Perineural invasion as a candidate prognostic marker beyond AJCC 8 staging in resected duodenal adenocarcinoma: a single-center retrospective cohort study

Background. Duodenal adenocarcinoma (DA) is a rare gastrointestinal malignancy with limited DA-specific evidence on the prognostic role of perineural invasion (PNI) and the performance of AJCC 8th-edition staging. We described PNI, AJCC 8 discrimination, and adjuvant-chemotherapy subgroup associations in a single-center cohort. Methods. We retrospectively analyzed 51 patients with curatively resected, histologically invasive DA (2013-2025). Overall survival (OS) and disease-free survival (DFS) were estimated by Kaplan-Meier analysis; prognostic associations by Cox regression. Model discrimination was quantified by the C-index; adjuvant-chemotherapy associations were explored across pre-specified subgroups. Analyses were exploratory and hypothesis-generating. Results. Median follow-up was 34.9 months; 26 patients (51%) died and 32 (63%) recurred, with the highest recurrence frequency 6-12 months after surgery. AJCC 8 staging discriminated modestly (C-index 0.595); no adjacent stage pair differed significantly after Bonferroni correction (minimum raw pairwise P = 0.051). Among candidate factors, PNI had the largest effect estimate (univariable HR 2.08, 95% CI 0.88-4.90, P = 0.095) and the largest incremental discrimination when added to a stage + T + N base model (delta C-index +0.062; likelihood-ratio P = 0.145), exceeding the increments from tumor size (+0.046), differentiation (+0.034), and sex (+0.016). Adjuvant chemotherapy was associated with hazard-ratio reductions in PNI-positive (HR 0.19, 95% CI 0.02-1.59), stage III (HR 0.36, 95% CI 0.12-1.15), and node-positive (HR 0.36, 95% CI 0.12-1.15) subgroups; none reached statistical significance, consistent with limited power in subgroups of 8-22 patients. Conclusion. In this small single-center cohort, PNI showed the largest prognostic effect estimate among candidate variables and the largest incremental discrimination beyond AJCC 8 stage, although neither reached statistical significance and AJCC 8 discriminated only modestly. These hypothesis-generating findings - directionally concordant with larger published DA series - support formal evaluation of PNI as a stratification variable in multicenter cohorts and in individual-patient-data meta-analyses of duodenal adenocarcinoma, rather than a change in current practice.