Neoadjuvant chemotherapy or upfront surgery in localized pancreatic cancer: a contemporary analysis

Neoadjuvant chemotherapy is considered a new treatment option for potentially resectable pancreatic cancer. However, data are not well established on overall survival and delaying surgery in resectable pancreatic cancer, as well as on those patients that ultimately cannot undergo surgery. We analyzed pancreatic cancer patients treated in a tertiary hospital from January 2016 to December 2020. Patients with resectable stage I and II pancreatic cancer were evaluated regarding surgery, neoadjuvant treatment, and other clinical demographics. The survival function was estimated using the Kaplan-Meier method, and the relationship between the variables of interest and the overall survival (OS) was assessed by adopting the proportional regression Cox models. A total of 216 patients were evaluated. 81 of them with resectable/borderline resectable disease and 135 with unresectable /metastatic disease at diagnosis. Median OS for stage I and II disease were 36 and 28 months, respectively. For resectable pancreatic cancer median OS was 28 months, for borderline resectable pancreatic cancer median OS was 11 months. Median OS for stage III (locally advanced) and stage IV (metastatic) were 10 and 7 months, respectively (p < 0.0001). Median OS of 9 months were obtained for patients with stage I and II that did not undergo surgery compared to 25 months in patients that underwent surgery in any time (p < 0.001). Comparing patients with localized disease, median OS for patients treated with upfront surgery was 28 months, compared to 15 months in patients treated with neoadjuvant approach (p = 0.04). Most patients that did not undergo surgery have decline of performance status or disease progression on neoadjuvant treatment. On multivariable analysis in pancreatic cancer stages I and II, including age, sex, borderline or resectable disease, CA 19-9, positive lymph nodes and neoadjuvant treatment, the surgery was the only factor associated with improved overall survival (p = 0.04). Upfront surgery should still be considered a standard of care approach for resectable pancreatic cancer. Biomarker driven studies and randomized trials with combination therapies are necessary to address neoadjuvant chemotherapy and delaying surgery in purely resectable pancreatic cancer.