A 58-year-old man from rural India presents with a 4-month history of progressive dysphagia, early satiety, and unintentional weight loss of 8 kg. Upper endoscopy reveals a large ulcerated lesion in the gastric antrum. Biopsies confirm adenocarcinoma. CT chest and abdomen shows no distant metastases, but there is involvement of the perigastric lymph nodes. What is the most appropriate next step in management?

Explanation

## Clinical Context This patient has locally advanced gastric cancer (T3/T4 with N+ disease) without distant metastases — a potentially curable situation. The key decision is whether to proceed directly to surgery or optimize resectability with preoperative chemotherapy. ## Rationale for Neoadjuvant Chemotherapy **Key Point:** Neoadjuvant chemotherapy (FLOT regimen: fluorouracil, leucovorin, oxaliplatin, docetaxel) followed by curative resection is the standard of care for locally advanced gastric cancer (Stage IB–III) in patients with adequate performance status. **High-Yield:** The FLOT4 trial (2019) demonstrated a 5-year overall survival benefit of ~16% with neoadjuvant FLOT + surgery vs. surgery alone in locally advanced gastric/gastroesophageal junction cancers. This is now the preferred approach in major international guidelines (NCCN, ESMO, ASCO). **Clinical Pearl:** Neoadjuvant chemotherapy achieves three goals: - Downsizes the primary tumor and lymph nodes, improving R0 resection rates - Treats micrometastatic disease early - Allows assessment of chemosensitivity (pathologic response predicts prognosis) ## Why This Sequence? | Step | Rationale | |------|----------| | **Confirm staging** | CT already rules out M1 disease; EUS can refine T/N but will not change the decision to give neoadjuvant therapy | | **Neoadjuvant FLOT** | 4 cycles over ~12 weeks; improves R0 resection and survival | | **Restaging** | CT/EUS post-chemotherapy to confirm resectability | | **Subtotal/total gastrectomy** | D2 lymphadenectomy; type depends on tumor location | | **Adjuvant therapy** | If high-risk features persist post-op | **Mnemonic:** **FLOT-SURGERY** — *F*luorouracil, *L*eucovorin, *O*xaliplatin, *T*axane → then Surgery for locally advanced gastric cancer. ## Why Not the Other Options? Immediate surgery without neoadjuvant therapy is inferior: it misses the survival benefit of systemic therapy and may result in incomplete (R1/R2) resection if the tumor is not downsized. Palliative chemotherapy is reserved for metastatic (M1) disease or poor performance status — this patient is fit and has no distant metastases. EUS staging is useful for early-stage tumors (T1–T2) to decide endoscopic vs. surgical resection; it does not change the management of locally advanced disease requiring chemotherapy. [cite:Harrison 21e Ch 297]