Microscopic Size Measurements Predict Outcomes in Post‐Neoadjuvant Resections of Pancreatic Ductal Adenocarcinoma (PDAC)

BACKGROUND: Pancreatic ductal adenocarcinomas (PDACs) are increasingly treated with neoadjuvant therapy. However, the American Joint Committee on Cancer (AJCC) 8th Edition T staging based on tumor size does not reflect treatment effect, which often results in multiple, small foci of residual tumor in a background of mass-forming fibrosis. Thus, we evaluated the performance of AJCC 8th Edition T staging in predicting patient outcomes using a microscopic tumor size measurement method. METHODS AND RESULTS: 106 post-neoadjuvant therapy pancreatectomies were reviewed, and all individual tumor foci were measured. T stages based on gross size (GS) and the largest single microscopic focus size (MFS) were examined in association with clinicopathologic variables and patient outcomes. 63/106 (59%) were locally advanced; 78% received FOLFIRINOX treatment. Average GS and MFS were 2.5cm and 1.1cm, respectively; 9 cases each were classified as T0, 35 and 85 cases as T1, 42 and 12 cases as T2, and 20 and 0 cases as T3, based on the GS and MFS, respectively. Higher GS- and MFS-based T stages were significantly associated with higher tumor regression grade, lymphovascular and perineural invasion, and higher N stage. Furthermore, higher MFS-based T stage was significantly associated with shorter disease-free survival (DFS) (p<0.001) and shorter overall survival (OS) (p=0.002). GS was significantly associated with OS (p=0.046), but not with DFS. CONCLUSIONS: In post-neoadjuvant PDAC resections, MFS-based T staging is superior to GS-based T staging for predicting patient outcomes, suggesting that microscopic measurements have clinical utility beyond the conventional use of GS measurements alone.