Microscopic size measurements in post-neoadjuvant therapy resections of pancreatic ductal adenocarcinoma (PDAC) predict patient outcomes.

AIMS: Pancreatic ductal adenocarcinomas (PDACs) are increasingly being treated with neoadjuvant therapy. However, the American Joint Committee on Cancer (AJCC) 8th edition T staging based on tumour size does not reflect treatment effect, which often results in multiple, small foci of residual tumour in a background of mass-forming fibrosis. Thus, we evaluated the performance of AJCC 8th edition T staging in predicting patient outcomes by the use of a microscopic tumour size measurement method. METHODS AND RESULTS: One hundred and six post-neoadjuvant therapy pancreatectomies were reviewed, and all individual tumour foci were measured. T stages based on gross size with microscopic adjustment (GS) and the largest single microscopic focus size (MFS) were examined in association with clinicopathological variables and patient outcomes. Sixty-three of 106 (59%) were locally advanced; 78% received FOLFIRINOX treatment. The average GS and MFS were 25 mm and 11 mm, respectively; nine 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 the MFS, respectively. Higher GS-based and MFS-based T stages were significantly associated with higher tumour 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 therapy 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.