Health status and mental distress in people with cancer and comorbid conditions: The Australian National Health Survey analysis

Abstract Introduction Data on the impact of specific comorbidities on health outcomes is limited. We compared health status and mental distress between individuals with and without cancer according to comorbidity type. Methods A cross‐sectional analysis using data from the Australian National Health Survey 2017–18 including all respondents aged ≥25 years with and without a history of cancer. The odds of poor health and mental distress were reported according to cancer status, and specific individual and cluster of comorbidities. Results There were 1982 individuals (52% female) with cancer and 12,635 (51% female) without cancer. Individuals with cancer were older, and more likely to have a comorbidity compared with those without cancer. They were more likely to report poor health than those without cancer for each specific comorbidity; except for skin conditions and infectious diseases; with the adjusted odds ratio (aOR) ranging from 1.34 (95% CI = 1.01–1.79) for digestive disorders to 2.93 (95% CI = 1.62–5.29) for blood conditions. The strongest association with poor health (aOR 2.79, 95% CI = 2.27–3.43) and mental distress (aOR 9.01, 95% CI = 7.25–11.20) was observed for those with a comorbid mental illness. Exploratory cluster analysis identified four distinct comorbidity clusters: low comorbidity, musculoskeletal, respiratory and cardiometabolic; cancer survivors in the cardiometabolic cluster had a higher odds of reporting poor health (aOR 3.50, 95% CI = 2.48–4.92) and mental distress (aOR 2.33, 95% CI = 1.53–3.55) than those with a low comorbidity. Conclusions Comorbidities in cancer survivors were common and associated with inferior health status, although the magnitude of the effect varied by comorbidity type. Risk assessment and management of comorbidities should be an important priority for cancer care and research.


| INTRODUCTION
The coexistence of one or more chronic health conditions ('comorbidities') is common in people with cancer, 1,2 with over 60% of cancer survivors suffering from at least one comorbidity [3][4][5] and the prevalence of comorbidities is higher in cancer survivors compared with the general population.This may be due to shared risk factors between cancer and other chronic diseases such as smoking, obesity, inactivity and poor diet. 2 It is also possible that people with select chronic conditions are at higher risks of developing cancer such as the association between type 2 diabetes and an increased risk for several cancers including breast, colorectal, endometrial, pancreatic and liver cancer. 2,6Enhanced monitoring and diagnostic testing following cancer diagnosis may also increase the incidental finding of comorbidities. 3 Further, cancer treatment may contribute to the development of comorbidities, including cardiovascular diseases (associated with chemotherapy, immunotherapy, targeted therapy, endocrine therapy, or radiotherapy), 7 and osteoporosis (associated with endocrine therapy or chemotherapy-induced ovarian failure). 8In recognition to the accompanying risks of toxicity associated with cancer treatment, several clinical guidelines have been developed with suggested strategies for detection, prevention and management of cardiovascular complications and osteoporosis in cancer patients. 7,8omorbidity is associated with shorter survival and lower quality of life, with evidence suggesting worse outcomes in cancer survivors compared to the general population. 2 While prior Australian studies showed that people with cancer had a greater number of chronic diseases, poorer health status and a higher level of distress than people without cancer, 1,3 data on the influence of specific comorbidities on health outcomes is limited.A greater understanding on the burden of individual comorbidity is needed to identify population most affected who may benefit the most from prevention and early intervention.
The objective of this study was to assess the patterns of health outcomes in individuals with cancer and comorbidities.We compared the prevalence and strength of the association between comorbidity, health status and mental distress in individuals with and without cancer according to comorbidity type.We also examined the patterns of multimorbidity by identifying clusters of conditions and their associations with health outcomes.

| Data source
We performed a cross-sectional analysis using data from the Australian National Health Survey 2017-2018.The survey population was randomly selected using a stratified multistage area approach and covered a representative sample of 21,315 individuals residing in private dwellings in urban and rural areas from across all Australian states and territories (response rate: 76.1% and the details have been described elsewhere). 9The survey excluded people living in non-private dwellings such as hospitals, hotels, nursing homes and short-stay caravan parks, as well as people residing in very remote areas of Australia and discrete communities.The trained Australian Bureau of Statistics interviewers conducted personal interviews with the selected sample population and collected a range of health-related information including long-term health conditions, health status and health risk factors.We obtained basic unit record information including demographic, and health characteristics for each person that participated in the survey. 10tudy population consisted of all survey respondents aged ≥25 years (selected based on the survey's predefined age groups) and included individuals with and without a history of cancer (skin malignant neoplasms and/or malignant neoplasms of other sites or site unknown).We categorised the study population into two groups (cancer versus non-cancer) and included all cancer cases (whether cancer is current or in remission) to reflect the characteristics of cancer survivorship.Of note, the information on types and stages of cancer, as well as the date of cancer diagnosis was not available.

| Comorbidity
The survey collected health-related data including information on common health conditions.Participants were asked if they have any long-term health conditions that have lasted or are expected to last, for 6 months or more.These health conditions were coded using the International Classification of Diseases 10th revision (ICD-10) and were categorised into broad disease grouping including diseases of circulatory, respiratory, nervous, digestive, genitourinary, musculoskeletal and endocrine systems, disorders of blood, skin, eye, mental and behavioural problems and certain infections (Table S1).We identified all the coexisting health conditions reported by the study population that were both 'current' and longterm.If a person reported having multiple health conditions that fell in the same broad disease grouping, we counted that disease grouping once only.A total of 12 broad disease groupings ('comorbidity') were included in our analysis.

| Outcome measures
The outcome measures were self-reported health status and mental distress.
Health status measured a person's perception of health at a given time point, where the study population was asked 'In general would you say that your health is excellent, very good, good, fair or poor?'.3][14] We grouped the measurement of health status into two categories (poor health status with a rating of fair or poor vs. good health status with a rating of excellent, very good or good). 1 Mental distress was measured by the Kessler Psychological Distress Scale-10 (K10) which assessed a person's level of psychological fatigue, nervousness, agitation and depression in the last 4 weeks. 15The 10-item questionnaire used a five-level response scale to each question that were scored from five through to one with a maximum total score of 50 (indicating severe distress) and a minimum total score of 10 (indicating no distress). 15,16The validity of the K10 as a measure of psychological distress has been demonstrated in previous study based on the data of sensitivity and specificity presented. 16We grouped the level of mental distress into two categories (low-moderate level of distress with a K10 score of 10-21 vs. high-very high level of stress with a K10 score of 22-50). 1,15

| Statistical analysis
Descriptive statistics were used to compare the demographic and characteristics of subjects based on their cancer status.The self-reported outcomes of poor health status and mental distress were assessed using separate multivariate logistic regression models with each specific broad disease grouping as the exposure variable and adjustment for sociodemographic factors including sex, age, country of birth, highest education level, geographical location, and socioeconomic status by household income, and lifestyle factors including smoker status, dietary intake, alcohol consumption, physical activity and body mass index.The number of other broad disease groupings (i.e.conditions other than the specific disease grouping of interest) was also included each model.Results were reported as adjusted odds ratio (aOR) with 95% confidence intervals (CIs).
We also performed a k-modes cluster analysis, to explore patterns of multimorbidity (i.e. two or more chronic health conditions excluding cancer) by cancer status. 17he optimal number of clusters was determined using the modified Elbow method, which suggested 4 to 6 clusters.The 4-cluster solution was selected based on parsimony and alignment with clinical experience.Based on the prevalence of broad disease groupings within each cluster, we subjectively labelled the four clusters according to the most dominant conditions.
We assigned weighting to the study population by using the 2016 Census Australian population as the standard population (by 5-year age groups and sex).The weight was applied in all analyses.Analysis was conducted using SAS statistical software version 9.4 and Python version 3.9.13 for the K-modes clustering.

| Comorbidities and odds of poor health/mental distress
Amongst individuals with cancer and a comorbidity, the odds of reporting either poor health or mental distress was more than six times higher than those without cancer and without a comorbidity (Table 3).Amongst the specific broad diseases, individuals with cancer and each specific broad disease were more likely to report poor health than those without cancer for each broad disease grouping except for skin conditions and infectious diseases.The aOR ranged from 1.34 (95% CI = 1.01-1.79)for digestive disorders to 2.93 (95% CI = 1.62-5.29)for blood conditions.
A comorbid mental illness was associated with the highest odds of reporting both poor health (aOR 2.79, 95% CI = 2.27-3.43)and mental distress (aOR 9.01, 95% CI = 7. 25-11.20) in individuals with cancer.This was followed by comorbid musculoskeletal and nervous system disorders (aOR of reporting poor health status ranged from 1.68 to 2.11 and aOR of reporting mental distress ranged from 1.43 to 1.67).
A comorbid blood condition was associated with an increased odds of reporting poor health (aOR 2.93, 95% CI = 1.62-5.29)but not distress (aOR 1.27, 95% CI = 0.68-2.35) in individuals with cancer.Similar patterns were observed for comorbid genitourinary, circulatory, eye, endocrine, respiratory and digestive systems (in order of decreasing magnitude odds of reporting poor health status).

| Cancer and non-cancer clusters
About 70% (n = 1418) of individuals with cancer and nearly 50% (n = 6081) of those without cancer had multimorbidity (≥2 comorbidities).Four distinct and similar patterns Across the four clusters, for both those with and for those without cancer, those in cluster 4 (cardiometabolic cluster) were older compared with those in clusters 1-3 (Table 4, Figure 1).Individuals in cluster 4 were also more likely to have a lower education level and a lower socioeconomic status compared with those in other clusters.In contrast, individuals in cluster 1 (low comorbidity) were younger, more likely to have a postgraduate/bachelor's degree qualification and a higher socioeconomic status compared with those in clusters 2-4.When assessing the odds of poor health and mental distress broken down by cancer status and cluster, compared to cluster 1 (low comorbidity), those in clusters 2-4 were more likely to report poor health amongst those with cancer (aORs: 2.27-3.50)and those without cancer (aORs: 2.50-4.66)(Figure 2).Individuals in clusters 2-4 also had higher odds of mental distress than those in cluster 1 for both those with cancer (aORs: 1.66-2.33)and for those without cancer (aORs: 3.10-8.47).Cardiometabolic disease (cluster 2) was associated with the highest odds of reporting both poor health (aOR 3.50, 95% CI = 2.48-4.92)and mental distress (aOR 2.33, 95% CI = 1.53-3.55)amongst individuals with cancer.

| DISCUSSION
In this first Australian study that assessed the effects of comorbid conditions on health outcomes in individuals with cancer, we found that the presence of comorbidity was more prevalent and associated with a poor health status in cancer survivors as compared to individuals without cancer; and the magnitude of the association varied by comorbidity type.A comorbid mental illness was associated with the worst self-reported health status and mental distress in cancer survivors.Our study provides an important overview on the patterns of health outcomes in the context of different comorbidities.

Comorbidity status by broad disease groupings
Adjusted odds ratios a (95% confidence interval)

Self-reported health status Mental distress
Poor health versus good health (reference)

High distress versus low distress (reference)
Endocrine  118 (23)   90 (22)   119 ( 28) 547 ( 13) 614 ( 17) 429 ( 13) 357 ( 23) Decile 5-6 106 (17)   87 (17)   72 (18)   65 (15)   779 (18)   606 (17)   561 (17)   229 (15)   Decile 7-8 100 ( 16) 61 (12)   36 ( 9) 36 ( 8) 916 ( 21) 621 (18)   712 (22)   184 (12)   Decile 9-10 136 (22)   72 ( 14) 49 ( 12) 24 (6)   1011 (23)   596 (17)   735 (23)   186 (12)   Missing 67 (11)   56 (11)   44 (11)   44 ( 10) 606 ( 14) 417 (12)   365 (11)   201 (13)   Number of chronic conditions (excl cancer) Median (Q1, Q3) Diseases of eye and adnexa 45 (7)   59 (11)   56 ( 14) 90 Diseases of nervous system 47 (7)   41 (8)   79 (19)   48 (11)   214 ( 5) 497 ( 14) 359 (11)   131 ( 8) The worst health outcomes (e.g. a higher odds of mental distress as measured by the K10 score as an indicator for the needs of mental health services) 16 amongst cancer survivors with comorbid mental illness observed in our study are consistent with prior research which showed that mental condition after cancer had negative impacts on physical morbidity and mortality. 18,19Previous studies showed that while the incidence of cancer was similar in people with psychiatric disorders to that in the general population, those with mental illness were more likely to have metastases at cancer diagnosis and were less likely to receive cancer treatments which may contribute to their poorer health outcome. 20,21Cancer diagnosis, and the resulting fear of cancer recurrence can lead to psychological distress and the development of new mental health issues such as depression and anxiety which can adversely impact health status. 22,23Our findings of worst outcomes in cancer survivors with comorbid mental illness are particularly significant as the psychosocial needs for cancer survivors remain frequently unmet. 18usculoskeletal disorder was the most common comorbidity reported amongst cancer survivors in our study and was also associated with poor health status and mental distress.Musculoskeletal disorders are the leading contributor to disability and chronic pain in Australia. 24 higher prevalence of musculoskeletal conditions in people with cancer may be due to cancer treatment such as hormonal therapy-induced osteoporosis and arthralgia in people with breast or prostate cancer, the most prevalent cancers in Australia.25,26 Musculoskeletal symptoms are known to contribute to hormonal therapy discontinuation which may have negative implications on cancer outcomes.26 In addition to cancer, the functional limitations, pain and distress caused by musculoskeletal conditions can have deleterious effect on an individual's ability to stay mobile and altered quality of life, leading to physical and social decline.27 Our findings highlight the importance of the assessment and management of musculoskeletal conditions as part of the standard practice in cancer care.
Although there were no significant differences in mental distress in individuals with cancer and comorbid conditions including diseases of blood, genitourinary, circulatory, eye, endocrine, respiratory and digestive systems as compared to individuals without cancer and without the specific comorbidity type, the presence of those illnesses increased the odds of reporting poor health.Cardiovascular conditions, deserve particular attention as they affect a significant proportion of people with cancer and are the leading cause of premature non-cancer death amongst long-term cancer survivors, underscoring the importance of their proactive assessment and management. 28,29ur exploratory analysis of patterns of multimorbidity showed that 70% of individuals with cancer had multimorbidity with four distinct patterns of clustering observed, which was also observed in individuals without cancer.A high prevalence of cardiometabolic diseases in cancer group (cluster 4) may be the reflection of the risk factors shared between cancer and cardiometabolic diseases or cardiovascular toxicity associated with cancer treatment or a reflection of the older age of individuals in the cancer cohort. 1,2Most cancer cases occur in older age groups whereby the coexistence of multiple chronic diseases is common as the incidence of chronic diseases increases with age. 2 Our results were consistent with prior studies which showed that cardiovascular diseases was associated with poor health-related quality of life in the general population. 30Further, the clusters with a higher number of comorbidity (clusters 2-4) comprised a higher proportion of individuals with a lower socioeconomic status when compared to those with a low comorbidity (cluster 1) in both the cancer and non-cancer groups, consistent with what is observed in people with multimorbidity in the general population. 31A systematic review included 24 cross-sectional studies that examined the association between socioeconomic status and the occurrence of multimorbidity showed that a lower versus higher socioeconomic status (as measured by education level and area-based deprivation) was generally linked to an increased risk of multimorbidity. 31r findings suggests that the presence of multimorbidity, particularly in those with cardiometabolic diseases and socioeconomic disparity should alert clinicians to a higher risk for inferior outcomes.Our results highlight the importance of the management of multiple chronic diseases as outlined in the 'National Strategic Framework for Chronic Conditions' including integrating primary care into the model of care for cancer survivors. 32Future research into the development of cluster-specific care management may also be of value. 33ur research has several limitations.While we were able to adjust for several important characteristics including sex, age, sociodemographic such as socioeconomic status by household income and education level, lifestyle factors and presence of other health conditions, the health data used in this study was self-reported which may be subject to response bias.The information was not available in the dataset including cancer stage/ type and treatment as well as the dates when cancer and other health conditions were diagnosed.Therefore, we were not able to perform further subgroup analysis by types of cancer.We were also not able to differentiate the sequences of comorbidities development and health outcomes in relation to cancer diagnosis.Nonetheless, our study provided an important overview on the effects of individual comorbid conditions on health outcomes given that there is limited data available in the Australian context.

F I G U R E 1
The prevalence distribution of the study population characteristics by cancer status and clusters of multimorbidity.The percentage (%) of the characteristics in each cluster is shown.
The percentage (%) of the characteristics in each cluster is shown.In conclusion, comorbidities in people with cancer are common and associated with inferior health status.The strongest association with poor health and mental distress was observed for those with a mental illness and those in the cluster with a high prevalence of cardiometabolic diseases.Risk assessment and management of comorbidities should be an important priority for cancer care and research.As we are not the data custodians, we are not authorised to make the data available.With the appropriate approvals, the data may be accessed through the Australian Bureau of Statistics.

ETHICS STATEMENT
Ethics approval was not required for the analysis of deidentified National Health Survey basic microdata.
F I G U R E 2 Adjusted odds ratios for poor health status and mental distress by cancer status and by cluster of multimorbidity.
a The logistic regression model was adjusted for sociodemographic factors including sex, age, country of birth, highest education level, geographical location, and socioeconomic status by household income, and lifestyle factors including smoker status, dietary intake (whether meet fruit and vegetables consumption guidelines), alcohol consumption in the last 12 months, physical activity in the past week and body mass index.Self-reported health status: poor health versus good health (reference); mental distress: high distress versus low distress (reference). a The logistic regression model was adjusted for sociodemographic factors including sex, age, country of birth, highest education level, geographical location, and socioeconomic status by household income, and lifestyle factors including smoker status, dietary intake (whether meet fruit and vegetables consumption guidelines), alcohol consumption in the last 12 months, physical activity in the past week, and body mass index.
Self-reported health status: poor health vs. good health (reference); Mental distress: high distress vs. low distress (reference).

4
The characteristics of study population by cancer status and cluster of multimorbidity.
T A B L E 1 of clustering were observed in both the cancer and noncancer groups (Table4).Cluster 1 (low comorbidity) represented 32% of those with cancer and 34% of those without cancer and was characterised by a relatively low prevalence of each disease grouping ranging from 0% to 28% in the cancer group and 0-9% in the non-cancer group.

status by broad disease groupings Adjusted odds ratios a (95% confidence interval) Self-reported health status Mental distress Poor health versus good health (reference) High distress versus low distress (reference)
Prevalence of comorbidity and self-report health outcomes by cancer status.Adjusted odds ratios for poor health status and mental distress by comorbidity status.
T A B L E 2