Gastric & Stomach Cancer

Early gastric cancer often causes no symptoms or only vague symptoms such as persistent indigestion, mild upper abdominal discomfort, early satiety, or nausea — symptoms easily confused with common conditions like gastritis. As the disease progresses, alarm symptoms develop including unexplained weight loss, vomiting, difficulty swallowing, black or tarry stools, or a palpable abdominal mass. Anyone over 55 with new-onset dyspepsia, or anyone with alarm symptoms, should have an urgent upper GI endoscopy.

The Lauren classification divides gastric adenocarcinomas into intestinal-type and diffuse-type. Intestinal-type forms gland-like structures, is associated with H. pylori infection and intestinal metaplasia, is more common in older males, and tends to spread to the liver. Diffuse-type is characterized by poorly cohesive cells including signet ring cells, has a more aggressive growth pattern, spreads to the peritoneum early, and is associated with CDH1 mutations in hereditary cases. Diffuse-type is generally associated with a less favorable prognosis and is less sensitive to chemotherapy.

Before starting treatment, four key molecular tests should be performed on tumor tissue: (1) HER2 IHC and reflex FISH — determines eligibility for trastuzumab and T-DXd; (2) MSI/MMR testing by PCR or IHC — identifies MSI-H/dMMR tumors eligible for pembrolizumab; (3) PD-L1 CPS by IHC — determines eligibility for first-line immunotherapy; and (4) EBV EBER ISH — identifies EBV-positive subtype. Increasingly, CLDN18.2 IHC and FGFR2 testing are also being added to standard profiling at specialist centers.

HER2-positive gastric cancer means the tumor overexpresses the HER2 protein or has HER2 gene amplification, occurring in approximately 15–20% of cases. HER2-positive status qualifies patients for trastuzumab (Herceptin) added to first-line platinum/fluoropyrimidine chemotherapy, which significantly improves outcomes compared to chemotherapy alone (ToGA trial). After progression on trastuzumab, trastuzumab deruxtecan (T-DXd/Enhertu) is approved and shows dramatic response rates in this population.

Yes. Checkpoint inhibitors are now established treatments for gastric cancer in specific settings. Nivolumab + chemotherapy (CheckMate-649) is approved first-line for HER2-negative advanced gastric/GEJ cancer. Pembrolizumab + trastuzumab + chemotherapy (KEYNOTE-811) is approved for HER2-positive disease. Pembrolizumab monotherapy is approved for MSI-H tumors. Nivolumab monotherapy is approved in third-line or later in some regions. MSI-H gastric cancer in particular has high immunotherapy response rates and represents one of the most immunotherapy-responsive solid tumors.

For localized early-stage gastric cancer meeting specific criteria, endoscopic submucosal dissection (ESD) — performed through the endoscope without external surgery — is a curative option. For locally advanced disease, surgery (total or subtotal gastrectomy with D2 lymphadenectomy) combined with perioperative chemotherapy (FLOT) is the standard curative approach. For metastatic disease, surgery is not the primary treatment; systemic therapy is. The type of surgery and whether surgery is needed should be determined by a multidisciplinary specialist team.

East Asia has historically high rates of H. pylori infection, which is the primary cause of intestinal-type gastric cancer. Dietary factors — including high consumption of salt-preserved and smoked foods — combined with genetic predisposition and high H. pylori prevalence have contributed to elevated incidence. China, Japan, and South Korea have consequently developed the highest-volume gastric cancer treatment programs globally, with specialized surgical expertise, active clinical trial programs, and early detection strategies not yet common in lower-incidence Western countries.

Linitis plastica is a diffuse form of gastric cancer in which the entire stomach wall is infiltrated by malignant cells, causing it to become rigid and leather-bottle shaped. It is associated with the diffuse-type (signet ring cell) histology, is more common in younger patients, and has a poor prognosis due to early peritoneal dissemination and limited response to chemotherapy. Surgical resection is often not possible or beneficial. Specialist oncology review is essential for patients with this diagnosis.

Yes. CancerFax supports gastric cancer patients by reviewing medical reports and molecular test results, ensuring HER2/MSI/PD-L1/EBV testing has been performed, coordinating specialist second opinions, identifying targeted therapy and immunotherapy options relevant to the molecular profile, and connecting patients with specialist gastric oncology programs in China, South Korea, India, and internationally. Contact CancerFax to share your reports and begin the process.