An R0 resection margin does improve overall survival after PDAC resection- real-world evidence from 6.000 cases from the German Cancer Registry Group

Background: To date surgical resection is the only curative treatment option for pancreatic ductal adenocarcinoma (PDAC). However, survival rates are poor. Resection margins have long been used as a surrogate to evaluate success of the surgery. Their prognostic value and biologic implications remain disputed. Methods: Data was obtained from pooled data of 17 clinical cancer registries in Germany collated by the German Cancer Registry Group of the Association of German Tumor Centers. Overall and disease-free survival (OS/DFS) after 5.997 PDAC resections with documented margin status were analyzed using Kaplan-Meier analyses. Subgroups by type of surgery and lymph node involvement were analyzed. Cox regression for OS and multivariable regression analysis for the endpoint resection margin negative/positive (R0/R1) were performed. Results: Both the median OS (19.3 vs. 13.4 months, R0/R1, respectively) and DFS (14.2 vs. 10.9 months, R0/R1, respectively) were improved for margin negative cases (R0). These differences were also observed after stratifying for lymph node involvement or the type of surgery (pancreas head resection, left resection, or total pancreatectomy). Cox regression revealed a positive margin (R1) to be independently associated with a poor survival (hazard ratio 1.41). Tumor size, perineural invasion, and lymph node involvement were the strongest predictors of a margin-positive resection (R1) in multivariable regression analysis. Conclusion: In this large population-based study, margin status was an independent risk factor for OS and DFS after PDAC resection, even after controlling for confounding factors. Therefore, resection margin is not only a mediator variable between tumor biology and outcome.