Type of neoadjuvant treatment strategy is associated with differential pathologic responses in pancreatic ductal adenocarcinoma

Background: Tumor fibrosis after neoadjuvant treatment (NAT) for pancreatic ductal adenocarcinoma (PDAC) correlates with treatment response. Herein we assessed how different NAT strategies influence pathologic responses and survival. Methods: Patients with surgically resected PDAC who received NAT (1991–2020) were included. Descriptive statistics compared outcomes amongst fibrosis groups (none, minor <50 ​%, partial 51%–94 ​%, major ≥95 ​%) and NAT (chemotherapy alone, chemoradiation, or chemotherapy ​+ ​chemoradiation (total neoadjuvant therapy, TNT)). Results: Patients with major fibrosis most often received TNT (65.8 ​%, p ​< ​0.001). Major fibrosis was associated with the greatest rate of downstaging (77.8 ​%, p ​< ​0.001), highest R0 margin rate (100 ​%, p ​< ​0.01), and lowest mean positive lymph node ratio (0.80, p ​< ​0.01). Amongst complete responders, 11/14 (78.6 ​%) received TNT. Median overall (66.3 months, p ​= ​0.003) and disease-free (54.7months, p ​= ​0.05) survival were highest with major fibrosis. Conclusions: Major fibrosis and complete pathologic responses after NAT are most frequent with a TNT strategy and are associated with improved outcomes.