Management of stomach cancer
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Management of Stomach (Gastric) Cancer
Classification
Gastric cancers are nearly 90–95% adenocarcinomas. Lauren's classification divides them into:
- Intestinal type — glandular pattern; driven by H. pylori, dietary factors, chronic atrophic gastritis → intestinal metaplasia → dysplasia → carcinoma
- Diffuse type — poorly differentiated, signet-ring cell morphology; linked to CDH1 (E-cadherin) loss; associated with hereditary diffuse gastric cancer syndrome
- Mixed type
Molecular subtypes (TCGA): EBV-positive, microsatellite instability-high (MSI-H), genomically stable (GS), chromosomal instability (CIN).
Staging Workup
Imaging
- CT chest/abdomen/pelvis: evaluates nodal involvement and distant metastases
- Endoscopic ultrasound (EUS): the most accurate modality for T and N staging, particularly for early lesions and determining resectability
- Staging laparoscopy: recommended before planned curative resection; detects occult peritoneal disease in up to 20–30% of patients considered resectable by CT alone — currently underused (fewer than 10% of eligible patients undergo it)
- PET scan: used in select cases for distant metastasis detection
HER2 testing — mandatory at diagnosis; approximately 20% of gastric/GEJ adenocarcinomas overexpress HER2 (more common in intestinal type); guides trastuzumab use
PD-L1 (CPS) and MSI/MMR testing — mandatory; guides immunotherapy eligibility
Surgery
Surgery remains the only potentially curative treatment.
Type of Resection
| Tumor Location | Procedure |
|---|---|
| Distal (antrum, pylorus) | Subtotal/distal gastrectomy |
| Proximal (fundus, cardia, GEJ) | Total or proximal gastrectomy (often preferred: total) |
| Diffuse/linitis plastica | Total gastrectomy |
Lymphadenectomy
- D2 lymphadenectomy is the standard of care for curative resection (removal of perigastric nodes + nodes along celiac trunk branches)
- D1 (perigastric only) is inferior
- At least 15 lymph nodes should be examined for adequate staging
Reconstruction
- Roux-en-Y gastrojejunostomy after total gastrectomy
- Billroth II after distal gastrectomy
Margin Assessment
- R0 resection (microscopically negative margins) is the goal
- Proximal margin ≥5 cm for diffuse type; ≥3 cm for intestinal type is ideal
Perioperative (Neoadjuvant + Adjuvant) Chemotherapy
Standard of care for resectable gastric cancer (Stage IB–III):
FLOT Regimen (preferred in Europe/increasingly worldwide)
- Docetaxel + Oxaliplatin + Leucovorin + 5-FU
- 4 cycles pre-op + 4 cycles post-op
- Superior to ECF/ECX in the FLOT4 trial (OS 50 vs 35 months)
ECF/ECX/EOF/EOX (older standards)
- Epirubicin + Cisplatin + 5-FU (ECF) — MAGIC trial established perioperative chemotherapy benefit (5-year OS: 36% vs 23%)
- Variations replace 5-FU with capecitabine (ECX) or oxaliplatin for cisplatin (EOF/EOX)
Adjuvant therapy (post-surgery only)
- S-1 (tegafur/gimeracil/oteracil) — standard in Japan/East Asia (ACTS-GC trial)
- Capecitabine + oxaliplatin (CAPOX/XELOX) — CLASSIC trial: improved 3-year DFS vs surgery alone
- Chemoradiation — MacDonald regimen (5-FU/leucovorin + 45 Gy radiation) still used in some centers, especially after D0/D1 resection
Early Gastric Cancer: Endoscopic Resection
For T1a tumors (confined to mucosa) meeting specific criteria:
- Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD)
- Curative for well-differentiated lesions ≤2 cm without ulceration, no lymphovascular invasion
- ESD preferred for en-bloc resection of larger lesions
- Widely used in Japan and Korea where screen-detected early cancers are common
Metastatic / Advanced Disease
First-Line Chemotherapy
HER2-negative:
- FOLFOX or CAPOX (preferred backbone) ± immunotherapy
- DCF/mDCF (docetaxel + cisplatin + 5-FU) in fit patients
- Cisplatin + 5-FU (CF) remains a backbone globally
HER2-positive (~20% of cases):
- Trastuzumab + chemotherapy (CAPOX or CF) — ToGA trial: first targeted therapy to improve OS in gastric cancer (median OS 13.8 vs 11.1 months)
Immunotherapy
| Biomarker | Agent | Setting |
|---|---|---|
| PD-L1 CPS ≥5 | Nivolumab + chemo | 1st line (CheckMate-649) |
| PD-L1 CPS ≥1 | Pembrolizumab + chemo | 1st line (KEYNOTE-590/811) |
| MSI-H / dMMR | Pembrolizumab | 2nd line+ (accelerated approval) |
| HER2+ | Trastuzumab + pembrolizumab + chemo | 1st line (KEYNOTE-811) |
Nivolumab (CheckMate-649) demonstrated significant OS benefit with FOLFOX/CAPOX in PD-L1 CPS ≥5 tumors and is now a standard first-line option in many guidelines.
Second-Line and Beyond
- Ramucirumab (VEGFR-2 antibody) ± paclitaxel — REGARD and RAINBOW trials
- Docetaxel or paclitaxel monotherapy
- Irinotecan monotherapy
- Pembrolizumab in MSI-H tumors
- Trastuzumab deruxtecan (T-DXd) — in HER2+ disease after progression (DESTINY-Gastric01)
Radiation Therapy
- Not routinely used in the perioperative setting outside North America
- Post-operative chemoradiation (45 Gy + 5-FU) used after suboptimal (<D2) surgery (MacDonald/INT-0116 regimen)
- Palliative radiation: for pain from bone metastases, bleeding, or obstruction
Supportive & Palliative Care
Critical to overall management:
- Nutrition: jejunal enteral feeding or total parenteral nutrition to address malnutrition and surgical optimization
- Correction of metabolic abnormalities from vomiting and obstruction
- Gastric outlet obstruction: endoscopic stenting or surgical bypass (gastrojejunostomy) for palliation
- Ascites: paracentesis for symptomatic malignant ascites
- Multidisciplinary team involvement: oncology, surgery, nutrition, gastroenterology, palliative care
Prognosis
| Stage | Approximate 5-Year Survival |
|---|---|
| Stage IA | ~90% |
| Stage IB | ~70% |
| Stage II | ~40–50% |
| Stage III | ~20–30% |
| Stage IV (metastatic) | <5% |
Overall prognosis remains poor because most patients (~60–70%) present with locally advanced or metastatic disease in Western countries. Early detection programs (as in Japan/South Korea) achieve much better outcomes.
Sources: Goldman-Cecil Medicine, 26th Ed. | Mulholland & Greenfield's Surgery, 7th Ed. | SCHWARTZ'S Principles of Surgery, 11th Ed.
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