Prognostic value of microscopic tumor mapping in post-neoadjuvant therapy specimens to predict recurrence after surgery: A prospective cohort study

Abstract

Background: Although various pathologic grading systems evaluating tumor response to neoadjuvant therapy (NAT) in pancreatic ductal adenocarcinoma (PDAC) exist, their prognostic value to predict recurrence after surgery has not been validated in. This study aimed to show that microscopic tumor mapping in post-NAT specimens could predict postoperative oncologic outcomes. Methods: Among patients who underwent pancreaticoduodenectomy after NAT for PDAC between 2019 and 2021, 44 pathological responders with College of American Pathologists (CAP) scores 1 or 2 were prospectively enrolled. Microscopic mapping was performed to identify residual tumor loci within the macroscopic tumor bed using 4 mm 2 -sized pixels. Patients were divided into large extent (LE, n = 22) and small extent (SE, n = 22) groups with a cutoff value of 300 mm 2 . Survival outcomes were compared between the two groups, and the diagnostic performance of microscopic tumor mapping was evaluated with receiver operating (ROC) curves. Results: Recurrence and cancer-related mortality rates were significantly higher in the LE group (18.2% vs. 50.0%, p = 0.026; 0 vs. 18.2%, p = 0.001). 1-year and 3-year disease-free survival rates were significantly lower in the LE group compared to the SE group (95.5% vs. 54.5% and 80.4% vs. 50.0%, respectively; p = 0.010). When ROC curves were compared, the area under curve (AUC) was 0.759 for pathologic response measured by microscopic tumor mapping, which was higher compared to the CAP score (AUC 0.586). Conclusions: Evaluation of residual tumor in post-NAT specimens by microscopic tumor mapping is a significant predictor for early recurrence after surgery, with better performance in predicting recurrence compared to the CAP score.