Impact of pathological complete response after DCF neoadjuvant chemotherapy followed by surgery on survival in esophageal squamous cell carcinoma: A supplementary analysis of JCOG 1109.

457 Background: JCOG1109, a multicenter three-arm phase III trial, evaluated three neoadjuvant treatment regimens for advanced esophageal squamous cell carcinoma (ESCC): cisplatin and 5-fluorouracil (CF); docetaxel, cisplatin, and 5-fluorouracil (DCF); and cisplatin, 5-fluorouracil, and radiation therapy (CF-RT). The trial demonstrated the superiority of neoadjuvant DCF therapy in improving overall survival (OS). In the trial, neoadjuvant DCF showed a pathological complete response (pCR: ypT0N0M0) rate of 16.8%, and pCR is expected to be associated with the improved survival. We investigated prognostic factors and predictors of pCR in patients who received neoadjuvant DCF. Methods: This analysis included eligible patients from JCOG1109 who underwent surgery after neoadjuvant DCF therapy. Prognostic factors of OS were examined using Cox regression with clinical and pathological factors as covariates. Predictors of pCR were assessed using logistic regression with preoperative factors, and the diagnostic performance metrics of clinical CR (cCR: cT0N0M0) for pCR were calculated. Results: Of the 601 patients enrolled in JCOG1109, 181 patients underwent neoadjuvant DCF followed by surgery and completed pathological evaluation, making them eligible for the present analysis. Multivariable analyses of pre- and postoperative factors showed that pCR vs non-pCR; hazard ratio (HR) 0.149, p=0.0020, performance status (PS) 1 vs 0; HR 0.172, p=0.0047, serum albumin (Alb) 4.0, and cT1-2 were favorable prognostic factors. Median overall survival was not reached for pCR and was 9.9 years for non-pCR. The 5-year overall survival rate was 93.8% for pCR and 61.4% for non-pCR. Multivariable analysis of preoperative factors potentially associated with pCR showed that cCR vs non-cCR; odds ratio (OR) 6.615, p=0.0221, age ≥65 vs <65; OR 2.713, p=0.0296, and cT1-2 cT3 vs cT1-2; OR 0.381, p=0.0393 were significantly associated with pCR. The sensitivity, specificity, positive predictive value, and negative predictive value of cCR for pCR were 15.6%, 97.9%, 62.5%, 84.3%, respectively. Conclusions: pCR is an independent prognostic factor in neoadjuvant DCF for ESCC. cT1-2 and high serum Alb were also associated with improved survival, consistent with previous reports. cCR significantly associated with pCR, but the sensitivity and positive predictive value need further improvement for predicting pCR.