When survival models fail: An interpretable anomaly-detection approach for high-risk phenotypes in resected solid pseudopapillary tumors.

Authors

Claudio Ricci, Laura Alberici, Vincenzo D'Ambra, Carlo Ingaldi, Marco Fichera, Martina Casarotto, Federico Pisani, Riccardo Casadei

Published in

Surgery. Volume 197. Pages 110381. Jun 09, 2026. Epub Jun 09, 2026.

Abstract

Solid pseudopapillary tumor of the pancreas is a rare neoplasm with an excellent prognosis after resection. Conventional survival models are unreliable because of the low number of cancer-specific deaths. This study aimed to identify clinicopathologic patterns associated with the "high-risk phenotype" through an interpretable anomaly-detection framework.
Patients undergoing pancreatic resection for solid pseudopapillary tumors were identified from the Surveillance, Epidemiology, and End Results registry (2000-2021). Cancer-specific death was modeled as an ultrarare event using 2 unsupervised algorithms: Isolation Forest and Local Outlier Factor. Group differences in anomaly scores were assessed using the Mann-Whitney U test with Cliff's δ as effect size. Feature relevance was explored using a Random Forest surrogate model with SHapley Additive exPlanations interpretation. The final calculator was externally validated on a cohort reconstructed through a systematic review.
In the Surveillance, Epidemiology, and End Results cohort (n = 387), patients who died from solid pseudopapillary tumors showed significantly higher anomaly scores (Isolation Forest = -0.07 ± 0.06 vs 0.02 ± 0.05; P = .007; δ = 0.783). The most influential contributors to the death-like anomaly pattern were lymph node ratio (0.204 ± 0.083), hospital type (0.168 ± 0.037), male sex (0.130 ± 0.028), atypical resection (0.120 ± 0.028), and stage IV disease (0.096 ± 0.047). The model achieved an in-sample area under the receiver operating characteristic curve of 0.892, a cross-validation area under the receiver operating characteristic curve of 0.733 ± 0.351, and an external-validation area under the receiver operating characteristic curve of 0.975.
An interpretable anomaly-detection approach can identify hidden high-risk phenotypes within apparently indolent diseases. In resected pancreatic solid pseudopapillary tumors, elevated lymph node ratio, treatment in nonmetropolitan settings, and male sex define the "high-risk phenotype."

PMID:
42407332
Bibliographic data and abstract were imported from PubMed on 07 Jul 2026.

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