Machine learning-based analysis of ⁶⁸Ga-PSMA-11 PET/CT images for estimation of prostate tumor grade

Early diagnosis of prostate cancer, the most common malignancy in men, can improve patient outcomes. Since the tissue sampling procedures are invasive and sometimes inconclusive, an alternative image-based method can prevent possible complications and facilitate treatment management. We aim to propose a machine-learning model for tumor grade estimation based on ⁶⁸ Ga-PSMA-11 PET/CT images in prostate cancer patients. This study included 90 eligible participants out of 244 biopsy-proven prostate cancer patients who underwent staging ⁶⁸Ga-PSMA-11 PET/CT imaging. The patients were divided into high and low-intermediate groups based on their Gleason scores. The PET-only images were manually segmented, both lesion-based and whole prostate, by two experienced nuclear medicine physicians. Four feature selection algorithms and five classifiers were applied to Combat-harmonized and non-harmonized datasets. To evaluate the model's generalizability across different institutions, we performed leave-one-center-out cross-validation (LOOCV). The metrics derived from the receiver operating characteristic curve were used to assess model performance. In the whole prostate segmentation, combining the ANOVA algorithm as the feature selector with Random Forest (RF) and Extra Trees (ET) classifiers resulted in the highest performance among the models, with an AUC of 0.78 and 083, respectively. In the lesion-based segmentation, the highest AUC was achieved by MRMR feature selector + Linear Discriminant Analysis (LDA) and Logistic Regression (LR) classifiers (0.76 and 0.79, respectively). The LOOCV results revealed that both the RF_ANOVA and ET_ANOVA models showed high levels of accuracy and generalizability across different centers, with an average AUC value of 0.87 for the ET_ANOVA combination. Machine learning-based analysis of radiomics features extracted from ⁶⁸Ga-PSMA-11 PET/CT scans can accurately classify prostate tumors into low-risk and intermediate- to high-risk groups.