What is the recommended treatment approach for local advanced gastric carcinoma?

Treatment Approach for Locally Advanced Gastric Carcinoma

For locally advanced gastric carcinoma, perioperative chemotherapy with FLOT regimen (docetaxel, oxaliplatin, 5-FU/leucovorin) is the recommended standard treatment approach, as it demonstrates improved survival outcomes compared to other regimens. 1

Initial Assessment and Staging

• Accurate clinical staging is essential using combined examination modalities (EUS, CT, PET/CT) to determine resectability 1
• Laparoscopic exploration with cytological examination of intraperitoneal washings is recommended prior to initiating treatment to detect occult metastases 1
• Multidisciplinary team (MDT) discussion should guide treatment decisions, especially for complex cases 1

Treatment Algorithm Based on Resectability

For Resectable Locally Advanced Gastric Cancer:

1. Perioperative Chemotherapy (Preferred Approach)

   • FLOT regimen (docetaxel, oxaliplatin, 5-FU/leucovorin) is the current standard with superior outcomes 1
   • Alternative regimens include:
     • ECF (epirubicin, cisplatin, 5-FU) or modified ECF 1
     • XELOX (oxaliplatin, capecitabine) 1
     • FOLFOX (oxaliplatin, 5-FU) 1
     • SOX (oxaliplatin, S-1) 1

2. Surgical Approach

   • Radical D2 gastrectomy is the standard surgical procedure 2
   • Subtotal gastrectomy is preferred for distal tumors; proximal or total gastrectomy for proximal tumors 1

3. Post-Surgery Treatment

   • Continue with the same chemotherapy regimen used preoperatively 1
   • For patients who fail to achieve R0 resection, postoperative chemoradiotherapy is recommended 1

For Gastroesophageal Junction (GEJ) Carcinoma:

• Neoadjuvant chemoradiotherapy followed by radical D2 gastrectomy is recommended for stage III GEJ carcinoma 1
• This approach reduces local recurrence and tends to prolong survival compared to preoperative chemotherapy alone 1

For Unresectable Locally Advanced Gastric Cancer:

1. For patients with good performance status (ECOG 0-1):

   • Concurrent chemoradiotherapy is the preferred approach 1
   • Recommended chemoradiotherapy regimens include:
     • Capecitabine + paclitaxel 1
     • Cisplatin + 5-FU/capecitabine/S-1 1
     • Oxaliplatin + 5-FU/capecitabine/S-1 1
     • Paclitaxel + 5-FU/capecitabine/S-1 1

2. Re-evaluation after treatment:

   • Assess tumor response to determine if surgical resection is possible 1
   • If resectable, proceed with surgery 1
   • If still unresectable, consider sequential chemotherapy or additional chemoradiotherapy 1

3. For patients with poor performance status (ECOG 2):

   • Best supportive care or symptomatic treatment 1
   • Consider palliative interventions (bypass surgery, endoscopic treatment, stenting, palliative radiotherapy) to improve symptoms 1

Evidence Strength and Considerations

• Perioperative chemotherapy has demonstrated superior outcomes compared to surgery alone in multiple studies 1
• Concurrent chemoradiotherapy has shown better tumor downstaging and pathological remission compared to chemotherapy or radiotherapy alone in unresectable cases 1
• The FLOT4-AIO study showed prolonged median disease-free survival, overall survival, higher pathological response rate, and R0 resection rate compared to ECF/ECX regimens 1

Common Pitfalls and Caveats

• Inadequate staging may lead to inappropriate treatment selection; comprehensive staging including laparoscopic exploration is crucial 1
• Toxicity management is essential, particularly with three-drug regimens like FLOT 1
• For patients unsuitable for concurrent chemoradiotherapy due to extensive tumor or lymph node invasion, chemotherapy or radiotherapy alone may be considered 1
• Radiation fields should be carefully planned to minimize toxicity while ensuring adequate coverage of the tumor and regional lymph nodes 1
• Regular re-evaluation of tumor response during treatment is necessary to identify opportunities for surgical intervention 1

Special Considerations

• For HER2-positive advanced gastric cancer, trastuzumab in combination with chemotherapy should be considered 3
• S-1 regimens have shown slight improvement in overall survival compared to 5-FU-containing regimens, but dosing varies between Asian and non-Asian populations 4
• Oxaliplatin-containing regimens may offer survival benefits over cisplatin-containing regimens, particularly in elderly patients 4