What is the recommended neoadjuvant strategy for a gastroesophageal (GE) junction tumor?

Neoadjuvant Strategy for Gastroesophageal Junction Tumors

Perioperative chemotherapy or neoadjuvant chemoradiotherapy is weakly recommended as the preferred neoadjuvant strategy for resectable advanced gastroesophageal (GE) junction tumors. 1

Treatment Options Based on Current Evidence

The management of GE junction tumors presents unique challenges due to their anatomical location at the boundary between the esophagus and stomach. Based on the most recent clinical practice guidelines, there are several evidence-based approaches:

Recommended Neoadjuvant Strategies:

1. Perioperative Chemotherapy:

   • FLOT regimen (5-FU, leucovorin, oxaliplatin, and docetaxel) has become standard in Western countries 1
   • In East Asia, SOX regimen (S-1 plus oxaliplatin) has shown superiority 1
   • Subgroup analyses show benefit for GE junction tumors similar to gastric cancer 1

2. Neoadjuvant Chemoradiotherapy:

   • The POET trial (though prematurely terminated) showed a trend toward improved 3-year overall survival with neoadjuvant chemoradiotherapy (47.4%) compared to neoadjuvant chemotherapy alone (27.7%) 1
   • Higher pathologic complete response rates are achieved with combined chemoradiotherapy 2
   • Reduced risk of locoregional recurrence (OR 0.6) 2

Alternative Approach:

• Upfront Surgery with Adjuvant Chemotherapy:
  • May be acceptable for some patients with advanced GE junction cancer 1
  • This approach is more common in East Asia 1

Clinical Decision-Making Algorithm

1. Assess tumor characteristics:

   • Siewert classification (Type I, II, or III)
   • Clinical stage
   • Histological subtype

2. Consider patient factors:

   • Performance status
   • Comorbidities (especially cardiac or renal dysfunction which may contraindicate certain chemotherapy agents) 1
   • Ability to tolerate multimodality therapy

3. Select neoadjuvant strategy:

   • For most patients: Perioperative chemotherapy or neoadjuvant chemoradiotherapy
   • For patients with cardiac dysfunction: Avoid epirubicin-containing regimens 1
   • For patients with renal dysfunction: Avoid cisplatin-containing regimens 1

Important Considerations and Caveats

• Tumor downstaging: Patients whose tumors are downstaged after neoadjuvant therapy experience significantly improved survival and lower rates of both local (6% vs 13%) and systemic recurrence (19% vs 29%) 3

• Multidisciplinary assessment: All patients should undergo multidisciplinary evaluation before surgery to determine the optimal treatment plan 1

• Technical considerations for radiation therapy:

  • Target volume includes tumor bed and regional nodes, 2 cm beyond proximal and distal margins 1
  • Regional node irradiation is modified based on tumor location 1
  • For GE junction tumors specifically, include paracardial and para-esophageal lymph node beds 1

• Treatment response assessment: Post-neoadjuvant staging is more predictive of outcomes than pre-treatment staging, highlighting the importance of restaging after neoadjuvant therapy 3

• Ongoing research: The optimal approach for GE junction tumors remains an area of active investigation, with studies examining the role of immunotherapy in combination with standard approaches 1

While both neoadjuvant chemoradiotherapy and perioperative chemotherapy are acceptable approaches, the decision should be based on the specific characteristics of the tumor, patient factors, and institutional expertise. The evidence suggests that either approach can improve outcomes compared to surgery alone, with chemoradiotherapy offering better local control but potentially higher toxicity 2.