Real-world Incremental Costs of Opportunistic Upper Gastrointestinal Endoscopy Added to Colorectal Cancer Screening and the Economic Burden of Gastric Cancer Management: a Retrospective Cohort Study - Study Protocol
Conditions: Gastric Cancer (GC), Gastric Adenocarcinoma
Sponsor: Unidade Local De Saúde Do Norte Alentejano

Study Protocol 
Title: Real-world incremental costs of opportunistic upper gastrointestinal 
endoscopy added to colorectal cancer screening and the economic burden of 
gastric cancer management: an economic study. 
 
 
 NCT:  
Date: 01/03/2026 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Authors 
1. Mourato B., MD  
a. A2iliation:   
i. NOVA National School of Public Health, Public Health Research 
Centre, Comprehensive Health Research Center, CHRC, LA-REAL, 
CCAL, NOVA University Lisbon, Lisbon, Portugal, Lisbon, Portugal;  
ii. Unidade Local de Saúde do Alto Alentejo, Hospital Doutor José 
Maria Grande, Portalegre, Portugal;  
b. Contacts: email: mbb.mourato@ensp.unl.pt; Address: Hospital Doutor José Maria 
Grande, Avenida de Santo António, 7300-853, Portalegre; 
c. Contributions: Main author; Study designer.  
d. ORCID: 0000-0002-9242-1560 
2. Pinto P., MD 
a. ATiliation:  Unidade Local de Saúde do Alto Alentejo, Hospital Doutor José Maria 
Grande Portalegre, Portugal; 
b. Contacts: email: pedro.c.pinto@ulsaale.min-saude.pt; Address: Hospital Doutor 
José Maria Grande, Avenida de Santo António, 7300-853, Portalegre; 
c. Contributions: Study collaborator; 
d. ORCID: 0009-0006-8270-992X 
3. Veira J., MD 
a. ATiliation:  Unidade Local de Saúde do Alto Alentejo, Hospital Doutor José Maria 
Grande Portalegre, Portugal; 
b. Contacts: email:  
c. Contributions: Study collaborator; 
d. ORCID:  
 
4. Vidinha M., MPharm 
a. ATiliation:  Unidade Local de Saúde do Alto Alentejo, Hospital Doutor José Maria 
Grande, Portalegre, Portugal;  
b. Contacts: email: ana.m.vidinha@ulsaale.min-saude.pt; Address: Hospital Doutor 
José Maria Grande, Avenida de Santo António, 7300-853, Portalegre; 
c. Contributions: Study collaborator; 
d. ORCID:  
5. Carvalho V.,  
a. ATiliation:  Unidade Local de Saúde do Alto Alentejo, Hospital Doutor José Maria 
Grande, Portalegre, Portugal;  

b. Contacts: email: Vasco.Carvalho@ulsaale.min-saude.pt; Address: Hospital Doutor 
José Maria Grande, Avenida de Santo António, 7300-853, Portalegre; 
c. Contributions: Study collaborator; 
d. ORCID:  
6. Pratas N., MD 
a. ATiliation:  Unidade Local de Saúde do Alto Alentejo, Hospital Doutor José Maria 
Grande Portalegre, Portugal; 
b. Contacts: email: nuno.f.c.pratas@gmail.com; Address: Hospital Doutor José Maria 
Grande, Avenida de Santo António, 7300-853, Portalegre; 
c. Contributions: Study collaborator; 
d. ORCID: 0000-0002-6980-3675 
7. Capote H., MD 
a. ATiliation:  Unidade Local de Saúde do Alto Alentejo, Hospital Doutor José Maria 
Grande Portalegre, Portugal; 
b. Contacts: email: hugocapote@gmail.com; Address: Hospital Doutor José Maria 
Grande, Avenida de Santo António, 7300-853, Portalegre; 
c. Contributions: Study collaborator; 
d. ORCID: 0000-0002-6980-3675 
8. Fronteira, I., PhD 
a. ATiliation: NOVA National School of Public Health, Public Health Research 
Centre, Comprehensive Health Research Center, CHRC, LA-REAL, CCAL, 
NOVA University Lisbon, Lisbon, Portugal, Lisbon, Portugal 
b. Contacts: email: ines.fronteira@ensp.unl.pt; Address: Avenida Padre Cruz, 1600-
560 Lisboa.  
c. Contributions: Study designer; Intellectual contributor; Reviewer. 
d. ORCID: 0000-0003-1406-4585 
9. Dinis, R., PhD 
a. ATiliation: Hospital do Espírito Santo de Évora, Portugal,  
b. Contacts: email: rui.p.dinis@ulsna.min-saude.pt; Address: Largo do Sr. Da 
Probreza, 7000-811 Évora; 
c. Contributions: Study designer; Study collaborator; Reviewer.  
d. ORCID: 0000-0002-2101-0027 
 
10. Areia M., PhD  
a. ATiliation 
i. Instituto Português de Oncologia de Coimbra, Portugal; 
ii. RISE@CI-IPO (Health Research Network), Portuguese Oncology Institute of 
Porto (IPO Porto) 

b. Contacts: email:  miguel.areia75@gmail.com ; Address: Avenida Bissaya Barreto 
98, 3000-075 Coimbra. 
c. Contributions: Study designer, Intellectual contributor; Reviewer. 
d. ORCID: 0000-0001-9787-8175 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

1. Background and Rationale 
Gastric cancer remains a major cause of cancer-related mortality in Europe[1], with 
diagnosis frequently occurring at advanced stages, leading to substantial clinical 
and economic burden. Opportunistic strategies integrating upper gastrointestinal 
endoscopy (esophagogastroduodenoscopy) (EGD) with organized colorectal 
cancer screening have been proposed as a pragmatic approach to improve early 
detection in intermediate-risk countries [2], [3], [4], [5]. 
In Portugal, a cost–utility analysis model by Areia et al. demonstrated that 
combining 
EGD 
with 
colonoscopy 
in 
individuals 
with 
positive 
fecal 
immunochemical testing (FIT) may represent a cost-effective strategy, whereas 
stand-alone gastric cancer screening was not [2]. However, evidence based on real-
world cost data from clinical practice remains limited. 
The number needed to screen (NNS) is deﬁned as the inverse of the absolute risk 
reduction (ARR) in gastric cancer-related mortality between screened and non-
screened populations. The ARR represents the attributable risk diWerence, 
calculated as the diWerence in mortality risk between individuals not undergoing 
screening and those undergoing endoscopic screening. [6]. 
Early-stage gastric cancer is associated with less intensive treatment and 
substantially lower healthcare costs compared to advanced disease, supporting 
the hypothesis that stage shift may result in economic beneﬁt [4]. 
This study aims to estimate and compare: 
1. the incremental direct medical cost per participant attributable to the 
addition of an opportunistic EGD performed during an already scheduled 
colorectal cancer screening colonoscopy following a positive FIT result.  
2. the real-world costs associated with the diagnosis and management of 
gastric cancer over a 10-year period in the same institution. 
2. Objectives 
1. To estimate the total incremental cost of the opportunistic EGD screening 
component during the study period. 
2. To estimate the mean and total real-world costs of gastric cancer 
management, overall and stratified by disease stage and treatment intent. 

3. To describe treatment pathways and clinical outcomes of gastric cancer 
patients. 
4. To identify major cost drivers of gastric cancer management. 
5. To compare the total cost of opportunistic screening plus treatment of early-
stage gastric cancer (stage I) with the cost of treatment of advanced-stage 
disease (stage II–IV or III–IV). 
6. To estimate the potential cost savings associated with stage shift induced by 
opportunistic screening. 
7. Estimated cost per stage shift (i.e., cost required to convert one advanced-
stage diagnosis into an early-stage diagnosis). 
 
3. Study Design 
This is a real-world cost analysis based on two observational cohorts: 
1. Cohort A – Opportunistic screening cohort 
A cohort of FIT-positive individuals undergoing colonoscopy for colorectal 
cancer screening, with the addition of opportunistic EGD during the same 
procedure. 
2. Cohort B – Gastric cancer cohort 
A retrospective cohort including all patients diagnosed with gastric 
adenocarcinoma in the institution over a 10-year period. 
The observational components will be reported according to STROBE guidelines, 
and the economic components according to CHEERS recommendations. When 
routinely collected healthcare data are used, RECORD principles will be followed. 
4. Setting 
The study will be conducted at Unidade Local de Saúde do Alto Alentejo, Portugal, 
including two centers participating in the opportunistic screening strategy. 
5. Perspective, Time Horizon, and Currency 
Perspective 
The primary analysis will adopt the healthcare provider / National Health Service 
(SNS) perspective, including direct medical costs only. 
Time Horizon 
• 
Screening cohort: from February 2023 to February 2025. 

• 
Gastric cancer cohort: 
o cumulative costs from diagnosis to death or end of 5-years follow-up. 
Currency and Price Year 
All costs will be expressed in euros (€) and adjusted to a common price year (March 
2026), using appropriate inflation indices when necessary. 
6. Study Population 
Cohort A – Opportunistic Screening 
Inclusion criteria 
• Eligible participants were adults aged 50 to 75 years or older who had been 
referred for colonoscopy as part of the national colorectal cancer screening 
programme, following a positive FIT. To be included, individuals also needed 
to provide informed consent and agree to undergo an EGD endoscopy for the 
screening of potential upper gastrointestinal precancerous conditions or 
lesions.  
Exclusion criteria 
• Exclusion criteria included a prior diagnosis of gastric cancer, as well as any 
condition that would prevent the safe performance of the EGD or the 
collection of gastric mucosal biopsies. Previous EGD was not listed as an 
exclusion criterion. 
Index date 
• 
Date of the combined colonoscopy + EGD procedure. 
Cohort B – Gastric Cancer 
Inclusion criteria 
• 
Patients with gastric adenocarcinoma, diagnosed and treated at Unidade 
Local de Saúde do Alto Alentejo between 2015 and 2020.  
 

Exclusion criteria 
• 
Other types of gastric tumors. 
• 
Gastric involvement from metastatic disease of another primary tumor. 
Index date 
• 
Date of pathological diagnosis of gastric cancer. 
7. Data Sources 
Data will be extracted from routinely collected hospital databases, including: 
• 
Electronic medical records; 
• 
Endoscopy and pathology databases; 
• 
Surgical and hospitalization records; 
• 
Oncology treatment databases; 
• 
Imaging and diagnostic services; 
• 
Institutional mortality records. 
When multiple sources are available, predefined rules will be applied to resolve 
discrepancies. 
8. Variables Collected 
For economic comparison purposes: 
• 
Early-stage gastric cancer will be defined as stage I disease 
• 
Advanced-stage gastric cancer will be defined as stage II–IV (or 
alternatively III–IV in sensitivity analysis) 
Screening Cohort 
• 
Demographics (age, sex). 
• 
Procedure characteristics (EGD and colonoscopy completeness, 
sedation). 
• 
Endoscopic findings and biopsies. 
• 
Pathology results. 
• 
Complications and related hospitalizations. 
• 
Follow-up procedures directly related to screening. 
 

Gastric Cancer Cohort 
• 
Demographics. 
• 
Tumor characteristics and stage at diagnosis (TNM/AJCC). 
• 
Treatment intent (curative vs palliative). 
• 
Treatments received (surgery, chemotherapy, radiotherapy, palliative). 
• 
Number of consultations and hospital admissions. 
• 
Dates of death and overall survival. 
Data will be anonymized prior to analysis, and access to identiﬁable information 
will be restricted to authorized investigators only. 
9. Costing Methodology 
Costing Approach 
A hybrid costing approach will be used, quantifying healthcare resource utilization 
at the individual patient level and multiplying by unit costs. 
Unit Costs 
Unit costs will be obtained from official national tariffs and/or institutional 
accounting systems. Alternative cost sources will be explored in sensitivity 
analyses. 
Incremental Cost Deﬁnition for the Screening Strategy 
The economic evaluation will estimate only the additional costs generated by the 
opportunistic EGD, assuming that colonoscopy, sedation, and baseline procedural 
infrastructure were already required for colorectal cancer screening. 
Accordingly, the following incremental resources will be considered: 
• 
EGD procedure and reprocessing; 
• 
Disposable biopsy forceps; 
• 
Specimen collection containers; 
• 
Histopathological processing and analysis of gastric biopsies. 

Costs related to colonoscopy performance, sedation, patient preparation, 
recovery, and baseline endoscopy unit operation will not be included, as these 
would occur regardless of the addition of EGD. 
Direct estimation of marginal infrastructure costs (procedure room occupancy 
time, utilities such as electricity and water, and personnel time) may not be 
individually measurable within routine accounting systems. Therefore, these 
components will be considered implicitly incorporated within institutional 
procedure tariffs when applicable. 
Cost Estimation – Gastric Cancer Cohort 
Healthcare resource utilization will be collected at the individual patient level and 
will include: 
• 
Surgical treatment episodes, including operating room procedures and 
consumables; 
• 
Systemic therapy regimens, number of treatment lines, and cycles 
administered; 
• 
Radiotherapy treatments (number of fractions or total dose); 
• 
Hospitalizations related to cancer treatment or complications; 
• 
Day-hospital oncology episodes; 
• 
Outpatient consultations related to gastric cancer management. 
Unit costs for surgical procedures, systemic therapy administration, 
hospitalizations, outpatient visits, and radiotherapy will be obtained from 
institutional accounting systems and/or official national tariffs. 
Follow-up diagnostic examinations will be included in the economic model using a 
standardized surveillance schedule based primarily on NCCN recommendations, 
while acknowledging that real-world follow-up is heterogeneous and that ESMO 
recommends an individualized approach. In line with ESMO guidance, regular 
follow-up is considered appropriate for symptom assessment, psychological 
support, and early detection of recurrence, but ESMO does not define a detailed 

surveillance timetable. Therefore, for costing purposes, a pragmatic NCCN-based 
schedule will be adopted. 
For all patients undergoing curative-intent treatment, clinical follow-up visits will be 
assumed every 6 months during years 1–2 and annually during years 3–5, 
corresponding to a total of 7 follow-up consultations over 5 years. A complete blood 
count and basic chemistry panel will be costed at each scheduled visit as a 
standardized analytical assumption, although laboratory tests are described in the 
guideline as clinically indicated rather than mandatory. 
For stage II–III disease, contrast-enhanced CT of the chest, abdomen and pelvis will 
be assumed every 6 months during the first 2 years and annually thereafter until 
year 5, totaling 7 CT scans. For stage I disease, routine CT surveillance will not be 
included in the base-case analysis and imaging will be considered only if clinically 
indicated. 
Routine endoscopic surveillance will not be included in the base-case model. In 
accordance with NCCN-based follow-up principles, upper gastrointestinal 
endoscopy will be considered only when clinically indicated, and routine 
endoscopy after total gastrectomy will not be assumed. Given persistent variation 
in practice regarding surveillance of the gastric remnant after subtotal gastrectomy, 
endoscopy may instead be explored in sensitivity analyses. 
PET/CT will not be included as a routine surveillance examination and will be 
reserved for problem-solving in cases of suspected recurrence or equivocal 
findings on conventional imaging. 
Because guideline recommendations for postoperative gastric cancer surveillance 
remain heterogeneous and several investigations are classified as clinically 
indicated, the study will use a base-case standardized schedule and test 
alternative surveillance intensities in sensitivity analyses. 
 
 

Comparative Economic Analysis 
A comparative analysis will be conducted to evaluate the economic implications of 
stage shift associated with opportunistic screening. 
The following comparison will be performed: 
• 
Strategy A (Screening scenario): Incremental cost of opportunistic EGD 
screening + cost of diagnosis and treatment of stage I gastric cancer. 
• 
Strategy B (No screening / usual care scenario): Cost of diagnosis and 
treatment of advanced-stage gastric cancer (stage II–IV). 
Mean per-patient costs will be estimated for each stage group using real-world data 
from the gastric cancer cohort. 
The analysis will estimate: 
• 
Cost difference between early-stage and advanced-stage disease 
• 
Incremental cost required to detect one stage I cancer 
• 
Potential cost offsets associated with earlier diagnosis 
The previously deﬁned number needed to screen (NNS) will be incorporated as an 
external eWectiveness input in the comparative economic analysis and explored in 
sensitivity analyses. The NNS parameter will be explored in sensitivity analyses to 
account for uncertainty in screening eWectiveness. 
Costs from the screening cohort and gastric cancer cohort will be integrated 
analytically to model the economic impact of early detection. 
Optional Societal Costs (Exploratory Analysis) 
Indirect costs related to productivity losses due to work absenteeism and 
premature mortality may be explored in secondary analyses using publicly available 
national wage statistics. These estimates will be considered exploratory due to 
limitations inherent to retrospective data collection, and use of assumptions due to 
the general lack of available data. 

The study does not directly estimate cost-eWectiveness metrics such as QALYs, 
limiting full health economic evaluation. 
10. Outcomes 
Economic Outcomes 
• 
Incremental cost per screening EGD. 
• 
Incremental cost per early-stage gastric cancer detected. 
• 
Total and mean incremental screening cost per patient.  
• 
Total and mean cost per gastric cancer patient. 
• 
Costs stratified by stage and treatment intent. 
• 
Cost diWerence between early and advanced-stage disease. 
• 
Estimated cost savings per patient associated with stage shift. 
Clinical Outcomes 
• 
Stage distribution at diagnosis. 
• 
Treatment patterns. 
• 
Overall survival. 
11. Statistical Analysis 
Costs will be summarized using means, medians, and interquartile ranges. 
Confidence intervals for mean costs will be estimated using non-parametric 
bootstrap methods. Missing data patterns will be described and addressed using 
appropriate methods. 
12. Ethical Considerations 
The study will be conducted in accordance with national regulations and approved 
by the institutional ethics committee. Data will be pseudonymized, and no direct 
patient contact will occur. 
All participants in the opportunistic screening cohort provided informed consent at 
the time of inclusion in the screening programme. Patients in the gastric cancer 
cohort had previously provided informed consent for the use of their clinical data in 
research, including prior institutional studies (e.g., MGPT study). 

The current study will use fully anonymized data, and no additional patient contact, 
intervention, or data collection beyond routine clinical records will be performed. 
13. Strengths and Limitations 
This study provides real-world cost data from routine clinical practice but is limited 
by its retrospective design and lack of a contemporaneous non-screened 
comparator. 
14. Expected Impact 
The results will inform decision-makers on the economic burden of gastric cancer 
and the potential budgetary implications of implementing opportunistic combined 
endoscopic screening strategies in intermediate-risk settings. 
 
References 
[1] International Agency for Research on Cancer, ‘Global Cancer Observatory 
2022 - Stomach’. 2022. [Online]. Available: 
https://gco.iarc.fr/today/en/dataviz/maps-
heatmap?mode=population&cancers=7 
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intermediate gastric cancer risk’, UEG Journal, vol. 6, no. 2, pp. 192–202, Mar. 
2018, doi: 10.1177/2050640617722902. 
[3] I. Lansdorp-Vogelaar, Meester, RGS, Laszkowska, M, Escudero, FA, Ward, ZJ, 
and Yeh, JM, ‘Cost-effectiveness of prevention and early detection of gastric 
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50–51, 2021, doi: 10.1016/j.bpg.2021.101735. 
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[5] M. B. Mourato et al., ‘Gastric Cancer Endoscopic Screening in an Intermediate-
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e70061, Jul. 2025, doi: 10.1111/hel.70061. 
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