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Yeo et al. BMC Cancer (2019) 19:900 https://doi.org/10.1186/s12885-019-6116-0 RESEARCH ARTICLE Open Access Endoscopic ultrasound staging in patients with gastro-oesophageal cancers: a systematic review of economic evidence Seow Tien Yeo1* , Nathan Bray1, Hasan Haboubi2, Zoe Hoare3 and Rhiannon Tudor Edwards1 Abstract Background: The sensitivity of endoscopic ultrasound (EUS) in staging gastro-oesophageal cancers (GOCs) has been widely studied. However, the economic evidence of EUS staging in the management of patients with GOCs is scarce. This review aimed to examine all economic evidence (not limited to randomised controlled trials) of the use of EUS staging in the management of GOCs patients, and to offer a review of economic evidence on the costs, benefits (in terms of GOCs patients’ health-related quality of life), and economic implications of the use of EUS in staging GOCs patients. Methods: The protocol was registered prospectively with PROSPERO (CRD42016043700; http://www.crd.york.ac.uk/ PROSPERO/display_record.php?ID=CRD42016043700). MEDLINE (ovid), EMBASE (ovid), The Cochrane Collaboration Register and Library (including the British National Health Service Economic Evaluation Database), CINAHL (EBSCOhost) and Web of Science (Core Collection) as well as reference lists were systematically searched for studies conducted between 1996 and 2018 (search update 28/04/2018). Two authors independently screened the identified articles, assessed study quality, and extracted data. Study characteristics of the included articles, including incremental cost-effectiveness ratios, when available, were summarised narratively. Results: Of the 197 articles retrieved, six studies met the inclusion criteria: three economic studies and three economic modelling studies. Of the three economic studies, one was a cost-effectiveness analysis and two were cost analyses. Of the three economic modelling studies, one was a cost-effectiveness analysis and two were cost-minimisation analyses. Both of the cost-effectiveness analyses reported that use of EUS as an additional staging technique provided, on average, more QALYs (0.0019–0.1969 more QALYs) and saved costs (by £1969–£3364 per patient, 2017 price year) compared to staging strategy without EUS. Of the six studies, only one included GOCs participants and the other five included oesophageal cancer participants. Conclusions: The data available suggest use of EUS as a complementary staging technique to other staging techniques for GOCs appears to be cost saving and offers greater QALYs. Nevertheless, future studies are necessary because the economic evidence around this EUS staging intervention for GOCs is far from robust. More health economic research and good quality data are needed to judge the economic benefits of EUS staging for GOCs. PROSPERO Registration Number: CRD42016043700. Keywords: Costs, Effects, QALYs, Economic review, Endoscopic ultrasound, EUS staging, Staging techniques, Gastro-oesophageal cancers * Correspondence: s.t.yeo@bangor.ac.uk 1 Centre for Health Economics and Medicines Evaluation (CHEME), Bangor University, Ardudwy, Normal Site, Holyhead Road, Bangor, Gwynedd LL57 2PZ, UK Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Yeo et al. BMC Cancer (2019) 19:900 Background Gastro-oesophageal (oesophageal or gastric, or both) cancers (GOCs) are one of the most common cancers in the UK with approximately 16,000 people diagnosed in 2015 [1, 2]. Oesophageal and gastric cancers were the seventh and fourteenth most common cause of cancer death respectively in the UK in 2016, as shown from the latest available statistics reported by the Cancer Research United Kingdom (CRUK) [1, 2]. It is estimated that a total of around 12,500 people died from these cancers in 2016 – that is 34 deaths per day [1, 2]. Accurate staging of GOCs is vital for determining prognosis and planning appropriate treatment. Accurate staging in the management of GOCs will not only help avoid unnecessary surgical interventions but also will ultimately help reduce the financial pressure on the NHS, which is particularly important given the limited resources available to cancer services and the growing incidence of GOCs [3]. Accurate staging of GOCs can be achieved by a combination of investigative techniques. The techniques used for staging GOC include computer tomography (CT), endoscopic ultrasound (EUS), positron emission tomography (PET) and adjuncts to staging include magnetic resonance imaging (MRI), bronchoscopy, laparoscopy and trans-abdominal ultrasound [4]. CT has been recommended for use at initial staging assessment to determine whether the cancer cells have spread from the primary site of its origin into new areas of the body (i.e. metastasis); but in the absence of metastatic disease, EUS has been advocated as the preferred technique for the assessment and prediction of operability [4]. This is due to the fact that EUS is superior to CT for local regional staging of oesophageal and gastric tumours [4]. Studies and guidelines for the management of oesophageal and gastric cancer have reported that EUS has superior tumour invasion (T) and loco-regional nodal (N) staging ability over CT and PET given its sensitivity, particularly for detection of regional lymph node metastases, although the complementary nature of these investigative techniques must be recognised [5–10]. The sensitivity of EUS for staging of GOC has been widely evaluated; however, the economic evidence of EUS staging in the management of GOC patients is scarce. Furthermore, the effectiveness and cost-effectiveness of EUS staging of GOC had not been assessed, particularly in the form of randomised controlled trials (RCT), until the establishment of “COGNATE” trial - a HTA-funded RCT UK study [11]. Given that the economic evidence of EUS for staging of GOC is scant, conducting a systematic review of the economic evidence on EUS staging in patients with GOC is therefore important. It not only gives a meaningful evidencebased insight, from an economic perspective, for researchers and clinical experts in this field but also healthcare commissioners. In view of that, this systematic review aimed to Page 2 of 19 examine all economic evidence (not just from RCTs) of the use of EUS staging in the management of patients with GOC. Systematic reviews of economic evaluations review studies that evaluated both the effectiveness in terms of health effects (usually measured as life-years gained (LYGs) or quality-adjusted-life-years (QALYs), accounting for the quality-of-life outcomes) and cost of the alternative interventions assessed. Economic evaluation is performed by undertaking either a cost-effectiveness analysis (CEA), cost-utility analysis (CUA), cost-consequences analysis (CCA), costbenefit analysis (CBA) or cost-minimisation analysis (CMA). When clinical outcome expressed in natural units (e.g. LYGs, lives saved, improvement in pain score etc) are used as health effects in an economic analysis, this is often referred to as CEA with its parameter of interest being called incremental cost-effectiveness ratio (ICER). Whereas, when QALY, a common unit, is used as health effect in an economic analysis, then this is often referred to as CUA though CEA is preferred by some authors and the resulting parameter of interest is called incremental cost-utility ratio (ICUR). The ICER/ICUR is then compared with the official or approximate willingness to pay (WTP) ceiling ratio for a unit of effect, that is, threshold used for decision making. CCA reports costs and outcomes in disaggregated form for each alternative [12]. CBA converts clinical outcomes into monetary units so that a net benefit (or cost) can be estimated [12]. CMA measures which alternative has the least cost, this method is only applied when the outcomes of alternative interventions have been proven to be equivalent. The protocol of this systematic review was registered prospectively with PROSPERO, an international prospective register of systematic reviews (Registration number 2016:CRD42016043700; http://www.crd.york.ac.uk/PROSPERO/display_record. php?ID=CRD42016043700) [13]. This paper offers a review of economic evidence on the costs, benefits (in terms of GOC patients’ health-related quality of life), and economic implications of the use of EUS for staging GOC patients. Methods This review was carried out and reported in accordance with the published updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [14, 15]. Searches and study selection Searches for this systematic review were conducted using a range of electronic databases: MEDLINE (ovid), EMBASE (ovid), The Cochrane Collaboration Register and Library (including Cochrane Central Register of Controlled Trials (CCRCT), Cochrane Reviews, Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), British National Health Service Economic Evaluation Database (NHS EED), Cochrane Methodology Register (CMR)), CINAHL (EBSCOhost), Web of Science (Core Yeo et al. BMC Cancer (2019) 19:900 Collection). Searches were restricted to publications from the last 20 years (1996–2016) as per the registered protocol on PROSPERO (Registration number 2016:CRD42016043700) [13]. To ensure that the review was as up-to-date as possible, the searches were re-run on all databases to cover 2016– 2018 (search update on 28/04/2018). In order to ensure a comprehensive search was achieved and any relevant research had not been missed, online searches were also conducted through the following internet search engines and appropriate websites to identify grey literature, reports, ongoing and unpublished studies from conference papers and abstracts: Google, Google Scholar, Department of Health (DoH), National Institute for Health and Clinical Excellence (NICE), National Institute for Health Research (NIHR) Journals Library, NIHR UK Clinical Trials Gateway, The National Cancer Research Institute (NCRI), Cancer Research Wales (CRW), Wales Cancer Research Centre (WCRC), Welsh Government (WG), Health and Care Research Wales (HCRW), CRUK and other relevant charitable organisation websites. The reference lists of papers that were included in the review were searched for further publications that had not been identified in the electronic searches. Contacts with study authors were made to locate further relevant literature and publications. Guided by the review objectives, the search terms as shown in Table 1 were developed using the PICO framework [16, 17]. The PICO framework was utilised to help shape, design and construct the search process to identify all relevant published and unpublished materials from various sources. Titles, abstracts and full-text papers were searched for using these search terms. The search strategy for each of the five electronic databases was developed, checked and tested by an information specialist before finalising the search terms; this process was informed by the search strategy of a wider evidence synthesis that includes a systematic review of non-economic studies of treatments for resectable adenocarcinoma of the stomach, gastro-oesophageal junction and lower oesophagus [18]. An example of search strategy used in the Medline Ovid database is as shown in the additional file (see Additional file 1). Inclusion and exclusion criteria Table 2 presents the inclusion and exclusion criteria, using the economic evidence review design framework outlined in the University of York Centre for Reviews and Dissemination (2009) [12]: Population, Interventions, Comparators, Outcomes, and Type of Evidence. Due to resources constraints, only studies written in English were included. This includes international studies that have been translated or written in English. Page 3 of 19 Data extraction Titles and abstracts of all studies identified were screened and assessed for relevance against the inclusion criteria by two independent reviewers (STY and NB). The inclusion or exclusion of each study was checked and confirmed. All potentially relevant full-text papers were then obtained and screened against the inclusion criteria, with disagreements resolved through discussion until agreements were achieved collectively. Disagreements occurred when for example the reviewers had different views on whether a retrieved paper should be included in the review. Following screening, relevant information from all fulltext papers included in the review were extracted by the primary reviewer (STY) using an adapted standardised form [12], and checked by the second reviewer (NB). Two adapted standardised forms were developed and used for data extraction – one for economic studies and another for economic modelling studies. Quality assessment The quality of all full-text papers included in the review were assessed and rated independently by the two reviewers using the Critical Appraisal Skills Programme (CASP) economic evaluation checklist [19] tool for economic studies and the Philips et al’s economic modelling checklist [20] tool for economic modelling studies. The papers were critically appraised to assess to what extent the content of these papers complied with the criteria of good practice in economic evaluation and if there was any obvious bias. Disagreements between the reviewers were resolved through discussion until agreements were achieved collectively. Disagreements occurred when for example the reviewers had different score on an included paper. Data synthesis All studies included in the review were summarised and compared across studies in a narrative form to answer the review objectives. The aims, methods, and results of the studies reviewed were synthesised narratively. This demonstrates the heterogeneity of the studies in terms of characteristics [12]. Due to the heterogeneity of the studies in terms of the study type and outcomes across the studies, meta-analysis was not appropriate [12]. Costs were converted into British pounds sterling, £, using the appropriate exchange rate published in the International Monetary Fund [21] and inflated to 2017 price year using the hospital and community health services (HCHS) index [22–25] for the studies included in the review. Results Literature search: identification of studies Overall, the search from 1996 to 2016 identified 197 potentially relevant studies, six of which fulfilled the Yeo et al. BMC Cancer (2019) 19:900 Page 4 of 19 Table 1 Search terms by category, guided by PICO framework, for the systematic review No. Search Term Category Search Terms 1. Disease neoplas* OR cancer*OR carcin* OR tumo* OR adenocarcinoma* OR squamous cell carcinoma* OR malig* OR metasta* AND 2. Type of disease gastro* OR oesophag* OR esophag* OR gastro-oesophag* OR gastro-esophag* OR gastroesophag* junction* OR gastro-esophag* junction* OR gastrooesophag* junction* OR gastro-oesophag* junction* OR esophagogastric junction* OR esophago-gastric junction* OR oesophagogastric junction* OR oesophago-gastric junction* OR oesophageal squamous cell carcinoma* OR esophageal squamous cell carcinoma* OR gut* OR gullet* OR food pipe OR stomach OR upper GI OR upper-GI OR upper gastrointestin* OR upper-gastrointestin* OR upper digestive tract* OR upper-digestive tract* OR intraepithelial OR intramucosal OR node* OR nodal AND 3. Intervention endosono* OR EUS OR endoscopic ultraso* OR endoscopic-ultraso* OR EUS-FNA OR Yeo et al. BMC Cancer (2019) 19:900 Page 5 of 19 Table 1 Search terms by category, guided by PICO framework, for the systematic review (Continued) No. Search Term Category Search Terms EUS-fine needle aspiration OR EUS fine-needle aspiration OR Endosonography-guided FNA OR Endoscopic ultrasound-fine needle aspiration OR Endoscopic ultrasound-guided fine needle aspiration OR Endoscopic ultrasound-guided fine-needle aspiration OR Endoscopic-ultrasound-guided fine-needle aspiration OR Endoscopic ultrasound guided fine needle aspiration OR Echoendoscop* OR Echo-endoscop* AND Staging OR Preoperative staging OR Pre-operative staging AND 4. Outcome econom* OR health economics OR economic evaluation OR cost-effective* OR cost effect* OR cost utility OR cost-utility OR cost-conseq* OR cost conseq* OR cost-benefit OR cost benefit OR cost-minimisation OR cost minimisation OR cost-minimization OR cost minimization OR cost* OR cost* analys* OR unit cost OR unit-cost OR unit-costs OR unit costs OR drug cost OR drug costs OR hospital costs OR health-care costs OR health care cost OR Yeo et al. BMC Cancer (2019) 19:900 Page 6 of 19 Table 1 Search terms by category, guided by PICO framework, for the systematic review (Continued) No. Search Term Category Search Terms medical cost OR medical costs OR cost* efficacy* OR cost* analys* OR cost* allocation* OR cost* control* OR cost* illness* OR cost* affordable* OR cost* fee* OR cost* charge* economic model* OR markov* OR budget* OR healthcare economics OR health care economics OR cost analys* OR health-care cost* OR health care cost* OR hrqol OR Health related quality of life OR health-related quality of life OR quality-adjusted life year* OR quality adjusted life year* OR qaly OR Quality of life OR quality-of-life OR QoL inclusion criteria and were included in the review (Fig. 1). Of the six studies included, three were economic analysis studies and three were economic modelling studies. To ensure that the review was as up-to-date as possible, the searches were re-run on all databases to cover 2016–2018 (search update on 28/04/2018); 30 potentially relevant papers were identified but none met the inclusion criteria. In such case, the final number of studies included in the review remained at six. Study descriptions Tables 3 and 4 summarises the characteristics of the six studies included in the review. There were three economic analysis studies (Table 3) and three economic modelling studies (Table 4). Five of the studies included in the review were US studies, and one was a UK study. Of the three economic analysis studies, two were cost analyses [26, 27] and one was a cost-effectiveness analysis [11]. Of the three economic modelling studies, two were cost-minimisation analyses [29, 30] and one was a cost-effectiveness analysis [31]. All of the three economic modelling studies used decision tree modelling techniques to explore staging strategies. The six studies included in the review differed quite markedly in terms of their design. Only one study used primary cost and outcome data collected in prospective evaluation [11], one study used data collected in prospective case series [27], one study used retrospective data [26], and the remaining three studies synthesised data from secondary sources in a decision tree model [29–31]. Of the six studies, only one [11] was a randomised controlled trial and included participants diagnosed with gastro-oesophageal cancer (i.e. oesophageal, gastro-oesophageal junction or gastric cancer); the other five were non-trial studies and included participants diagnosed with oesophageal cancer. Amongst the six studies, Russell et al. (2013) [11] was again the only study which evaluated costs of health care resource use Yeo et al. BMC Cancer (2019) 19:900 Page 7 of 19 Table 2 Inclusion and exclusion criteria for the systematic review Inclusion Criteria Exclusion Criteria Population All adults (aged 19 and above) who had cancer (i.e. localised tumour) of the oesophagus, stomach or gastro-oesophageal junction; free of metastatic disease. Population aged below 19 years and had metastatic oesophageal, gastro-oesophageal or gastric cancer. Interventions Use of endoscopic ultrasound (EUS) (also known as endosonography, echoendoscopy) staging in patient with oesophagus, gastro-oesophageal and gastric cancer. Use of endoscopy only or ultrasound only, and use of EUS for non-cancer staging purposes e.g. treatment of cancer Comparators Standard staging algorithm e.g. trans-abdominal ultrasound scan, computed tomography (CT) scan. Partial economic evaluations, when no formal comparator was used, were included. Outcomes All relevant full economic evaluation studies outcomes including (but not be restricted to) cost per QALY and cost per life-year gained; All other relevant economic outcomes including (but not be restricted to) resource use, direct and indirect costs, incremental benefits e.g. quality-adjusted survival or quality-adjusted life years (QALYs), health-related quality of life, cancer-specific quality of life and utility gained – this includes partial economic evaluation studies outcomes, which costs or consequences alone of a single intervention (e.g. EUS staging of GOC) were described, were included. Type of Evidence Full economic evaluation evidence (i.e. cost-effectiveness, Non-research studies such as editorials, case reports or other cost-utility and cost-benefit analyses) related to EUS staging descriptive studies. of oesophageal, gastro-oesophageal junction and gastric cancer were considered. Other economic studies that contain partial economic evaluation or no evaluation context (e.g. cost analyses, cost-description studies, cost-outcome descriptions, budgetary studies, outcome-description studies in terms of utility gained, health-related quality of life and cancer-specific quality of life measures such as QALYs and FACT-G score) were also considered. Economic evaluation studies conducted alongside RCTs, non-RCTs, quasi-experimental trials, epidemiological research, cohort studies, and modelling studies were considered. General Language – English. Years – 1996-2016 and 2016–2018 covering secondary care contacts and hospital prescribed drugs in addition to cost of EUS, collected prospectively in the trial. In terms of health outcome measures, two studies [11, 31] included quality-adjusted life year (QALY) as the measure of effect and conducted a cost-effectiveness analysis to assess the gain in QALYs relative to the costs of different staging strategies. The remaining four studies [26, 27, 29, 30] did not explore QALY or other quality of life measures but only cost. Quality assessment Each of the six studies included in the review were critically appraised against the appropriate source of quality appraisal checklist: the CASP economic evaluation checklist [19] was used for the three economic studies, and Philips et al’s economic modelling checklist [20] was used for the All outcomes unrelated to economic evidence of EUS staging of the oesophagus, gastro-oesophageal junction or gastric cancer. Language – Not written or translated into English. Years – Before 1996. remaining three economic modelling studies. Table 5 and Table 6 summarised the quality assessment of the three economic studies and three economic modelling studies, respectively. Table 5 shows the study quality of the three economic studies was generally good, scoring on average greater than 75%, although only one study [11] met all quality criteria on the CASP economic evaluation checklist. The study by Shumaker et al. (2002) [26] scored the second highest, followed by Chang et al. (2003) [27]. Of these three economic studies, two had missing key information: Chang et al. (2003) [27] reported neither cost perspective, cost inflation, discounting nor price year, and sensitivity analysis was not undertaken; likewise, Shumaker et al. (2002) [26] did not state whether their reported costs were discounted or inflated as appropriate. Table 6 shows the study quality of the three economic modelling studies included in the review was Yeo et al. BMC Cancer (2019) 19:900 Page 8 of 19 Fig. 1 Flowchart of the study selection process satisfactory, scoring moderately well on the Philips et al’s economic modelling checklist. In descending order of quality, the study by Wallace et al. (2002) [31] scored the highest followed by Harewood et al. (2002) [30] and Hadzijahic et al. (2000) [29]. One study [29] did not state the perspective of the model and all three [29–31] did not specify the time horizon of the decision tree model. There was insufficient detail of how parameters in the model were identified [31] and how data were modelled [30]. There was also a lack of clarity with regards to the source of probabilities and cost data used in the decision tree model [29]. Data synthesis results All of the six studies included in the review exhibit EUS as a complementary imaging technique to other imaging modalities such as CT and PET scanning for staging gastro-oesophageal cancer. This is in agreement with a previously published meta-analysis study of diagnostic test characteristics for EUS, CT, and PET scanning [8], concluding that the three approaches were complementary. Results from three of the economic studies [11, 26, 27] show staging of oesophageal or gastro-oesophageal cancer with EUS could potentially save costs. Similarly, results from two of the modelling studies [29, 30] show that EUS or EUS-fine-needle aspiration biopsy (FNA) is the least costly staging technique for oesophageal cancer. The study by Wallace et al. (2002) [31] shows that EUS-FNA in addition to CT scan is the least costly strategy than all other strategies i.e. CT alone, CT+ thoracoscopy and laparoscopy (TL), CT + EUS-FNA + TL, CT + PET+EUS-FNA and PET+EUSFNA. Results from the two studies [11, 31] in which qualityadjusted life year (QALY) and cost data were available demonstrate the use of EUS [11] or EUS-FNA [31] as an additional staging technique for gastro-oesophageal cancer offered more QALYs and costed less, on average, compared to staging techniques without EUS. Russell et Aims of the study To determine (1) the relative proportions of each oesophageal cancer stage in a group of patients referred for preoperative staging with EUS, (2) the proportion of patients with EUS stage 1 and 4 tumours that would not be treated with combined modality therapy, and (3) to estimate the potential cost savings of performing preoperative EUS in oesophageal cancer patients. To determine the impact of EUS combined with FNA on patients’ choice of therapy and on the cost of care. Authors, year, country Shumaker et al. (2002) [26], USA. Chang et al. (2003) [27], USA Patients diagnosed with oesophageal cancer (squamous-cell or adenocarcinoma) who were referred to the University of California’s Irvine Medical Center for preoperative EUS staging between August 1993 and August 1997 (n = 60, 39 men, 21 Patients with oesophageal cancer receiving preoperative staging with EUS (n = 180, 82% men and mean age 66.5 years). Type of participants (n) Cost analysis alongside prospective case series. Cost analysis using a retrospective review of a large multicentre national computerised endoscopic database. Data between February 1998 and October 2000 were extracted, reviewed and analysed. Type of study, methodology Price year: 2000 Currency: US dollars (USD$) Not stated specifically, the authors described their cost analyses were based on the published direct costs of endosonographyguided aspiration biopsy and thoracotomy published in 1997 (Gress et al., 1997). Currency: US Not stated specifically, the study was undertaken in California, USA. Price year, currency (unit) Not stated specifically, the authors described US Medicare data Study perspective NA: cost analysis study alongside prospective case series. NA: retrospective review of a large national endoscopic database. Type of intervention / staging technique Table 3 Summary table of the structure of the three economics papers included in the review NA NA Method of delivery Based on the data used in the cost analyses, the length of followup was, on average, 17 months (range 1– 51 months). NA Length of follow-up The cost of EUSFNA biopsy based on the published direct costs of endosonographyguided aspiration biopsy (Gress et al., 1997) was estimated at $1975 per patient (outpatient) (£3528 per patient, 2017 price year). The cost of EUS for preoperative staging of oesophageal cancer was estimated at $634 per patient (£697 per patient, 2017 price year) Cost of intervention / staging technique Cost analysis study: the cost of care for these patients was calculated to explore whether or not the use of EUS decreases the cost of managing patients with oesophageal cancer. Cost analysis study: the potential cost savings of performing preoperative EUS in oesophageal cancer patients. Type of economic analysis conducted Patients’ decisions on whether to undergo medical or surgical treatment correlated significantly with their overall tumour staging, suggesting that the information provided by Preoperative staging of oesophageal cancer with EUS can facilitate cost savings by reducing the need for additional treatments in stage 1 and 4 oesophageal cancer (a significant proportion of patients – 26% in this series). Outcomes / results / conclusionsa Yeo et al. BMC Cancer (2019) 19:900 Page 9 of 19 Aims of the study To examine whether the addition of EUS to usual staging uses resources costeffectively. Authors, year, country Russell et al. (2013) [11], UK Patients with proven cancer of the oesophagus, stomach or gastrooesophageal junction; medically fit for both surgery (even if not planned) and chemotherapy, free of metastatic disease and had not started treatment. Both their ASA (America Society of Anesthesiologists) grading and their WHO women and mean age 68 ± 10 years). These patients were all being considered for surgical resection and had undergone standard evaluation including CT which showed no evidence of distant metastases. Type of participants (n) Costeffectiveness analysis alongside a multi-centre randomised controlled trial (RCT) namely ‘COGNATE trial’. The study explored whether giving EUS scan in addition to standard staging algorithms would be more costeffective compared to Type of study, methodology NHS perspective, focusing on health-care resources used by participants including investigation, treatment and palliation, and other elements of secondary and pharmaceutical care. Study perspective Type of intervention / staging technique Price year 2008 Cancer Currency: Pounds staging with Sterling (£) EUS vs. without EUS dollars (USD$) Price year, currency (unit) Patients randomised to intervention group received EUS scan in addition to standard staging algorithms. Patients randomised to control group received standard staging algorithms. Method of delivery Table 3 Summary table of the structure of the three economics papers included in the review (Continued) Study follow-up period was 54 months or until death, whichever came first. Main analyses of the study (including health economic analysis) used 48 months. Length of follow-up The cost of EUS scan was £551 (day case) (£648, 2017 price year), £1477 (outpatient) (£1737, 2017 price year) and £3781 (inpatient) (£4447, 2017 price year). Cost of intervention / staging technique Costeffectiveness analysis using QALY as a measure of effect – The difference in cost and QALY between intervention and control groups was calculated; the probabilities of the EUS intervention being costeffective at different willingness-topay thresholds Type of economic analysis conducted EUS reduced net use of health-care resources by £2860 (£3364, 2017 price year) and had an increase of 0.1969 in estimated mean QALYs. Combining these estimated benefits and savings yields probability of 96.6% that EUS is costeffective in the sense of achieving the EUS played a significant role in patients’ decisionmaking. EUSguided therapy potentially reduces the cost of managing patients with oesophageal cancer by USD$12,340 per patient (£10,510 per patient, 2017 price year) due to reduced number of thoracotomies undertaken (patient choice). Outcomes / results / conclusionsa Yeo et al. BMC Cancer (2019) 19:900 Page 10 of 19