Residual esophageal cancer after neoadjuvant chemoradiotherapy frequently involves the mucosa and submucosa

Objectives: To gain insight into the exact location of residual esophageal cancer in the esophageal wall and regional lymph nodes after neoadjuvant chemoradiotherapy (nCRT) and to determine the pattern of regression. Background: Data from the recently published chemoradiotherapy for oesophageal cancer followed by surgery study trial showed that 49% of squamous cell carcinomas and 23% of adenocarcinomas had a pathologically complete response (pCR) in the resection specimen after nCRT. These results impose the ethical imperative to reconsider the necessity of esophagectomy with its substantial morbidity and mortality in patients with pCR. However, it remains challenging to accurately identify these patients before resection. Methods: Between January 2003 and July 2011, all patients with esophageal cancer in a tertiary referral center, who underwent nCRT (5 weekly courses of carboplatin and paclitaxel plus 41.4 Gy concurrent radiotherapy) and surgical resection, were analyzed. The resection specimens were carefully re-evaluated by an experienced gastrointestinal pathologist. Tumor regression grade (TRG) was meticulously scored for each specific layer of the esophageal wall and for all removed lymph nodes. Results: One hundred two consecutive patients were included. Seventy-one (70%) of 102 patients were noncomplete responders (≥TRG2) and in 63 of these patients (89%), residual tumor cells were seen in the mucosa and/or submucosa. Five of 8 patients without involvement of the mucosa and the submucosa had isolated remnants in the muscle layer (5/102 = 5%); the other 3 patients had tumor cells only in a single lymph node (3/102 = 3%). The surrounding stroma showed the highest percentage of TRG1 (= pCR: 47%). In patients with pretreatment lymph node positivity, the percentage of TRG1 in all lymph nodes was also favorable (52%). Overall regression showed a nonrandom mixed pattern of both concentric regression and regression toward the lumen. Conclusions: After nCRT for esophageal cancer, both the mucosa and the submucosa show frequent residual malignant involvement. The surrounding stroma and the regional lymph nodes show the highest percentage of pCR and the overall regression pattern is most frequently a mixed pattern of both concentric regression and regression toward the lumen. This overall regression pattern lends support to careful testing of a wait-and-see approach in a subgroup of patients with esophageal cancer after nCRT.

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