Impact of Preoperative Time Intervals for Neoadjuvant Chemoradiotherapy on Short-term Postoperative Outcomes of Esophageal Cancer Surgery: A Population-Based Study Using the Dutch Upper Gastrointestinal Cancer Audit (DUCA) Data

Objective: To clarify the impact of the preoperative time intervals on short-term postoperative and pathologic outcomes in patients with esophageal cancer who underwent neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy. Background: The impact of preoperative intervals on patients with esophageal cancer who received multimodality treatment remains unknown. Methods: Patients (cT1-4aN0-3M0) treated with nCRT plus esophagectomy were included using the Dutch national DUCA database. Multivariate logistic regression was used to determine the effect of different time intervals upon short-term postoperative and pathologic outcomes: diagnosis-to-nCRT intervals (≤5, 5-8, and 8-12 weeks), nCRT-to-surgery intervals (5-11, 11-17, and >17 weeks) and total preoperative intervals (≤16, 16-25, and >25 weeks). Results: Between 2010 and 2021, a total of 5052 patients were included. Compared with diagnosis-to-nCRT interval ≤5 weeks, the interval of 8 to 12 weeks was associated with a higher risk of overall complications (P=0.049). Compared with nCRT-to-surgery interval of 5 to 11 weeks, the longer intervals (11-17 and >17 weeks) were associated with a higher risk of overall complications (P=0.016; P<0.001) and anastomotic leakage (P=0.004; P=0.030), but the interval >17 weeks was associated with lower risk of ypN+ (P=0.021). The longer total preoperative intervals were not associated with the risk of 30-day mortality and complications compared with the interval ≤16 weeks, but the longer total preoperative interval (>25 weeks) was associated with higher ypT stage (P=0.010) and lower pathologic complete response rate (P=0.013). Conclusions: In patients with esophageal cancer undergoing nCRT and esophagectomy, prolonged preoperative time intervals may lead to higher morbidity and disease progression, and the causal relationship requires further confirmation.