A 58-year-old man from rural India presents with progressive dysphagia and epigastric pain for 4 months. Upper endoscopy reveals a 5 cm ulcerated lesion in the gastric antrum with biopsy-confirmed adenocarcinoma. CT chest and abdomen shows no distant metastases, but there is thickening of the gastric wall with regional lymph node involvement (T3N2M0). The patient is fit for surgery with good performance status. What is the most appropriate next step in management?

Explanation

## Clinical Context This is a locally advanced gastric cancer (T3N2M0) in a fit patient — a scenario where neoadjuvant chemotherapy has proven survival benefit. ### Rationale for Neoadjuvant Chemotherapy **Key Point:** Neoadjuvant chemotherapy is the standard of care for locally advanced gastric cancer (Stage IB–III) in fit patients, based on landmark trials (MAGIC, FLOT4). **High-Yield:** The MAGIC trial demonstrated that perioperative chemotherapy (epirubicin + cisplatin + 5-FU) improved overall survival from ~24% to ~36% at 5 years in resectable gastric/GE junction cancers. More recent data favour FLOT (fluorouracil + leucovorin + oxaliplatin + docetaxel) regimens. ### Why Neoadjuvant Over Direct Surgery? 1. **Downstaging potential:** Chemotherapy may convert borderline-resectable tumours to clearly resectable ones and reduce nodal burden. 2. **Improved R0 resection rate:** Better local control and fewer positive margins. 3. **Systemic disease control:** Early treatment of micrometastases. 4. **Survival benefit:** Class 1A evidence in fit patients with locally advanced disease. ### Post-Neoadjuvant Pathway After 3 cycles of neoadjuvant chemotherapy: - Reassess with CT and endoscopy - If resectable → proceed to radical subtotal/total gastrectomy with D2 lymphadenectomy - If unresectable → escalate to palliative care **Clinical Pearl:** Fit patients with T3N2M0 gastric cancer who receive neoadjuvant chemotherapy followed by surgery have significantly better outcomes than surgery alone. This is the standard in high-volume centres and aligns with NCCN, ESMO, and IGCA guidelines. ### Why Not the Other Options? | Option | Why Not | |--------|----------| | Direct surgery without neoadjuvant | Misses the survival benefit of chemotherapy; suboptimal for locally advanced disease | | EUS before chemotherapy | EUS is useful for early staging but does not change management in a patient already confirmed to have T3N2 disease on CT; delays chemotherapy initiation | | Palliative chemotherapy | Patient is fit and has resectable disease; palliative approach is premature and denies curative intent | [cite:MAGIC Trial (Cunningham et al. 2006), FLOT4 Trial (Al-Batran et al. 2016)]