What is the current recommendation for treating gastroesophageal junction cancers: chemotherapy (chemo) + radiation therapy (RT) or chemotherapy alone?

Treatment Recommendation for Gastroesophageal Junction Cancers

For resectable, locally advanced gastroesophageal junction adenocarcinoma, either perioperative chemotherapy or neoadjuvant chemoradiotherapy is recommended, with neoadjuvant chemoradiotherapy potentially offering superior overall survival benefits. 1

Evidence-Based Treatment Algorithm

For Resectable Disease (Stages I-III)

The most recent 2024 international consensus guidelines provide a nuanced recommendation that acknowledges both Eastern and Western evidence 1:

Primary Options (both acceptable):

• Perioperative chemotherapy (chemotherapy before and after surgery) 1
• Neoadjuvant chemoradiotherapy (chemo+RT before surgery) followed by surgery 1

Alternative approach:

• Upfront surgery followed by adjuvant chemotherapy may be acceptable, particularly following gastric cancer treatment paradigms 1

Comparative Effectiveness Analysis

A 2019 network meta-analysis specifically examining GEJ cancers found that preoperative chemoradiotherapy ranked highest for overall survival (P-score = 0.823), outperforming perioperative chemotherapy (P-score = 0.591) and preoperative chemotherapy alone (P-score = 0.428) 2. This represents the most direct comparative evidence available for GEJ-specific treatment.

The landmark evidence supporting combined modality therapy includes 1:

• Chemoradiotherapy benefit: Meta-analysis showing HR 0.81 for mortality with preoperative chemoradiotherapy versus surgery alone, corresponding to 13% absolute survival improvement at 2 years 1
• Perioperative chemotherapy: The MAGIC trial demonstrated survival benefits with perioperative chemotherapy for gastroesophageal cancers 1

Histology-Specific Considerations

For adenocarcinoma (the predominant GEJ histology):

• Both neoadjuvant chemoradiotherapy and perioperative chemotherapy show efficacy 1
• The Dutch CROSS trial showed HR 0.82 for adenocarcinoma with chemoradiotherapy 1
• Standard regimens include carboplatin/paclitaxel with concurrent radiation or perioperative FLOT chemotherapy 3

Critical Decision Points

Choose neoadjuvant chemoradiotherapy when:

• Patient has good performance status and can tolerate combined modality therapy 3
• Tumor characteristics suggest higher local control needs 2
• Following esophageal cancer treatment paradigms 1

Choose perioperative chemotherapy when:

• Following gastric cancer treatment paradigms 1
• Patient preference for avoiding radiation 1
• Siewert type II or III tumors with more gastric characteristics 1

Choose upfront surgery + adjuvant therapy when:

• Early-stage disease (T1-T2) 1
• Patient cannot tolerate neoadjuvant therapy 1

Unresectable or Metastatic Disease

For unresectable/metastatic GEJ adenocarcinoma, chemotherapy is the primary treatment and should follow gastric cancer regimens 1. Essential biomarker testing before first-line therapy includes HER2, PD-L1 CPS, MSI, and claudin 18.2 1.

Common Pitfalls to Avoid

• Do not use radiation alone without chemotherapy for resectable disease—combined chemoradiation is superior 1
• Do not skip multidisciplinary evaluation—treatment decisions require input from surgical oncology, medical oncology, radiation oncology, and gastroenterology 1
• Do not proceed without adequate staging—CT chest/abdomen, PET-CT, and endoscopic ultrasound are essential before treatment planning 1
• Do not perform inadequate lymphadenectomy—at least 15 lymph nodes should be examined for proper staging 1
• Laparoscopy should be considered for Siewert type II or III tumors to detect occult peritoneal disease 1

Strength of Evidence

The 2024 international guidelines rate this recommendation as weak (65% consensus for perioperative chemotherapy or neoadjuvant chemoradiotherapy) with Level C evidence 1. This reflects the lack of head-to-head trials directly comparing these approaches specifically in GEJ cancers, though both strategies have Category 1 evidence supporting combined modality therapy over surgery alone 1.