What is the role of chemotherapy and radiation therapy in treating esophageal cancer?

Role of Chemotherapy and Radiation Therapy in Esophageal Cancer Treatment

Combined chemoradiation therapy is the standard treatment for inoperable esophageal cancer, while surgical resection remains the primary approach for early-stage disease with chemoradiation playing important roles in multimodal treatment strategies depending on disease stage and patient factors. 1

Treatment Approach Based on Disease Stage

Early Stage Disease (T1-T2, N0)

• Surgical excision is recommended as the primary treatment for stages I and II (disease localized to the esophagus) 1
• For patients who are inoperable or refuse surgery, combination chemoradiotherapy is the standard treatment 1
• Radiotherapy alone is an option when chemotherapy is contraindicated 1
• For adenocarcinoma of the gastroesophageal junction, preoperative chemoradiation therapy should be considered, preferably within a clinical trial 1

Locally Advanced Disease (T3, N0-1, M0)

• No single standard approach exists, but options include: 1
  • Surgical excision
  • Chemoradiation therapy
  • Chemoradiation therapy followed by surgery
• The RTOG schedule (four cycles of 5-FU-cisplatin at weeks 1,5,8,11 with radiotherapy 50 Gy in 25 fractions over 5 weeks) is considered standard for inoperable cases 1
• Combined chemoradiation is superior to radiotherapy alone for non-surgical treatment, with level of evidence B 1, 2

Advanced Disease (T4, N0-1)

• For disease without tracheal mucosal invasion: palliative surgery, chemoradiation therapy, or radiotherapy alone (if chemotherapy is contraindicated) are options 1
• For disease with tracheal mucosal involvement: endoscopic treatments for dysphagia and respiratory compromise or radiotherapy with or without chemotherapy for patients with reasonable performance status 1
• For patients with esophageal-respiratory tract fistulae: placement of an esophageal and/or tracheo-bronchial stent is standard treatment 1

Metastatic Disease

• For patients with good performance status (PS1-2): combination chemoradiotherapy followed by chemotherapy alone (if there is evidence of objective response) 1
• For patients with poor performance status (PS3-4): endoscopic therapy for palliation of dysphagia is standard 1
• For patients with resected primary tumor and good performance status: chemotherapy, preferably within a clinical trial 1

Specific Chemotherapy and Radiation Protocols

• The standard chemoradiation regimen includes cisplatin and 5-fluorouracil with concurrent radiation therapy 1, 2
• Weekly carboplatin-paclitaxel combined with radiation (41.4 Gy in 23 fractions) has shown improved survival compared to surgery alone 3
• Modified radiation therapy at 50.4 Gy has demonstrated reduced late toxicities without compromising efficacy 4
• Concurrent chemoradiotherapy has been shown to prolong survival compared to radiation therapy alone when given as definitive treatment 4, 2

Comparative Effectiveness

• Combined chemotherapy and radiation therapy is superior to radiation therapy alone for non-surgical treatment of esophageal cancer, with improved local control, decreased distant metastases, and better survival rates 1, 2
• Median survival with chemoradiation has been shown to be 12.5 months compared to 8.9 months with radiation alone 2
• Preoperative chemoradiation therapy has shown promise in improving outcomes when followed by surgical excision, with studies showing up to 79% of patients having no residual cancer at the time of resection 5

Common Pitfalls and Caveats

• Chemoradiation therapy carries significant toxicity, including esophagitis, thrombosis, infection, and hematologic complications 6, 2
• Late toxicities can be lethal for patients who achieve complete response, even years after treatment 4
• Salvage treatment for residual or recurrent disease remains challenging and should be considered at the time of starting initial treatment 4
• The risk of metastasis increases significantly if cancer penetrates into the submucosa, highlighting the importance of accurate staging 1
• Preoperative chemoradiation therapy has not been proven superior to surgery alone in operable subjects with stage I and II epidermoid cancer of the thoracic esophagus (level of evidence B) 1

Special Considerations

• For patients with adenocarcinoma of the esophagus or esophagogastric junction, preoperative chemoradiation therapy has shown efficacy (level of evidence B) 1
• Endoscopic therapy represents the standard for patients unfit for other treatments 1
• For patients with tracheoesophageal fistula, placement of an airway stent and/or tracheo-bronchial stent is the standard treatment 7
• Nutritional support should be considered before chemotherapy or radiation therapy 7