What is the recommended management for gastric antral adenocarcinoma?

Management of Gastric Antral Adenocarcinoma

For gastric antral adenocarcinoma, the management depends critically on clinical stage: very early disease (T1a, well-differentiated, <2cm, non-ulcerated) can be treated with endoscopic submucosal dissection (ESD), while stage IB and above requires perioperative chemotherapy (preferably FLOT or ECF regimen for 3 cycles pre- and post-operatively) combined with D2 gastrectomy with examination of at least 15-16 lymph nodes. 1, 2

Mandatory Initial Steps

All cases must be discussed at a multidisciplinary team meeting before any treatment decision, including surgeons, medical and radiation oncologists, gastroenterologists, radiologists, and pathologists. 3, 1, 2 When local expertise is unavailable, refer to an expert center before proceeding. 1

Complete Staging Workup

The following staging investigations are necessary before treatment planning:

• Physical examination with complete blood count to assess for iron deficiency anemia 1, 2
• Liver and renal function tests to determine appropriate therapeutic options 1, 2
• Upper endoscopy with biopsy reviewed by an experienced pathologist, documenting tumor size, description, location, distance from gastroesophageal junction, and any extension 3, 4
• Contrast-enhanced CT of chest, abdomen, and pelvis using multidetector CT scanners with 5mm slices 1, 2, 4
• Endoscopic ultrasound (EUS) for accurate T and N staging in potentially operable tumors, though note that EUS is less useful specifically for antral tumors 3, 1
• Diagnostic laparoscopy with peritoneal washings to exclude occult peritoneal metastases in all patients with cT3-T4 lesions or those considered potentially resectable 3, 5, 1, 4
• HER2 testing on biopsy specimens for molecular biomarker assessment 1, 2

Common pitfall: Omitting laparoscopy in potentially resectable cases may miss peritoneal metastases not detected on imaging in 10-20% of cases. 1

Treatment Algorithm Based on Stage

Very Early Disease (T1a)

Endoscopic submucosal dissection (ESD) is the preferred curative treatment when ALL of the following criteria are met: 3, 1

• Confined to mucosa (T1a)
• Well or moderately differentiated (G1-2)
• Non-ulcerated lesion
• ≤2 cm in diameter
• No lymphovascular invasion

ESD is preferred over endoscopic mucosal resection (EMR) for lesions >10mm due to higher complete resection rates. 1 This procedure should only be performed in experienced medical centers. 3

Post-endoscopic resection surveillance includes first follow-up endoscopy at 6 months, then annual endoscopy thereafter, as recurrence risk is 10-20%. 1

Critical caveat: Never attempt endoscopic resection for diffuse-type (signet ring cell) gastric cancer regardless of size or depth, as these require upfront surgery. 1

Localized Disease (Stage IB and Above)

The standard approach is perioperative chemotherapy combined with surgical resection. 1, 2

Perioperative Chemotherapy

Preferred regimen: Triplet chemotherapy with fluoropyrimidine + platinum compound + docetaxel (FLOT regimen) for 3 cycles pre-operatively and 3 cycles post-operatively. 1

Alternative regimen: ECF (epirubicin 50 mg/m², cisplatin 60 mg/m², continuous 5-FU 200 mg/m²/day) for 3 cycles pre- and post-operatively, which improves 5-year survival from 23% to 36.3%. 3, 2 ECX (substituting capecitabine for 5-FU) is commonly used as an alternative. 2

The perioperative approach has been adopted as standard of care in most of the UK and parts of Europe based on the UK MRC randomized trial. 3

Surgical Resection

D2 gastrectomy is the standard surgical approach for resectable gastric cancer classified as cT1N+ and cT2-4N-/+. 3, 2, 6, 7

For antral tumors specifically, distal gastrectomy is appropriate with adequate resection margins of ≥3 cm for Borrmann I-II tumors and ≥5 cm for Borrmann III-IV tumors. 2

D2 lymphadenectomy involves removal of perigastric (D1) and second-tier lymph nodes along the named vessels of the celiac axis. 5, 2, 7 At least 15-16 lymph nodes must be examined pathologically for adequate staging, with optimal examination of at least 25 lymph nodes. 3, 5, 2, 7

Splenectomy is not routinely recommended unless the tumor directly involves the spleen, as it increases postoperative complications without survival benefit. 2

Critical pitfall: Inadequate lymph node evaluation (fewer than 15 nodes) leads to understaging and suboptimal treatment planning. 2

Post-operative Chemotherapy

Complete the remaining 3 cycles of the same preoperative chemotherapy regimen if R0 resection was achieved, for a total of 6 cycles perioperatively. 5, 1

Locally Advanced Unresectable Disease

Concurrent chemoradiotherapy is recommended for patients with unresectable locally advanced gastric cancer with good performance status. 2 Chemotherapy regimens used with radiation include capecitabine + paclitaxel, cisplatin + 5-FU/capecitabine, or oxaliplatin + 5-FU/capecitabine. 2

Re-evaluate for potential surgical resectability after treatment response. 2

Metastatic Disease (Stage IV)

Palliative chemotherapy is recommended for patients with stage IV disease and good performance status. 2

For HER2-positive disease: Trastuzumab plus fluoropyrimidine/capecitabine + cisplatin is the standard first-line therapy. 5

For HER2-negative disease: Cisplatin plus fluoropyrimidine-based regimens are first-line therapy. 5, 2

Special Considerations for Bulky Nodal Disease

Bulky nodal disease is potentially resectable if: 5

• Level 3 or 4 lymph nodes are NOT highly suspicious on imaging
• No invasion or encasement of major vascular structures
• No distant metastases or peritoneal seeding

For resectable bulky nodal disease, administer 2-3 cycles of combination chemotherapy before surgery, followed by D2 lymphadenectomy and completion of perioperative chemotherapy. 5

Key Pitfalls to Avoid

• Never skip laparoscopy for clinical stage IB-III disease, as occult peritoneal metastases change management in 10-20% of cases 1
• Never proceed with surgery before multidisciplinary team discussion 1, 2
• Never perform routine splenectomy as it increases complications without survival benefit 2
• Never accept inadequate lymph node harvest (<15 nodes) as it leads to understaging 2, 7