Impact of Mediating and Confounding Variables on the Volume-Outcome Association in the Treatment of Pancreatic Cancer

Background. High-volume centers (HVC), academic centers (AC), and longer travel distances (TD) have been associated with improved outcomes for patients undergoing surgery for pancreatic adenocarcinoma (PAC). Effects of mediating variables on these associations remain undefined. The purpose of this study is to examine the direct effects of hospital volume, facility type, and travel distance on overall survival (OS) in patients undergoing surgery for PAC and characterize the indirect effects of patient-, disease-, and treatment-related mediating variables. Patients and Methods. Using the National Cancer Database, patients with non-metastatic PAC who underwent resection were stratified by annual hospital volume (< 11, 11-19, and >= 20 cases/year), facility type (AC versus nonAC), and TD (>= 40 versus < 40 miles). Associations with survival were evaluated using multiple regression models. Effects of mediating variables were assessed using mediation analysis. Results. In total, 19,636 patients were included. Treatment at HVC or AC was associated with lower risk of death [hazard ratio (HR) 0.90, confidence interval (CI) 0.88-0.92; HR 0.89, CI 0.86-0.91, respectively]. TD did not impact OS. Patient-, disease-, and treatment-related variables explained 25.5% and 41.8% of the survival benefit attained from treatment at HVC and AC, reducing the survival benefit directly attributable to each variable to 4.9% and 6.4%, respectively. Conclusions. Treatment of PAC at HVC and AC was associated with improved OS, but the magnitude of this benefit was less when mediating variables were considered. From a healthcare utilization and cost-resource perspective, further research is needed to identify patients who would benefit most from selective referral to HVC or AC.

Automated summary

The study found that treatment at high-volume centers (HVC) and academic centers (AC) was associated with improved overall survival (OS) for patients with pancreatic adenocarcinoma (PAC). However, considering mediating variables reduced the magnitude of this benefit. Further research is needed to identify patients who would benefit most from selective referral to HVC or AC.