Approach

History

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 gastroesophageal junction.[3] Patients may present with gastrointestinal (GI) bleeding (melena).[3]

Upper GI endoscopy with biopsy

The initial diagnostic test. Upper GI endoscopy with biopsy allows precise localization of the primary tumor and acquisition of tissue for diagnosis, histologic classification, and molecular biomarkers.[25]​​​​[26] ​The European Society for Medical Oncology (ESMO) recommends multiple biopsies (5-8) to confirm the representation of the tumor.[26] 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.[25]

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

Subsequent investigations

Tumor staging is essential to ensure that patients are selected for appropriate treatment.[26]

Laboratory investigations

Recommended initial tests include:[25][26]

  • Complete blood count to assess for iron deficiency anemia

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

  • H pylori testing/screening.

Computed tomography (CT) scan

Chest, abdomen, and pelvis CT scans with oral and intravenous contrast are recommended for all patients to detect local or distant lymphadenopathy and metastatic disease or ascites.[25][26]

Endoscopic ultrasound (EUS)

EUS can determine the proximal and distal extent of the tumor and accurate tumor and node staging, especially if early stage disease is suspected or early versus locally advanced disease needs to be determined.[25][26]

Positron emission tomography (PET)/CT scan

PET/CT imaging may improve staging by detecting involved lymph nodes or metastatic disease, which would make the patient ineligible for curative therapy.[25][26]​ However, the accuracy of fluorodeoxyglucose (FDG)-PET may be low in some gastric cancer types (e.g., diffuse and mucinous) because of low FDG uptake.[27][28] The ESMO does not recommend FDG-PET routinely.​[26]

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.[26]

The National Comprehensive Cancer Network recommends laparoscopy with cytology for clinical stage T1b or higher to evaluate for peritoneal spread when considering chemoradiation or surgery, unless a palliative resection is planned.[25]

Pathologic examination and biomarker testing

Biopsy tissue should be examined to confirm histologic cancer type, cancer grade, and presence or absence of invasion.[25]

Targeted therapies may be indicated for patients with high microsatellite instability/mismatch repair deficiency tumors, patients with high tissue tumor mutation burden status, and patients with neurotrophic tropomyosin-related kinase (NTRK) gene fusion-positive tumors.[25]

Immunohistochemistry (IHC), in situ hybridization, or targeted polymerase chain reaction should be considered first for the identification of biomarkers, followed by next-generation sequencing.[25]​

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.[25]

Testing for HER2 overexpression using IHC or fluorescent in-situ hybridization is recommended for patients who have confirmed or suspected 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.[25]

Liquid biopsy is another method of testing in patients with advanced or metastatic disease and disease progression who are unable to undergo a traditional biopsy.[25]​

If limited tissue is available for testing or if the patient is unable to undergo a traditional biopsy, sequential testing of single biomarkers or limited molecular diagnostic panels will exhaust the sample.[25]​ Under such circumstances, comprehensive genomic profiling via a validated next-generation sequencing assay should be considered. Targeted biomarkers include: HER2 overexpression/amplification, PD-L1 expression by IHC, MSI status, mismatch repair deficiency, tumor mutational burden, NTRK gene fusions, RET gene fusions, and BRAF V600E mutations.[25]​

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