Impact of Chemoradiation-to-Surgery Interval on Pathological Complete Response and Short- and Long-Term Overall Survival in Esophageal Cancer Patients

Background: The impact of the neoadjuvant chemoradiation-to-surgery (CRT-S) interval in patients with esophageal cancer is not clear. We aimed to determine the relationship between CRT-S interval and pathological complete response rate (pCR) and overall survival (OS). Methods: National Cancer Data Base patients with CRT followed by surgery were studied. CRT-S interval was studied as a continuous (weeks) and categorical variable (quintiles: 15–37, 38–45, 46–53, 54–64, and 65–90 days, with n = 1016, 1063, 1081, 1083, and 938 patients, respectively). Results: A total of 5181 patients were included; 81% had adenocarcinoma. There was a significant increase of pCR rate across quintiles (18%, 21%, 24%, 25%, and 29%, p < 0.001) and per week increase of CRT-S interval [odds ratio (OR) 1.11, p < 0.001]. The 90-day mortality increased as CRT-S increased across quintiles (5.7%, 6.2%, 6.8%, 8.5%, and 8.2%, p = 0.02) and through weeks (OR 1.05, p = 0.03). Mean OS across CRT-S quintiles was 36.4, 35.1, 33.9, 33.2, and 30.7 months, respectively. Multivariate Cox regression showed significantly worse OS per week increase in CRT-S interval [hazard ratio (HR) 1.02, p = 0.02], especially among the last quintile (CRT-S = 65–90 days: HR 1.2, p = 0.009). The squamous cell carcinoma (SCC) and pCR groups had similar OS across CTR-S intervals. Conclusions: Despite the higher pCR rate with longer CRT-S interval, surgery is optimal less than 65 days after CRT to avoid worse 90-day mortality and achieve better OS. In patients with SCC and those with pCR, prolonged CRT-S interval had no impact on OS. Further studies are needed to consolidate our findings.