Effect of surgical resection on survival following neoadjuvant chemotherapy in patients with stage I-II pancreatic adenocarcinoma.

255 Background: Pancreatic adenocarcinoma (PDAC) is a lethal malignancy, representing the 4th leading cause of cancer deaths. Our 2011 institutional protocol guides that patients with Stage I/II PDAC receive neoadjuvant chemotherapy (FOLFIRINOX or gemcitabine- nab-paclitaxel); a similar protocol is followed with patients with Stage III disease. The aim of the study is to determine if potentially curative surgery provides added survival benefit, compared to neoadjuvant chemotherapy alone. Methods: Patients who received neoadjuvant chemotherapy and who were diagnosed with stage I-III PDAC from 2011-2017 at a tertiary medical center were included in this prospectively-collected, retrospective analysis. The primary endpoint was overall survival (OS). Kaplan-Meier curves are compared using Log-rank. Cox proportional hazards were used to adjust for confounders. Results: 105 patients met inclusion criteria: 38 (36%) had Stage I disease (n = 18 had neoadjuvant chemotherapy and surgery [N+S], n = 20 had neoadjuvant chemotherapy [N] alone), 44 (42%) had stage II (N+S n = 20, N n = 24), 23 (22%) had stage III (N+S n = 4, N n = 19). There was no difference in 5-year OS regardless of treatment regimen in patients with Stage I (median OS N+S 22.5 mo vs N 27.9 mo; p = 0.99, HR 1.00, 95%CI 0.74-1.35) or Stage II disease (median OS N+S 28.7 mo vs N 27.6 mo; p = 0.69; HR 1.06, 95%CI 0.79-1.41). There is a trend towards improved OS with N+S in those with Stage III disease (median OS N+S 46.0 mo vs N 14.5 mo, p = 0.08), but the number who underwent resection is low (17%), limiting this analysis. Conclusions: In patients with Stage I-II PDAC, potentially curative surgery may not provide additional survival benefit beyond that afforded by modern day neoadjuvant chemotherapy. Stage III outcomes are limited by small numbers, and the impact of surgery is unclear. It may be possible that the locally unresectable tumor that is rendered resectable with neoadjuvant chemotherapy may be associated with a more favorable biology, such that surgery offers added survival benefit. Additional large-scale trials are needed to confirm whether newer therapies may obviate the need for resection in select patients.