What are the treatment options for esophageal cancer?

Treatment of Esophageal Cancer

Multimodality therapy is the standard of care for locally advanced esophageal cancer, with treatment selection based on histology, tumor stage, and location. 1

Early-Stage Disease (Tis-T1a N0)

• Surgery is the treatment of choice for early esophageal cancer. 2
• Endoscopic mucosal resection is an acceptable alternative in specialized centers, achieving equal cure rates with less invasive intervention. 1, 2
• For carefully selected low-risk cT2N0 lesions (well-differentiated, <2 cm), surgery alone may be considered after multidisciplinary discussion. 1

Locally Advanced Resectable Disease

For Adenocarcinoma (T2-T3 N0-1 M0)

Either preoperative chemoradiotherapy OR perioperative chemotherapy should be offered—both are acceptable standard approaches. 1

Perioperative Chemotherapy Option:

• The FLOT regimen (docetaxel, oxaliplatin, leucovorin, and fluorouracil) is the standard of care for esophageal adenocarcinoma, especially for smaller tumors at the esophagogastric junction. 2
• Traditional cisplatin/5-FU perioperative chemotherapy remains an alternative standard regimen. 2

Preoperative Chemoradiotherapy Option:

• Cisplatin/5-FU combined with 40-50.4 Gy radiation is the standard regimen. 1, 2
• Recent meta-analyses demonstrate significant survival benefits, particularly for high-risk patients. 2
• Postoperative complications may be more severe with chemoradiotherapy compared to chemotherapy alone—consider patient tolerance based on tumor location and comorbidities. 1

For Squamous Cell Carcinoma (T2-T3 N0-1 M0)

Preoperative chemotherapy or preoperative chemoradiotherapy should be offered, as both increase complete resection rates and improve survival. 3

• Standard preoperative chemotherapy consists of cisplatin/5-FU. 3
• Standard chemoradiotherapy includes cisplatin/5-FU combined with 50.4 Gy radiation. 3
• For tumors in the upper third of the esophagus, definitive chemoradiotherapy (50.4-60 Gy) with close surveillance and salvage surgery for progression is a reasonable alternative to upfront surgery. 2, 3

Surgical Considerations

Transthoracic esophagectomy with two-field lymph node resection is recommended for intrathoracic squamous cell carcinoma. 1, 2

• At least 6 regional lymph nodes should be examined, though 16-20 lymph nodes is preferred for adequate staging. 2
• Minimally invasive esophagectomy is preferred over open approaches in experienced centers due to lower morbidity and improved quality of life. 2
• Transhiatal esophagectomy offers lower morbidity but may reduce long-term survival compared to transthoracic approach with en bloc lymphadenectomy. 2

Definitive Chemoradiotherapy (Non-Surgical Candidates)

For patients who are not surgical candidates or refuse surgery, definitive chemoradiotherapy with 50.4-60 Gy is the standard curative-intent treatment. 1, 2

• Doses of 60 Gy and higher are recommended in Europe and Japan based on multicenter study experience. 2
• Combined chemoradiation is superior to radiotherapy alone. 1, 3
• Salvage surgery remains an option for local progression after definitive chemoradiotherapy. 2

Metastatic Disease (M1)

Systemic Therapy:

Platinum/fluoropyrimidine doublet combinations (oxaliplatin or cisplatin with 5-FU or capecitabine) are the standard first-line regimen for patients with good performance status (ECOG 0-2). 4

• HER2 testing is mandatory for all adenocarcinomas—if HER2-positive, add trastuzumab to cisplatin/fluoropyrimidine combination, which significantly improves survival. 4
• Taxanes (docetaxel or paclitaxel) are recommended as second-line monotherapy or in first-line combinations. 4
• The value of palliative chemotherapy is less proven in squamous cell carcinoma—best supportive care or monotherapy should be strongly considered as alternatives to combination chemotherapy. 4

Local Palliation for Dysphagia:

Single-dose brachytherapy is the preferred option for dysphagia relief, providing better long-term symptom control with fewer complications than metal stent placement. 4

• Metal stent placement is recommended for long tumors located at least 2 cm from the cricopharyngeal muscle when brachytherapy is not feasible. 4
• Expandable metal stents are preferred over plastic stents and should be coated to decrease tumor ingrowth. 4

Esophagobronchial Fistula:

• If fistula is present at diagnosis, esophageal and/or tracheobronchial stent placement is the standard treatment. 4
• Small-dose fractions of radiotherapy with or without chemotherapy can be used for patients with reasonable performance status but without established fistula. 4

Response Evaluation and Follow-Up

• Response is routinely evaluated through symptomatic progression, esophagogram, endoscopy with biopsies, and CT scan. 2, 3, 4
• In adenocarcinomas, FDG-PET can predict tumor response early, though this does not currently change therapeutic strategy. 2, 4
• Regular follow-up after initial treatment has no proven impact on outcome except for patients who may be candidates for salvage surgery—focus should be on symptoms, nutrition, and psychosocial support rather than routine imaging. 2, 4

Critical Pitfalls to Avoid

• Do not proceed with chemotherapy without HER2 testing in adenocarcinoma—this represents a missed opportunity for targeted therapy. 4
• Do not use combination chemotherapy in squamous cell carcinoma without recognizing its limited benefit compared to adenocarcinoma. 4
• Avoid high-dose radiotherapy (>55-60 Gy) in patients who might later require salvage surgery, as this increases postoperative mortality. 4
• Do not overlook nutritional support—enteral nutrition should be considered before chemotherapy or radiotherapy. 4