Preoperative downstaging of pancreatic cancer is associated with improved survival after multi-agent chemotherapy, but not after radiation

Background: Downstaging has been associated with improved survival for many cancers. However, the impli-cations of downstaging are unclear for pancreatic cancer in an era of effective neoadjuvant systemic chemotherapy.Methods: NCDB retrospective cohort study of resected pancreatic carcinoma treated with neoadjuvant therapy. Results: The study included 73,985 patients: 66,589 with no neoadjuvant therapy, 2,102 neoadjuvant radiation therapy (N-RT), 3,195 neoadjuvant multiagent chemotherapy (N-MAC) and 2.099 with both neoadjuvant radi-ation and multiagent chemotherapy. There was increased use of N-MAC over the period of this study. Patients selected for treatment with N-MAC had longer survival from surgery on univariate (23.1 vs. 18.7 months, p = < 0.01) and multivariate analyses HR 0.81 (0.76-0.87, p < 0.001) compared to those selected with N-RT. Downstaging was similar in N-RT and N-MAC groups (25.1 vs. 24.1%, p = 0.43). Downstaging following N-MAC was associated with a survival benefit, HR 0.85 (0.74-0.98). However, downstaging following N-RT was not associated with a survival advantage, HR 1.12 (0.99-0.99).Conclusion: Clinicians have rapidly adopted N-MAC for treatment of pancreatic cancer. Although the rates of downstaging are similar between treatment groups, response translates into increased survival only with N-MAC and not with N-RT.