NCCN 2025 Guidelines for Stomach Cancer Treatment
The NCCN 2025 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 based on 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, 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 2, 1
- Subtotal gastrectomy is preferred for distal gastric cancers, while proximal or total gastrectomy is recommended for proximal tumors 2, 1
- Surgery alone is insufficient therapy for most patients in Western countries, necessitating additional treatment modalities 2
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 2, 1
- Postoperative chemotherapy is an option after a modified D2 lymph node dissection 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+) 2, 1
- Two-drug cytotoxic regimens are preferred for patients with advanced disease due to lower toxicity 1
- Preferred first-line regimens include fluoropyrimidine and cisplatin (Category 1) 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) 2, 1
Second-Line and Subsequent Therapy
- Ramucirumab, as a single agent or in combination with paclitaxel (preferred), is recommended for second-line therapy 2
- Pembrolizumab is recommended for MSI-H/dMMR or TMB-H tumors as second-line or subsequent therapy 2, 1
- Dostarlimab-gxly is an alternative option to pembrolizumab for MSI-H/dMMR tumors 2, 1
- Trifluridine-tipiracil is recommended for patients previously treated with two lines of therapy 2
- Docetaxel is an option for second-line therapy in patients with good performance status 3
Biomarker-Directed Therapy
- Entrectinib and larotrectinib are recommended for second-line or subsequent therapy for NTRK gene fusion-positive tumors 2
- Trastuzumab deruxtecan may be considered for HER2-positive gastric cancer after first-line therapy 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 2
- For gastric outlet obstruction, endoscopic placement of self-expanding metal stents is a safe and effective palliative treatment 2
- Percutaneous decompressive gastrostomy has been associated with palliative benefit for patients with gastric outlet obstruction 2
- Pain control may be achieved with radiation therapy or pain medications 2
Clinical Considerations and Pitfalls
- Gastrectomy is not recommended in metastatic gastric cancer unless required for palliation of symptoms 2
- Careful consideration of performance status and medical comorbidities is essential when selecting treatment regimens 1
- Early palliative care referral and nutritional support should be integrated into the treatment plan 2
- The NCCN panel encourages patients with gastric cancer to participate in well-designed clinical trials investigating novel therapeutic strategies 2, 1