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Comparative Effectiveness of Upfront Esophagectomy vs Induction Chemoradiation in Clinical Stage T2N0 Esophageal Cancer
Tara R Semenkovich, Roheena Panni, Theodore Thomas, Leisha C Elmore, Jessica L Hudson, Bryan F Meyers, Benjamin D Kozower, Varun Puri
Washington University in St. Louis, St. Louis, MO

OBJECTIVES: The purpose was to determine whether upfront esophagectomy or induction chemoradiation followed by esophagectomy confers improved survival in patients with clinically staged T2N0 (cT2N0) esophageal cancer, and to assess the impact of the diagnostic uncertainty of endoscopic ultrasound (EUS) on the expected benefit of chemoradiation in this group of patients.
METHODS: A decision analysis model (Figure 1) was created to represent two treatment strategies for cT2N0 esophageal cancer patients who are potential surgical candidates: 1) upfront esophagectomy followed by adjuvant therapy for patients who are upstaged and 2) induction chemoradiation for all cT2N0 patients followed by esophagectomy. Value estimates for variables within the model were obtained from a literature review, and median survival for specific pathologic subgroups within the tree was derived primarily from the National Cancer Database. The primary endpoint was expected survival for the two treatment strategies in the model. Staging uncertainty of endoscopic ultrasound was introduced into the model by varying the probability that a patient would be pathologically upstaged in sensitivity analyses.
RESULTS: The baseline decision analysis model showed comparable survival for both treatment strategies: upfront esophagectomy patients had an expected overall survival of 48.3 months versus 45.9 months for patients undergoing induction chemoradiation. Results of a sensitivity analysis demonstrated a benefit of induction chemoradiation if the probability of pathologic upstaging is greater than 48.1%, which is within the published range of 32-65% probability of pathologic upstaging after clinical T2N0 diagnosis (Table 1).
CONCLUSIONS: The optimal treatment strategy for cT2N0 esophageal cancer is dependent upon the accuracy of EUS staging. Our results suggest that these patients may benefit from routine induction chemoradiation if the probability of upstaging is greater than 48.1%. Factors such as knowledge of individual institutional variation in rates of upstaging or incorporation of additional high-risk clinical or pathologic features to EUS data may aid in clinical decision making to recommend induction chemoradiation for cT2N0 patients who are surgical candidates.

Table 1. Published diagnostic accuracy of EUS in patients staged cT2N0 undergoing upfront surgery
StudyNpT2N0pT0-1N0pT3N0 / pTxN1-3
Rice et al (2007)5313.0%55.0%32.0%
Stiles et al (2011)4012.5%22.5%65.0%
Crabtree et al (2013)75227.4%25.9%46.7%
Hofstetter et al (2014)49914.0%44.0%42.0%
Hardacker et al (2014)688.5%42.8%48.5%
Speicher et al (2014)159926.7%31.7%41.6%
Tekola et al (2014)3821.0%47.0%32.0%
Samson et al (2016)93254.3%45.7%
Range8.5-27.4%22.5-55%32-65%


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