Prolonged Time to Surgery in Patients with Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer.

Objective: To investigate whether prolonged time to surgery negatively affects survival, pathological outcome or postoperative complications in patients with histologically proven residual disease after neoadjuvant chemoradiotherapy for locally advanced esophageal cancer.

Summary background data: Historically, the standard time to surgery (TTS) has been six to eight weeks after completion of nCRT. The effect of prolonged TTS is gaining interest, with contradicting results on survival and surgical morbidity. It can be hypothesized that, in patients with residual disease six weeks after completion of nCRT, prolonged TTS might be associated with worse survival and higher morbidity.

Methods: Patients with locally advanced esophageal cancer who had biopsy-proven residual disease six weeks after nCRT and underwent surgery, were categorized according to interval to surgery (TTS>12w vs. TTS≤12w). Primary outcome of this study was overall survival. Secondary outcomes were disease-free survival, surgical outcomes, pathological outcomes, and postoperative complications. Multivariable Cox regression was used for comparing survival and logistic regression for other outcomes, adjusted for the confounders age, cT, cN, Charlson comorbidity index, weight loss during nCRT, and WHO performance score after completion of nCRT.

Results: Forty patients were included for TTS>12w and 127 for TTS≤12w. TTS>12w was associated with better overall survival (adjusted hazard ratio (aHR) 0.46, 95%CI 0.24-0.90), and disease-free survival (aHR 0.48, 95%CI 0.24-0.94), but also with more postoperative respiratory complications (aOR 3.66, 95%CI 1.52-9.59). Other outcomes were comparable between both groups.

Conclusion: Prolonged TTS in patients with histologically proven residual disease after completion of nCRT for esophageal cancer did not have a negative effect on overall and disease-free survival, but patients did have a higher risk for postoperative respiratory complications.