Prognostic stratification and treatment patterns in pancreatic adenocarcinoma with mixed subtypes based on an exploratory retrospective cohort study

Abstract Background Pancreatic adenocarcinoma with mixed subtypes (p‑AMs) is a rare malignancy, and evidence to guide clinical management remains lacking. This study aimed to develop a prognostic model and explore treatment patterns across risk strata. Methods Using the Surveillance, Epidemiology, and End Results (SEER) database, we developed a treatment‑free baseline nomogram based on independent prognostic factors identified by multivariable Cox regression. Patients were stratified into low‑ and high‑risk groups according to the median risk score. Treatment effects were then explored within each risk stratum using the log‑rank test, with P values adjusted for multiple comparisons. Results Age, tumor grade, and M status were incorporated into a nomogram that demonstrated a bootstrap‑corrected C‑index of 0.609 (95% CI: 0.554–0.665). The high‑risk group ( n = 60) showed significantly worse survival than the low‑risk group ( n = 91; log‑rank P = 0.008). In the low‑risk group, trimodal therapy (surgery + chemotherapy + radiotherapy) was associated with more favorable survival compared with surgery only (HR = 0.48,95%CI:0.24–0.97, P = 0.04) and surgery plus chemotherapy ((HR = 0.46,95%CI: 0.25–0.83, P = 0.01). No significant difference was observed between surgery only and surgery plus chemotherapy in either the low‑risk ( P = 0.96) or high‑risk ( P = 0.52) group. Conclusion Our findings suggest that a treatment‑free baseline nomogram may assist in stratifying p‑AMs patients by prognostic risk, though this observation requires further validation. Within this exploratory framework, the addition of chemotherapy to surgery did not appear to confer additional survival benefit. The association between trimodal therapy and improved outcomes in the low‑risk group raises the hypothesis that radiotherapy may warrant further investigation in selected patients.