What is the recommended initial treatment for mid esophageal squamous cell carcinoma?

Treatment of Mid Esophageal Squamous Cell Carcinoma

For mid esophageal squamous cell carcinoma, the recommended initial treatment is preoperative chemoradiotherapy followed by surgery for locally advanced disease, or definitive chemoradiotherapy with salvage surgery as needed for patients with good response to initial therapy. 1, 2

Treatment Algorithm Based on Disease Stage

Early Disease (Tis-T1a N0)

• Surgery is the treatment of choice for early-stage disease with no lymph node involvement 1, 2
• Transthoracic esophagectomy with two-field lymph node resection is the recommended surgical approach for intrathoracic squamous cell carcinoma 1
• At least six regional lymph nodes should be dissected and examined during surgery 1

Locally Advanced Disease (T3-T4 N0-1)

• Surgery alone is suboptimal treatment since complete tumor resection is not possible in approximately 30% of pT3 and 50% of pT4 tumors 1
• Patients benefit from preoperative therapy, particularly preoperative chemoradiotherapy, which increases rates of complete tumor resection, improves local tumor control, and improves survival 1, 2
• Preoperative chemoradiotherapy has shown a survival benefit in phase III trials, with a 13% absolute difference in survival at 2 years compared to surgery alone 1
• The standard chemotherapy regimen typically includes cisplatin and 5-fluorouracil combined with radiotherapy 1, 3

Definitive Chemoradiotherapy Option

• Due to its high complete response rate, chemoradiotherapy with close surveillance and salvage surgery for relapse may be considered as a definitive treatment for locally advanced disease 1
• This approach is supported by results from French (FFCD 9102) and German (Stahl 2005) trials 1
• Patients with good tumor response to initial chemoradiotherapy may not require surgery and can be treated with definitive chemoradiotherapy alone 1, 4

Important Considerations and Caveats

Treatment Selection Factors

• Primary interdisciplinary planning of treatment is mandatory for optimal outcomes 1, 2
• Patient fitness significantly impacts treatment options - consider performance status, respiratory function, and comorbidities 2
• Preoperative chemoradiotherapy may increase postoperative mortality, requiring careful patient selection 1

Response Evaluation

• Response to therapy should be routinely evaluated by symptomatic evolution, esophagogram, endoscopy (with biopsies), and CT scan 1
• Pathologic complete response rates of up to 40% have been reported with intensive chemoradiotherapy regimens, which correlate with improved survival 3

Potential Complications

• Preoperative chemoradiotherapy can cause significant toxicities including neutropenia (60%), febrile neutropenia (34%), and nutritional issues requiring support (50%) 3
• Late toxicities after definitive chemoradiotherapy can be serious and sometimes lethal even years after treatment 4
• Modified radiation therapy regimens at doses of 50.4 Gy may reduce late toxicities without reducing efficacy 4

Follow-Up

• Regular follow-up after initial therapy has not been shown to significantly influence outcomes 1, 2
• Follow-up visits should focus on symptoms, nutrition, and psychosocial problems 1
• For patients who received definitive chemoradiotherapy, close surveillance is needed to identify candidates for salvage surgery if recurrence occurs 1, 2

Treatment Outcomes

• Studies show improved survival with multimodality treatment compared to surgery alone, with 2-year survival rates of approximately 60% versus 32% with surgery alone 5
• Patients achieving pathologic complete response after chemoradiotherapy have significantly better outcomes (2-year survival 78%, median survival 58 months) compared to those with residual disease (2-year survival 46%, median survival 22.4 months) 3