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

[OBJECTIVE] We aimed to determine if advances in neoadjuvant therapy affected recurrence patterns and survival outcomes after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC).

[BACKGROUND] Data are limited on how modern multimodality therapy affects PDAC recurrence and postrecurrence survival.

[METHODS] 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 during 1998-2004, 2005-2011, and 2012-2018.

[RESULTS] The study included 727 patients (203, 251, and 273 in the 1998-2004, 2005-2011, and 2012-2018 cohorts, respectively). The 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 with earlier cohorts, the 2012-2018 cohort had a lower conditional risk of recurrence in postoperative year 1 and a higher risk in postoperative year 2. Overall survival increased over time (median, 30.6, 33.6, and 48.7 mo, P < 0.005), driven by improved postrecurrence overall survival (median, 7.8, 12.5, and 12.6 mo; 3-year rate, 7%, 10%, and 20%; P < 0.005).

[CONCLUSIONS] 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 postrecurrence survival remarkably improved over time, reflecting improved multimodality regimens for recurrent disease.