Background: Results from the Dutch CROSS trial have shown that in 49% of the squamous cell carcinomas and 23% of the adenocarcinomas no viable tumor cells could be identified in the resection specimen after nCRT. This raises the question, whether this subgroup could reliably be identified after nCRT? First, we analyzed the potential impact of the delay between nCRT and the surgical resection on the grade of pathological tumor response, to possibly gain insight into the optimal timing of clinical restaging. Second, we described the location of residual tumor in the esophagus after nCRT, to potentially better target clinical restaging.
Methods: Patients treated with nCRT (5 weekly courses of Carboplatin and Paclitaxel with 41.4 Gy concurrent radiotherapy) for resectable esophageal cancer between 2002 and 2011 were identified. The interval between nCRT and surgery, and the corresponding tumor regression grade (=TRG) in the resection specimen, including adjacent lymph nodes, were determined. For patients from the coordinating center, the TRG was also scored for each individual layer of the esophageal wall and for all resected lymph nodes.
Results: Two hundred and forty-seven patients were included in the first part of the study. Median age was 59.8 years and the majority of patients (74.5%) had an adenocarcinoma. A radical resection was performed in 234/247 (95%) patients. The median interval between nCRT and surgery was 47 days [p25-p75: 39-56]. The percentage of pathologically complete responders (TRG1) was higher in patients with an interval of more than 55 days (≥p75) as compared to patients with a shorter interval (<p75) (43% vs. 24%; p= 0.005).
However, there was no significant difference in disease-free survival (DFS) between patients with an interval above or below the 75 th percentile (HR 1.01 95% CI0.63-1.62). In a subgroup (N=102) from the coordinating center, 71 patients were non-complete responders, of whom 89% (63/71) had residual tumor in the (sub)mucosa. Eight patients had no residual tumor in the (sub)mucosa; five of whom had tumor in the muscle layer and three of whom had tumor in a single lymph node. No patient had tumor in the surrounding stroma
(T3) only.
Conclusion: In patients with a relatively long interval (>p75) between nCRT and surgery, significantly more pathologically complete responders were observed. These results support a prolongation of the interval between nCRT and subsequent resection in order to facilitate the identification of complete responders. In the great majority of incomplete responders, residual tumor is present in the
(sub)mucosa. (Cyto)histological biopsies should therefore be focused on these two layers.