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. 2019 Oct 1;154(10):943-951.
doi: 10.1001/jamasurg.2019.2272.

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

Thomas Hank  1 , Marta Sandini  1 , Cristina R Ferrone  1 , Clifton Rodrigues  1 , Maximilian Weniger  1 , Motaz Qadan  1 , Andrew L Warshaw  1 , Keith D Lillemoe  1 , Carlos Fernández-Del Castillo  1
Affiliations

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

Thomas Hank et al. JAMA Surg. .

Abstract

Importance: 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Hank reported grants from German Cancer Aid during the conduct of the study. Dr Weniger reported grants from Deutsche Forschungsgmeinschaft during the conduct of the study. Dr Qadan reported personal fees from Olympus outside the submitted work. Dr Warshaw reported being a partner in a preoperative process consulting group, OR DX+RX, Solutions for Surgical Safety. No other disclosures were reported.

Figures

Figure.
Figure.. Clinically Relevant Pancreatic Fistula (CR-POPF) and Survival
Survival after resection in patients who underwent upfront resection (A) or received neoadjuvant therapy (B). Vertical bars indicate censoring of patients alive at their last follow-up.
See this image and copyright information in PMC

Comment in

References

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