What is the NCCN (National Comprehensive Cancer Network) guideline for gastric cancer treatment?

NCCN Guidelines for Gastric Cancer Treatment

The NCCN guidelines for gastric cancer recommend a multidisciplinary team approach with treatment options including surgery with D1+ or modified D2 lymph node dissection, perioperative chemotherapy, postoperative chemoradiation, and targeted therapies for specific biomarkers. 1

Diagnosis and Staging

• Universal testing for microsatellite instability (MSI) by PCR/next-generation sequencing or mismatch repair (MMR) by immunohistochemistry is recommended for all newly diagnosed patients 1
• HER2 and PD-L1 testing should be performed if metastatic adenocarcinoma is documented or suspected 1
• Comprehensive staging includes endoscopic ultrasound (preferred for early-stage disease), chest/abdomen/pelvic CT with contrast, and FDG-PET/CT evaluation if no evidence of metastatic disease 1
• Endoscopic resection is essential for accurate staging of early-stage cancers (T1a or T1b) 1

Surgical Management

• For resectable locoregional cancer, gastrectomy with a D1+ or modified D2 lymph node dissection is recommended, performed by experienced surgeons in high-volume centers 1
• Subtotal gastrectomy is preferred for distal gastric cancers, while proximal or total gastrectomy is recommended for proximal tumors 1
• Surgery alone is insufficient therapy for most patients with locally advanced disease in Western countries 1

Perioperative and Adjuvant Treatment

• Perioperative chemotherapy or postoperative chemoradiation plus chemotherapy is the preferred approach for localized gastric cancer 1
• Postoperative chemoradiation is preferred after complete gastric resection for patients with T3-T4 tumors and node-positive T1-T2 tumors 1
• Postoperative chemotherapy is recommended following primary D2 lymph node dissection 1
• Capecitabine combined with oxaliplatin is recommended as adjuvant therapy after radical operation (Category 1) 2

Treatment of Advanced/Metastatic Disease

• For HER2-positive advanced or metastatic gastric cancer, trastuzumab should be added to first-line chemotherapy (confirmed by immunohistochemistry and FISH for IHC 2+) 1
• Two-drug cytotoxic regimens are preferred for patients with advanced disease due to lower toxicity 1
• Preferred first-line regimens include:
  • Fluoropyrimidine (fluorouracil or capecitabine) and cisplatin (Category 1) 1
  • Fluoropyrimidine (fluorouracil or capecitabine) and oxaliplatin 1
• Nivolumab combined with chemotherapy is recommended as first-line therapy for tumors with PD-L1 expression levels by CPS of ≥5 (Category 1) or CPS of <5 (Category 2B) 1
• Ramucirumab, as a single agent or in combination with paclitaxel (preferred), is included as an option for second-line therapy 1, 3

Biomarker-Directed Therapy

• Pembrolizumab is recommended for MSI-H/dMMR or TMB-H tumors as second-line or subsequent therapy 1
• Dostarlimab-gxly is an alternative option to pembrolizumab for MSI-H/dMMR tumors 1
• Entrectinib and larotrectinib are recommended for second-line or subsequent therapy for NTRK gene fusion-positive tumors 1
• Assessment of tumor biomarkers should include mismatch repair defect (dMMR), microsatellite instability (MSI-H), PD-L1, and tumor Epstein-Barr virus (EBV) status 2

Palliative Care/Best Supportive Care

• Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer 1
• For acute bleeding, endoscopic assessment and treatment should be performed 1
• For obstruction, options include endoscopic stenting, surgical bypass (gastrojejunostomy), or venting gastrostomy 1
• Pain control may be achieved with radiation therapy or pain medications according to NCCN Guidelines for Adult Cancer Pain 1
• Nausea and vomiting should be treated according to NCCN Guidelines for Antiemesis 1

Clinical Considerations and Pitfalls

• Compliance with NCCN Guidelines is associated with significantly improved outcomes (median survival of 20 vs. 7 months for non-compliant care) 4
• Patients with complete TNM staging are more likely to receive guideline-compliant care than those with only summary staging 4
• The NCCN panel encourages patients with gastric cancer to participate in well-designed clinical trials investigating novel therapeutic strategies 1
• Careful consideration of performance status and medical comorbidities is essential when selecting treatment regimens 1
• Cisplatin and oxaliplatin may be used interchangeably depending on toxicity profile 1
• Infusional fluorouracil and capecitabine may be used interchangeably without compromising efficacy 1

Future Directions

• Immunotherapy is becoming increasingly important in gastric cancer treatment, with ongoing trials evaluating novel combinations 2
• Neoadjuvant therapy continues to evolve with emerging evidence supporting its role in locally advanced gastric cancer 5
• Docetaxel-based FLOT regimen shows potential in adjuvant therapy for gastric cancer 2