A national analysis evaluating the role of neoadjuvant chemoradiotherapy in upper esophageal cancer.
Authors: Sabbagh Saad , Iska Sindu , Jabbal Iktej Singh , Itani Mira , Mohanna Mohamed , Dominguez Barbara , Liang Hong , Nahleh Zeina A. , Nagarajan Arun 
Published: June 2023

e16102

Background: Patients with cervical esophageal tumors are associated with poor survival outcomes with a 5-year overall survival (OS) of 30%. While surgical resection is a necessary component of trimodality therapy for thoracic and abdominal esophageal tumors management, the role of surgery is unclear for cervical and upper-third tumors due to the associated high morbidity and mortality of surgery resulting from the proximity to anatomical structures in the region. Higher chances of postoperative complications and subsequent functional deficits are reported due to neurovascular and organ compromise. Definitive chemoradiation (DCR) without surgery is, therefore, the generally accepted treatment for upper esophageal tumors. Our study aimed to analyze the survival benefits of performing surgical resection after chemoradiotherapy (NCR) versus DCR in non-metastatic clinical stage T1-T4a cervical and upper third esophageal cancers. Methods: Patients diagnosed with cervical and upper third esophageal cancers between 2004 and 2017 staged as clinical T1-T4a were included from the National Cancer Database. Demographic data and clinicopathological tumor characteristics were assessed using chi-square analysis to assess baseline differences between the two groups. Our primary outcome was to evaluate the role of surgery as a treatment modality by comparing differences in OS between the NCR and DCR groups using Kaplan Meier (KM) and Cox proportional hazards analysis. Results: N = 2310 patients that met the inclusion criteria were identified with NCR group comprising 7.6% (n = 177) and DCR group comprising 92.4% (n = 2133) of the sample. Tumor histology was predominately of squamous cell carcinoma subtype (89%). Patients receiving NCR were seen to have prolonged median OS (31.840 months) than those undergoing DCR (21.320 months). Cumulative survival in the NCR group was higher at 1-year, 3-year, and 5-year time periods (0.85 vs. 0.67, 0.47 vs. 0.38, and 0.38 vs. 0.28, overall p < 0.001). In addition, patients in the NCR arm had a better prognosis after adjusting for significant covariables (HR 1.306, p 0.010). A proportional increase in HR was observed with increasing tumor size (2-5cm: HR 1.388 p 0.002, 5-10cm: HR 1.455 p 0.002, ref value < 2cm p 0.001). Finally, no statistical significance was observed between the two groups when a subgroup analysis for patients with clinical T2 and T3 stage was performed. Conclusions: In our study, performing a surgical resection after chemoradiotherapy versus chemoradiotherapy alone showed potential survival benefits in patients with cervical and upper-third esophageal cancers. With the advancement in surgical techniques and better understanding of favorable criteria for surgical eligibility, such as lower T staging, improving outcomes with surgery is possible. Future large scale clinical trials would aid in setting guidelines for the optimal management in these patients.