Perioperative Therapy in Stage IA-III Pancreatic Cancer – A Cross-validation of the National Cancer Database and the German Cancer Registry

Purpose: The aim of this study is to assess the outcome of perioperative treatment regimens in stage IA-III pancreatic cancer (PDAC) in a cross-validation of the German Cancer Registry of the German Working Group of Cancer Centers (WGCC/ADT) and the National Cancer Database (NCDB). Methods and material: Patients undergoing oncologic resection for clinical stage IA-III PDAC with operation alone (OP), neoadjuvant therapy and operation (neo+OP), operation and adjuvant therapy (OP+adj) and neoadjuvant therapy, operation and adjuvant therapy (neo+OP+adj) were identified from both registries between 2000 and 2018. Long-term overall survival rates (OS) associated with perioperative treatment regimens were analyzed by Kaplan Meier method and Cox regression after prospensity score-based matching. Results: 1611 patients from the WGCC/ADT database and 29081 patients from the NCDB with oncologic resection for stage IA-III PDAC were included. While neo+OP and neo+OP+adj failed to show a benefit in OS as compared to OP alone for stage IA-IIA patients in the WGCC/ADT registry, OS rates were improved for stage IIB-III patients with neo+OP (10.0m vs. 18.2m, HR 0.746, 95%CI 0.530-0.978, p=0.043) and neo+OP+adj (10.0m vs. 19.9m, HR 0.559, 95%CI 0.398-0.784, p=0.010). In stage IA-IIA and stage IIB-III patients neo+OP (p<0.001) and neo+OP+adj (p<0.001) improved OS rates as compared to OP alone in the NCDB registry. Neo+OP was associated with prolonged overall survival rates as compared to OP+adj for both stage IA-IIA (27.1m vs. 25.3m, HR 1.066, 95%CI 1.010-1.126, p<0.001) and IIB-III patients (25.8m vs. 20.8m, HR 1.305, 95%CI 1.225-1.390, p<0.001). In the NCDB registry, neo+OP+adj was associated with improved OS rates as compared to neo+OP for both stage IA-IIA (27.1m vs. 36.6m, HR 0.716, 95%CI 0.614-0.836, p<0.001) and IIB-III patients (25.8m vs. 28.6m, HR 0.860, 95%CI 0.717-0.978, p<0.001). Neoadjuvant radiochemotherapy was not associated with an improved OS as compared to neoadjuvant chemotherapy alone in either registry. Conclusion: The cross-validation study of the NCDB and WGCC/ADT registries demonstrated a survival benefit with neoadjuvant therapy in both stage IA-IIA and stage IIB-III PDAC. Neoadjuvant therapy combined with adjuvant therapy is associated with improved overall survival as compared to neoadjuvant or adjuvant therapy alone. Concepts and outcomes of perioperative therapy remained widely consistent in both registries.