Appraisal of the American Joint Committee on Cancer Staging Parameters in Patients Undergoing Resection after Neoadjuvant Treatment for Pancreatic Ductal Adenocarcinoma

Abstract

Purpose: The AJCC staging system has been modeled following upfront pancreatectomy, while its prognostic performance in patients receiving neoadjuvant treatment (NAT) is unknown. Our aim was to appraise the AJCC staging parameters in patients undergoing pancreatectomy after NAT for pancreatic ductal adenocarcinoma. Methods: All pancreatectomies after NAT at two academic institutions (2013-2017) were reviewed (n=389). Metrics of prognostic performance were compared between the AJCC-7th and -8th editions. A modified T-status definition, encompassing both size and extrapancreatic extension, was assessed. Results: The AJCC-7th T-status significantly predicted survival, although survival curves of ypT2 and ypT3 overlapped. The AJCC-8th T-status improved prognostic stratification, yet the significance remained driven by the favorable prognosis of ypT1. N-status was strongly associated with survival in both editions (Figure). The overall prognostic performance was improved in the 8th edition as confirmed by: C-index, Uno’s AUC over three years, and time-dependent ROC curves at 1-2-3 years postoperatively. The 3-year net reclassification index was 23.8%. The modified T-status further improved these metrics. At multivariable Cox regression, a significant interaction was detected between adjuvant treatment and T- and N- status, suggesting a potential survival benefit in tumors >2cm, those with extrapancreatic extension and/or lymph node metastases. Conclusion: In patients receiving pancreatectomy after NAT, the AJCC-8th edition shows a greater prognostic accuracy. While the performance of the new N-status appears solid, T-status classification might be further optimized. In particular, incorporating extrapancreatic extension in the current size-based definition seems valuable. Adjuvant therapy displays a heterogeneous effect on survival in the different T- and N-status classes, with possible clinical implications.