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Original Investigation |

Association Between Clinically Staged Node-Negative Esophageal Adenocarcinoma and Overall Survival Benefit From Neoadjuvant Chemoradiation

Emmanuel Gabriel, MD, PhD1; Kristopher Attwood, PhD2; William Du, MD1; Rebecca Tuttle, MD1; Raed M. Alnaji, MD1; Steven Nurkin, MD, MS1; Usha Malhotra, MD3; Steven N. Hochwald, MD1; Moshim Kukar, MD1
[+] Author Affiliations
1Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York
2Department of Biostatistics, New Center for Excellence, Buffalo, New York
3Department of Medical Oncology, Roswell Park Cancer Institute, Buffalo, New York
JAMA Surg. 2016;151(3):234-245. doi:10.1001/jamasurg.2015.4068.
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Importance  While neoadjuvant chemoradiation for esophageal cancer improves oncologic outcomes for a broad group of patients with locally advanced and/or node-positive tumors, it is less clear which specific subset of patients derives most benefit in terms of overall survival (OS).

Objective  To determine whether neoadjuvant chemoradiation based on esophageal adenocarcinoma histology has similar oncologic outcomes for patients treated with surgery alone when stratified by clinical nodal status.

Design, Setting, and Participants  A retrospective analysis using the American College of Surgeons National Cancer Database from 1998 to 2006. Patients with esophageal adenocarcinoma histology and clinical stage T1bN1-N3 or T2-T4aN−/+M0 were divided into 2 treatment groups: (1) neoadjuvant chemoradiation followed by surgery and (2) surgery alone. Subset analysis within each treatment group was performed for clinically node-negative patients (cN−) vs node-positive patients (cN+) in conjunction with pathological nodal status. A propensity score–adjusted analysis, which included patient demographics, comorbidity status, and clinical T stage, was also performed.

Main Outcome and Measures  The primary outcome was 3-year OS. Secondary outcomes included margin status, postoperative length of stay, unplanned readmission rate, and 30-day mortality.

Results  A total of 1309 patients were identified, of whom 539 received neoadjuvant chemoradiation followed by surgery and 770 received surgery alone. Of the 1309 patients, 41.2% (n = 539) received neoadjuvant chemoradiation and 47.2% (n = 618) were cN+. Median follow-up for the entire cohort was 73.3 months (interquartile range, 64.1-93.5 months). The 3-year OS was better for neoadjuvant chemoradiation followed by surgery compared with surgery alone (49% vs 38%, respectively; P < .001). Stratifying based on clinical nodal status, the propensity score–adjusted OS was significantly better for cN+ patients who received neoadjuvant chemoradiation (hazard ratio, 0.52; 95% CI, 0.42-0.66; P < .001). In contrast, there was no difference in OS for cN− patients based on treatment (hazard ratio, 0.84; 95% CI, 0.65-1.10; P = .22).

Conclusions and Relevance  Patients with cN+ esophageal adenocarcinoma benefit significantly from neoadjuvant chemoradiation. However, patients with cN− tumors treated with neoadjuvant chemoradiation plus surgery do not derive a significant OS benefit compared with surgery alone. This finding may have significant implications on the use of neoadjuvant chemoradiation in patients with cN− disease.

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Figure 1.
Flow Diagram of Patient Inclusion and Exclusion Criteria From the National Cancer Database (NCDB) Esophageal Cancer Participant User File
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Figure 2.
Overall Survival Between Treatment Groups For the Entire Cohort (A) and Excluding Complete Pathologic Responders (B)
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Figure 3.
Overall Survival Among the Clinical Node-Negative Patients (A) and Clinically Node-Positive Patients (B) and the True Node-Negative Patients (C) and True Node-Positive Patients (D) Based on Treatment Group
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