Management of T4a N1 M0 Gastric Cancer
For T4a N1 M0 gastric cancer, the optimal management is perioperative chemotherapy (preferably FLOT regimen) followed by D2 gastrectomy with lymphadenectomy, then completion of postoperative chemotherapy. 1
Treatment Algorithm
Step 1: Initial Staging and Preparation
- Complete staging with laparoscopy and peritoneal lavage to exclude occult metastatic disease before initiating treatment 1
- Assess medical fitness for surgery and systemic therapy 1
- Obtain multidisciplinary team evaluation including surgical oncology 1
Step 2: Neoadjuvant/Perioperative Chemotherapy (Category 1 Recommendation)
Perioperative chemotherapy is the standard of care for T4a N1 M0 disease and should be administered before surgery. 1
Preferred regimen options include: 1
- FLOT (5-fluorouracil, leucovorin, oxaliplatin, docetaxel) - 4 cycles preoperatively 2
- FOLFOX (leucovorin, fluorouracil, oxaliplatin) 1
- SOX (S-1 plus oxaliplatin) 1
Alternative regimens: 1
- PF (cisplatin plus 5-fluorouracil)
- XELOX (capecitabine plus oxaliplatin)
Step 3: Restaging After Neoadjuvant Therapy
- Reassess resectability after completing neoadjuvant chemotherapy 1
- Proceed to surgery if no disease progression and patient remains medically fit 1
Step 4: Surgical Resection
Perform D2 gastrectomy with D2 lymphadenectomy (removal of ≥15 lymph nodes for adequate staging). 1, 3
- T4a tumors invade the serosa (visceral peritoneum) and are considered resectable 1
- Achieve R0 resection with adequate margins (minimum 3-5 cm depending on growth pattern) 3
- Standard gastrectomy with resection of at least two-thirds of the stomach 3
Step 5: Postoperative Management Based on Resection Status
If R0 resection achieved: 1
- Complete postoperative chemotherapy (Category 1) - continue the preoperative regimen for 4 additional cycles if perioperative approach was used 1
- This applies specifically to patients with T3-T4 any N or any T N1 tumors who received D2 lymphadenectomy 1
If R1 resection (microscopic positive margins): 1
If R2 resection (macroscopic residual disease): 1
- Options include chemoradiation or palliative management 1
Special Considerations and Nuances
MSI-H/dMMR Tumors
- For patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, neoadjuvant/perioperative immunotherapy can be considered (Category 2A) 1
Chemoradiation vs. Chemotherapy Alone
- The NCCN 2025 guidelines prioritize postoperative chemotherapy (Category 1) over chemoradiation for patients who received adequate D2 lymphadenectomy 1
- Postoperative chemoradiation is reserved for: 1
- Patients with inadequate lymph node dissection (less than D2)
- High-risk features for local recurrence
- Positive surgical margins (R1/R2 resection)
Critical Pitfalls to Avoid
Do not proceed directly to surgery without neoadjuvant therapy - T4a N1 disease qualifies for perioperative chemotherapy, which improves resectability and survival 1, 2
Do not perform inadequate lymphadenectomy - D2 dissection with ≥15 lymph nodes is essential for proper staging and oncologic control 1, 3
Do not omit postoperative chemotherapy after R0 resection - completion of systemic therapy is Category 1 for T4a N1 disease with D2 dissection 1
Do not confuse T4a with T4b - T4a (serosa invasion) is resectable, while T4b (invasion of adjacent organs like spleen, colon, liver, pancreas) requires different management considerations 1
Evidence Quality Assessment
The recommendations are based on the most recent NCCN 2025 guidelines 1, which represent the highest quality evidence for this specific tumor stage. The Chinese Society of Clinical Oncology (CSCO) 2019 guidelines 1 provide concordant recommendations supporting perioperative chemotherapy for cT3-4aN+ M0 disease. The evidence consistently supports a multimodal approach prioritizing systemic therapy combined with adequate surgical resection to optimize survival outcomes.