Timing After Neoadjuvant Therapy Predicts Mortality in Patients Undergoing Esophagectomy: a Propensity Score-Matched Analysis

Background Currently most surgeons allow 6-12 weeks after neoadjuvant therapy prior to recommending esophagectomy. Given that complete pathologic response correlates to improved survival, some have advocated a longer interval should be entertained to increase the pathologic response. The impact of an expanded neoadjuvant therapy-surgery timing is not currently well understood.Methods Utilizing the National Cancer Database, we identified patients with esophageal cancer who underwent neoadjuvant therapy followed by esophagectomy. Patients were divided into 3-time intervals: < 6 weeks, 6-12 weeks, and > 3 months.Results We identified 9256 patients who received neoadjuvant therapy followed by esophagectomy. There were 7858 (84.9%) males and 1398 (15.1%) females with a median age of 62. The median lymph nodes harvested decreased as timing increased (p < 0.001) and mean lymph nodes positive decreased as timing increased, p = 0.01. The complete response rate also increased as timing increased, p < 0.001. However, this improvement in pathologic complete response did not translate into an increase in median survival. Ninety-day mortality increased as the timing from neoadjuvant therapy increased: 6.4%, 7.9%, and 10.2%, respectively, p = 0.002.Conclusion Our data demonstrates that patients who have a prolonged neoadjuvant therapy- esophagectomy interval will have a substantial increase in 90-day mortality. While there was an increase in pathologic complete response rates, this did not translate into an improvement in survival. The current recommendations of a neoadjuvant therapy-surgery timing of 6-12 weeks should remain.