A 58-year-old man from rural Maharashtra presents with a 4-month history of progressive dysphagia, early satiety, and weight loss of 8 kg. Upper endoscopy reveals a 5 cm ulcerated lesion in the gastric antrum with irregular margins. Biopsies confirm adenocarcinoma. CT staging shows a T3N2M0 tumour with no distant metastases. The patient is fit for surgery with normal renal and hepatic function. What is the most appropriate next step in management?

Explanation

## Clinical Context This is a locally advanced gastric cancer (T3N2M0) in a fit patient. The presence of nodal involvement (N2) and transmural invasion (T3) classifies this as Stage IIIA disease, which carries a high risk of both local recurrence and distant metastases. ## Rationale for Neoadjuvant Chemotherapy **Key Point:** Neoadjuvant chemotherapy (NACT) is the standard of care for locally advanced gastric cancer (Stage IB–III) in fit patients, as demonstrated by the MAGIC trial and subsequent meta-analyses. **High-Yield:** The MAGIC trial (2006) showed that perioperative chemotherapy (ECF: epirubicin, cisplatin, 5-FU) improved 5-year overall survival from 23% to 36% in gastric and gastro-oesophageal junction cancers. Neoadjuvant therapy: - Downsizes the primary tumour, potentially converting unresectable to resectable disease - Treats micrometastases early - Improves R0 resection rates - Allows assessment of chemosensitivity before major surgery **Clinical Pearl:** In this case, the patient is fit, has no metastases, and the tumour is resectable. NACT is indicated to improve long-term survival. ## Management Algorithm ```mermaid flowchart TD A[Gastric adenocarcinoma T3N2M0]:::outcome --> B{Fit for surgery?}:::decision B -->|Yes| C{Resectable disease?}:::decision B -->|No| D[Palliative care]:::action C -->|Yes, Stage IB-III| E[Neoadjuvant chemotherapy]:::action C -->|No| F[Palliative chemotherapy ± bypass]:::action E --> G[Restaging CT/EUS after 3 cycles]:::action G --> H{Response adequate?}:::decision H -->|Yes| I[Subtotal gastrectomy + D2 dissection]:::action H -->|No| J[Consider alternative strategy]:::decision I --> K[Adjuvant chemotherapy]:::action ``` ## Standard Chemotherapy Regimen | Regimen | Agents | Cycles | Notes | |---------|--------|--------|-------| | ECF | Epirubicin, Cisplatin, 5-FU | 3 pre-op, 3 post-op | MAGIC trial standard | | ECX | Epirubicin, Cisplatin, Capecitabine | 3 pre-op, 3 post-op | Oral alternative to 5-FU | | DCF | Docetaxel, Cisplatin, 5-FU | 3 pre-op, 3 post-op | Higher response but more toxicity | **Key Point:** After 3 cycles of NACT (8–10 weeks), restaging with CT and endoscopic ultrasound (EUS) is performed. If the patient remains fit and disease is still resectable, proceed to surgery. Adjuvant chemotherapy (3 more cycles) follows recovery from surgery. ## Why NOT Immediate Surgery? Direct surgery without NACT in Stage III disease is associated with: - Higher rates of R1/R2 resection - Increased perioperative morbidity - Worse 5-year survival (23% vs 36% with perioperative therapy) **Warning:** Palliative bypass is reserved for unresectable or metastatic disease; this patient has resectable, locally advanced disease and deserves curative intent.