Amogh Hiremath1, Rakesh Shiradkar1, Pingfu Fu2, Amr Mahran3, Ardeshir R Rastinehad4, Ashutosh Tewari5, Sree Harsha Tirumani6, Andrei Purysko7, Lee Ponsky3, Anant Madabhushi8. 1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA. 2. Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA. 3. Urology Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA. 4. Department of Urology, Lenox Hill Hospital, Northwell Health, New York, NY, USA. 5. Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 6. Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA. 7. Department of Radiology and Nuclear Medicine, Cleveland Clinic, Cleveland, OH, USA. 8. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA; Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH, USA. Electronic address: axm788@case.edu.
Abstract
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 & 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.
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 & 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.
Authors: Indrani Bhattacharya; Yash S Khandwala; Sulaiman Vesal; Wei Shao; Qianye Yang; Simon J C Soerensen; Richard E Fan; Pejman Ghanouni; Christian A Kunder; James D Brooks; Yipeng Hu; Mirabela Rusu; Geoffrey A Sonn Journal: Ther Adv Urol Date: 2022-10-10