Early versus delayed surgery following neoadjuvant chemoradiation for esophageal cancer: a systematic review and meta-analysis

Abstract

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery, is the mainstay of managing locally advanced esophageal cancer. However, the optimal timing of surgery after neoadjuvant therapy is not defined clearly. Methods: A systematic search of PubMed, Embase and Cochrane databases was conducted. 6–8 weeks were used as a cut-off to define early and delayed surgery groups. Overall Survival (OS) was the primary outcome, whereas pathological complete resolution (pCR), R0 resection, anastomotic leak, perioperative mortality, pulmonary complications, and major complication (> Clavien-Dindo grade 2) rates were secondary outcomes. Cohort studies and national registry bases studies were analysed separately. Survival data were pooled as Hazard Ratio (HR) and the rest as Odds Ratio (OR). According to heterogeneity, fixed-effect or random-effect models were used. Results: Twelve retrospective studies, one RCT, and six registry-based studies (13,600 participants) were included. Pooled analysis of cohort studies showed no difference in OS (HR 1.03, CI 0.91–1.16), pCR (OR 0.98, CI 0.80–1.20), R0 resection (OR 0.90, CI 0.55–I.45), mortality (OR 1.03, CI 0.59–1.77), pulmonary complications (OR 1.26, CI 0.97–1.64) or major complication rates (OR 1.29, CI 0.96–1.73). Delayed surgery led to increased leak (OR 1.48, CI 1.11–1.97). Analysis of registry studies showed that the delayed group had a better pCR rate (OR 1.12, CI 1.01–1.24), with no improvement in survival (HR 1.01, CI 0.92–1.10). Delayed surgery was associated with increased mortality (OR 1.35, CI 1.07–1.69) and major complication rate (OR 1.55, CI 1.20–2.01). Available RCT reported surgical outcomes only. Conclusion: National registry-based studies’ analysis shows that delay in surgery is riskier and leads to higher mortality and major complication rates. Further, well-designed RCTs are required.