What is the recommended treatment approach for a 72-year-old patient with moderately differentiated tubular adenocarcinoma of the stomach, T4 disease, with local invasion into adjacent structures (pancreas/duodenum) and no distant metastases?

Treatment of T4 Gastric Adenocarcinoma with Local Invasion

For this 72-year-old patient with T4 gastric adenocarcinoma invading adjacent structures (pancreas/duodenum) without distant metastases, perioperative chemotherapy followed by en bloc surgical resection with D2 lymphadenectomy is the recommended treatment approach. 1, 2

Initial Staging and Multidisciplinary Evaluation

• Laparoscopy with peritoneal washings is mandatory before initiating treatment to exclude occult peritoneal metastases, which are common in T4 disease 1
• Multidisciplinary team evaluation including surgical oncology, medical oncology, radiation oncology, gastroenterology, radiology, and pathology is required 1
• Assess medical fitness for major surgery and systemic therapy, particularly important given the patient's age of 72 years 1, 2

Perioperative Chemotherapy (Preferred Approach)

The perioperative chemotherapy approach has become standard of care in Europe and is increasingly adopted worldwide, with superior outcomes compared to surgery alone. 1

Preoperative Chemotherapy Regimen Options

• FLOT regimen (docetaxel, oxaliplatin, leucovorin, 5-fluorouracil) is the preferred first-line option for 4 cycles preoperatively 2, 3
• ECF/ECX regimen (epirubicin 50 mg/m², cisplatin 60 mg/m², 5-FU/capecitabine) improved 5-year survival from 23% to 36.3% in the landmark UK MRC trial, administered for 3 cycles preoperatively 1
• Alternative regimens include FOLFOX and SOX 2
• Capecitabine-based regimens (ECX) are preferred over continuous infusion 5-FU to avoid central venous access devices 1

Benefits of Neoadjuvant Approach

• Downstaging of tumor to facilitate R0 resection 1
• Early treatment of micrometastatic disease 1, 2
• Assessment of tumor biology and chemosensitivity 1, 2

Surgical Resection

En bloc resection of the stomach with involved adjacent structures (pancreas/duodenum) is required for T4 disease to achieve R0 resection. 1

Surgical Principles

• Total or subtotal gastrectomy depending on tumor location, with en bloc resection of invaded structures (pancreas, duodenum) 1
• D2 lymphadenectomy is mandatory, removing perigastric (D1) and celiac axis lymph nodes (D2), with examination of at least 15 lymph nodes 1, 2
• Achieve negative microscopic margins (R0 resection); typically 4 cm from gross tumor for non-T4 disease, but adequate margins may require more extensive resection in T4 disease 1
• Splenectomy only if spleen or hilum is directly involved 1
• Consider placement of feeding jejunostomy tube for postoperative nutritional support 1

Common Pitfall

Attempting resection without adequate preoperative staging (laparoscopy) risks non-curative surgery in patients with occult peritoneal disease. 1

Postoperative Management

Completion of Perioperative Chemotherapy

• Complete the remaining 4 cycles of the same preoperative regimen (FLOT or ECF/ECX) if R0 resection was achieved 1, 2
• Postoperative chemotherapy should begin within 4-6 weeks of surgery once adequate recovery 2

Alternative: Postoperative Chemoradiation

Postoperative chemoradiation is reserved for specific situations and is NOT the preferred approach after adequate D2 lymphadenectomy. 1, 2

• Consider postoperative chemoradiation (45 Gy in 25 fractions with 5-FU/leucovorin) if: 1
  • Inadequate lymph node dissection (<D2) was performed
  • Positive or close surgical margins (R1 resection)
  • Patient did not receive perioperative chemotherapy
• The INT-0116 trial showed 15% improvement in 5-year survival with postoperative chemoradiation, but this benefit was primarily in patients with suboptimal (D0/D1) surgery 1
• Postoperative chemoradiation has higher toxicity (54% grade 3-4 hematologic, 33% grade 3-4 GI toxicity) and is less accepted in Europe due to concerns about late toxicity 1

Special Considerations for This Patient

Age-Related Factors

• At 72 years, carefully assess performance status, comorbidities, and organ function before recommending intensive perioperative chemotherapy 1
• Dose modifications may be necessary based on tolerance 3

If Surgery Not Feasible

If the patient is medically unfit for major surgery or refuses surgery, definitive chemoradiation is an alternative option. 1, 4

• Concurrent chemoradiation with cisplatin + 5-FU/capecitabine or oxaliplatin + 5-FU/capecitabine 1
• Patients with locally advanced gastric cancer treated with chemoradiation without surgery have 5-year survival of approximately 18% 4
• Re-evaluate for potential surgical resection if significant tumor response occurs 1

Molecular Testing Considerations

• MSI-H/dMMR testing should be performed; if positive, consider perioperative immunotherapy 1, 2
• HER2 testing for potential targeted therapy in metastatic setting if disease progresses 1

Treatment Algorithm Summary

1. Laparoscopy with peritoneal washings → If negative for metastases, proceed 1
2. Perioperative chemotherapy: FLOT or ECF/ECX for 4 cycles preoperatively 1, 2
3. Restaging after preoperative chemotherapy to assess resectability 1
4. En bloc surgical resection with D2 lymphadenectomy (total/subtotal gastrectomy + pancreas/duodenum resection) 1, 2
5. Complete 4 additional cycles of same chemotherapy regimen postoperatively if R0 resection achieved 1, 2
6. Reserve postoperative chemoradiation only for inadequate surgery or positive margins 1, 2