Abstract

PurposeQuantitative prostate-specific membrane antigen (PSMA) PET analysis may provide for non-invasive and objective risk stratification of primary prostate cancer (PCa) patients. We determined the ability of machine learning-based analysis of quantitative [18F]DCFPyL PET metrics to predict metastatic disease or high-risk pathological tumor features.MethodsIn a prospective cohort study, 76 patients with intermediate- to high-risk PCa scheduled for robot-assisted radical prostatectomy with extended pelvic lymph node dissection underwent pre-operative [18F]DCFPyL PET-CT. Primary tumors were delineated using 50–70% peak isocontour thresholds on images with and without partial-volume correction (PVC). Four hundred and eighty standardized radiomic features were extracted per tumor. Random forest models were trained to predict lymph node involvement (LNI), presence of any metastasis, Gleason score ≥ 8, and presence of extracapsular extension (ECE). For comparison, models were also trained using standard PET features (SUVs, volume, total PSMA uptake). Model performance was validated using 50 times repeated 5-fold cross-validation yielding the mean receiver-operator characteristic curve AUC.ResultsThe radiomics-based machine learning models predicted LNI (AUC 0.86 ± 0.15, p < 0.01), nodal or distant metastasis (AUC 0.86 ± 0.14, p < 0.01), Gleason score (0.81 ± 0.16, p < 0.01), and ECE (0.76 ± 0.12, p < 0.01). The highest AUCs reached using standard PET metrics were lower than those of radiomics-based models. For LNI and metastasis prediction, PVC and a higher delineation threshold improved model stability. Machine learning pre-processing methods had a minor impact on model performance.ConclusionMachine learning-based analysis of quantitative [18F]DCFPyL PET metrics can predict LNI and high-risk pathological tumor features in primary PCa patients. These findings indicate that PSMA expression detected on PET is related to both primary tumor histopathology and metastatic tendency. Multicenter external validation is needed to determine the benefits of using radiomics versus standard PET metrics in clinical practice.

Highlights

  • In primary prostate cancer (PCa), risk stratification is crucial to determine prognosis and treatment strategies

  • We investigated whether machine learning-based analysis of quantitative [18F]DCFPyL positron emission tomography computed tomography (PET-CT) data predicts metastatic disease and high-risk tumor features in patients with intermediate- and high-risk primary PCa scheduled to undergo robot-assisted radical prostatectomy and Extended pelvic lymph node dissection (ePLND)

  • The present study demonstrates that quantitative [18F]DCFPyL PET-CT metrics predict disease risk in primary PCa patients, indicating that prostate-specific membrane antigen (PSMA) expression detected on PET is related to both local tumor histopathology and metastatic tendency

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Summary

Introduction

In primary prostate cancer (PCa), risk stratification is crucial to determine prognosis and treatment strategies. Extended pelvic lymph node dissection (ePLND) is the current standard for identification of lymph node metastases [1,2,3]. This procedure, is invasive and associated with complications such as lymphocele, venous thrombosis, and extended hospital stays [4, 5]. Patients at risk for lymph node involvement (LNI) are selected using clinical nomograms, but these lack adequate performance [3]. Histopathology data (e.g., Gleason score, GS) used as input for these nomograms are based on error-prone prostate biopsies [6]. A novel biomarker able to pre-operatively stratify high- and low-risk patients is highly needed

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