Survival benefit of recurrence-focused treatment after surgery for pancreatic ductal adenocarcinoma: A propensity score matched analysis of patients from a Dutch National and US institutional cohort

Background It is unclear whether recurrence-focused treatment (RFT) improves survival in all patients with recurrent pancreatic ductal adenocarcinoma (PDAC). This study aimed (1) to evaluate post-recurrence survival (PRS) in patients treated with RFT versus best supportive care (BSC)-only, and (2) to assess potential effect modification by prognosis at recurrence. Methods This observational cohort study included patients with local or distant recurrence after PDAC resection (2014-2022) at all Dutch pancreatic surgery centers and NYU Langone Health. Patients with unknown RFT or survival status were excluded. Prognosis at recurrence was defined using a previously established PRS risk score, stratifying patients into worse (≥174.5) and better (<174.5) prognostic subgroups. Propensity score matching (PSM) was performed in the overall cohort, and within subgroups. Median PRS in RFT versus BSC-only patients was estimated and compared using Kaplan-Meier curve analysis and the log-rank test. Multivariable Cox regression with robust standard errors clustered by matched pair was used to adjust for residual imbalance after PSM, with results presented as hazard ratios (HR) and 95% confidence intervals (95%CI). Results Overall, 1,423 patients were included. After PSM, 344 RFT patients were matched to 344 BSC-only patients. The multivariable analysis included ECOG performance score and country as a random effect. PRS was 10 (95%CI 9-12) months for RFT versus 4 (95%CI 3-4) months for BSC-only (adjusted HR0.38, 95%CI: 0.30-0.48, P<0.001). In the worse prognosis group, PRS was 10 (95%CI 9-11) versus 3 (95%CI 3-4) months (adjusted HR0.38, 95%CI: 0.30-0.50, P<0.001). In the better prognosis group, PRS was 18 (95%CI 12-27) months versus 8 (95%CI 4-14) months (adjusted HR0.24, 95%CI: 0.10-0.45, P<0.001). Conclusions Treatment for PDAC recurrence was associated with significantly longer PRS compared with BSC-only, irrespective of prognosis at recurrence. The survival benefit associated with RFT supports its consideration in the management of patients with PDAC recurrence