range of tumour types, including those with a high burden such as pancreatic and brain cancer4,15,20. Research on the long-term and late effects of treatment, and on the mental health of the growing population of survivors, is needed3. Finally, studies should test whether treatment of anxiety and depression improves not only symptoms and quality of life but also adherence, recurrence and survival, in order to determine whether the associations seen in cohort studies are modifiable9,19.
CONCLUSIONS
Anxiety and depression are common in patients with cancer. Approximately one third of patients in hospital-based settings meet criteria for a mood, anxiety or adjustment disorder, and a similar or greater proportion report clinically relevant symptoms on screening questionnaires. The burden is higher than in the general population, varies by tumour type, and is associated with younger age, female sex, social deprivation and a heavy burden of somatic symptoms, although associations with age and tumour site are not uniform across studies.
Anxiety and depression have independent and additive negative associations with quality of life, particularly in mental-health domains, and are associated with higher cancer-specific and all-cause mortality, with a modest but consistent relative risk of about 1.2 to 1.3 in large meta-analyses. The evidence on the biological mechanisms that might link them to cancer progression remains largely hypothetical, and the available data cannot establish that treating these conditions improves survival.
Despite the availability of effective psychological and collaborative care interventions, most patients with major depression do not receive potentially effective treatment. The practical implications are that oncology services should offer education to all patients, screen routinely with validated instruments for both anxiety and depression, assess symptom burden comprehensively, and provide stepped, evidence-based care aligned with current guidelines. Future research should clarify the temporal relationships between psychological distress and cancer outcomes, should study anxiety in its own right, and should test integrated care models in more diverse settings.
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APPENDICES
Table 1. Principal sources contributing to the synthesis:
| First author (year), reference | Study design | Population and sample size | Principal relevance |
|---|---|---|---|
| Mitchell (2011) [1] | Meta-analysis of interview-based studies | 94 studies; over 14,000 patients in oncology, haematology and palliative care settings | Prevalence of depression, anxiety and adjustment disorder |
| Pitman (2018) [2] | Clinical review | Adults with cancer | Recognition and management in clinical practice |
| Niedzwiedz (2019) [3] | Evidence review of systematic reviews | People living with and beyond cancer | Contributing factors, prevalence and care options |
| Hartung (2017) [4] | Multicentre cross-sectional study with population comparison | 4,020 patients; 5,018 comparison participants | Depressive symptoms by cancer site |
| Mehnert (2014) [5] | Multicentre epidemiological study using diagnostic interviews | 2,141 interviewed patients | Four-week prevalence of mental disorders |
| Walker (2014) [6] | Analysis of routine screening data | 21,151 patients in Scotland | Major depression by cancer site and treatment gap |
| Brown (2010) [7] | Cross-sectional secondary analysis | 397 patients with pain and/or depression | Anxiety, depression and quality of life |
| Satin (2009) [8] | Meta-analysis | 26 studies; 9,417 patients | Depression, disease progression and mortality |
| Wang (2020) [9] | Meta-analysis of cohort studies | 51 cohort studies; 2,611,907 participants | Cancer incidence and mortality |
| Andersen (2023) [10] | Clinical practice guideline | Adult cancer survivors | Management of anxiety and depression |
| Linden (2012) [14] | Cross-sectional study of consecutive patients | 10,153 patients | Anxiety and depression by cancer type, sex and age |
| Zeilinger (2022) [15] | Cross-sectional study using HADS | 7,509 outpatients | Prevalence across 13 cancer types |
| Naser (2021) [16] | Cross-sectional study using HADS, PHQ-9 and GAD-7 | Inpatients and outpatients in Jordan | Prevalence and risk factors |
| Pinquart (2010) [17] | Meta-analysis | Patients with cancer and community cohorts | Depression and cancer mortality |
| Wang (2020) [18] | Meta-analysis of cohort studies | 17 studies; 282,203 patients with breast cancer | Recurrence and mortality in breast cancer |
| Bortolato (2017) [19] | Narrative mechanistic review | Patients with cancer | Biobehavioural pathways |
| Sharpe (2014) [20] | Randomised effectiveness trial | 500 patients with cancer and major depression | Integrated collaborative care |
Abbreviations: HADS, Hospital Anxiety and Depression Scale; PHQ-9, Patient Health Questionnaire-9; GAD-7, Generalized Anxiety Disorder-7.
Source: Prepared by the authors.
