147: MAJOR PATHOLOGIC RESPONSE IN ESOPHAGEAL ADENOCARCINOMA: IS THE TIME RIPE FOR A NEW PARADIGM IN DEFINING RESPONSE TO TREATMENTS?

Abstract

Abstract Background and aim Adenocarcinoma of the esophagus is still burdened by low 5-year survival. A complete pathologic response after neoadjuvant treatment is associated with improved long-term survival, however this result is rarely achieved. The aim of this study was to evaluate the impact of tumor regression grade (TRG), according to Mandard, on long-term survival. The primary endpoint was to determine whether the survival benefit associated with a complete tumor regression could be achieved also with a subtotal tumor response (TRG2). Secondly, we analyzed how TRG predicts survival in chemotherapy (CT) or chemoradiotherapy (CRT) treated patients and the relationship with nodal status (ypN). Methods We evaluated all consecutive patients who underwent esophagectomy for cancer at Padova University Hospital and Mainz University Hospital. Inclusion criteria were histologically confirmed ADK involving the thoracic esophagus or Siewert I and II cancers, treated by neoadjuvant CT or CRT and surgery. Patients with Siewert III or cervical cancer and those who underwent upfront surgery were excluded from the study. Kaplan-Maier analysis was used to estimate overall survival (OS) according to the TRG and ypN. Results Overall, 270 patients were recruited in the study period. The median OS was 50 months (range 1–134). TRG 1 and 2 were associated with improved survival (P < 0.0001), this finding was further confirmed in the CRT patients’ subgroup (P < 0.0001) (Figure). Survival curves for TRG 1 and TRG 2 patients were similar, both among ypN0 (P = 0.0185) and ypN+ patients (P = 0.013). In the CT group these findings were confirmed in the whole subgroup (P = 0.0001) and ypN+ (P = 0.007) but not in patients without lymph node involvement (P = 0.58). Conclusion Tumor regression after neoadjuvant treatment is significantly associated with long term survival irrespective of the nodal status. In the overall study population and among CRT treated patients, the long-term survival was comparable between TRG 1 and TRG 2 patients. This finding allowed us to support the criterion of a Major Pathologic Response, which includes both TRG 1 and 2 ypN0 patients, potentially creating a homogeneous and larger subgroup of subjects to be evaluated in future clinical trials and studies.