Preoperative chemoradiotherapy diminishes the risk of postoperative pancreatic fistula after pancreatoduodenectomy

Abstract

Purpose: Postoperative pancreatic fistula (POPF) remains the main cause of morbidity and mortality after pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC). The impact of preoperative chemotherapy (PCT) or preoperative chemoradiotherapy (PCRT) on the risk of POPF and other postoperative complications is unknown. It has been hypothesized that radiotherapy induces fibrosis and hereby reduces the rate of POPF but data are lacking. We aim to investigate the association between immediate surgery, PCT, and PRCT with the occurrence of POPF and other postoperative complications in patients undergoing pancreatoduodenectomy for PDAC. Method: All patients who underwent pancreatoduodenectomy for PDAC were identified in the mandatory nationwide prospective Dutch Pancreatic Cancer Audit (DPCA; 2014-2019). Differences in POPF grade B/C and other postoperative complications after immediate surgery, PCT and PCRT were analyzed. Results: Overall, 1751 patients were included, of whom 1551 patients (88.6%) underwent immediate surgery, 101 (5.8%) received PCT, and 100 (5.7%) received PCRT. The risk of POPF was 8.4% with immediate surgery, 5.9% with PCT, and 2.0% with PCRT. The risk of POPF was significantly diminished with preoperative treatment (PCT or PCRT; OR:0.454;p=0.030), particularly with PCRT (OR:0.224; p=0.023) compared to immediate surgery. Firm pancreas texture (i.e. pancreatic fibrosis) was most often observed during surgery in the PCRT cohort (52.4% immediate surgery, 63.0% PCT, 77.3% PCRT; p=0.001). Other postoperative complications did not differ between treatment groups. Conclusion: Preoperative therapy, especially chemoradiotherapy, is associated with a reduced risk of POPF in patients after pancreatoduodenectomy for PDAC. This may be related to increased pancreatic fibrosis and deserves further study.