Tailoring Adjuvant Chemotherapy After Pancreatic Cancer Resection Using Morphology-Based Risk Stratification

Adjuvant chemotherapy (ACT) is the standard of care after resection for pancreatic ductal adenocarcinoma (PDAC); however, not all patients may derive equal benefit. This study explored morphological parameters to help tailor ACT indications. This retrospective study included patients who underwent upfront resection for PDAC between 2013 and 2019 at two tertiary centers. Independent prognostic factors were identified using multivariable Cox regression. Optimal cut-offs were determined via maximally selected log-rank statistics. The impact of ACT on overall survival (OS) was evaluated in subgroups stratified by prognostic determinants. Among 326 included patients, 62.3% received ACT. Independent OS predictors included resection margin status (HR = 4.89, p < 0.001), lymph node ratio (LNR) (HR = 20.6, p < 0.001), tumor grade, multivisceral resection, and ACT. Notably, in a specific subgroup combining R0 resection with highly favorable nodal parameters (N0 with ≥ 19 examined lymph nodes, or N+ with LNR ≤ 0.0833), ACT did not significantly improve OS (HR = 0.78, p = 0.296). These hypothesis-generating findings suggest that precise morphology-based risk stratification might identify a PDAC subpopulation deriving limited benefit from ACT. While rigorous prospective validation is required, these criteria offer a framework for future trials exploring personalized, de-escalated systemic therapy.