Borderline Resectable Pancreatic Cancer Patients Have Superior Survival Following Neoadjuvant Therapy Compared to Upfront Resectable Patients

Abstract

The role of neoadjuvant chemoradiotherapy (neoCRT) and/or chemotherapy (neoCHT) in patients with pancreatic ductal adenocarcinoma (PDAC) is not well defined. We hypothesized that borderline resectable pancreatic cancer (BR-PDAC) patients receiving neoCHT and/or neoCRT have equivalent survival compared to upfront resectable (UR-PDAC) patients, despite having more locally advanced disease. This is an IRB approved retrospective study of 315 surgically operable PDAC patients treated at an NCI Comprehensive Cancer Center within an academic quaternary referral center between 2011 and 2018. Data were abstracted from the electronic medical record using an institutional cancer registry and the National Surgical Quality Improvement Program (NSQIP). 315 patients were eligible for analysis, including 81 patients who received neoadjuvant therapy (71 BR-PDAC, 10 UR-PDAC) and 234 who underwent upfront resection. Patients had significantly improved median survival following R0 resection vs R1 resection (2.1 vs 1.0 yr; p < 0.0001), who had G2 vs GIII/IV disease (2.0 vs 1.2 yr; p = 0.0002), were node-negative (2.6 vs 1.7 yr; p = 0.0012), or having receipt of adjuvant CHT (2.3 vs 1.1 yr; p < 0.0001). Although indicated, only 72.9% of patients who did not receive neoCHT were able to receive adjuvant CHT. BR-PDAC patients, who all received neoCHT and/or neoCRT, had equivalent R1 resection rates (25.9%) compared to UR-PDAC patients (18.8%); p = 0.17, despite having more locally advanced disease. BR-PDAC patients also had superior median OS compared to UR-PDAC patients (28.6 vs 19.7 mo; p = 0.049). 1-year median OS was 91.4% vs 66.3% and 2-year OS was 56.5% vs 41.9% for BR-PDAC patients vs UR-PDAC resectable patients, respectively. Our data show that neoCRT and/or neoCHT has a clinically significant benefit in PDAC patients. R0 resection and receipt of adjuvant CHT was confirmed to be strongly associated with improved survival, and neoadjuvant therapy in BR-PDAC patients resulted in equivalent R0 resection rates as UR-PDAC patients. Many UR-PDAC patients were unable or unwilling to receive adjuvant CHT, whereas all BR-PDAC patients received CHT prior to resection. These data support the role for neoCRT and neoCHT in BR-PDAC patients, and highlight a potential role for neoadjuvant therapy in upfront resectable patients.