Association of high-dose postoperative opioids with recurrence risk in esophageal squamous cell carcinoma: reinterpreting ERAS protocols for long-term oncologic surgery outcomes

Esophageal squamous cell carcinoma (ESCC) is associated with a poor prognosis and high postoperative recurrence rate. Although postoperative opioid use has been associated with cancer recurrence, its relevance in ESCC has not been determined. Therefore, this study investigated whether high-dose postoperative opioid use was associated with recurrence risk in patients with ESCC. For this retrospective analysis, the medical records of patients who were diagnosed with ESCC and who underwent surgery between January 2006 and December 2010 in the National Cancer Center, Korea were evaluated. Total opioid administration over a 10-day period, from during surgery to postoperative day 9, was calculated. A cutoff value was determined using receiver operating characteristic curve analysis, and patients were classified into the high-use and low-use groups. The primary and secondary outcomes of the study were freedom from recurrence and overall survival, respectively. After propensity score matching, the effect of opioid use on freedom from recurrence and overall survival was evaluated using the Kaplan-Meier method. The final analysis set included 258 patients. The cumulative opioid dose cutoff point was 1783.5 mg of oral morphine. High-dose postoperative opioid use was a significant factor affecting recurrence (Hazard ratio [HR], 2.162; 95% confidence interval [CI], 1.583-2.954; P < 0.0001). In contrast, postoperative opioid use was not associated with death (HR, 1.274; 95% CI, 0.922-1.761; P = 0.1422). In patients with ESCC, compared with low-dose opioid use, high-dose intraoperative and postoperative opioid use was significantly associated with an increased risk of recurrence. However, opioid dosage did not affect overall survival.