Lymph Node Level Classification in Gastric Adenocarcinoma
Level 3 and Level 4 lymph nodes in gastric adenocarcinoma represent distant para-aortic lymph node stations that indicate unresectable disease and are considered criteria for locoregionally advanced cancer requiring systemic chemotherapy rather than primary surgical resection.
Definition and Anatomical Location
Level 3 and Level 4 nodes are para-aortic lymph node stations located along the abdominal aorta, classified as distant metastases (M1) rather than regional lymph nodes in gastric cancer. 1
Specific Anatomical Boundaries:
- Level 3 (N3) nodes: Para-aortic lymph nodes along the celiac artery and its branches 1
- Level 4 (N4) nodes: More distant para-aortic lymph nodes extending further along the aorta 1
The Japanese classification system provides more granular detail, defining para-aortic nodes as stations 16a2 (between the upper margin of the celiac artery origin and lower border of the left renal vein) and 16b1 (between the lower border of the left renal vein and upper border of the inferior mesenteric artery origin) 1. These stations are not considered regional gastric lymph nodes and metastasis to these locations is classified as M1 disease 1.
Clinical Significance and Treatment Implications
The presence of Level 3 or Level 4 lymph node involvement that is highly suspicious on imaging or confirmed by biopsy represents a criterion of unresectability for cure. 1, 2 This designation fundamentally changes the treatment approach:
Primary Treatment Strategy:
- Systemic chemotherapy is the optimal management, not surgical resection 2
- These patients should be managed as having locoregionally advanced or metastatic disease 1, 2
- Do not proceed directly to surgery when Level 3/4 nodes are identified 2
Evidence Against Prophylactic Dissection:
The randomized controlled trial JCOG 9501 definitively demonstrated that prophylactic para-aortic lymphadenectomy (PAND) does not improve survival compared to standard D2 lymphadenectomy 1. The 5-year overall survival rates were 70.3% with D2+PAND versus 69.2% with D2 alone, showing no significant difference 1. This high-quality evidence establishes that extending dissection to these distant nodes offers no benefit and should not be performed prophylactically 1.
Distinction from Regional Lymph Nodes
It is critical to understand that Level 3/4 nodes are fundamentally different from the regional lymph node stations:
Regional Lymph Nodes (N1 and N2):
- N1 nodes: Perigastric lymph nodes along the lesser curvature (stations 1,3,5) and greater curvature (stations 2,4,6) 1
- N2 nodes: Nodes along the left gastric artery (station 7), common hepatic artery (station 8), celiac artery (station 9), and splenic artery (stations 10,11) 1
These regional nodes (stations 1-12 and 14v) are appropriate targets for D1 or D2 lymphadenectomy during curative resection 1.
Key Distinction:
Level 3/4 para-aortic nodes are classified as distant metastases, not regional nodes, which is why their presence indicates unresectable disease 1, 2. This contrasts sharply with N1/N2 regional nodes, where metastases can still be addressed with curative intent surgery and appropriate lymphadenectomy 1.
Staging and Prognostic Impact
When Level 3/4 nodes are involved, the prognosis is poor even if R0 resection might technically be possible 1. The level of lymph node metastasis clearly correlates with survival, with distant node involvement (Level III) showing 5-year survival rates of only 26% compared to 67% for perigastric nodes (Level I) 3.
Common Pitfalls to Avoid
- Do not confuse Level 3/4 nodes with N3 staging: N3 in the TNM system refers to 7 or more positive regional lymph nodes, not anatomical Level 3/4 para-aortic nodes 1
- Do not attempt primary surgical resection when Level 3/4 nodes are identified on imaging or biopsy 1, 2
- Do not perform prophylactic para-aortic lymphadenectomy as it provides no survival benefit and increases morbidity 1
- Adequate staging with CT imaging and potentially laparoscopy is essential to identify these nodes preoperatively 1, 2