Progression of Site-specific Recurrence of Pancreatic Cancer and Implications for Treatment

Abstract

Objective: To analyze postrecurrence progression in the context of recurrence sites and assess implications for postrecurrence treatment.

Background: Most patients with resected pancreatic ductal adenocarcinoma (PDAC) recur within 2 years. Different survival outcomes for location-specific patterns of recurrence are reported, highlighting their prognostic value. However, a lack of understanding of postrecurrence progression and survival remains.

Methods: This retrospective analysis included surgically treated patients with PDAC at NYU Langone Health (2010-2021). Sites of recurrence were identified at the time of diagnosis and further follow-up. Kaplan-Meier curves, log-rank test, and Cox regression analyses were applied to assess survival outcomes.

Results: Recurrence occurred in 57.3% (196/342) patients with a median time to recurrence of 11.3 months (95% CI: 12.6-16.5). The first site of recurrence was local in 43.9% of patients, liver in 23.5%, peritoneal in 8.7%, lung in 3.6%, whereas 20.4% had multiple sites of recurrence. Progression to secondary sites was observed in 11.7%. Only lung involvement was associated with significantly longer survival after recurrence compared with other sites (16.9 vs 8.49 months, P = 0.003). In local recurrence, 21 (33.3%) patients were alive after 1 year without progression to secondary sites. This was associated with a CA19-9 of <100 U/mL at the time of primary diagnosis ( P = 0.039), nodal negative disease ( P = 0.023), and well-moderate differentiation ( P = 0.042) compared with patients with progression.

Conclusion: Except for lung recurrence, postrecurrence survival after PDAC resection is associated with poor survival. A subset of patients with local-only recurrence do not quickly succumb to systemic spread. This is associated with markers for favorable tumor biology, making them candidates for potential curative re-resections when feasible.

Figure 1:

Kaplan-Meier Curves for site-specific survival outcomes. A) describes Recurrence-free Survival (time from surgery to recurrence), B) Overall Survival (time from Surgery to death), and C) Survival after Recurrence (time recurrence to death). P-values are calculated for with log-rank test for multiple groups. Group comparisons yielded longer time to recurrence for liver versus local recurrence. Shorter survival after recurrence was observed for multiple sites of recurrence versus local and lung recurrence and peritoneal versus lung recurrence.

Figure 2:

Alluvial plot for post recurrence progression of disease. Time points were chosen for time of diagnosis of recurrence, 3 months, 6 months, and 12 months. Only patients with at least 12 months follow up or death after recurrence were included. This graph demonstrates that 33% of patients with local recurrence remain local for at least one year after recurrence whereas for other sites, fast progression to other sites or death is observed.