Survival rates and safety associated with chemoradiotherapy followed by surgery and chemoradiotherapy alone for patients with T4 esophageal cancer: a systematic review and meta-analysis.

Background: The optimal treatment approach for T4 esophageal cancer is not well established. We aimed to perform a systematic review and meta-analysis to determine the survival rates and safety of chemoradiotherapy followed by surgery (CRT-S) and chemoradiotherapy alone (CRT) in patients with T4 N M0 esophageal cancer.

Materials And Methods: We searched databases for eligible prospective or retrospective studies. The outcomes of interest were overall survival (OS) at 1, 3 and 5 years, treatment-related fistula formation and mortality rates. Meta-analyses were performed using the random effects models separately for studies evaluating CRT-S and CRT. Subgroup analyses were performed based on histology, radiation dose, chemotherapy regimen and duration of the interval between CRT and surgery.

Results: We identified 23 studies including 1,119 patients with predominantly squamous cell carcinoma (93%) and adenocarcinoma (3%) histology. The OS rates of patients receiving CRT-S were 65%, 36% and 20% at 1, 3 and 5 years, respectively. The OS rates of patients receiving CRT were 30%, 11% and 10% at 1, 3 and 5 years, respectively. Treatment-related fistula formation rates were 4% for CRT-S and 9% for CRT. Treatment-related mortality rates were 3% for both groups. Subgroup analyses showed that the interval of >2 months between CRT and surgery was associated with significantly improved OS rates at 1, 3 and 5 years.

Conclusion: Chemoradiotherapy is an efficacious treatment approach for T4 esophageal cancer, with clinically acceptable rates of treatment-related fistula formation and mortality. Tri-modality approach with surgery can be considered in carefully selected patients. Our study findings should be interpreted with caution due to the lack of high-quality evidence. Randomized controlled trials are warranted to confirm these findings.