For many patients whose pancreatic ductal adenocarcinoma (PDAC) is locally advanced, neoadjuvant therapy has been proposed as a way to decrease tumor burden. Pancreatic ductal adenocarcinoma is generally thought to be resistant to chemotherapy and radiation, however, response to neoadjuvant therapy in PDAC has been described in a subset of patients. The SMAD4 status is considered to be an important molecular feature which distinguishes two subsets of PDAC, SMAD4-positive and -negative tumors. The objective of this study was to evaluate the neoadjuvant treatment response rate as well as compare the different clinicopathologic variables between SMAD4-positive and -negative tumors.
We analyzed the data of patients who underwent surgical resection for PDAC from 2009–2019. Our cohort from a single institution included 233 patients.
Of the 233 cases, 143 (61.4%) were SMAD4-negative and 90 (38.6%) were SMAD4-positive. Overall, SMAD4-positive tumors with neoadjuvant therapy had better treatment response and better tumor regression scores. In addition, SMAD4-positive tumors had a significantly lower lymph node metastasis rate in both the neoadjuvant and nonneoadjuvant setting.
Further characterization of the role of SMAD4 within the context of neoadjuvant therapy will lead to improved personalized therapeutic strategies.