Machine learning-based prediction of invisible intraprostatic prostate cancer lesions on 68 Ga-PSMA-11 PET/CT in patients with primary prostate cancer

68 Ga-PSMA PET/CT has high specificity and sensitivity for the detection of both intraprostatic tumor focal lesions and metastasis. However, approximately 10% of primary prostate cancer are invisible on PSMA-PET (exhibit no or minimal uptake). In this work, we investigated whether machine learning-based radiomics models derived from PSMA-PET images could predict invisible intraprostatic lesions on 68 Ga-PSMA-11 PET in patients with primary prostate cancer.In this retrospective study, patients with or without prostate cancer who underwent 68 Ga-PSMA PET/CT and presented negative on PSMA-PET image at either of two different institutions were included: institution 1 (between 2017 and 2020) for the training set and institution 2 (between 2019 and 2020) for the external test set. Three random forest (RF) models were built using selected features extracted from standard PET images, delayed PET images, and both standard and delayed PET images. Then, subsequent tenfold cross-validation was performed. In the test phase, the three RF models and PSA density (PSAD, cut-off value: 0.15 ng/ml/ml) were tested with the external test set. The area under the receiver operating characteristic curve (AUC) was calculated for the models and PSAD. The AUCs of the radiomics model and PSAD were compared.A total of 64 patients (39 with prostate cancer and 25 with benign prostate disease) were in the training set, and 36 (21 with prostate cancer and 15 with benign prostate disease) were in the test set. The average AUCs of the three RF models from tenfold cross-validation were 0.87 (95% CI: 0.72, 1.00), 0.86 (95% CI: 0.63, 1.00), and 0.91 (95% CI: 0.69, 1.00), respectively. In the test set, the AUCs of the three trained RF models and PSAD were 0.903 (95% CI: 0.830, 0.975), 0.856 (95% CI: 0.748, 0.964), 0.925 (95% CI:0.838, 1.00), and 0.662 (95% CI: 0.510, 0.813). The AUCs of the three radiomics models were higher than that of PSAD (0.903, 0.856, and 0.925 vs. 0.662, respectively; P = .007, P = .045, and P = .005, respectively).Random forest models developed by 68 Ga-PSMA-11 PET-based radiomics features were proven useful for accurate prediction of invisible intraprostatic lesion on 68 Ga-PSMA-11 PET in patients with primary prostate cancer and showed better diagnostic performance compared with PSAD.