GASTRIC & ESOPHAGEAL CANCER:
WORLD-LEADING EXPERTISE IN CHINA & INDIA

Every patient with gastric or GEJ adenocarcinoma must have the following tests before any treatment decision: HER2 by IHC with FISH confirmation for IHC 2+ cases (determines trastuzumab + pembrolizumab + chemo eligibility), MSI/MMR status by IHC for MLH1/MSH2/MSH6/PMS2 (MSI-H determines pembrolizumab monotherapy eligibility and exempts from standard chemo), PD-L1 CPS score (threshold varies: CPS ≥5 for CheckMate 649/ORIENT-16; CPS ≥1 for KEYNOTE-811 in HER2+; CPS ≥10 for KEYNOTE-590 in esophageal), and EBV in situ hybridisation. CLDN18.2 IHC is increasingly standard at Chinese specialist centres for HER2-negative, MSS tumours. A biopsy without all these results is incomplete for treatment planning, and CancerFax reviews each patient's biomarker workup as the first step before routing to any specialist.

Peritoneal metastases are present in 20–30% of patients with locally advanced gastric cancer (cT3–T4) that appear M0 (no distant metastasis) on CT or PET imaging. Without staging laparoscopy, these patients would proceed to surgery under the assumption of curative resectability, only to have peritoneal metastases discovered at operation — resulting in a futile laparotomy, prolonged recovery, and delayed systemic therapy. Staging laparoscopy with peritoneal cytology takes 30–60 minutes under general anaesthetic, visualises the peritoneal surface directly, and obtains cytological washings for cancer cell detection. Positive cytology alone (without visible peritoneal nodules) upstages the patient to M1 and redirects treatment from surgical to systemic. This step should be performed for all patients with cT3–T4 or node-positive gastric cancer being considered for curative resection. It is standard at Chinese specialist gastric cancer units and at the best Indian centres — but is consistently omitted at non-specialist facilities.

D2 lymphadenectomy is the systematic removal of lymph nodes in both the perigastric region (D1 nodes immediately adjacent to the stomach) and the nodes along the major vessels of the celiac axis — including nodes along the left gastric vessels (station 7), common hepatic vessels (station 8), celiac axis (station 9), proximal splenic vessels (station 11p), and hepatoduodenal ligament (station 12a). The minimum standard is removal and examination of 15–25 lymph nodes; Chinese national guidelines recommend a minimum of 15 nodes examined. Chinese gastric surgeons achieve a median of 25–35 nodes in D2 procedures. The clinical significance is direct: more thorough lymph node staging reduces understaging; removal of occult nodal micrometastases reduces local-regional recurrence; and long-term follow-up of randomised trials (including the Dutch D1D2 study at 15-year follow-up) confirms improved overall survival with D2 dissection without splenectomy or pancreatectomy. Patients being offered D1 dissection at non-specialist centres should seek surgical review at a D2-standard centre before proceeding.

Potentially yes — this is one of the most important questions in early gastric cancer management. ESD (endoscopic submucosal dissection) achieves 5-year overall survival rates exceeding 97% for early gastric cancer meeting Japanese absolute or expanded indications, with a curative rate equivalent to surgery but without the morbidity of major abdominal surgery. Absolute ESD indications include differentiated-type adenocarcinoma limited to the mucosa (T1a) without ulceration, of any size, or with ulceration if <3cm. Expanded indications validated in large Asian cohorts include undifferentiated cancers <2cm without ulceration, differentiated T1b SM1 cancers <3cm without lymphovascular invasion, and differentiated cancers <3cm with ulceration. The critical prerequisite is accurate EUS (endoscopic ultrasound) T-staging to confirm the tumour is within mucosal or superficial submucosal depth. If a patient with T1 gastric cancer has not had EUS and ESD assessment at a specialist endoscopy centre, referral for this evaluation before surgery is strongly recommended. CancerFax facilitates ESD assessment at specialist Chinese endoscopy centres for patients where surgery may be avoidable.

China has developed and NMPA-approved four domestically produced anti-PD-1 antibodies for gastric and esophageal cancer indications: sintilimab (Innovent Biologics), tislelizumab (BeiGene), camrelizumab (Hengrui Medicine), and penpulimab. These agents have been studied in Chinese patients in registrational Phase III trials and have demonstrated efficacy non-inferior to or comparable with pembrolizumab and nivolumab in their respective trial populations. The critical clinical and economic advantage is cost: Chinese-developed PD-1 inhibitors cost approximately USD 800–2,000 per month in Chinese oncology clinics, compared to USD 15,000–20,000 per cycle for pembrolizumab or nivolumab in Western markets. For patients from South Asia, Southeast Asia, the Middle East, and Africa who cannot afford imported immunotherapy, treatment at Chinese specialist centres with NMPA-approved sintilimab or tislelizumab provides access to immunotherapy of equivalent clinical benefit at 5–10 times lower cost. This is one of the strongest economic arguments for upper GI cancer treatment in China.

Claudin 18.2 (CLDN18.2) is a tight junction protein normally restricted to gastric mucosa but preserved in approximately 35–40% of gastric cancers. Zolbetuximab, a monoclonal antibody targeting CLDN18.2, was studied in combination with mFOLFOX6 and CAPOX in CLDN18.2-positive, HER2-negative, MSS gastric cancer in the SPOTLIGHT and GLOW Phase III trials. Both trials demonstrated statistically significant improvement in both progression-free survival and overall survival compared with chemotherapy alone, representing the most important advance in first-line treatment for HER2-negative MSS gastric cancer in years. China has the largest clinical experience with zolbetuximab because CLDN18.2-positive gastric cancer is particularly prevalent in the Chinese patient population and because the drug was in active clinical development at Chinese centres before regulatory approval. CLDN18.2 testing by IHC has become routine at Chinese specialist upper GI cancer centres, and zolbetuximab is available at major Chinese centres. International patients with HER2-negative MSS gastric cancer should have CLDN18.2 testing performed, and if positive, treatment at a Chinese centre with zolbetuximab access should be considered.