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Extent of Resection Does Not Affect the National Failure to Treat Localized Pancreas Cancer with Post-Resection Adjuvant Chemotherapy
John R. Bergquist*1,2, Christopher R. Shubert1,2, Tommy Ivanics1,2, Rory Smoot1, Michael L. Kendrick1, David M. Nagorney1, Michael B. Farnell1, Mark J. Truty1
1Surgery, Mayo Clinic, Rochester, MN; 2Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
Introduction: Survival benefit of post-resection adjuvant chemotherapy has been well demonstrated for patients with localized pancreas adenocarcinoma (PDAC). Despite this, up to 40% of patients do not receive adjuvant therapy after curative intent resection. Due to higher expected perioperative morbidity for pancreatoduodenectomy (PD) compared to distal partial pancreatectomy (DPP), we hypothesized that patients undergoing the less morbid DPP would be more likely to receive adjuvant therapy and have associated survival benefit compared to those undergoing PD.
Methods: The National Cancer Data Base (2004-2012) was reviewed for patients with localized (AJCC Stage I/II) PDAC who underwent DPP and PD. Patients receiving neoadjuvant therapy were excluded. Univariate and multivariable analysis were used to identify factors associated with therapy receipt. Unadjusted Kaplan-Meier analysis and adjusted Cox proportional hazards modeling of overall survival (OS) were performed.
Results: 9503 patients underwent pancreatectomy for localized PDAC: 1645 (17.3%) DPP and 7858 (82.7%) PD. Despite less extensive resection, an equal proportion of patients did not receive adjuvant chemotherapy between groups (DPP 36.2% vs PD 36.0%, p=0.904). Prognostic characteristics were similar between groups except DPP patients had greater pre-operative comorbidity (Charlson Deyo 2+ 9.4% vs. 6.6%, p<0.001), fewer N1 lesions (50.2% vs. 70.0%, p<0.001), and a lower rate of positive margin (20.1% vs. 23.9%, p=0.004). Of patients with data on surgical approach, DPP were more likely to be completed in minimally invasive fashion (p<0.001). DPP had shorter length of stay (median 7 vs 10 days, p<0.001), but 30-day readmission rates were equivalent (DPP 8.7% vs. PD 8.2%, p=0.448). There was no difference in type of treatment center (academic vs. community, p=0.23) or in receipt of radiation therapy (35.4% vs 37.6%, p=0.248). Multivariable analysis confirmed that type of procedure was not independently associated with receipt of adjuvant chemotherapy (p=0.385). Median OS was improved for patients receiving adjuvant chemotherapy compared to surgery alone (PD 22.2 vs. 15.1 months, p<0.001; DPP 25.4 vs. 17.4 months, p<0.001, Figure). This result was confirmed on multivariable analysis controlling for significant demographic and pathologic factors (adjuvant therapy/surgery alone HR 0.56 p<0.001; PD/DPP HR 0.98, p=0.74).
Conclusions: Patients with localized PDAC who undergo DPP are equally unlikely to receive post-resection adjuvant chemotherapy as are patients undergoing PD. Patients with localized PDAC who receive post-resection adjuvant therapy have improved survival regardless of surgical procedure performed. These data suggest that factors unrelated to extent of resection and associated morbidity are driving the nationwide failure to provide adjuvant therapy in patients with localized PDAC.
 Unadjusted Kaplan-Meier estimates of overall survival for PDAC patients undergoing pancreatoduodenectomy (left panel) and distal partial pancreatectomy (right panel) with surgery alone vs. surgery plus post-resection adjuvant chemotherapy.
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