Role of Adjuvant Therapy in Esophageal Cancer Patients after Neoadjuvant Therapy and Esophagectomy: A Systematic Review and Meta-Analysis.

OBJECTIVE To analyze esophageal cancer patients who previously underwent neoadjuvant therapy followed by a curative resection to determine whether additional adjuvant therapy is associated with improved survival outcomes. SUMMARY BACKGROUND DATA Neoadjuvant therapy followed by surgery is the standard of care for locally advanced esophageal cancer, while adjuvant therapy is typically employed for patients with residual disease. However, the role of adjuvant therapy after a curative resection is still uncertain. METHODS MEDLINE, EMBASE, and CENTRAL databases were searched for studies comparing patients with esophageal cancer who underwent neoadjuvant therapy and curative resection with and without adjuvant therapy. Primary outcome was overall survival (OS), and random effects meta-analysis was conducted where appropriate. Grading of recommendations, assessment, development, and evaluation was used to assess the certainty of evidence. RESULTS Ten studies involving 6,462 patients were included. When compared to patients who received neoadjuvant therapy and esophagectomy alone, adjuvant therapy groups experienced a significant decrease in mortality by 48% at 1 year (RR 0.52, 95% CI 0.41-0.65, P < 0.001, moderate certainty). This reduction in mortality was carried through to 5-year follow-up (RR 0.91, 95% CI 0.86-0.96, P < 0.001, moderate certainty). The difference between the adjuvant therapy and the control group was uncertain regarding the secondary outcomes. CONCLUSIONS Adjuvant therapy after neoadjuvant treatment and esophagectomy with negative resection margins provide an improved OS at 1 and 5 years with moderate to high certainty of evidence, but the benefit for disease-free survival and locoregional/distal recurrence remain uncertain due to limited reporting of these outcomes.