Added Value of [18F]PSMA-1007 PET/CT and PET/MRI in Patients With Biochemically Recurrent Prostate Cancer: Impact on Detection Rates and Clinical Management.

BACKGROUND: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) can change management in a large fraction of patients with biochemically recurrent prostate cancer (BCR). PURPOSE: To investigate the added value of PET to MRI and CT for this patient group, and to explore whether the choice of the PET paired modality (PET/MRI vs. PET/CT) impacts detection rates and clinical management. STUDY TYPE: Retrospective. SUBJECTS: 41 patients with BCR (median age [range]: 68 [55-78]). FIELD STRENGTH/SEQUENCE: 3T, including T1-weighted gradient echo (GRE), T2-weighted turbo spin echo (TSE) and dynamic contrast-enhanced GRE sequences, diffusion-weighted echo-planar imaging, and a T1-weighted TSE spine sequence. In addition to MRI, [18F]PSMA-1007 PET and low-dose CT were acquired on the same day. ASSESSMENT: Images were reported using a five-point Likert scale by two teams each consisting of a radiologist and a nuclear medicine physician. The radiologist performed a reading using CT and MRI data and a joint reading between radiologist and nuclear medicine physician was performed using MRI, CT, and PET from either PET/MRI or PET/CT. Findings were presented to an oncologist to create intended treatment plans. Intrareader and interreader agreement analysis was performed. STATISTICAL TESTS: McNemar test, Cohen's κ, and intraclass correlation coefficients. A P-value <0.05 was considered significant. RESULTS: 7 patients had positive findings on MRI and CT, 22 patients on joint reading with PET/CT, and 18 patients joint reading with PET/MRI. For overall positivity, interreader agreement was poor for MR and CT (κ = 0.36) and almost perfect with addition of PET (PET/CT κ = 0.85, PET/MRI κ = 0.85). The addition of PET from PET/CT and PET/MRI changed intended treatment in 20 and 18 patients, respectively. Between joint readings, intended treatment was different for eight patients. DATA CONCLUSION: The addition of [18F]PSMA-1007 PET/MRI or PET/CT to MRI and CT may increase detection rates, could reduce interreader variability, and may change intended treatment in half of patients with BCR. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

The impact of pre-processing and disease characteristics on reproducibility of T2-weighted MRI radiomics features.

PURPOSE: To evaluate the reproducibility of radiomics features derived via different pre-processing settings from paired T2-weighted imaging (T2WI) prostate lesions acquired within a short interval, to select the setting that yields the highest number of reproducible features, and to evaluate the impact of disease characteristics (i.e., clinical variables) on features reproducibility. MATERIALS AND METHODS: A dataset of 50 patients imaged using T2WI at 2 consecutive examinations was used. The dataset was pre-processed using 48 different settings. A total of 107 radiomics features were extracted from manual delineations of 74 lesions. The inter-scan reproducibility of each feature was measured using the intra-class correlation coefficient (ICC), with ICC values > 0.75 considered good. Statistical differences were assessed using Mann-Whitney U and Kruskal-Wallis tests. RESULTS: The pre-processing parameters strongly influenced the reproducibility of radiomics features of T2WI prostate lesions. The setting that yielded the highest number of features (25 features) with high reproducibility was the relative discretization with a fixed bin number of 64, no signal intensity normalization, and outlier filtering by excluding outliers. Disease characteristics did not significantly impact the reproducibility of radiomics features. CONCLUSION: The reproducibility of T2WI radiomics features was significantly influenced by pre-processing parameters, but not by disease characteristics. The selected pre-processing setting yielded 25 reproducible features.

Pseudo-T2 mapping for normalization of T2-weighted prostate MRI.

OBJECTIVE: Signal intensity normalization is necessary to reduce heterogeneity in T2-weighted (T2W) magnetic resonance imaging (MRI) for quantitative analysis of multicenter data. AutoRef is an automated dual-reference tissue normalization method that normalizes transversal prostate T2W MRI by creating a pseudo-T2 map. The aim of this study was to evaluate the accuracy of pseudo-T2s and multicenter standardization performance for AutoRef with three pairs of reference tissues: fat/muscle (AutoRefF), femoral head/muscle (AutoRefFH) and pelvic bone/muscle (AutoRefPB). MATERIALS AND METHODS: T2s measured by multi-echo spin echo (MESE) were compared to AutoRef pseudo-T2s in the whole prostate (WP) and zones (PZ and TZ/CZ/AFS) for seven asymptomatic volunteers with a paired Wilcoxon signed-rank test. AutoRef normalization was assessed on T2W images from a multicenter evaluation set of 1186 prostate cancer patients. Performance was measured by inter-patient histogram intersections of voxel intensities in the WP before and after normalization in a selected subset of 80 cases. RESULTS: AutoRefFH pseudo-T2s best approached MESE T2s in the volunteer study, with no significant difference shown (WP: p = 0.30, TZ/CZ/AFS: p = 0.22, PZ: p = 0.69). All three AutoRef versions increased inter-patient histogram intersections in the multicenter dataset, with median histogram intersections of 0.505 (original data), 0.738 (AutoRefFH), 0.739 (AutoRefF) and 0.726 (AutoRefPB). DISCUSSION: All AutoRef versions reduced variation in the multicenter data. AutoRefFH pseudo-T2s were closest to experimentally measured T2s.

Relative Enhanced Diffusivity in Prostate Cancer: Protocol Optimization and Diagnostic Potential.

BACKGROUND: Relative enhanced diffusivity (RED) is a potential biomarker for indirectly measuring perfusion in tissue using diffusion-weighted magnetic resonance imaging (MRI) with 3 b values. PURPOSE: To optimize the RED MRI protocol for the prostate, and to investigate its potential for prostate cancer (PCa) diagnosis. STUDY TYPE: Prospective. POPULATION: Ten asymptomatic healthy volunteers and 35 patients with clinical suspicion of PCa. SEQUENCE: 3T T2 - and diffusion-weighted MRI with b values: b = 0, 50, [100], 150, [200], 250, [300], 400, 800 s/mm2 (values in brackets were only used for patients). ASSESSMENT: Monte Carlo simulations were performed to assess noise sensitivity of RED as a function of intermediate b value. Volunteers were scanned 3 times to assess repeatability of RED. Patient data were used to investigate RED's potential for discriminating between biopsy-confirmed cancer and healthy tissue, and between true and false positive radiological findings. STATISTICAL TESTS: Within-subject coefficient of variation (WCV) to assess repeatability and receiver-operating characteristic curve analysis and logistic regression to assess diagnostic performance of RED. RESULTS: The repeatability was acceptable (WCV = 0.2-0.3) for all intermediate b values tested, apart from b = 50 s/mm2 (WCV = 0.3-0.4). The simulated RED values agreed well with the experimental data, showing that an intermediate b value between 150-250 s/mm2 minimizes noise sensitivity in both peripheral zone (PZ) and transition zone (TZ). RED calculated with the b values 0, 150 and 800 s/mm2 was significantly higher in tumors than in healthy tissue in both PZ (P < 0.001, area under the curve [AUC] = 0.85) and PZ + TZ (P < 0.001, AUC = 0.84). RED was shown to aid apparent diffusion coefficient (ADC) in differentiating between false-positive findings and true-positive PCa in the PZ (AUC; RED = 0.71, ADC = 0.74, RED+ADC = 0.77). DATA CONCLUSION: RED is a repeatable biomarker that may have value for prostate cancer diagnosis. An intermediate b value in the range of 150-250 s/mm2 minimizes the influence of noise and maximizes repeatability. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:1900-1910.

18F-Fluciclovine PET/MRI for preoperative lymph node staging in high-risk prostate cancer patients.

OBJECTIVE: To investigate the diagnostic potential of simultaneous 18F-fluciclovine PET/MRI for pelvic lymph node (LN) staging in patients with high-risk prostate cancer. METHODS: High-risk prostate cancer patients (n=28) underwent simultaneous 18F-fluciclovine PET/MRI prior to surgery. LNs were removed according to a predefined template of eight regions. PET and MR images were evaluated for presence of LN metastases according to these regions. Sensitivity/specificity for detection of LN metastases were calculated on patient and region basis. Sizes of LN metastases in regions with positive and negative imaging findings were compared with linear mixed models. Clinical parameters of PET-positive and -negative stage N1 patients were compared with the Mann-Whitney U test. RESULTS: Patient- and region-based sensitivity/specificity for detection of pelvic LN metastases was 40 %/87.5 % and 35 %/95.7 %, respectively, for MRI and 40 %/100 % and 30 %/100 %, respectively, for PET. LN metastases in true-positive regions were significantly larger than metastases in false-negative regions. PET-positive stage N1 patients had higher metastatic burden than PET-negative N1 patients. CONCLUSION: Simultaneous 18F-fluciclovine PET/MRI provides high specificity but low sensitivity for detection of LN metastases in high-risk prostate cancer patients. 18F-Fluciclovine PET/MRI scan positive for LN metastases indicates higher metastatic burden than negative scan. KEY POINTS: • 18F-Fluciclovine PET/MRI has high specificity for detection of lymph node metastasis. • 18F-Fluciclovine PET/MRI lacks sensitivity to replace ePLND. • 18F-Fluciclovine PET/MRI may be used to aid surgery and select adjuvant therapy. • 18F-Fluciclovine PET-positive patients have more extensive disease than PET-negative patients. • Size of metastatic lymph nodes is an important factor for detection.

En bloc radical cystectomy: An overview of the technique and oncological results.

Objectives: To reduce recurrence after radical cystectomy (RC), we developed a technique based on the principles of the circumferential resection margin used during total mesorectal excision for rectal cancer, namely, en bloc radical cystectomy (EbRC). Patients and methods: The study included all patients in Mid-Norway (population of 739 k) with high-grade superficial or muscle invasive bladder cancer considered for radical treatment according to European guidelines, from January 2012 to August 2021, except for three patients receiving trimodal therapy. One hundred forty-five patients were treated with EbRC and 188 patients with standard RC (stdRC). There were no exclusion criteria. Both groups included open and robot-assisted techniques. EbRC entails cystectomy with extended pelvic lymph node dissection. The technique focuses on systematic uninterrupted mobilisation of all lymphatic tissue from the circumferential resection margin towards the bladder pedicles, and resecting the tissue en bloc with the bladder. Results: The 3-year recurrence-free survival (RFS) was 86% for EbRC versus 67% for stdRC. The hazard ratio for overall survival in multivariable cox regression analyses after EbRC versus stdRC was 0.30 (95% CI 0.16-0.57, p ≤ 0.001). The improved outcomes persisted in propensity score-matched analyses. There were no differences in Clavien-Dindo 3 and 4 complications (12.4% vs. 11.7%), nor 90-day mortality (2.1% vs. 1.6%). Conclusion: Improved oncological results with EbRC versus stdRC mirror the historical data after total mesorectal excision was initiated over 35 years ago in rectal cancer surgery. EbRC is safe and the preliminary oncological results are promising.

Multiparametric Prostate MRI in Biopsy-Naïve Men: A Prospective Evaluation of Performance and Biopsy Strategies.

OBJECTIVES: This study aims to prospectively estimate the diagnostic performance of multiparametric prostate MRI (mpMRI) and compare the detection rates of prostate cancer using cognitive targeted transrectal ultrasound (TRUS) guided biopsies, targeted MR-guided in-bore biopsies (MRGB), or both methods combined in biopsy-naïve men. METHODS: The biopsy-naïve men referred for mpMRI (including T2-weighted, diffusion-weighted and dynamic contrast enhanced MRI) due to prostate cancer suspicion (elevated prostate-specific antigen or abnormal digital rectal examination) were eligible for inclusion. The images were scored according to Prostate Imaging Reporting and Data System (PI-RADS) v2, and men with PI-RADS 1-2 lesions were referred for routine systematic TRUS, while those with PI-RADS 3-5 lesions were randomized to MRGB or cognitive targeted TRUS. Men randomized to MRGB were referred to a secondary TRUS 2 weeks after MRGB. Gleason grade group ≥2 was defined as clinically significant prostate cancer. The performance of mpMRI was estimated using prostate cancer detected by any biopsy method as the reference test. RESULTS: A total of 210 men were included. There was no suspicion of prostate cancer after mpMRI (PI-RADS 1-2) in 48% of the men. Among these, significant and insignificant prostate cancer was diagnosed in five and 11 men, respectively. Thirty-five men who scored as PI-RADS 1-2 did not undergo biopsy and were therefore excluded from the calculation of diagnostic accuracy. The overall sensitivity, specificity, negative predictive value, and positive predictive value of mpMRI for the detection of significant prostate cancer were 0.94, 0.63, 0.92, and 0.67, respectively. In patients with PI-RADS 3-5 lesions, the detection rates for significant prostate cancer were not significantly different between cognitive targeted TRUS (68.4%), MRGB (57.7%), and the combination of the two biopsy methods (64.4%). The median numbers of biopsy cores taken per patient undergoing systematic TRUS, cognitive targeted TRUS, and MRGB were 14 [8-16], 12 [6-17], and 2 [1-4] respectively. CONCLUSIONS: mpMRI, in a cohort of biopsy-naïve men, has high negative predictive value, and our results support that it is safe to avoid biopsy after negative mpMRI. Furthermore, MRGB provides a similar diagnosis to the cognitive targeted TRUS but with fewer biopsies.

The Reproducibility of Deep Learning-Based Segmentation of the Prostate Gland and Zones on T2-Weighted MR Images.

Volume of interest segmentation is an essential step in computer-aided detection and diagnosis (CAD) systems. Deep learning (DL)-based methods provide good performance for prostate segmentation, but little is known about the reproducibility of these methods. In this work, an in-house collected dataset from 244 patients was used to investigate the intra-patient reproducibility of 14 shape features for DL-based segmentation methods of the whole prostate gland (WP), peripheral zone (PZ), and the remaining prostate zones (non-PZ) on T2-weighted (T2W) magnetic resonance (MR) images compared to manual segmentations. The DL-based segmentation was performed using three different convolutional neural networks (CNNs): V-Net, nnU-Net-2D, and nnU-Net-3D. The two-way random, single score intra-class correlation coefficient (ICC) was used to measure the inter-scan reproducibility of each feature for each CNN and the manual segmentation. We found that the reproducibility of the investigated methods is comparable to manual for all CNNs (14/14 features), except for V-Net in PZ (7/14 features). The ICC score for segmentation volume was found to be 0.888, 0.607, 0.819, and 0.903 in PZ; 0.988, 0.967, 0.986, and 0.983 in non-PZ; 0.982, 0.975, 0.973, and 0.984 in WP for manual, V-Net, nnU-Net-2D, and nnU-Net-3D, respectively. The results of this work show the feasibility of embedding DL-based segmentation in CAD systems, based on multiple T2W MR scans of the prostate, which is an important step towards the clinical implementation.

Detection of Recurrent Prostate Cancer With 18F-Fluciclovine PET/MRI.

OBJECTIVE: Simultaneous PET/MRI combines soft-tissue contrast of MRI with high molecular sensitivity of PET in one session. The aim of this prospective study was to evaluate detection rates of recurrent prostate cancer by 18F-fluciclovine PET/MRI. METHODS: Patients with biochemical recurrence (BCR) or persistently detectable prostate specific antigen (PSA), were examined with simultaneous 18F-fluciclovine PET/MRI. Multiparametric MRI (mpMRI) and PET/MRI were scored on a 3-point scale (1-negative, 2-equivocal, 3-recurrence/metastasis) and detection rates (number of patients with suspicious findings divided by total number of patients) were reported. Detection rates were further stratified based on PSA level, PSA doubling time (PSAdt), primary treatment and inclusion criteria (PSA persistence, European Association of Urology (EAU) Low-Risk BCR and EAU High-Risk BCR). A detailed investigation of lesions with discrepancy between mpMRI and PET/MRI scores was performed to evaluate the incremental value of PET/MRI to mpMRI. The impact of the added PET acquisition on further follow-up and treatment was evaluated retrospectively. RESULTS: Among patients eligible for analysis (n=84), 54 lesions were detected in 38 patients by either mpMRI or PET/MRI. Detection rates were 41.7% for mpMRI and 39.3% for PET/MRI (score 2 and 3 considered positive). There were no significant differences in detection rates for mpMRI versus PET/MRI. Disease detection rates were higher in patients with PSA≥1ng/mL than in patients with lower PSA levels but did not differ between patients with PSAdt above versus below 6 months. Detection rates in patients with primary radiation therapy were higher than in patients with primary surgery. Patients categorized as EAU Low-Risk BCR had a detection rate of 0% both for mpMRI and PET/MRI. For 15 lesions (27.8% of all lesions) there was a discrepancy between mpMRI score and PET/MRI score. Of these, 10 lesions scored as 2-equivocal by mpMRI were changed to a more definite score (n=4 score 1 and n=6 score 3) based on the added PET acquisition. Furthermore, for 4 of 10 patients with discrepancy between mpMRI and PET/MRI scores, the added PET acquisition had affected the treatment choice. CONCLUSION: Combined 18F-fluciclovine PET/MRI can detect lesions suspicious for recurrent prostate cancer in patients with a range of PSA levels. Combined PET/MRI may be useful to select patients for appropriate treatment, but is of limited use at low PSA values or in patients classified as EAU Low-Risk BCR, and the clinical value of 18F-fluciclovine PET/MRI in this study was too low to justify routine clinical use.

Prostate-Specific Membrane Antigen PET/Magnetic Resonance Imaging for the Planning of Salvage Radiotherapy in Patients with Prostate Cancer with Biochemical Recurrence After Radical Prostatectomy.

This article presents an overview of the current literature on PET imaging with prostate-specific membrane antigen ligands, especially focusing on the potential role of simultaneous PET/magnetic resonance imaging for the planning of salvage radiotherapy in patients with prostate cancer with biochemical recurrence after radical prostatectomy.