Trends Over Time in Recurrence Patterns and Survival Outcomes after Neoadjuvant Therapy and Surgery for Pancreatic Cancer.

Abstract

We aimed to determine if advances in neoadjuvant therapy affected recurrence patterns and survival outcomes after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). Data are limited on how modern multimodality therapy affects PDAC recurrence and post-recurrence survival. Patients who received neoadjuvant therapy followed by curative-intent pancreatectomy for PDAC during 1998-2018 were identified. Treatments, recurrence sites and timing, and survival were compared between patients who completed neoadjuvant therapy and pancreatectomy in 1998-2004, 2005-2011, and 2012-2018. The study included 727 patients (203, 251, and 273 in the 1998-2004, 2005-2011, and 2012-2018 cohorts, respectively). Use of neoadjuvant induction chemotherapy increased over time, and regimens changed over time, with >80% of patients treated in 2012-2018 receiving FOLFIRINOX or gemcitabine with nab-paclitaxel. Overall, recurrence sites and incidence (67.5%, 66.1%, and 65.9%) remained stable, and 85% of recurrences occurred within 2 years of surgery. However, compared to earlier cohorts, the 2012-2018 cohort had lower conditional risk of recurrence in postoperative year 1 and higher risk in postoperative year 2. Overall survival increased over time (median, 30.6, 33.6, and 48.7mo, P < 0.005), driven by improved post-recurrence overall survival (median, 7.8, 12.5, and 12.6mo; 3-year rate, 7%, 10%, and 20%; P < 0.005). We observed changes in neoadjuvant therapy regimens over time and an associated shift in the conditional risk of recurrence from postoperative year 1 to postoperative year 2, although recurrence remained common. Overall survival and post-recurrence survival remarkably improved over time, reflecting improved multimodality regimens for recurrent disease.