Machine learning models for enhanced diagnosis and risk assessment of prostate cancer with ⁶⁸Ga-PSMA-617 PET/CT

Prostate cancer (PCa) is highly heterogeneous, making early detection of adverse pathological features crucial for improving patient outcomes. This study aims to predict PCa aggressiveness and identify radiomic and protein biomarkers associated with poor pathology, ultimately developing a multi-omics marker model for better clinical risk stratification.

In this retrospective study, 191 patients with PCa or benign prostatic hyperplasia confirmed via ⁶⁸Ga-PSMA-617 PET/CT scans were analyzed. Radiomic features were extracted from scan contours, and six machine learning algorithms were used to predict malignancy and adverse pathological features like Gleason score, ISUP group, tumor stage, lymph node infiltration, and perineural invasion. Feature selection and dimensionality reduction were performed using minimum redundancy maximum relevance and least absolute shrinkage and selection operator methods. Proteomics analysis on 39 patients identified protein biomarkers, followed by correlation analysis between radiomic features and identified proteins.

The radiomics model showed an AUC of 0.938 for predicting malignant prostate lesions and 0.916 for adverse pathological features in the test set, with validation set AUCs of 0.918 and 0.855, respectively. Three quantitative radiomic features and ten protein molecules associated with adverse pathology were identified, with significant correlations observed between radiomic features and protein biomarkers. Radioproteomic analysis revealed that molecular changes in protein molecules could influence imaging biomarkers.

The machine learning models based on 68 Ga-PSMA-617 PET/CT radiomic features performed well in stratifying patients, supporting clinical risk stratification and highlighting connections between radiomic characteristics and protein biomarkers.