Approach

Patients with gastric cancer typically present with abdominal pain and weight loss.[3]​ For newly diagnosed patients, a comprehensive evaluation is recommended, including a complete history and physical examination, laboratory tests (FBC, comprehensive metabolic panel, and Helicobacter pylori screening), and oesophagogastroduodenoscopy (OGD) with biopsy.[39]​ Tumour staging is essential to ensure that patients are selected for appropriate treatment and is primarily done using computed tomography (CT). Diagnostic laparoscopy with peritoneal cytology is advised for patients with potentially resectable locoregional disease to detect occult peritoneal metastases.[39] All newly diagnosed patients should undergo testing for microsatellite instability (MSI) or mismatch repair (MMR) status, PD-L1 expression, and, if advanced/metastatic disease is suspected, HER2 and CLDN18.2. Next-generation sequencing may be considered for additional molecular profiling.[39]

Clinical presentation

Weight loss and persistent abdominal pain are the most common presenting symptoms in patients with gastric cancer, although dysphagia is common in cancers of the proximal stomach or gastro-oesophageal junction.[3] Complete history and comprehensive physical examination are recommended.​[39]

Laboratory tests

Recommended laboratory tests include:[39][40]​​ 

  • Full blood count to assess for iron deficiency anaemia

  • Renal function tests and liver function tests to determine appropriate therapeutic options

H pylori testing/screening: perform in patients with early-stage gastric cancer, and give appropriate treatment to eradicate the infection. See Gastritis. H pylori testing of close family members is also recommended.[11][20]​​​​[37]​​​[39]

OGD with biopsy

The initial diagnostic test. OGD with biopsy 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 histological and molecular interpretation, especially in the setting of an ulcerated lesion.[39]

Once the diagnosis is established, patients should undergo further staging to determine the extent of their disease.

Pathological examination and biomarker testing

Biopsy tissue should be examined to confirm histological cancer type, cancer grade, and presence or absence of invasion.[39]

Targeted therapies may be indicated for patients with high microsatellite instability (MSI)/mismatch repair deficiency tumours, patients with high tissue tumour mutation burden status, and patients with neurotrophic tropomyosin-related kinase (NTRK) gene fusion-positive tumours.[39]

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]

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 over-expression 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]​

Liquid biopsy can be used to evaluate circulating tumour DNA by means of a blood test.[39]​ 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.

If limited tissue is available for testing or if patients with metastatic or advanced gastric cancer are not able to undergo a traditional biopsy, comprehensive genomic profiling via a validated next-generation sequencing assay should be considered.[39]​ Targeted biomarkers include: HER2 overexpression/amplification, PD-L1 expression by IHC, MSI status, mismatch repair deficiency, tumour mutational burden, CLDN18.2, NTRK gene fusions, RET gene fusions, and BRAF V600E mutations.[39]​ 

Tumour staging

Tumour staging is essential to ensure that patients are selected for appropriate treatment.[40]​ CT scans are routinely recommended for all patients.[39]​ Other modalities should be considered based on an individual basis. These include endoscopic ultrasound (EUS), endoscopic resection (for early-stage cancers), or staging laparoscopy. Fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT may be performed if advanced or metastatic disease is suspected or if clinically indicated, but it is less sensitive for diffuse or mucinous tumours.[39]

CT scan

Chest, abdomen, and pelvis CT scans with oral and intravenous contrast are routinely recommended for all patients to detect local or distant lymphadenopathy and metastatic disease or ascites.[39][40]

EUS

EUS can determine the proximal and distal extent of the tumour and accurate tumour and node staging, especially if early-stage disease is suspected or early versus locally advanced disease needs to be determined.[39][40]

Endoscopic resection

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]

Laparoscopy

Staging laparoscopy should be considered, as peritoneal and metastatic disease <5 mm in size may be missed, even with high-quality CT scans.

The ESMO 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 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]

PET/CT scan

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 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]​​ 

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