Residual tumor characteristics of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy

Objective: The study was to investigate the characteristics of residual tumors of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy.

Methods: The resection specimens of 187 patients undergoing surgery after neoadjuvant chemoradiotherapy in Zhongshan Hospital of Fudan University were reevaluated. Tumor regression grade determined by residual tumor ratios was scored for each specific layer of the esophageal wall and all removed lymph nodes for 4 grades as tumor regression grade 1, 0% residual tumors, tumor regression grade 2, less than 10%; tumor regression grade 3, 10% to 50%; tumor regression grade 4, greater than 50%. The pretreatment pathologic tumor stage and pretreatment pathologic lymph node stage before neoadjuvant chemoradiotherapy were recorded reflecting the original depth of primary tumor and number of originally involved lymph nodes, respectively. According to regression directionality, regression pattern was classified into 4 categories as type I: regression toward the lumen, type II: regression toward the invasive front, type III: concentric regression, and type IV: scattered regression. Statistical analyses were performed using Mann-Whitney, chi-square, Cochran Q tests, and Kendall τ-b coefficient, appropriately.

Results: A total of 138 patients have residual tumors, and 97 patients (70.3%), 100 patients (72.5%), 89 patients (64.5%), 63 patients (45.7%), and 68 patients (49.3%) have malignant cells in mucosa, submucosa, muscularis propria, adventitia/surrounding stroma, and lymph nodes, respectively. A total of 115 patients (83.3%) had residual tumors in the mucosa or submucosa, but 63 (54.8%) were graded as tumor regression grade 2 with small amounts of tumors in these 2 layers, 9 patients (6.5%) had residual tumors only in the deep 2 layers, and 14 patients (10.1%) had residual tumors only in lymph nodes. Overall, 86 patients (62.7%) with residual tumors are difficult to identify via present techniques. In patients with tumors that involved all esophageal layers before neoadjuvant chemoradiotherapy, only muscularis propria contained residual tumors significantly more frequently than the adventitia/surrounding stroma (P < .001). The random type IV and nonrandom regression patterns of type I to III were comparable with 48.9% and 51.1%, respectively. In patients with positive lymph node before neoadjuvant chemoradiotherapy, only a small portion of patients (29.2%, 28/96) achieved ypN0 status (nodes pathological complete response), even worse than the primary lesions (33.6%, 63/187) in esophageal squamous cell carcinoma.

Conclusions: The small amount of viable tumor cells in the superficial layers, low pathological complete response rate of lymph nodes, and diverse regression patterns lead to difficulty of detecting residual tumors in esophageal squamous cell carcinoma.