Factors Associated with Pathologic Complete Response After Neoadjuvant Chemoradiotherapy for Esophageal Cancer.

PURPOSE/OBJECTIVE(S) Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the standard of care for patients with locally advanced esophageal cancer. Factors associated with pCR remain incompletely defined. The goal of this study was to identify the factors correlated with pCR and to explore the impact of these factors on survival. MATERIALS/METHODS We retrospectively analyzed the patients with esophageal cancer from a single institution treated with nCRT plus esophagectomy between July 2017 and June 2020.Histologic response was categorized by a 3-point tumor regression grade (TRG) system for surgical specimens. Disease-free survival (DFS)and overall survival (OS) were defined as the interval between surgery and the date of recurrence or death from any cause. RESULTS A total of 192 patients were included for analysis in the study with 64 (33.33%) achieved pCR. Follow-up time ranged from 0.4 to 41.4 months from surgery, with a median follow-up of 17.8 months. Patients with pCR had significantly improved DFS (log-rank P = 0.002) and OS (log-rank P = 0.015) compared with patients with non-pCR. On univariate analysis, gender (male), histologic type (squamous carcinoma), therapy sequence (concomitant chemoradiotherapy), radiation dose (≥40Gy), and interval time to surgery (≥66 days) were associated with a higher rate of pCR. On multivariable analysis, female (adjusted odds ratio (adjusted OR): 4.89; 95% confidence interval (95% CI): 1.90 to 12.58; P = 0.001), radiation dose ≥40Gy (adjusted OR: 10.50; 95% CI: 1.23 to 89.75; P = 0.032), and interval time to surgery ≥66 days (adjusted OR: 2.22; 95% CI: 1.10 to 4.46; P = 0.026) were independently associated with a higher rate of pCR. Further increasing the dosage of radiation more than 45 Gy (≥46) resulted in the decreasing of pCR rate (45.6% vs. 23.8%; 2 = 6.093, P = 0.014). Further prolonging the timing of esophagectomy to 80 days after completion of nCRT did not result in a significant higher rate of pCR (35.1% vs. 51.7; c2 = 2.509, P = 0.113). Gender, radiation dose and interval time to surgery had no effect on DFS (HR: 0.594 (0.269-1.312), P = 0.198; HR: 1.102 (0.555-2.188), P = 0.781 and HR: 0.789 (0.459-1.357), P = 0.392; respectively) and OS (HR: 0.944; 0.391-2.281), P = 0.898; HR: 0.873 (0.380-2.009), P = 0.750 and HR: 0.922 (0.465-1.828), P = 0.816; respectively). CONCLUSION Delaying surgery beyond 65 days (≥66 days) after nCRT and increasing radiation dose to 40Gy improve the probability of achieving pCR with no detrimental effect on DFS and OS. A longer interval between nCRT and surgery than 80 days brings no more significant benefit of pCR rate and a further increase of radiation dose to 46 Gy or more is unnecessary.