Conditional recurrence-free survival after curative esophagectomy: individual patient data analysis of 11 trials

Background
Most recurrences after curative surgery for esophageal cancer occur within 2 years. Conventional recurrence-free survival (RFS), calculated from the time of surgery, may underestimate prognosis for patients who remain recurrence-free during the early postoperative years. This study aimed to evaluate conditional RFS and recurrence timing to inform individualized follow-up strategies.

Methods
An individual patient data (IPD) analysis was conducted using randomized controlled trials (RCTs) comparing perioperative treatments for resectable esophageal or gastroesophageal junction cancer. Conditional RFS, defined as the probability of remaining recurrence-free for an additional y years given x years already survived without recurrence (RFSy|RFSx), was estimated.

Results
IPD from 10 phase III and 1 phase II RCTs were analyzed (n = 2268 patients with R0 resection). In squamous cell carcinoma (SCC), RFS5|RFS0 was 47.9%, which increased to 63.0%, 72.5%, 78.2%, and 81.2% at RFS5|RFS1–4. Among patients who recurred, 58.8% of pN-positive cases recurred within 1 year and 81.7% within 2 years, compared with 42.8% and 69.9% in pN0. At baseline (RFS5|RFS0), patients with pN-positive disease or pM1 disease had worse 5-year RFS than those with pN0 or pM0 disease. However, among patients who remained recurrence-free for 4 years after surgery (RFS5|RFS4), the pattern was reversed, with advanced groups showing better subsequent 5-year RFS. Similar trends were observed in adenocarcinoma.

Conclusions
Conditional RFS improves over time, particularly in advanced-stage esophageal cancer. Although advanced cases are typically monitored more intensively, findings suggest comparable follow-up intensity may be appropriate once patients remain recurrence-free for a certain postoperative period.