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Long-Term Survival Based on Pathologic Response to Neoadjuvant Therapy in Esophageal Cancer
Gregory Tiesi*, Heather Stuart, Danny Yakoub, Eli Avisar, Nipum merchant, Alan S. Livingstone, Dido Franceschi
Division of Surgical Oncology, University of Miami, Miller School of Medicine, Miami, FL
Background: Neoadjuvant therapy has become the standard of care for patients with locally advanced esophageal cancer. The addition of radiation to neoadjuvant chemotherapy has been shown to significantly improve complete response rates, but has not been shown to improve survival. Complete (pCR) and partial (pPR) pathologic response to treatment have been identified as important prognostic markers for survival. The purpose of this study was to determine the long-term outcomes of patients receiving neoadjuvant chemotherapy alone (CA) compared with chemoradiation (CRT), stratified by pathologic response rates.
Methods: Data from a prospectively maintained database of esophagectomies performed for cancer (1999 - 2012) was analyzed. 298 locally advanced esophageal cancer patients that underwent either neoadjuvant CA (n = 232) or CRT (n = 66) followed by esophagectomy were identified. Preoperative and pathologic staging were compared to assess treatment response. Overall survival (OS) was determined and compared using Kaplan-Meier statistics.
Results: The pCR rate for patients in the CRT group was 27.3% compared to 11.7% in the CA group (p < 0.01, median follow-up: 49.5 vs. 64.4 months; respectively). There was no difference in the pPR rate between CRT (50%) and CA (49.6%). For patients with a pCR, 10-year OS was similar between the CA and CRT groups (74% vs. 64%). However, patients that had a pPR had significantly improved 10-year OS with CA (67%) as compared with CRT (34%, p < 0.002). When combining pCR and pPR, 10-year OS remained significantly greater in the CA group (69%) versus the CRT group (43%, p<0.003). CA patients that had a pPR had significantly improved OS compared with non-responders (pNR)(67% vs. 27%, p < 0.0001). Conversely, OS for CRT pPR patients was similar to pNRs (p = 0.45). (Figure)
Conclusions: Complete pathologic response after neoadjuvant therapy is a strong predictor of long-term OS. Neoadjuvant CA improves OS regardless of the degree of response, suggesting that response to chemotherapy in the primary tumor and lymph nodes may be a surrogate for control of systemic disease. The addition of radiation therapy enhances pCR rates but does not appear to improve OS compared with neoadjuvant CA alone.
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