Microscopic tumor mapping of post-neoadjuvant therapy pancreatic cancer specimens to predict post-surgical recurrence: A prospective cohort study

Abstract

Background

Although various pathological grading systems are available for evaluating the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant therapy (NAT), their prognostic value has not been thoroughly validated. This study examined whether microscopic tumor mapping of post-NAT specimens could predict tumor recurrence.

Methods

This prospective study enrolled 52 patients who underwent pancreaticoduodenectomy after NAT for PDAC between 2019 and 2021. Microscopic mapping was performed to identify residual tumor loci within the tumor bed using 4 mm² pixels. Patients were divided into small extent (SE; n = 26) and large extent (LE; n = 26) groups using a cutoff value of 226 mm². The diagnostic performance for predicting tumor recurrence was evaluated using receiver operating characteristic (ROC) curves.

Results

Carbohydrate antigen 19-9 levels were normalised after NAT in more patients in the SE group (SE 21 [80.8%] vs. LE 13 [50.0%]; P = 0.041). Tumor size (P < 0.001), T stage (P < 0.001), positive lymph node yield (P = 0.024), and perineural invasion rate (P = 0.018) were significantly greater in the LE group. The 3-year disease-free survival rate was significantly lower in the LE group (SE 83.3% vs. LE 50.0%, P = 0.004). The area under the ROC curve for mapping extent was 0.743, which was greater than that of the other tumor response scoring systems.

Conclusions

Microscopic tumor mapping of the residual tumor in post-NAT specimens is a significant predictor of post-surgical recurrence, and offers better prognostic performance than the current grading systems.