Chemo-radiation alone associated with higher risk of death compared to chemo-radiation plus surgery in esophageal squamous cell carcinoma

BackgroundThe management of esophageal squamous cell carcinoma remains controversial. There is widespread belief that chemoradiation provides a survival benefit over trimodal therapy even in patients with resectable disease. These paradigms are largely based on studies from the early 2000’s that report surgical mortality rates up to 20%. Additionally, risks for squamous cell put these patients at higher risk for non-cancer causes of death, which further skew survival-based studies. We sought to clarify these outcomes in a large-scale database study.MethodsWe examined all patients with esophageal cancer from 2004 to 2020 in the Surveillance, Epidemiology, and End Results (SEER) database. Demographics, treatment type, race, cancer stage, and survival were analyzed. Hazard ratios were calculated compared to trimodal therapy for each treatment type.ResultsThere were 74,918 patients with esophageal cancer from 2004 to 2020; 25,270 with squamous cell and 42,585 with adenocarcinoma. All treatments had significantly higher risks of death compared to trimodal therapy (see Table). The minimum increased risk of death without surgery was 2x higher compared to trimodal therapy. Mortality was lower when surgery was combined with either chemotherapy or radiation alone. Non - cancer causes of death were more common in squamous cell carcinoma (21% v. 19%, p < 0.0001). A preponderance of these causes are closely associated with smoking and alcohol use. These include lung cancer, head and neck cancers, liver failure and COPD. The final analysis will include stage-based treatment, and 4385 patients who were offered surgery but refused. Table: 1464P Hazard ratio by treatment type and histology of esophageal cancer Cancer type and treatment Hazard ratio (95% CI, p, 0.0001) All esophageal cancer Chemo-radiation 2.151 (2.081 – 2.224) Chemotherapy alone 3.102 (2.985 – 3.223) Radiation alone 4.235 (4.058 – 4.419) No treatment 5.533 (5.344 – 5.727) Squamous cell carcinoma Chemo-radiation 1.929 (1.801 – 2.066) Chemotherapy alone 3.221 (2.972 – 3.491) Radiation alone 3.887 (3.595 – 4.204) No treatment 6.368 (5.932 – 6.836) Adenocarcinoma Chemo-radiation 2.386 (2.294 – 2.482) Chemotherapy alone 3.112 (2.978 – 3.252) Radiation alone 4.621 (4.378 – 4.878) No treatment 5.116 (4.913, 5.328) ConclusionsThis study suggests that trimodal therapy confers a substantial advantage even to patients with esophageal squamous cell carcinoma. While further investigation is warranted, chemoradiation should not be considered a one-size-fits-all treatment option, and surgery must remain a consideration for operable cases.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.