Approach

Patients with gastric cancer typically present with abdominal pain and weight loss.[3]​ Oesophagogastroduodenoscopy with biopsy demonstrating carcinoma is required to confirm the diagnosis. Staging based on imaging is essential.

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]​ Patients may present with gastrointestinal (GI) bleeding (melaena).[3]

Oesophagogastroduodenoscopy (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.[26]​​​​​[27] The European Society for Medical Oncology (ESMO) recommends multiple biopsies (5-8) to confirm the representation of the tumour.[27] The National Comprehensive Cancer Network (NCCN) in the US 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.[26]

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

Laboratory tests

Recommended laboratory tests include:[26][27]

  • Full blood count to assess for iron deficiency anaemia

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

  • Helicobacter pylori testing/screening. Screening should be performed in patients with early gastric cancer, and appropriate treatment must be given to eradicate the infection. H pylori testing of close family members is also recommended.

Tumour staging

Tumour staging is essential to ensure that patients are selected for appropriate treatment.[27]​ Computed tomography (CT) scans are routinely recommended for all patients.[26]​ Other modalities should be considered based on an individual basis.

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.[26][27]

Endoscopic ultrasound (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.[26][27]

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.[27]

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.[26]

Positron emission tomography (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 fluorodeoxyglucose (FDG)-PET/CT imaging offers several potential advantages over FDG-PET or CT scans alone.[26] However, the accuracy of FDG-PET may be low in some gastric cancer types (e.g., diffuse and mucinous) because of low FDG uptake.[28][29]​ 

Pathological examination and biomarker testing

Biopsy tissue should be examined to confirm histological cancer type, cancer grade, and presence or absence of invasion.[26]

Targeted therapies may be indicated for patients with high microsatellite instability/mismatch repair deficiency tumours, patients with high tissue tumour mutation burden status, and patients with neurotrophic tropomyosin-related kinase (NTRK) gene fusion-positive tumours.[26]

Immunohistochemistry (IHC), in situ hybridisation, or targeted polymerase chain reaction should be considered first for the identification of biomarkers, followed by next-generation sequencing.[26]

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.[26]

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 may be considered in locally advanced, recurrent, or metastatic gastric cancer, to determine their eligibility for PD-1 inhibitors.[26]​

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 zolbetuximab is being considered.[26]​

Liquid biopsy can be used to evaluate circulating tumour DNA by means of a blood test.[26]​ 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.[26]​ 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.[26]​ 

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