Association of waiting time from diagnosis to neoadjuvant chemoradiotherapy on interval distant metastases in esophageal cancer patients: A study based on the Netherlands cancer registry

Introduction: In patients with resectable esophageal cancer, interval distant metastases may be detected following neoadjuvant-intent chemoradiotherapy ((n)CRT). The specific association between the waiting time from diagnosis to the initiation of (n)CRT and interval metastases remains unclear. Methods: Patients with esophageal cancer (cT1-4a N0-3 M0) received CRT with or without surgery were extracted from the Netherlands Cancer Registry. Multivariable logistic and cox regression analyses were used to compare different waiting times (≤4, 4–8 and >8weeks) on the risk of interval metastases, post-(n)CRT short-term metastases (detected preoperatively, intraoperatively, or postoperatively within 120 days after CROSS regimen CRT) and overall survival (OS). Subgroup analysis based on cN stage was performed. Results: Between 2015 and 2021, a total of 4394 patients were included. Compared to the waiting ≤4 weeks, the waiting >8 weeks was associated with higher risk of interval metastases (p-value = 0.045),but the longer waiting times were not associated with higher risk of post-(n)CRT short-term metastases or worse OS. In the cN0 subgroup, compared to the waiting ≤4 weeks, the waiting 4–8weeks (p-value = 0.049; p-value = 0.046) and >8 weeks (p-value = 0.006; p-value = 0.006) was associated with higher risk of interval metastases and post-(n)CRT short-term metastases, but was not associated with worse OS. In the cN + subgroup, the longer waiting times were not associated with interval metastases or post-(n)CRT short-term metastases or OS. Conclusion: A longer waiting time from diagnosis to the initiation of (n)CRT was associated with a higher risk of interval metastases, but not with an increased risk of post-(n)CRT short-term metastases or worse OS.