Association Between Pancreatic Fistula and Long-term Survival in the Era of Neoadjuvant Chemotherapy

Abstract

In the past decade, the use of neoadjuvant therapy (NAT) has increased for patients with borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Data on pancreatic fistula and related overall survival (OS) in this setting are limited. OBJECTIVE To compare postoperative complications in patients undergoing either upfront resection or pancreatectomy following NAT, focusing on clinically relevant postoperative pancreatic fistula (CR-POPF) and potential associations with OS. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study was conducted on data from patients who underwent pancreatic resection for PDAC at the Massachusetts General Hospital from January 1, 2007, to December 31, 2017, EXPOSURES Pancreatic cancer surgery with or without NAT. MAIN OUTCOMES AND MEASURES Overall morbidity and CR-POPF rates were compared between NAT and upfront resection. Factors associated with CR-POPF were assessed with univariate and multivariate analysis. Survival data were analyzed by Kaplan-Meier curves and a Cox proportional hazards regression model. RESULTS Of 753 patients, 364 were men (48.3%); median (interquartile range) age was 68 (61-75) years. A total of 346 patients (45.9%) received NAT and 407 patients (54.1%) underwent upfront resection. At pathologic examination, NAT was associated with smaller tumor size (mean [SD], 26.0 [15.3] mm vs 32.7 [14.4] mm; P < .001), reduced nodal involvement (102 [25.1%] vs 191 [55.2%]; P < .001), and higher R0 rates (257 [74.3%] vs 239 [58.7%]; P < .001). There were no significant differences in severe complication rate or 90-day mortality. The rate of CR-POPF was 3.6-fold lower in patients receiving NAT vs upfront resection (13 [3.8%] vs 56 [13.8%]; P < .001). In addition, factors associated with CR-POPF changed after NAT, and only soft pancreatic texture was associated with a higher risk of CR-POPF (38.5% vs 6.3%; P < .001). Survival analysis showed no differences between patients with or without CR-POPF after upfront resection (26 vs 25 months; P = .66), but after NAT, a worse overall survival rate was observed in patients with CR-POPF (17 vs 34 months; P = .002). This association was independent of other established predictors of overall survival by multivariate analysis (hazard ratio, 2.80; 95% CI, 1.44-5.45; P < .002). CONCLUSIONS AND RELEVANCE Neoadjuvant therapy may be associated with a significant reduction in the rate of CR-POPF. In addition, standard factors associated with CR-POPF appear to be no longer applicable following NAT. However, once CR-POPF occurs, it is associated with a significant reduction in long-term survival. Patients with CR-POPF may require closer follow-up and could benefit from additional therapy.

Conversion Surgery for Advanced Pancreatic Cancer

“…Moreover, by applying a clinical burden score, complications appear to be associated with an increased clinical burden if they occur after NAT compared to upfront resections, resulting in prolonged hospitalizations [88]. Another study demonstrated a 3.6-fold decrease of clinically relevant pancreatic fistula in 364 patients undergoing pancreatic resection following NAT compared to a contemporaneous control group of 407 patients receiving upfront resections [89]. The authors observed a change in classical determinants of pancreatic fistula in the NAT setting; only soft pancreatic tissue remained associated with the occurrence of pancreatic fistula.…”

“…The authors observed a change in classical determinants of pancreatic fistula in the NAT setting; only soft pancreatic tissue remained associated with the occurrence of pancreatic fistula. While pancreatic fistula did not impact median overall survival after upfront resections (26 with vs. 25 months without) it was associated with a significantly reduced overall survival in NAT patients (17 vs. 34 months) [89].…”

Impact of neoadjuvant therapy on post‐operative pancreatic fistula: a systematic review and meta‐analysis

“…8,9,14,31 A recent observational study demonstrated a 3.6-fold reduction in POPF after NAT compared with upfront resection for pancreatic cancer, but the data could not be included in this meta-analysis as they pooled outcomes from PD and DP together. 32 A previous systematic review by Verma et al evaluated the impact of NAT on post-operative morbidity and mortality in patients with PC. 33 Their study demonstrated comparable rates of overall POPF and DGE in patients with and without NAT.…”

“…While this has led to marginal increments in long‐term survival, the impact of NAT on post‐operative outcomes, including POPF, remains unclear 0031. A recent observational study demonstrated a 3.6‐fold reduction in POPF after NAT compared with upfront resection for pancreatic cancer, but the data could not be included in this meta‐analysis as they pooled outcomes from PD and DP together 0032. A previous systematic review by Verma et al .…”

Which Factors Are Associated With Positive Resection Margin in Pancreatic Ductal Adenocarcinoma for Different Surgical Procedures? Results Based on a Standard Pathological Evaluation System-retrospective Cohort Study&nbsp;

“…With accurate assessment of resection margins by a standardized pathological examination protocol using LEEPP and DWMSIs, and with a single de nition of R1 using the 1 mm de nition, our study showed marked differences in the R1 resection rates for PD and DP when compared with the published rates of R1 resection [22][23][24][25][26]. In the current study, the rates of R1 resection were similar to the recently reported data for patients who underwent upfront surgery [27]. Previous studies reported R1 resection was frequently present in PV/SMV margins [28] and SMA margins [29], which was closely related to prognosis [30].…”