What is the optimal management of advanced and infiltrative gastric carcinoma with porta hepatis (lymph node) involvement?

Optimal Management of Advanced and Infiltrative Gastric Carcinoma with Porta Hepatis Lymph Node Involvement

For advanced and infiltrative gastric carcinoma with porta hepatis lymph node involvement, chemotherapy (Option B) is the optimal management approach, as porta hepatis lymph nodes represent Level 3-4 lymph nodes which are criteria for unresectability and should be managed as locoregionally advanced or metastatic disease. 1, 2

Understanding Porta Hepatis Lymph Node Involvement

• Porta hepatis lymph nodes are classified as Level 3-4 lymph nodes in gastric cancer staging 1
• Level 3 or 4 lymph node involvement that is highly suspicious on imaging or confirmed by biopsy is a criterion of unresectability for cure 1
• This represents locoregionally advanced disease that should not undergo primary surgical resection 1, 2

Why Not Surgery First (Option A is Incorrect)

• Total gastrectomy after only two cycles of FOLFOX is inappropriate because porta hepatis involvement indicates unresectable disease 1
• Surgery should only be considered after significant response to induction chemotherapy, and only if the disease becomes resectable 3
• Palliative gastric resection should not be performed unless the patient is symptomatic with obstruction 1
• The presence of Level 3-4 lymph node involvement represents a contraindication to curative surgical resection 1

Why Chemotherapy is the Correct Answer (Option B)

Systemic chemotherapy is the primary treatment modality for unresectable locoregionally advanced gastric cancer with porta hepatis lymph node involvement 2, 4

First-Line Chemotherapy Regimens:

• Fluoropyrimidine plus cisplatin (Category 1 recommendation) 2
• FLOT (docetaxel, oxaliplatin, leucovorin, 5-FU) is the current standard with superior outcomes for advanced disease 4, 5
• ECF (epirubicin, cisplatin, 5-FU) or modified ECF regimens 1
• DCF (docetaxel, cisplatin, 5-FU) for selected patients in good condition 6
• Two-drug cytotoxic regimens are preferred due to lower toxicity 2

Biomarker-Directed Therapy:

• For HER2-positive tumors, add trastuzumab to first-line chemotherapy 1, 2
• For PD-L1 CPS ≥5 tumors, nivolumab combined with chemotherapy is Category 1 1, 2
• For MSI-H/dMMR tumors, pembrolizumab or dostarlimab-gxly should be considered 1, 2

Potential for Conversion to Resectability:

• After significant response to induction chemotherapy, reassessment for potential surgical resection should be performed 3
• In a study of 20 patients with paraaortic lymph node metastasis (similar level to porta hepatis), induction chemotherapy followed by curative surgery achieved 5-year survival of 65% in selected responders 3
• Only patients showing good clinical response (overall response rate 80%) and achieving resectable status should proceed to surgery 3

Why Not Radiotherapy Alone (Option C is Incorrect)

• Radiotherapy as monotherapy is not recommended for advanced gastric cancer with distant lymph node involvement 2
• Concurrent chemoradiotherapy may be considered for unresectable locally advanced disease, but only in combination with chemotherapy, not radiotherapy alone 4
• Radiotherapy is primarily reserved for palliative management of bleeding, obstruction, or pain control 1, 2

Why Not EMR (Option D is Incorrect)

• EMR (endoscopic mucosal resection) is only indicated for early-stage gastric cancer limited to the mucosa (T1a) 1
• Absolute indications for EMR include intramucosal carcinoma <2 cm, well-differentiated tumors, and non-ulcerative lesions 1
• Advanced and infiltrative gastric cancer with porta hepatis lymph node involvement represents T3-T4 disease with distant nodal metastasis, which is an absolute contraindication to endoscopic therapy 1, 2

Treatment Algorithm

1. Confirm unresectability through staging CT, laparoscopy with peritoneal washings, and biopsy confirmation of porta hepatis lymph nodes 1, 2
2. Obtain biomarker testing: HER2, PD-L1, MSI/MMR status 2
3. Initiate systemic chemotherapy based on biomarker results and performance status 2, 4
4. Reassess after 2-3 cycles for response and potential conversion to resectability 3
5. If significant response achieved and disease becomes resectable, consider surgery with extended lymphadenectomy followed by completion of chemotherapy 3
6. If disease remains unresectable or progresses, continue palliative chemotherapy or transition to second-line regimens 2

Common Pitfalls to Avoid

• Do not proceed directly to surgery without adequate induction chemotherapy - porta hepatis involvement indicates unresectable disease 1
• Do not use radiotherapy as monotherapy - it must be combined with chemotherapy if used at all 4
• Do not consider endoscopic resection for infiltrative disease - this is only for superficial early cancers 1
• Do not abandon treatment - selected patients achieving good response to chemotherapy may become surgical candidates with potential for long-term survival 3