Prolonged time to surgery after neoadjuvant chemoradiotherapy increases histopathological response without affecting survival in patients with esophageal or junctional cancer

Objective: To determine the relation between time to surgery (TTS) after neoadjuvant chemoradiotherapy (nCRT) and pathologically complete response (pCR), surgical outcome, and survival in patients with esophageal cancer. Background: Standard treatment for potentially curable esophageal cancer is nCRT plus surgery after 4 to 6 weeks. In rectal cancer patients, evidence suggests that prolonged TTS is associated with a higher pCR rate and possibly with better survival. Methods: We identified patients treated with nCRT plus surgery for esophageal cancer between 2001 and 2011. TTS (last day of radiotherapy to day of surgery) varied mainly for logistical reasons. Minimal follow-up was 24 months. The effect of TTS on pCR rate, postoperative complications, and survival was determined with (ordinal) logistic, linear, and Cox regression, respectively. Results: In total, 325 patients were included. Median TTS was 48 days (p25- p75=40-60).After 45 days, TTSwas associated with an increased probability of pCR [odds ratio (OR) = 1.35 per additional week of TSS, P = 0.0004] and a small increased risk of postoperative complications (OR = 1.20, P < 0.001). Prolonged TTS had no effect on disease-free and overall survivals (HR = 1.00 and HR = 1.06 per additional week of TSS, P = 0.976 and P = 0.139, respectively). Conclusions: Prolonged TTS after nCRT increases the probability of pCR and is associated with a slightly increased probability of postoperative complications, without affecting disease-free and overall survivals. We conclude that TTS can be safely prolonged from the usual 4 to 6 weeks up to at least 12 weeks, which facilitates a more conservative wait-and-see strategy after neoadjuvant chemoradiotherapy to be tested.