Guillaume S Chevrollier1, Danica N Giugliano1, Francesco Palazzo1, Scott W Keith2, Ernest L Rosato1, Nathaniel R Evans Iii1, Adam C Berger3. 1. Department of Surgery, Sidney Kimmel Medical College of Thomas Jefferson University, 1100 Walnut Street, Suite 500, Philadelphia, PA, 19107, USA. 2. Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College of Thomas Jefferson University, 1015 Chestnut Street, Suite 520, Philadelphia, PA, 19107, USA. 3. Department of Surgery, Sidney Kimmel Medical College of Thomas Jefferson University, 1100 Walnut Street, Suite 500, Philadelphia, PA, 19107, USA. adam.berger@jefferson.edu.
Abstract
BACKGROUND: Survival for patients with locally advanced esophageal cancer remains dismal. Non-response to neoadjuvant chemoradiation (nCRT) portends worse survival. We hypothesized that patients undergoing up-front esophagectomy may have better survival than those who do not respond to nCRT. METHODS: We identified all patients undergoing esophagectomy with a pathologic stage of II or greater at our institution between 1994 and 2015 and separated them into two groups: those who received nCRT and those undergoing up-front esophagectomy. The neoadjuvant group was further separated into patients downstaged to pathologic stage 0 or I (responders) and patients with either the same or higher pathologic stage after nCRT, or with pathologic stage II disease or greater (non-responders). Overall survival was compared between groups using Kaplan-Meier statistics. Covariate-adjusted Cox modeling was used to estimate hazard ratios (HR) for mortality associated with non-response. RESULTS: Overall, 287 patients met inclusion criteria. Fifty-nine percent of the responders had pathologic complete response (pCR). The majority of non-responders and primary esophagectomy patients had stage II or III disease (94%). Median survival was 58.3 months in responders, 23.9 months in non-responders, and 29.1 months in primary esophagectomy patients (p < 0.01). The HR for mortality associated with non-response was 1.82 compared to response to nCRT (p < 0.01) and 1.09 compared to primary esophagectomy (p = 0.71). CONCLUSIONS: In patients with esophageal cancer who do not respond to nCRT, neoadjuvant therapy may represent a toxic and costly treatment modality that does not improve survival and may delay potentially curative resection. Further research is needed to identify potential non-responders with advanced resectable disease and allow individual tailoring of pre-surgical decision-making.
BACKGROUND: Survival for patients with locally advanced esophageal cancer remains dismal. Non-response to neoadjuvant chemoradiation (nCRT) portends worse survival. We hypothesized that patients undergoing up-front esophagectomy may have better survival than those who do not respond to nCRT. METHODS: We identified all patients undergoing esophagectomy with a pathologic stage of II or greater at our institution between 1994 and 2015 and separated them into two groups: those who received nCRT and those undergoing up-front esophagectomy. The neoadjuvant group was further separated into patients downstaged to pathologic stage 0 or I (responders) and patients with either the same or higher pathologic stage after nCRT, or with pathologic stage II disease or greater (non-responders). Overall survival was compared between groups using Kaplan-Meier statistics. Covariate-adjusted Cox modeling was used to estimate hazard ratios (HR) for mortality associated with non-response. RESULTS: Overall, 287 patients met inclusion criteria. Fifty-nine percent of the responders had pathologic complete response (pCR). The majority of non-responders and primary esophagectomy patients had stage II or III disease (94%). Median survival was 58.3 months in responders, 23.9 months in non-responders, and 29.1 months in primary esophagectomy patients (p < 0.01). The HR for mortality associated with non-response was 1.82 compared to response to nCRT (p < 0.01) and 1.09 compared to primary esophagectomy (p = 0.71). CONCLUSIONS: In patients with esophageal cancer who do not respond to nCRT, neoadjuvant therapy may represent a toxic and costly treatment modality that does not improve survival and may delay potentially curative resection. Further research is needed to identify potential non-responders with advanced resectable disease and allow individual tailoring of pre-surgical decision-making.
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