Toward Clinically Actionable Prediction of Recurrence and Metastatic Progression in Pancreatic Ductal Adenocarcinoma: A Systematic Review.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) has high rates of early recurrence (ER), occult metastasis, and poor survival despite curative-intent therapy. Predictive factors and models span clinical, biomarker, imaging, radiomics, pathologic, and molecular domains, but clinical readiness remains uncertain.

METHODS

We performed a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Five databases were searched for studies evaluating predictors or models of PDAC recurrence, metastasis, lymph node metastasis (LNM), occult metastatic disease, disease-free survival (DFS) or recurrence-free survival, or recurrence patterns. Studies were screened and coded for end point, modality, model type, validation, discrimination, calibration, clinical utility, and predictor timing.

RESULTS

Of 234 full-text records, 208 studies were included, comprising 144 prediction models and 64 predictor/prognostic factor studies. Computed tomography/radiomics (141/208), clinical/electronic health record variables (104/208), and serum/urine biomarkers (46/208) were the most common modalities. External validation, calibration, and decision-curve analyses were reported in 52, 36, and 38 model studies, respectively. AUCs ranged from 0.70 to 0.92 for ER, 0.75-0.95 for LNM, and 0.71-0.88 for liver or occult metastasis; DFS/relapse-free survival models had C-indices of 0.62-0.82. One externally validated occult-metastasis model had a C-statistic of 0.56. Model maturity was limited by retrospective design, heterogeneous end points, incomplete calibration reporting, and postoperative variables in preoperative models.

CONCLUSION

Prediction models for PDAC recurrence and metastatic progression are rapidly expanding, particularly through radiomics, machine learning, and multimodal modeling. Clinical translation requires decision-aligned design, transparent reporting, external validation, calibration, interpretability, and prospective evaluation of clinical utility.