Introduction
Endometrial cancer is the sixth most commonly occurring cancer in women, with over 380,000 estimated new cases worldwide and nearly 90,000 estimated deaths in 2018 [
1]. Both incidence and mortality rates have increased over the last decades, with obesity being one of the main risk factors [
2]. The increase in obesity has multiple underlying factors including socioeconomical factors, with a strong association between obesity and lower socioeconomic status (SES) in endometrial cancer patients and in the general population [
3,
4].
Socioeconomic status (SES) is a measure of an individual’s economic and sociological standing and is based on income, education and occupation [
5]. SES is considered to be an important predictor of health due to health inequalities [
6]; however, the relationship between socioeconomic deprivation and cancer is complex and multifaceted. The incidence of various cancers including endometrial cancer is higher in deprived groups [
7]. Furthermore, death rates are examined extensively and are shown to be higher among the most deprived for most types of cancer [
8]. However, the relationship between socioeconomic deprivation and survival in endometrial cancer patients is not fully established.
Whilst Body Mass Index (BMI) is related to SES and obesity is associated with an increased risk of surgical morbidity in endometrial cancer patients [
9], the relationship between socioeconomic deprivation and peri-operative morbidity is unclear.
In this systematic review, our aim is to establish the relationship between socioeconomic deprivation and survival in endometrial cancer patients. In addition, we aim to investigate the correlation between socioeconomic deprivation and peri-operative morbidity.
Objectives
-
To evaluate the association between socioeconomic deprivation and survival in endometrial cancer patients.
-
To assess the correlation between socioeconomic deprivation and peri-operative morbidity in endometrial cancer patients.
Methods
Study design
We conducted a systematic review of the literature to address the subject of socioeconomic deprivation and survival in endometrial cancer patients.
Eligibility criteria
We have used the following definition by Peter Townsend, sociologist, of socioeconomic deprivation: a lack of social and economic benefits which are considered to be basic necessities in a society [
10]. We have included studies with individual, area-based or both types of measures of socioeconomic deprivation in this review.
The following criteria were used to exclude articles from further consideration: not in English, contained no original data, meeting abstract only (no full article for review) or article did not apply to any of the review questions. We furthermore excluded articles that used indirect measures of socioeconomic deprivation such as marriage or insurance status only.
Types of studies
We included all study designs evaluating the association between socioeconomic status and survival or peri-operative outcomes in endometrial cancer patients as a primary outcome.
Search strategy and selection criteria
This review was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, and in accordance with the principles outlined in the Cochrane Handbook [
11]. We performed systematic searches in Medline (1946 until May 2018), Embase (1980 until May 2018) and Cinahl (1981 until May 2018) and the Cochrane Controlled Register of Trials. Search strategies were adapted accordingly to each database. The used search strategies are presented in Appendix 1. In addition, we searched grey literature including abstracts of scientific meetings as well as manually checking the reference lists of eligible studies to identify any additional studies to include in this review.
Types of outcome measures
-
Primary outcomes Survival including overall survival (OS), cause-specific survival (CSS) and recurrence-free survival (RFS).
-
Secondary outcomes Peri-operative morbidity in terms of peri-operative complications (intra-operative complications including nerve injury, bowel injury, bladder injury, ureter injury and vascular injury and postoperative complications including wound problems, fascia dehiscence, ileus, urinary tract infection, haemorrhage, pneumonia, pelvic abscess, haematoma, venous thromboembolism, sepsis, renal complications, cardiac complication and organ failure) and 30-day mortality.
Study selection
Two reviewers (HD and KG) independently assessed titles and abstracts of all identified studies. Those studies that clearly did not meet the inclusion criteria were excluded. Potentially relevant studies were retrieved in full text and were further reviewed for eligibility by both reviewers.
Data extraction was completed by two of the authors (HD and KG) using pre-determined forms which included study author names, publication dates, study designs, sample sizes, measures of socioeconomic deprivation, results of univariate analyses testing for zero-order association between socioeconomic deprivation and survival or peri-operative outcomes and the results of the multivariate analyses testing for association between socioeconomic deprivation and survival or peri-operative outcomes adjusting for control variables. Differences were resolved by consensus.
Assessment of risk bias
The risk of bias included in studies was assessed by two authors (HD and KG) independently using the Newcastle–Ottawa Quality Assessment Form for Cohort Studies which includes selection, comparability and outcome [
12]. Differences were resolved by consensus.
Data synthesis
We were unable to conduct a meta-analysis because of the heterogeneity in the included studies. However, we created summary tables of evidence from the included studies and then examined the relationship between various measures of socioeconomic deprivation and outcomes across studies.
Discussion
This review summarises the current literature about the association between socioeconomic deprivation and survival in endometrial cancer patients. The results of this systematic review suggest a worse survival for more socioeconomically deprived patients, with six studies showing low SES being associated with worse survival in univariate analysis, and three studies confirming poor outcome in multivariate analysis. However, two studies did not show an association.
Previous research has looked at possible explanations for the differences in cancer survival within different groups of deprivation, with stage at diagnosis being one of the most important factors [
23]. In cervical, breast and colorectal cancer these survival differences are related to the differences in participation rate in cancer screening programmes, in which women with lower SES and women living in urban areas are less likely to participate [
24]. For endometrial cancer, there is no routine screening; however, since patients present early with bleeding problems, it is usually diagnosed at an early stage, which leads to high survival rates [
14]. This suggests that SES impacts survival in endometrial cancer through other factors which may include BMI, age, smoking and comorbidities.
For endometrial cancer, factors that are associated with advanced stage at diagnosis include high-grade lesions, serous histologic subtype, older age and low SES [
21,
25,
26]. Patients with higher socioeconomic position might be more aware of symptoms and present quicker to a general practitioner or medical specialist, while low-SES patients tend to ignore early symptoms of disease such as postmenopausal bleeding [
21]. This could partially explain the differences in survival; however, most studies included in this review with the exception of two (Jensen et al. and NCIN) corrected for stage at diagnosis in their analyses. Therefore, it seems that regardless of stage at diagnosis, socioeconomic deprivation affects survival in endometrial cancer patients.
Other important factors in cancer survival in general and in endometrial cancer patients include BMI, with normal-weight women having better survival than obese patients [
23,
27]. One of the mechanisms that has been suggested to explain the differences in survival is the fact that obesity is associated with an increased risk of surgical morbidity [
9]; however, some studies have shown that it is not an independent predictor but likely related to other comorbid conditions [
28]. Since there is a strong relationship between obesity and socioeconomic deprivation in endometrial cancer patients [
4], this could potentially be an important factor affecting survival in deprived patients; however, the articles included in this review, with the exception of Seidelin et al., did not include or correct for BMI.
A third factor in cancer survival is comorbidity, previous research has shown a decreased survival for endometrial cancer patients with multiple comorbidities [
29]. Different reasons are reported such as delayed diagnosis, higher rate of postoperative complications, a reduction of the possibility of surgery and a lower tolerance of oncological treatment [
30]. Since the prevalence of comorbidity tend to be higher among endometrial cancer patients with higher levels of deprivation [
31], this could also affect survival. Of the articles included in this review, only Seidelin et al. corrected for comorbidity and found no difference in the odds ratio for death.
Furthermore age at diagnosis is an important factor in endometrial cancer survival [
32]. Elderly patients often have more aggressive histology and are less likely to receive surgical treatment or adjuvant therapy leading to under treatment [
33]. Furthermore an article by Poupon et al. [
33] showed 3-year OS rates to be lower than cancer specific survival rate, indicating that death in elderly is often a combination of death due to cancer as well as to causes other than cancer. All studies included in this review have adjusted for age at diagnosis with the exemption of Cheung et al. [
18].
Another element in survival in endometrial cancer is treatment received by patients [
34]. This is often influenced by patient characteristics such as age, comorbidities and patient preference. Furthermore, the type of treatment centre (cancer centre or smaller hospital) also influences the type of treatment offered to patients and influences survival in endometrial cancer patients [
35,
36]. Patients with low SES are less likely to afford travel costs to cancer centres, especially if they reside in rural counties. Only half of the studies included in this review have taken treatment into account.
Lastly, smoking status is an important aspect in survival in endometrial cancer, in which smokers show worse survival compared to non-smokers [
37], although some of the overall survival differences may be more attributable to associated comorbid conditions in smokers. None of the studies in this review have corrected for smoking status in their analysis.
BMI, comorbidities and smoking not only affect survival, but are also risk factors for peri-operative morbidity in endometrial cancer patients [
9,
38,
39]. Because of the correlation of SES with BMI, comorbidities and smoking status, we have tried to investigate if there is a relationship between socioeconomic deprivation and peri-operative morbidity; however, the current literature is scarce, and only one study was identified which did not show any association between income deprivation and 30-day postoperative mortality [
22]. Further research is needed to establish any relationship between socioeconomic deprivation and peri-operative morbidity including 30-day mortality in endometrial cancer patients.
The studies in this review have used different measures of mortality (age-standardised mortality rate, survival time, disease-specific survival, overall survival, 1- and 5-year survival, etc.), which is an important issue when comparing results. Endometrial cancer has a relatively high survival rate; however, the one-year survival will be very different to mortality rates and may reflect the individual’s underlying comorbidities which may lead to earlier demise. Therefore, it is difficult to compare all different measures of mortality.
Despite increasing recognition of the impact of socioeconomic deprivation on survival of endometrial cancer patients, questions about the strength of its impact and relationship with other prognostic factors remain. To address these questions, more studies are needed which measure socioeconomic deprivation with a standardised measure and also correct for other prognostic variables including BMI, comorbidities and smoking status. From this knowledge, interventions to improve survival in lower SES patients can then be introduced.
Overall completeness and applicability of evidence
The majority of women were diagnosed with stage I disease, consistent with reported incidence rates [
40]. Literature was scarce about the correlation between socioeconomic deprivation and peri-operative morbidity and we only found one study that evaluated peri-operative outcomes and SES in endometrial cancer patients.
Quality of evidence
The studies included were of a high degree of heterogeneity in study design and evaluated a variety of socioeconomic status measures, which lacked in uniformity. Different measures were used, each capturing a distinct aspect of SES, which may be correlated with other measures, but are not interchangeable [
41]. Furthermore, individual SES measures such as income and occupation differ from environmental SES measures, which are area-based, and these two measures often do not correlate well [
42]. These different measures can all impact results. Area-based measures may not accurately represent a patient’s socioeconomic deprivation status, since not all people living in low income are poor themselves. Furthermore, there is a large variety in definitions of socioeconomic deprivation: the definition of a deprived person living in the United States might be different from a deprived person living in Japan. In addition, in some studies, only one indicator of SES was used, while others used multiple measures. Furthermore, most studies have not adjusted for important confounders. Therefore, it is difficult to draw firm conclusions about the strength of the evidence.
Potential biases in review process
A comprehensive search of the literature with aid of librarian was performed by two reviewers independently, including a search of the grey literature. Reviewers assessed potentially eligible articles independently and discussed the differences found.
Comparison with the existing literature
A previous review done by Kogevinas et al. [
8] about socioeconomic differences in cancer survival included six studies about endometrial cancer and showed survival was poorest in low socioeconomic groups in five studies; in three of those studies, differences were statistically significant. However, the reverse pattern was seen in one study. The association of inequality in survival is supported by several studies that have assessed the association between SES and cancer survival in general and that also included endometrial cancer patients [
43‐
53], even though several other studies did not find any association between deprivation and mortality [
54‐
58].
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