Delta radiomic patterns on serial bi-parametric MRI are associated with pathologic upgrading in prostate cancer patients on active surveillance: preliminary findings

ObjectiveThe aim of this study was to quantify radiomic changes in prostate cancer (PCa) progression on serial MRI among patients on active surveillance (AS) and evaluate their association with pathologic progression on biopsy.MethodsThis retrospective study comprised N = 121 biopsy-proven PCa patients on AS at a single institution, of whom N = 50 at baseline conformed to the inclusion criteria. ISUP Gleason Grade Groups (GGG) were obtained from 12-core TRUS-guided systematic biopsies at baseline and follow-up. A biopsy upgrade (AS+) was defined as an increase in GGG (or in number of positive cores) and no upgrade (AS−) was defined when GGG remained the same during a median period of 18 months. Of N = 50 patients at baseline, N = 30 had MRI scans available at follow-up (median interval = 18 months) and were included for delta radiomic analysis. A total of 252 radiomic features were extracted from the PCa region of interest identified by board-certified radiologists on 3T bi-parametric MRI [T2-weighted (T2W) and apparent diffusion coefficient (ADC)]. Delta radiomic features were computed as the difference of radiomic feature between baseline and follow-up scans. The association of AS+ with age, prostate-specific antigen (PSA), Prostate Imaging Reporting and Data System (PIRADS v2.1) score, and tumor size was evaluated at baseline and follow-up. Various prediction models were built using random forest (RF) classifier within a threefold cross-validation framework leveraging baseline radiomics (Cbr), baseline radiomics + baseline clinical (Cbrbcl), delta radiomics (CΔr), delta radiomics + baseline clinical (CΔrbcl), and delta radiomics + delta clinical (CΔrΔcl).ResultsAn AUC of 0.64 ± 0.09 was obtained for Cbr, which increased to 0.70 ± 0.18 with the integration of clinical variables (Cbrbcl). CΔr yielded an AUC of 0.74 ± 0.15. Integrating delta radiomics with baseline clinical variables yielded an AUC of 0.77 ± 0.23. CΔrΔclresulted in the best AUC of 0.84 ± 0.20 (p < 0.05) among all combinations.ConclusionOur preliminary findings suggest that delta radiomics were more strongly associated with upgrade events compared to PIRADS and other clinical variables. Delta radiomics on serial MRI in combination with changes in clinical variables (PSA and tumor volume) between baseline and follow-up showed the strongest association with biopsy upgrade in PCa patients on AS. Further independent multi-site validation of these preliminary findings is warranted

An integrated nomogram combining deep learning, Prostate Imaging–Reporting and Data System (PI-RADS) scoring, and clinical variables for identification of clinically significant prostate cancer on biparametric MRI: a retrospective multicentre study

Summary: Background: Biparametric MRI (comprising T2-weighted MRI and apparent diffusion coefficient maps) is increasingly being used to characterise prostate cancer. Although previous studies have combined Prostate Imaging–Reporting &amp; Data System (PI-RADS)-based MRI findings with routinely available clinical variables and with deep learning-based imaging predictors, respectively, for prostate cancer risk stratification, none have combined all three. We aimed to construct an integrated nomogram (referred to as ClaD) combining deep learning-based imaging predictions, PI-RADS scoring, and clinical variables to identify clinically significant prostate cancer on biparametric MRI. Methods: In this retrospective multicentre study, we included patients with prostate cancer, with histopathology or biopsy reports and a screening or diagnostic MRI scan in the axial view, from four cohorts in the USA (from University Hospitals Cleveland Medical Center, Icahn School of Medicine at Mount Sinai, Cleveland Clinic, and Long Island Jewish Medical Center) and from the PROSTATEx Challenge dataset in the Netherlands. We constructed an integrated nomogram combining deep learning, PI-RADS score, and clinical variables (prostate-specific antigen, prostate volume, and lesion volume) using multivariable logistic regression to identify clinically significant prostate cancer on biparametric MRI. We used data from the first three cohorts to train the nomogram and data from the remaining two cohorts for independent validation. We compared the performance of our ClaD integrated nomogram with that of integrated nomograms combining clinical variables with either the deep learning-based imaging predictor (referred to as DIN) or PI-RADS score (referred to as PIN) using area under the receiver operating characteristic curves (AUCs). We also compared the ability of the nomograms to predict biochemical recurrence on a subset of patients who had undergone radical prostatectomy. We report cross-validation AUCs as means for the training set and used AUCs with 95% CIs to assess the performance on the test set. The difference in AUCs between the models were tested for statistical significance using DeLong's test. We used log-rank tests and Kaplan-Meier curves to analyse survival. Findings: We investigated 592 patients (823 lesions) with prostate cancer who underwent 3T multiparametric MRI at five hospitals in the USA between Jan 8, 2009, and June 3, 2017. The training data set consisted of 368 patients from three sites (the PROSTATEx Challenge cohort [n=204], University Hospitals Cleveland Medical Center [n=126], and Icahn School of Medicine at Mount Sinai [n=38]), and the independent validation data set consisted of 224 patients from two sites (Cleveland Clinic [n=151] and Long Island Jewish Medical Center [n=73]). The ClaD clinical nomogram yielded an AUC of 0·81 (95% CI 0·76–0·85) for identification of clinically significant prostate cancer in the validation data set, significantly improving performance over the DIN (0·74 [95% CI 0·69–0·80], p=0·0005) and PIN (0·76 [0·71–0·81], p<0·0001) nomograms. In the subset of patients who had undergone radical prostatectomy (n=81), the ClaD clinical nomogram resulted in a significant separation in Kaplan-Meier survival curves between patients with and without biochemical recurrence (HR 5·92 [2·34–15·00], p=0·044), whereas the DIN (1·22 [0·54–2·79], p=0·65) and PIN nomograms did not (1·30 [0·62–2·71], p=0·51). Interpretation: Risk stratification of patients with prostate cancer using the integrated ClaD nomogram could help to identify patients with prostate cancer who are at low risk, very low risk, and favourable intermediate risk, who might be candidates for active surveillance, and could also help to identify patients with lethal prostate cancer who might benefit from adjuvant therapy. Funding: National Cancer Institute of the US National Institutes of Health, National Institute for Biomedical Imaging and Bioengineering, National Center for Research Resources, US Department of Veterans Affairs Biomedical Laboratory Research and Development Service, US Department of Defense, US National Institute of Diabetes and Digestive and Kidney Diseases, The Ohio Third Frontier Technology Validation Fund, Case Western Reserve University, Dana Foundation, and Clinical and Translational Science Collaborative