What is the recommended treatment approach for a patient with bulky nodal disease gastric adenocarcinoma?

Treatment of Bulky Nodal Disease Gastric Adenocarcinoma

For patients with bulky nodal disease gastric adenocarcinoma, a multidisciplinary approach combining neoadjuvant chemotherapy followed by surgical resection with D2 lymphadenectomy is recommended, provided the disease is potentially resectable and other non-curative factors are absent. 1

Initial Staging and Assessment

• Perform staging laparoscopy with peritoneal cytology before initiating treatment to exclude occult peritoneal metastases, which are common in advanced gastric cancer and would change management from curative to palliative intent 1
• Obtain CT imaging to assess the extent of nodal disease and determine if lymphadenopathy is confined to resectable regions 1
• Test HER2 status in all patients, as trastuzumab-containing regimens are indicated for HER2-positive disease 1
• Assess performance status (PS 0-2 required for chemotherapy) and organ function before recommending systemic therapy 1

Criteria for Potential Resectability

Bulky nodal disease is considered potentially resectable if:

• Level 3 or 4 lymph nodes are NOT highly suspicious on imaging or confirmed by biopsy 1
• Para-aortic lymph node involvement, if present, is confined to the No. 16 a2-b1 region only 1
• No invasion or encasement of major vascular structures 1
• No distant metastases or peritoneal seeding 1

Treatment Algorithm for Resectable Bulky Nodal Disease

Neoadjuvant Chemotherapy (Preferred Approach)

Administer 2-3 cycles of combination chemotherapy before surgery:

• For HER2-negative disease: ECF (epirubicin, cisplatin, 5-FU) or modified ECF regimens (category 1) 1
• For HER2-positive disease: Trastuzumab plus fluoropyrimidine/capecitabine + cisplatin 1
• Alternative regimens: DCF (docetaxel, cisplatin, 5-FU) for patients with good performance status and bulky disease 1, 2

For bulky nodal disease with para-aortic lymphadenopathy confined to No. 16 a2-b1: Two courses of S-1 plus cisplatin followed by para-aortic lymph node dissection achieved a 5-year survival rate of 53% in a phase II trial 1

Surgical Resection

Perform adequate gastric resection with D2 lymphadenectomy:

• Distal gastrectomy for distal tumors, total gastrectomy for proximal tumors 1
• D2 lymphadenectomy must include perigastric lymph nodes (D1) and those along the named vessels of the celiac axis (D2) 1
• Examine at least 15 lymph nodes (optimally 25 or more) for accurate staging 1
• Achieve R0 resection with negative microscopic margins (typically 4 cm from gross tumor) 1
• Routine splenectomy is not required unless the spleen or hilum is involved 1

Postoperative Chemotherapy

Complete the remaining cycles of the same preoperative chemotherapy regimen (total of 6 cycles perioperatively) if R0 resection was achieved 1

Note: Only 28.5% of patients complete postoperative chemotherapy after perioperative regimens, but completion is associated with improved overall survival 3

Treatment for Unresectable Bulky Nodal Disease

If the disease is deemed unresectable due to:

• Level 3 or 4 lymph node involvement confirmed on imaging or biopsy 1
• Extensive nodal disease beyond resectable regions 1
• Invasion of major vascular structures 1

Then proceed with:

• Fluoropyrimidine-based chemoradiation for patients with good performance status and locoregionally advanced disease where distant metastases are absent 1
• Systemic chemotherapy alone for extensive nodal disease where wide irradiation fields would cause more harm than benefit 1
• Re-evaluate for surgical resectability after response to chemoradiation 1

Metastatic Disease Treatment

For patients with distant metastases or peritoneal seeding:

• HER2-positive: Trastuzumab plus fluoropyrimidine/capecitabine + cisplatin (category 1) 1
• HER2-negative: Cisplatin plus fluoropyrimidine (5-FU/capecitabine/S-1) as first-line therapy 1
• Alternative for fit patients with bulky disease: DCF or modified DCF regimens 1, 2
• Best supportive care alone for patients with poor performance status 1

Common Pitfalls to Avoid

• Do not proceed to surgery without staging laparoscopy in patients with bulky nodal disease, as imaging frequently misses peritoneal metastases that would change management from curative to palliative intent 1
• Do not perform palliative gastric resection unless the patient is symptomatic from obstruction or bleeding 1
• Do not accept inadequate lymph node evaluation (fewer than 15 nodes examined), as this leads to understaging and suboptimal treatment planning 1
• Do not use adjuvant chemoradiation as the primary strategy when perioperative chemotherapy is feasible, as the latter has become the preferred evidence-based approach with better completion rates 3
• Do not omit HER2 testing before initiating chemotherapy for unresectable or metastatic disease, as trastuzumab-containing regimens significantly improve outcomes in HER2-positive patients 1

Regional Variation in Practice

While adjuvant chemoradiation (INT-0116 approach) was the North American standard, perioperative chemotherapy has surpassed adjuvant chemoradiation as the preferred practice since 2011 based on the MAGIC trial results 3. However, national adoption remains suboptimal, with only 33.6% of stage III patients receiving evidence-based treatment 3.