Impact of Different Primary Treatment Strategies on Recurrence-Focused Treatment of Pancreatic Ductal Adenocarcinoma

Background: Increased application of neoadjuvant therapy (NAT) and adjuvant therapy (AT) could limit treatment options for pancreatic ductal adenocarcinoma (PDAC) recurrence. This study aimed to identify patterns of recurrence-focused treatment and survival following different primary treatment strategies. Methods: All patients who underwent PDAC resection in the Netherlands (2014–2019) were included. Patients were divided into five groups according to their primary treatment strategy: (1) resection only, (2) gemcitabine-based NAT + resection, (3) FOLFIRINOX-based NAT + resection, (4) resection + gemcitabine-based AT, and (5) resection + FOLFIRINOX-based AT. Differences in recurrence-focused treatment and post-recurrence survival (PRS) were assessed using multivariable logistic and Cox-proportional hazards analyses and were presented as odds ratios (ORs) and hazard ratios (HRs) with corresponding 95% confidence intervals (95% CIs), respectively. Results: In total, 1739 patients (median follow-up of 51 [interquartile range 34–64] months) were included, of whom 1272 (73%) had disease recurrence. In these patients, recurrence-focused treatment was administered in 64/124 (52%) after FOLFIRINOX-based NAT compared with 74/410 (18%) with resection only (OR 4.13 [95% CI 3.34–5.12]; P<0.001), 29/70 (41%) with gemcitabine-based NAT (OR 1.61 [95% CI 1.21–2.15]; P<0.001), 239/604 (39%) with gemcitabine-based AT (OR 1.73 [95% CI 1.43–2.09]; P<0.001), and 24/64 (38%) with FOLFIRINOX-based AT (OR 1.44 [95% CI 1.06–1.95]; P=0.02). Recurrence-focused treatment was associated with a median PRS of 11 (95% CI 10–13) months compared with 3 (95% CI 2–3) months in patients with best supportive care (HR 0.31 [95% CI 0.26–0.37]; P<0.001). Conclusions: Recurrence-focused treatment differs between patients with PDAC who received different primary treatment strategies and is associated with improved PRS.