Neoadjuvant chemotherapy improves outcomes in resectable pancreatic adenocarcinoma: an updated national cancer database analysis

Abstract

Presenter: Wade Christopher MD | Providence Saint John's Cancer Institute Background: Systemic chemotherapy has been shown to have a survival benefit for all stages of pancreatic adenocarcinoma. Historically adjuvant chemotherapy (AC) was given for all patients. However, recently there has been a shift towards neoadjuvant chemotherapy (NAC) for both resectable and borderline resectable pancreatic adenocarcinoma. This shift has been driven by the observation that many post-operative patients are unable to undergo treatment with AC secondary to surgical complications. The objective of this study was to compare survival and oncologic outcomes of NAC versus AC for early stage resectable pancreatic cancer. Methods: Patients age 18 years and older with stage I or II pancreatic adenocarcinoma in the 2010-2017 National Cancer Database were identified. Patients were grouped as receiving NAC + surgery compared to those patients who underwent upfront surgery +/- AC. Logistic regression evaluated the oncologic outcomes of positive resection margins and positive lymph nodes after NAC. Kaplan-Meier method followed by Cox proportional-hazards regression with inverse probability weighting (IPTW) using propensity score matching was used to compare overall survival (OS). Results: In 19,415 patients with early stage pancreatic adenocarcinoma who underwent surgery, upfront NAC led to a 13% risk reduction of a positive resection margin when compared to surgery +/- AC (odds ratio [OR]:0.87; 95%CI 0.78-0.97), and a 59% decreased risk of positive lymph nodes at the time of surgery (OR:0.41; 95%CI 0.38-0.45), after controlling for patient clinical and pathological risk factors. The median overall survival for all patients treated with NAC was 2.56 years versus 1.95 years for surgery +/- AC (3 and 5 year OS for NAC patients was 43.14% and 26.44%; 3 and 5 year OS for surgery +/- AC patients was 34.94% and 22.42%) (Log-rank p-value < 0.001). The subgroup of stage I patents had a median OS of 2.69 years with NAC versus 2.20 years for surgery +/- AC (Log-rank p-value < 0.001). The subgroup of stage II patients had a median OS of 2.49 years with NAC versus 1.75 years for surgery +/- AC (Log-rank p-value < 0.001). In the Cox proportional-hazards regression analyses with IPTW using propensity score matching, NAC also had a significant OS benefit for all patients (hazards ratio [HR]:0.80; 95%CI 0.78–0.83), as well as for Stage I (HR:0.89; 95%CI 0.84–0.94) and Stage II patients (HR:0.71; 95%CI 0.68–0.75) individually. The survival benefit of NAC remained when only patients that had both surgery and chemotherapy (HR:0.90; 95%CI 0.86–0.93) were evaluated. However, in this cohort, when stratified by clinical stage, NAC was only associated with an improved OS for stage II patients (HR:0.80; 95%CI 0.76–0.84) with no significant OS benefit from NAC for Stage I patients. Conclusion: NAC appears to confer a survival benefit for patients with early stage pancreatic adenocarcinoma. NAC also decreased the risk of a positive resection margin as well as positive lymph nodes at the time of surgical resection. In stage I patients that were able to receive both surgery and chemotherapy, the timing of chemotherapy did not impact survival.