What are the differences in surgical interventions between esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) according to National Comprehensive Cancer Network (NCCN) guidelines?

Surgical Intervention Differences Between Esophageal Squamous Cell Carcinoma and Adenocarcinoma

According to NCCN-aligned guidelines, the primary surgical difference is that esophageal squamous cell carcinoma (ESCC) can be definitively treated with chemoradiotherapy alone without surgery in responding patients, whereas esophageal adenocarcinoma (EAC) requires surgical resection as part of multimodality therapy when feasible. 1

Key Surgical Approach Differences

Squamous Cell Carcinoma - Surgery Optional in Responders

• ESCC patients have two acceptable treatment pathways: preoperative chemoradiotherapy followed by surgery OR definitive chemoradiotherapy without surgery, with the choice depending on response to initial therapy 1

• Approximately 50% of ESCC patients achieve complete pathologic response after chemoradiotherapy, meaning surgery may not provide additional benefit in these complete responders 1

• For ESCC patients who demonstrate clinical complete response to chemoradiotherapy (no dysphagia, normal esophagogram, normal endoscopy, and normal CT scan), definitive chemoradiotherapy without surgery is an acceptable definitive treatment 1

• Surgery remains beneficial for ESCC patients with residual locally advanced disease after chemoradiotherapy but offers no value for those with complete pathologic response 1

Adenocarcinoma - Surgery Required

• EAC patients should receive either preoperative chemoradiotherapy OR perioperative chemotherapy, both followed by surgical resection 1

• Surgery alone may be considered only for very early-stage EAC (clinical T2N0 with low-risk features: well-differentiated, <2 cm) after multidisciplinary discussion 1

• Definitive chemoradiotherapy without surgery is recommended for EAC only when surgery is not feasible due to medical contraindications or patient factors 1

Staging Differences Affecting Surgical Planning

Squamous Cell Carcinoma Staging

• Upper-aerodigestive tract endoscopy is required for ESCC staging to evaluate potential synchronous head and neck primaries 1

• ESCC has higher prevalence of micrometastases compared to adenocarcinoma, contributing to poorer prognosis after surgery alone 1

Adenocarcinoma Staging

• Laparoscopy is recommended for locally advanced (T3/T4) adenocarcinomas of the esophagogastric junction to rule out peritoneal metastases 1

• This staging procedure is not routinely performed for ESCC 1

Tumor Location Impact on Surgery

• ESCC more commonly occurs in the upper and middle thoracic esophagus, presenting greater surgical challenges 1

• Cervical esophageal tumors (typically squamous) are not treated with surgery due to high morbidity, mortality, and negative quality of life impact 1

• EAC predominantly presents in the lower esophagus and gastroesophageal junction, where surgical resection is more technically feasible 1

• Middle-third tumors carry higher risk of lung radiation exposure, while tumors involving the upper stomach risk gastric conduit exposure 1

Extent of Lymphadenectomy

• At least 16-18 and preferably 20 lymph nodes should be dissected and examined, with adequate nodal dissection within appropriate nodal fields (abdominal and thoracic) 1

• The specific lymph node stations resected vary considerably based on tumor location and histology, with no uniform worldwide strategy 2

• Transthoracic esophagectomy with two-field lymph node resection is recommended for intrathoracic ESCC 3

• Less extensive lymph node dissection may benefit more from the addition of radiation therapy 1

Preoperative Therapy Selection

For Adenocarcinoma

• Two equivalent options exist: preoperative chemoradiotherapy OR perioperative chemotherapy (FLOT regimen preferred) 1

• Preoperative chemotherapy should be considered for patients who are not candidates for radiation 1

• Cisplatin/5-fluorouracil combined with radiotherapy followed by surgery is considered optimal for locally advanced disease 1

For Squamous Cell Carcinoma

• Preoperative chemoradiotherapy is the standard approach when surgery is planned 1

• The subgroup analysis from the CROSS trial showed more pronounced benefit in ESCC (HR 0.34) compared to adenocarcinoma (HR 0.82) 1

• Patients with good tumor response to initial chemoradiotherapy may proceed with definitive chemoradiotherapy without surgery 1

Important Surgical Considerations

Postoperative Complications

• Postoperative complications may be more severe with chemoradiotherapy compared to chemotherapy alone 1

• Preoperative chemoradiotherapy may increase postoperative mortality, requiring careful patient selection 1

• Surgical mortality following transthoracic esophagectomy has decreased to <5% in modern series 1

Quality of Surgery Impact

• The addition of radiation therapy is expected to be more beneficial when surgery is less optimal or less extensive 1

• Adequate quality surgery requires clear surgical margins and adequate nodal dissection 1

• Transthoracic surgery has been associated with more favorable oncological outcomes compared to transhiatal approach, though not necessarily better quality of life 1

Common Pitfalls to Avoid

• Do not treat adenosquamous carcinoma like squamous cell carcinoma - it behaves more like adenocarcinoma with only 20% complete response to chemoradiation, requiring surgical resection 4

• Do not assume all ESCC patients require surgery - approximately half achieve complete pathologic response and may be managed with definitive chemoradiotherapy alone 1

• Do not proceed with surgery alone for locally advanced disease (T3-T4) - complete tumor resection is not possible in 30% of pT3 and 50% of pT4 tumors without neoadjuvant therapy 1

• Do not skip laparoscopy in locally advanced adenocarcinomas of the gastroesophageal junction - this can identify occult peritoneal metastases that would preclude curative resection 1