Neoadjuvant Treatment Mitigates the Survival Impact of Major Complications after Resection of Pancreatic Adenocarcinoma

Abstract

Postoperative major complications (PMCs) may prevent multimodality therapy (MMT) for pancreatic ductal adenocarcinoma (PDAC) patients by delaying adjuvant therapy (AT) following surgery-first (SF) sequencing. We hypothesized that neoadjuvant therapy (NT) mitigates the detrimental effect of PMCs on outcomes of resected patients. Characteristics of consecutive resected PDAC patients 7/2011-10/2018 were abstracted from a prospective database. PMCs were defined at 90-days as ACCORDION Grade ≥3. Overall survival (OS) was compared between patients with and without PMCs. Of 373 patients, most underwent NT (75%). PMCs occurred in 22% of SF and 20% of NT patients (p=0.71). Most went on to receive some form of AT (90% SF vs. 70% NT,p< 0.001). Median OS for NT and SF patients was 46 vs. 36 months (p=0.037). PMCs negatively impacted OS, with median OS 59 months for NT(-)PMC, 34 months for NT(+)PMC, 45 months for SF(-)PMC, and 20 months for SF(+)PMC (p< 0.001;Fig. 1A). There was a trend toward worse OS in NT(+)PMCs (p=0.06, Figure 1B). PMCs were not independent predictors of OS for NT patients. However, after adjustment for clinical classification, treatment sequencing, tumor size, and margin status, PMCs were independently-associated with OS (HR-1.60,p=0.010) among all patients, along with perineural invasion (HR-1.83, p=0.024), nodal positivity (HR-2.1,p< 0.001), and AT (HR-0.69,p=0.039). The deleterious effects of PMCs on OS for PDAC patients may be mitigated by NT. NT sequencing should be routinely considered given the significant risk of post-pancreatectomy morbidity.