Investigations
1st investigations to order
oesophagogastroduodenoscopy with biopsy
Test
Oesophagogastroduodenoscopy with biopsy is the initial diagnostic test. It allows precise localisation of the primary tumour and acquisition of tissue for diagnosis, histological classification, and molecular biomarkers.[39][40]
The European Society for Medical Oncology (ESMO) recommends multiple biopsies (5-8) to confirm the representation of the tumour.[40] The National Comprehensive Cancer Network (NCCN) recommends multiple biopsies (6-8) using standard size endoscopy forceps to provide adequately sized material for histologic and molecular interpretation, especially in the setting of an ulcerated lesion.[39]
Test biopsies for Helicobacter pylori via histology and/or urease testing (rapid urease test).
Result
ulcer or mass or mucosal changes; may also detect H pylori
CT of chest/abdomen/pelvis
FBC
comprehensive metabolic panel
Helicobacter pylori carbon-13 urea breath test or stool antigen test
Test
If, after endoscopy, the patient’s H pylori status is uncertain, establish whether the patient is infected with H pylori using the urea breath test or stool antigen test.
Screening for H pylori should be performed in patients with early-stage gastric cancer, and appropriate treatment must be given to eradicate the infection. H pylori testing of close family members is also recommended.[39]
Result
positive if H pylori is present
molecular and pathological tests
Test
Immunohistochemistry (IHC), in situ hybridisation, or targeted polymerase chain reaction should be considered first for the identification of biomarkers, followed by next-generation sequencing.[39]
Microsatellite instability (MSI) testing (by polymerase chain reaction or next-generation sequencing), or mismatch repair deficiency testing by IHC, should be conducted in newly diagnosed patients.[39]
Testing for HER2 overexpression using IHC or fluorescent in-situ hybridisation is recommended for all patients who have confirmed or suspected advanced/metastatic disease. PD-L1 testing by IHC is recommended for all newly diagnosed patients to determine their eligibility for PD-1 inhibitors.[39]
Claudin 18.2 (CLDN18.2) testing is recommended for patients who have confirmed or suspected unresectable locally advanced, recurrent, or metastatic gastric cancer and in whom anti-CLDN18.2 monoclonal antibody is being considered.[39]
Result
HER2-positive or HER2-negative; MSI-high or MSI-low or MSI-stable; MMR-deficient or no evidence of deficient mismatch repair; PD-L1 expression: positive (CPS ≥1) or negative (CPS <1); CLDN18.2 positive or CLDN18.2 negative
Investigations to consider
endoscopic ultrasound
endoscopic resection
Test
Early-stage cancers (T1a or T1b) are best diagnosed by endoscopic resection procedures, which includes endoscopic mucosal resection (EMR) or or endoscopic submucosal dissection (ESD).[39] Endoscopic resection can be used for assessment of small lesions and focal nodules ≤2 cm. Since a larger specimen can be obtained for assessment, these techniques provide greater information on degree of differentiation, presence of lymphovascular invasion, and depth of infiltration, aiding accurate T staging.[39]
Result
assesses depth of invasion (T), lymph vascular invasion, and degree of tumour differentiation
laparoscopy
Test
Staging laparoscopy should be considered, as peritoneal and metastatic disease <5 mm in size may be missed, even with high-quality CT scans.
The European Society for Medical Oncology recommends laparoscopy with or without peritoneal washing for malignant cells for all patients with stage 1B to 3 potentially resectable gastric cancers, to exclude radiologically occult metastatic disease.[40]
The US National Comprehensive Cancer Network (NCCN) recommends laparoscopy with cytology for clinical stage T1b or higher to evaluate for peritoneal spread when considering local therapy, unless a palliative resection is planned.[39]
Result
metastatic lesions
PET/CT scan
Test
Combined PET/CT imaging may improve staging by detecting involved lymph nodes or metastatic disease. It should be considered for patients whose CT scans show locally advanced disease to rule out distant metastases, which would make them ineligible for curative therapy. The NCCN notes that combined fluorodeoxyglucose (FDG)-PET/CT imaging offers several potential advantages over FDG-PET or CT scans alone.[39] However, the accuracy of FDG-PET may be low in some gastric cancer types (e.g., diffuse and mucinous) because of low FDG uptake.[41][42]
Result
metastatic disease
liquid biopsy
Test
Can be used to evaluate circulating tumour DNA (ctDNA) by means of a blood test. Liquid biopsy can detect mutations/alterations or fusions in DNA shed from gastric cancer, therefore helping identify alterations that can be targeted by available treatments. A negative result does not exclude the presence of tumour mutations or amplifications and should, therefore, be interpreted with caution.[39]
Result
ctDNA-positive or negative
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