The Impact of Complications after Resection of Pancreatic Ductal Adenocarcinoma on Disease Recurrence

Abstract

Introduction: Previous studies have shown that postoperative complications withhold pancreatic ductal adenocarcinoma (PDAC) patients from receiving adjuvant chemotherapy and disadvantage their survival. However, the exact impact of complications after surgery for PDAC on long-term oncological outcomes remains unclear. This study aimed to evaluate this impact on disease-free survival (DFS) in these patients. Method: A nationwide, stepped-wedge cluster randomized trial including all patients undergoing pancreatic resection was conducted from 2018-2019 (PORSCH trial, NL6671). For this study, a subset of patients with histologically proven PDAC was identified. Data on recurrence and survival were additionally collected. The impact of postoperative complications on DFS was evaluated using multivariable Cox regression analysis, adjusting for adjuvant treatment as time-varying covariate and other confounders. Complications included pancreatic fistula, delayed gastric emptying, postpancreatectomy hemorrhage, gastrojejunostomy leakage, biliary leakage (all ISGPS grade B/C), pneumonia and organ failure. Results: In total, 467 patients were included, with a median DFS of 15 (interquartile range [IQR] 8-23) months and median follow-up of 24 (IQR 19-31) months. Biliary leakage (hazard ratio (HR) 1.93 (95% confidence interval [CI] 1.02-3.63); p=0.04), leakage of the gastrojejunostomy (HR 2.67 (95% CI 0.99-7.16); p=0.05), single organ failure (HR 1.93 (95% CI 1.28-2.93); p=0.002) and multiple organ failure (HR 3.24 (1.62-6.48); p<0.001) were significantly associated with shorter DFS. Results are presented in Table 1. Conclusions: Organ failure, biliary leakage and gastrojejunostomy leakage are independently associated with shorter DFS in patients who underwent PDAC resection. Prevention of these complications might lead to improvement of long-term oncological prognosis.Tabled 1FP08-6Table 1. Impact of postoperative complications on disease-free survival in patients who underwent PDAC resection without 90-day surgery-related mortality (n=467)Complicationsn (% of total)HR (95% CI)*P-valuePancreatic fistula64 (14)1.09 (0.71-1.69)0.69Postpancreatectomy hemorrhage23 (5)1.31 (0.64-2.68)0.46Biliary leakage19 (4)1.93 (1.02-3.63)0.04Leakage gastrojejunostomy5 (1)2.67 (0.99-7.16)0.05Pneumonia28 (6)1.44 (0.82-2.53)0.21Single organ failure53 (11)1.93 (1.28-2.93)0.002Multiple organ failure14 (3)3.24 (1.62-6.48)< 0.001PDAC, pancreatic ductal adenocarcinoma; CI, confidence interval; HR, hazard ratio; ICU, intensive care unit; *Multivariable Cox regression analysis in 467 patients who underwent PDAC resection - each complication was tested separately, adjusted for age, gender, preoperative serum CA 19-9, tumor size, resection margin status (R0 vs. R1), tumor differentiation, number of positive lymph nodes, and perineural invasion as confounding factors, and adjuvant treatment as a time-varying covariate. Open table in a new tab PDAC, pancreatic ductal adenocarcinoma; CI, confidence interval; HR, hazard ratio; ICU, intensive care unit; *Multivariable Cox regression analysis in 467 patients who underwent PDAC resection - each complication was tested separately, adjusted for age, gender, preoperative serum CA 19-9, tumor size, resection margin status (R0 vs. R1), tumor differentiation, number of positive lymph nodes, and perineural invasion as confounding factors, and adjuvant treatment as a time-varying covariate.