Chemoradiotherapy followed by Active Surveillance Versus Standard Esophagectomy for Esophageal Cancer: A Systematic Review and Individual Patient Data Meta-Analysis

OBJECTIVE: To compare overall survival of patients with a clinically complete response (cCR) undergoing active surveillance versus standard esophagectomy.

SUMMARY BACKGROUND DATA: One-third of patients with esophageal cancer have a pathologically complete response in the resection specimen after neoadjuvant chemoradiotherapy. Active surveillance may be of benefit in patients with cCR, determined with diagnostics during response evaluations after chemoradiotherapy.

METHODS: A systematic review and meta-analysis was performed comparing overall survival between patients with cCR after chemoradiotherapy undergoing active surveillance versus standard esophagectomy. Authors were contacted to supply individual patient data. Overall and progression free survival were compared using random effects meta-analysis of randomized or propensity score matched data. Locoregional recurrence rate was assessed. The study-protocol was registered (PROSPERO:CRD42020167070).

RESULTS: Seven studies were identified comprising 788 patients, of which after randomization or propensity score matching yielded 196 active surveillance and 257 standard esophagectomy patients. All authors provided individual patient data. The risk of all-cause mortality for active surveillance was 1.08 (95%Confidence Interval (CI):0.62-1.87,p = 0.75) after intention-to-treat analysis and 0.93 (95%CI:0.56-1.54,p = 0.75) after per-protocol analysis. The risk of progression or all-cause mortality for active surveillance was 1.14 (95%CI:0.83-1.58,p = 0.36). Five-year locoregional recurrence rate during active surveillance was 40% (95%CI:26%-59%). 95% of active surveillance patients undergoing postponed esophagectomy for locoregional recurrence had radical resection.

CONCLUSIONS: Overall survival was comparable in patients with cCR after chemoradiotherapy undergoing active surveillance or standard esophagectomy. Diagnostic followup is mandatory in active surveillance and postponed esophagectomy should be offered to operable patients in case of locoregional recurrence.