What's the next step for a patient with gastroesophageal junction adenocarcinoma diagnosed by punch biopsy of the mucosa, without a visible mass on Esophagogastroduodenoscopy (EGD)?

Next Steps for GEJ Adenocarcinoma Diagnosed by Punch Biopsy Without Visible Mass on EGD

Proceed immediately with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) to obtain adequate tissue for accurate T-staging, as punch biopsy alone cannot determine depth of invasion, lymphovascular invasion, or tumor grade—all critical factors that determine whether the patient requires surgery, neoadjuvant therapy, or can be managed endoscopically. 1

Why Standard Biopsy Is Insufficient

• Punch biopsies can confirm the presence of adenocarcinoma but cannot accurately stage early gastric or GEJ cancers because they do not provide information about depth of invasion (T1a vs T1b), presence of lymphovascular invasion, or tumor differentiation 1
• Endoscopic resection is essential for accurate staging of early-stage cancers (T1a or T1b) and may be both diagnostic and therapeutic 1
• The absence of a visible mass does not exclude invasive cancer—early GEJ adenocarcinomas can present as flat mucosal lesions or subtle mucosal irregularities that require EMR/ESD for proper assessment 1

Immediate Staging Workup (Concurrent with EMR/ESD Planning)

While arranging endoscopic resection, complete the following staging investigations:

• CT chest, abdomen, and pelvis with oral and IV contrast to identify distant metastases 1, 2
• Endoscopic ultrasound (EUS) to evaluate T and N stage, particularly if early-stage disease is suspected or to differentiate early versus locally advanced disease 1, 2
• PET-CT from skull base to mid-thigh if locally advanced or metastatic disease is suspected (identifies occult metastases in 15-20% of cases) 1, 2
• Universal testing for microsatellite instability (MSI) by PCR/NGS or mismatch repair (MMR) by immunohistochemistry 1
• HER2, PD-L1, and CLDN18.2 testing if advanced/metastatic disease is documented or suspected 1
• Assess Siewert tumor type (I, II, or III) as this determines surgical approach 1, 2

Management Algorithm Based on EMR/ESD Results

If T1a Disease (Mucosal Invasion Only)

• Curative EMR/ESD criteria: Well-differentiated adenocarcinoma, no lymphovascular invasion, negative margins, no ulceration 1
• If curative resection achieved: Begin ablation of residual Barrett's esophagus (if present) 2-3 months post-ESD using radiofrequency ablation, repeated every 2-3 months until complete eradication 1
• Surveillance schedule: First EGD at 6 months, then every 6 months for 2 years, then annually 1

If T1b Disease (Submucosal Invasion <500 μm)

• First EGD at 3 months, then every 6 months for 2 years 1
• Consider EUS and CT surveillance to detect lymph node metastases (risk exists even with superficial invasion) 1
• If patient is medically fit and has high-risk features (poor differentiation, lymphovascular invasion), discuss surgical resection with multidisciplinary team 2

If T1b Disease (Submucosal Invasion ≥500 μm) or Deeper Invasion

• This represents noncurative endoscopic resection 1
• Proceed to surgical evaluation immediately for esophagectomy or extended total gastrectomy depending on Siewert type 2
• For Siewert type II-III tumors at GEJ: Neoadjuvant chemoradiation (preferred) or perioperative chemotherapy followed by surgery offers superior outcomes compared to surgery alone 2, 3, 4
• FLOT-based perioperative chemotherapy (5-FU/leucovorin/oxaliplatin/docetaxel) or CROSS regimen chemoradiation are both acceptable options, with FLOT showing slight superiority in recent network meta-analysis 4

Critical Pitfalls to Avoid

• Do not proceed directly to surgery or systemic therapy based on punch biopsy alone—you will miss the opportunity for curative endoscopic treatment in early-stage disease 1
• Do not perform EUS after neoadjuvant therapy—it has reduced accuracy for determining disease stage post-treatment 1
• Do not ablate Barrett's esophagus before resecting visible nodularity or dysplasia—endoscopic resection must come first 1
• Do not assume absence of visible mass means early disease—some T2-T3 tumors can present with subtle mucosal changes only 1
• Laparoscopy is optional but recommended if peritoneal carcinomatosis is suspected and not clearly visible on CT 1

Multidisciplinary Team Discussion

All patients must be discussed in an upper GI multidisciplinary tumor board before initiating definitive treatment, with participation from surgical oncology, medical oncology, radiation oncology, gastroenterology, radiology, and pathology 1, 2