eBulletin Newsletter

NCCN Flash Updates: NCCN Guidelines and NCCN Templates Updated for Gastric Cancer

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®), the NCCN Drugs & Biologics Compendium (NCCN Compendium^®), the NCCN Radiation Therapy Compendium™, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™) for Gastric Cancers These NCCN Guidelines^® are currently available as Version 1.2025.

Link directly to the Updates section of the NCCN Guidelines: Gastric Cancer

General

• Upper GI gastrointestinal (GI) endoscopy changed to Esophagogastroduodenoscopy (EGD) throughout the algorithm.

GAST-1

• Workup; Last bullet revised: Assess H. pylori status and conduct genetic testing as needed Test for H. pylori infection and eradicate in all patients with early gastric cancer if positive. Conduct genetic testing as needed and recommend H. pylori testing of close family members

GAST-1A

• Footnote i revised: Added link to Principles of Surveillance (GAST-H).
• Footnote m revised: "...performed to evaluate for peritoneal spread when considering chemoradiation or surgery local therapy. Laparoscopy..."

GAST-2

• Locoregional disease: Medically fit potentially resectable, cT2 or higher, Any N: Preoperative chemoradiation (category 2B) removed as a primary treatment option. (Also for first column; top pathway on GAST-3)

GAST-2A

• Footnote q revised: "...perioperative immunotherapy or surgery alone should be considered in consultation with a multidisciplinary team. The role of surgery after biopsy proven and radiologic/metabolic complete response on neoadjuvant immunotherapy is unclear." (Also for GAST-3)
• Footnote removed: The role of surgery after biopsy proven and radiologic/metabolic complete response on neoadjuvant immunotherapy is unclear. The role for surgery in the setting of favorable neoadjuvant response should be carefully discussed. (Also for GAST-3)

GAST-3

• Primary Treatment for Patients who are medically fit
  • Top pathway revised: Perioperative chemotherapy (category 1) or Preoperative chemoradiation (category 2B)
  • Neoadjuvant or perioperative ICI if tumor is microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR)
    • Outcome clarified: No evidence of disease
    • Additional Management for patients with no evidence of disease; Revised: Observation or Surgery
• Footnote removed: Principles of Radiation Therapy (GAST-C)
• Footnote removed: If surgery is not being considered for management, upper GI endoscopy and biopsy should be done.

GAST-4

• Column header revised: Surgical Outcomes/Clinical Pathologic Findings (Patients Have Not Received Preoperative Chemoradiation or Systemic Therapy

GAST-5

• Column header Revised: Surgical Outcomes/Clinical Pathologic Findings (Patients Have Received Preoperative Chemoradiation or Systemic Therapy)
• Postoperative Management:
  • R0 resection:
    • Observation (if received preoperative chemoradiation) removed as an option
    • Revised: Systemic therapy, if received preoperatively (category 1)
  • R1 resection revised: Chemoradiation (fluoropyrimidine-based), only if not received preoperatively. Also for R2 resection.

GAST-7

• Footnote bb revised: For patients undergoing total gastrectomy for curative intent, surveillance should follow these recommendations except for endoscopy. Endoscopy has no role in as clinically indicated for routine surveillance for total gastrectomy unless patients are symptomatic.

GAST-9

• 3rd column; Bullet revised: NGS may should be considered via a validated assay

GAST-A 3 of 4

• Treatment
  • New bullet and sub-bullets added
    • Several Japanese and American guidelines have expanded the indications for ESD to include:
      • Well to moderately differentiated cancer of any size, without ulceration
      • Well or moderately differentiated with submucosal (sm) layer invasion <500 micrometers
      • Well or moderately differentiated <3 cm with ulceration
      • Poorly differentiated <2 cm without ulceration
  • New bullet added: This may potentially be considered curative resection if the margins are negative, there is no LVI, and curative resection is limited to sm1. However, there is still a very small risk of lymph node involvement, so such decisions should be made following multidisciplinary discussions and careful explanation to the patient.

GAST-B 1 of 7

• Pathologic review; Specimen type
  • 3rd row revised: Gastrectomy, without prior chemoradiation
  • 4th row
    • Revised: Gastrectomy, with prior chemoradiation in unresectable gastric cancer treated with chemoradiation followed by surgery
    • Analysis/Interpretation/Reporting revised
      • 1st bullet revised: Tumor site should be thoroughly sampled for specimens s/p neoadjuvant therapy chemoradiation without grossly obvious residual tumor
      • 2nd bullet revised: For pathology report, include all elements as for of resection without prior chemoradiation plus and assessment of treatment effect
• New footnote d added: For patients with surgically managed cancer, ≥16 regional lymph nodes are removed and pathologically examined
  during resection for curative intent therapy.

GAST-B 2 of 7

• Assessment of Treatment Response revised: "Response of the primary tumor and lymph node metastases to previous chemotherapy and/or RT should be reported..."

GAST-B 3 of 7

• Assessment of Overexpression or Amplification of HER2 in Gastric Cancer revised: "...and MSIstatus. NGS can be considered instead of sequential testing for single biomarkers when limited diagnostic tissue is available or when the patient is unable to undergo a traditional biopsy. The use of IHC/ISH should be considered first, followed by additional NGS testing as appropriate. IHC/ISH/targeted PCR is the preferred approach to assess biomarkers initially. However, NGS testing through a CLIA-approved laboratory may be considered later in the clinical course of patients with sufficient tumor tissue available for testing. Repeat biomarker testing may be considered..."
• Footnote f revised:An FDA-approved biosimilar is an appropriate substitute for trastuzumab. An FDA-approved biosimilar is an appropriate substitute for any recommended systemic biologic therapy in the NCCN Guidelines.

GAST-B 5 of 7

• Microsatellite Instability (MSI) or Mismatch Repair (MMR) Testing; 1st bullet revised: "...Patients with MSI-H or dMMR tumors may should be referred to a genetics counselor for further assessment in the appropriate clinical context."

GAST-B 6 of 7

• Next-Generation Sequencing revised
  • "...by the FDA for use in gastric cancer. Immunohistochemistry/in situ hybridization/targeted PCR should be considered first for the identification of biomarkers, followed by NGS testing. If limited tissue is available, or the patient is unable to undergo a traditional biopsy, sequential testing of single biomarkers/limited molecular diagnostic panels will exhaust the sample. In these scenarios, or at the discretion of the treating physician, comprehensive genomic profiling via a validated NGS assay performed in a CLIA-approved laboratory should be considered.
    IHC/ISH/targeted PCR is the preferred approach to assess biomarkers, initially. However, NGS testing through a CLIA-approved laboratory may be considered later in the clinical course of patients with sufficient tumor tissue available for testing.
  • PD-L1 expression by immunohistochemistry
• Liquid Biopsy revised: The genomic alterations of solid cancers may be identified by evaluating circulating tumor DNA (ctDNA) in the blood, hence a form of “liquid biopsy.” Liquid biopsy is being used more frequently in patients with advanced disease, particularly those who are unable to have a clinical biopsy for disease surveillance and management. The detection of mutations/alterations or fusions in DNA shed from gastric carcinomas can identify targetable alterations or the evolution of clones with altered treatment response profiles. Therefore, when limited tissue is available or for patients who have metastatic or advanced gastric cancer who may be unable are not able to undergo a traditional biopsy, or for disease progression monitoring, testing using a validated NGS-based comprehensive genomic profiling assay performed in a CLIA-approved laboratory may be considered. A negative result should be interpreted with caution, as this does not exclude the presence of tumor mutations or amplifications.

GAST-C 4 of 5

• Palliative Procedures: Gastric resections should be reserved for the palliation of symptoms (eg, obstruction or uncontrollable bleeding) in patients with incurable disease when non-surgical options are not feasible such as endoscopic or interventional radiology procedures
  (ie, endoscopic stenting).

Principles of Systemic Therapy for Unresectable Locally Advanced, Recurrent, or Metastatic Disease

GAST-F 1 of 20

• New bullets added
  • An FDA-approved biosimilar is an appropriate substitute for any recommended systemic biologic therapy in the NCCN Guidelines.
  • A checkpoint inhibitor should be added to first-line chemotherapy for patients with advanced disease with PD-L1 CPS ≥1.
  • Nivolumab and hyaluronidase-nvhy is not approved for concurrent use with IV ipilimumab; however, for nivolumab monotherapy, nivolumab and hyaluronidase-nvhy subcutaneous injection may be substituted for IV nivolumab. Nivolumab and hyaluronidase-nvhy has different dosing and administration instructions compared to IV nivolumab.
  • Footnote removed: An FDA-approved biosimilar is an appropriate substitute for trastuzumab. (Also for all GAST-F pages)

GAST-F 3 of 20

• The regimens for preoperative chemoradiation were removed. The corresponding dosing schedules were also removed.
  • Paclitaxel and carboplatin (category 2B)
  • Fluorouracil and oxaliplatin (category 2B)
  • Fluorouracil and cisplatin (category 2B)
  • Fluoropyrimidine (fluorouracil or capecitabine) (category 2B)
• Footnote removed: Cisplatin may not be used interchangeably with oxaliplatin in this setting.

GAST-F 4 of 20

• First-line Therapy revised
  • Preferred Regimens; HER2 overexpression negative
    • Fluoropyrimidine (fluorouracil or capecitabine), oxaliplatin, and nivolumab (PD-L1 CPS ≥5) (category 1) for PD-L1 CPS ≥1 (category 1 for PD-L1 CPS ≥5)
    • Fluoropyrimidine (fluorouracil or capecitabine), oxaliplatin, and pembrolizumab for PD-L1 CPS ≥1 (category 1 for PD-L1 CPS ≥ 10 ≥5 ; category 2B for PD-L1 CPS 1 to <10)
    • New regimen added: Fluoropyrimidine (fluorouracil or capecitabine), oxaliplatin, and tislelizumab-jsgr for PD-L1 CPS ≥1 (category 1 for PD-L1 CPS ≥5)
    • Fluoropyrimidine (fluorouracil or capecitabine), cisplatin, and pembrolizumab for PD-L1 CPS ≥1
      (category 1 for PD-L1 CPS ≥10 ≥5 ; category 2B for PD-L1 CPS 1 to <10)
    • New regimen added: Fluoropyrimidine (fluorouracil or capecitabine), cisplatin, and tislelizumab-jsgr for PD-L1 CPS ≥1
      (category 1 for PD-L1 CPS ≥5)
  • Useful in Certain Circumstances
    • New systemic therapy options added: Entrectinib, larotrectinib, or repotrectinib for NTRK gene fusion-positive tumors (category 2B)
    • Removed: Fluoropyrimidine (fluorouracil or capecitabine), oxaliplatin, and nivolumab (PD-L1 CPS <5) (category 2B).

GAST-F 4A of 20

• Footnote e revised: If no prior checkpoint inhibitor therapy or no tumor progression while on therapy with a checkpoint inhibitor. (Applies to all GAST-F pages)
• Footnote h revised: Trastuzumab should be added to first-line chemotherapy for HER2 overexpression-positive adenocarcinoma. An FDA-approved biosimilar is an appropriate substitute for trastuzumab.

Principles of Systemic Therapy-Regimens and Dosing Schedules

GAST-F 11 of 20

• First-line therapy; Preferred Regimens; Dosing revised:
  • HER2 Overexpression Negative, CLDN18.2 Positive
    • Fluoropyrimidine (fluorouracil or capecitabine), oxaliplatin, and zolbetuximab-clzb
      Oxaliplatin 85 mg/m2 IV on Day 1
      Oxaliplatin 85 mg/m² IV on Day 1 (per study maximum of 12 doses)
      Leucovorin 400 mg/m² IV on Day 1
      Fluorouracil 400 mg/m² IV Push on Day 1
      Fluorouracil 1200 mg/m² IV continuous infusion
      over 24 hours daily on Days 1 and 2
      Zolbetuximab-clzb 800 mg/m² IV (first-dose only)
      on Day 1 (subsequent doses 400 mg/m²)
      Cycled every 14 days
      
      Capecitabine 850–1000 mg/m² PO BID on Days 1–14
      Oxaliplatin 130 mg/m2 IV on Day 1
      Oxaliplatin 130 mg/m² IV on Day 1 (per study maximum of 8 doses)
      Zolbetuximab-clzb 800 mg/m² IV (first-dose only)
      on Day 1 (subsequent doses 600 mg/m²)
      Cycled every 21 days

GAST-F 12 of 20

• First-line Therapy; Preferred Regimens; New dose schedule added:
  • Tislelizumab-jsgr with fluoropyrimidine and oxaliplatin or cisplatin
    Tislelizumab 200 mg IV on Day 1 every 21 days
    in combination with:
    
    Fluoropyrimidine and oxaliplatin
    Oxaliplatin 85 mg/m² IV on Day 1
    Leucovorin 200 mg/m² IV on Day 1
    Fluorouracil 1200 mg/m² IV continuous infusion over 24 hours daily on Days 1 and 2
    Cycled every 14 days for 12 cycles
    
    Capecitabine 850–1000 mg/m2 PO BID on Days 1–14
    Oxaliplatin 130 mg/m² IV on Day 1
    Cycled every 21 days (per study maximum of 6 doses)
    
    Fluoropyrimidine and cisplatin
    Cisplatin 60–80 mg/m² IV on Day 1
    Fluorouracil 750–800 mg/m² IV continuous infusion over 24 hours daily on Days 1–5
    Cycled every 21 days for 6 cycles
    
    Cisplatin 60–80 mg/m² IV on Day 1 (per study maximum of 6 doses)
    Capecitabine 850–1000 mg/m² PO BID on Days 1–14
    Cycled every 21 days

GAST-F 14 of 20

• First-line therapy; Useful in Certain Circumstances, new dosing added:
  • Entrectinib, larotrectinib, or repotrectinib (for NTRK gene fusion-positive tumors)
    Entrectinib 600 mg PO once daily
    
    Larotrectinib 100 mg PO twice daily
    
    Repotrectinib
    160 mg PO daily Days 1–14 of cycle 1
    160 mg PO BID Days 15–28 of cycle 1
    160 mg PO BID Days 1–28 of cycle 2 and beyond
    Cycled every 28 days

Principles of Systemic Therapy-References

GAST-F 17 of 20 through GAST-F 20 of 20

• The reference pages were updated to reflect the changes in the algorithm.

GAST-G 2 of 5

• Target Volume (General Guidelines)
  • Preoperative chemoradiation section along with sub-bullets below removed
    • Pretreatment diagnostic studies (EUS, EGD, FDG-PET, and CT scans) should be used to identify the tumor and pertinent nodal groups.
    • The relative risk of nodal metastases at a specific nodal location is dependent on both the site of origin of the primary tumor and other factors including width and depth of invasion of the gastric wall. Coverage of nodal areas may be modified based on clinical circumstances and the risks of toxicity.

GAST-G 5 of 5

• Reference removed: Ajani AJ, Winter K, Okawara GS, et al. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): Quality of combined modality therapy and pathologic response. J Clin Oncol 2006;24:3953-3958.

GAST-H 1 of 2

• New bullet added: All patients with H. pylori infection who underwent curative ER or gastric subtotal resection must receive an H. pylori eradication regimen. The choice and duration of the eradication regimen should follow the recommendations of the latest American (American College of Gastroenterology) or international (Maastricht consensus report) H. pylori guidelines.

GAST-H 2 of 2

• Reference 1 is new: Choi IJ, Kook MC, Kim YI, et al. Helicobacter pylori therapy for the prevention of metachronous gastric cancer. N Engl J Med 2018;378:1085-1095.

GAST-I 3 of 4

• Survivorship Care Planning and Coordination of Care; 4th bullet; 3rd sub-bullet revised: "...NCCN Disease-Specific Guidelines: Treatment by Cancer Type"

GAST-J 2 of 3

• Pain; 3rd bullet, New sub-bullet added: Severe uncontrolled pain following gastric stent placement should be treated with endoscopic removal of the stent once the uncontrollable nature of the pain is established.

ABBR-1

• The abbreviations page was updated as appropriate.

 

NCCN has published updates to the NCCN Chemotherapy Order Templates (NCCN Templates^®) for Gastric Cancer to reflect the currently published NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Gastric Cancer v1.2025.

• The following NCCN Templates^® have been deleted:
  • GAS24: CISplatin/Fluorouracil Days 1 – 5 with Concurrent Radiation
  • GAS25: PACLitaxel/CARBOplatin with Concurrent Radiation
  • GAS98: Fluorouracil Continuous Infusion/OXALIplatin with Concurrent Radiation

• The following New NCCN Template^® has been published:
  • GAS120: Nivolumab and hyaluronidase-nvhy

 

For the complete updated versions of the NCCN Guidelines, NCCN Guidelines with NCCN Evidence Blocks™, the NCCN Drugs & Biologics Compendium (NCCN Compendium^®), the NCCN Biomarkers Compendium^®, the NCCN Chemotherapy Order Templates (NCCN Templates^®), the NCCN Radiation Therapy Compendium™, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™), please visit NCCN.org.

To view the NCCN Guidelines for Patients^®, please visit NCCN.org/patientguidelines.

Free NCCN Guidelines apps for iPhone, iPad, and Android devices are now available! Visit NCCN.org/apps.

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