Survival after Margin-Positive Resection in the Era of Modern Chemotherapy for Pancreatic Cancer: Do Patients Still Benefit?

Background: R0 resection for pancreatic cancer is considered standard of care, but is not always achieved. This study looks at R1/R2 resection outcomes compared with chemotherapy alone. Our hypothesis is that patients with margin-positive disease have better outcomes than those receiving chemotherapy alone. Study design: Stage II pancreatic cancer patients who underwent R1/R2 surgery with/without neoadjuvant chemotherapy, from the National Cancer Database (NCDB) 2010 to 2017 were identified and compared with similar staged patients who received chemotherapy alone. The surgical group was then analyzed by subset based on receipt of chemotherapy: upfront surgery (+/- adjuvant therapy) and neoadjuvant therapy followed by surgery (+/- adjuvant therapy). Results: There were 11,699 Stage II pancreatic cancer patients included, 9,521 (81.4%) of whom were treated with chemotherapy alone, 15.7% (n = 1,836) had upfront surgery, and 2.9% (n = 342) had neoadjuvant therapy with surgery. R1/R2 neoadjuvant patients had the best overall survival at a mean of 19.75 months (95% CI 17.91, 22.28) compared with the upfront surgery group (17.77 months, 95% CI 15.64, 19.55) and the chemotherapy alone group (10.12 months, 95% CI 8.97, 11.50) (hazard ratio [HR] 0.46 upfront surgery and 0.32 neoadjuvant group, respectively, p < 0.0001). Even with R2 resection, survival was better in surgical patients compared with patients who underwent chemotherapy only (15.76 mo vs 10.22 mo, p = 0.06). Patients with R1/R2 resections had improved survival if they received neoadjuvant/adjuvant chemotherapy, though the survival rates were significantly lower than those with standard R0 resections (n = 16,129). Conclusions: R1 resection has benefit over chemotherapy alone in pancreatic cancer. Pancreatic cancer patients who are left with microscopic R1 disease have better survival than without surgery, particularly in the setting of neoadjuvant therapy.