Unilateral Pelvic Lymph Node Dissection in Prostate Cancer Patients Diagnosed in the Era of Magnetic Resonance Imaging-targeted Biopsy: A Study That Challenges the Dogma.

PURPOSE: Bilateral extended pelvic lymph node dissection at the time of radical prostatectomy is the current standard of care if pelvic lymph node dissection is indicated; often, however, pelvic lymph node dissection is performed in pN0 disease. With the more accurate staging achieved with magnetic resonance imaging-targeted biopsies for prostate cancer diagnosis, the indication for bilateral extended pelvic lymph node dissection may be revised. We aimed to assess the feasibility of unilateral extended pelvic lymph node dissection in the era of modern prostate cancer imaging. MATERIALS AND METHODS: We analyzed a multi-institutional data set of men with cN0 disease diagnosed by magnetic resonance imaging-targeted biopsy who underwent prostatectomy and bilateral extended pelvic lymph node dissection. The outcome of the study was lymph node invasion contralateral to the prostatic lobe with worse disease features, ie, dominant lobe. Logistic regression to predict lymph node invasion contralateral to the dominant lobe was generated and internally validated. RESULTS: Overall, data from 2,253 patients were considered. Lymph node invasion was documented in 302 (13%) patients; 83 (4%) patients had lymph node invasion contralateral to the dominant prostatic lobe. A model including prostate-specific antigen, maximum diameter of the index lesion, seminal vesicle invasion on magnetic resonance imaging, International Society of Urological Pathology grade in the nondominant side, and percentage of positive cores in the nondominant side achieved an area under the curve of 84% after internal validation. With a cutoff of contralateral lymph node invasion of 1%, 602 (27%) contralateral pelvic lymph node dissections would be omitted with only 1 (1.2%) lymph node invasion missed. CONCLUSIONS: Pelvic lymph node dissection could be omitted contralateral to the prostate lobe with worse disease features in selected patients. We propose a model that can help avoid contralateral pelvic lymph node dissection in almost one-third of cases.

When to order genomic tests: development and external validation of a model to predict high-risk prostate cancer at the genotypic level.

PURPOSE: The aim of this study was to develop a model to predict high-genomic-risk prostate cancer (PCa) according to Decipher score, a validated 22 gene prognostic panel. By doing so, one might select the individuals who are likely to benefit from genomic testing and improve pre-op counseling about the need for adjuvant treatments. METHODS: We retrospectively reviewed IRB-approved databases at two institutions. All patients had preoperative magnetic resonance imaging (MRI) and Decipher prostate radical prostatectomy (RP), a validated 22 gene prognostic panel. We used binary logistic regression to estimate high-risk Decipher (Decipher score > 0.60) probability on RP specimen. Area under the curve (AUC) and calibration were used to assess the accuracy of the model in the development and validation cohort. Decision curve analysis (DCA) was performed to assess the clinical benefit of the model. RESULTS: The development and validation cohort included 622 and 185 patients with 283 (35%) and 80 (43%) of those with high-risk Decipher. The multivariable model included PSA density, biopsy Gleason Grade Group, percentage of positive cores and MRI extracapsular extension. AUC was 0.73 after leave-one-out cross-validation. DCA showed a clinical benefit in a range of probabilities between 15 and 60%. In the external validation cohort, AUC was 0.70 and calibration showed that the model underestimates the actual probability of the outcome. CONCLUSIONS: The proposed model to predict high-risk Decipher score at RP is helpful to improve risk stratification of patients with PCa and to assess the need for additional testing and treatments.

Diagnosis of prostate cancer with magnetic resonance imaging in men treated with 5-alpha-reductase inhibitors.

PURPOSE: The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2). METHODS: This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients. RESULTS: 705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1-2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively. CONCLUSIONS: Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions. TRIAL REGISTRATION: The present study was registered at ClinicalTrials.gov number: NCT05078359.

Value of 68Ga-labeled bombesin antagonist (RM2) in the detection of primary prostate cancer comparing with [18F]fluoromethylcholine PET-CT and multiparametric MRI-a phase I/II study.

OBJECTIVES: The bombesin derivative RM2 is a GRPr antagonist with strong binding affinity to prostate cancer (PCa). In this study, the impact of [68Ga]Ga-RM2 positron emission tomography-computed tomography (PET-CT) for the detection of primary PCa was compared with that of [18F]FCH PET-CT and multiparametric magnetic resonance imaging (mpMRI). METHODS: This phase I/II study was conducted in 30 biopsy-positive PCa subjects. The patients were stratified into high (10 patients), intermediate (10 patients), and low risk (10 patients) for extraglandular metastases as defined by National Comprehensive Cancer Network (NCCN) criteria (NCCN Clinical Practice Guidelines in Oncology, 2016). The prostate gland was classified in 12 anatomic segments for data analysis of the imaging modalities as well as histopathologic findings. The segment with the highest radiotracer uptake was defined as the "index lesion." All cases were scheduled to undergo prostatectomy with pelvic lymph node (LN) dissection in intermediate- and high-risk patients. Intraprostatic and pelvic nodal [68Ga]Ga-RM2 and [18F]FCH PET-CT findings were correlated with mpMRI and histopathologic results. RESULTS: Of the 312 analyzed regions, 120 regions (4 to 8 lesions per patient) showed abnormal findings in the prostate gland. In a region-based analysis, overall sensitivity and specificity of [68Ga]Ga-RM2 PET-CT in the detection of primary tumor were 74% and 90%, respectively, while it was 60% and 80% for [18F]FCH PET-CT and 72% and 89% for mpMRI. Although the overall sensitivity of [68Ga]Ga-RM2 PET-CT was higher compared to that of [18F]FCH PET-CT and mpMRI, the statistical analysis showed only significant difference between [68Ga]Ga-RM2 PET-CT and [18F]FCH PET-CT in the intermediate-risk group (p = 0.01) and [68Ga]Ga-RM2 PET-CT and mpMRT in the high-risk group (p = 0.03). In the lesion-based analysis, there was no significant difference between SUVmax of [68Ga]Ga-RM2 and [18F]FCH PET-CT in the intraprostatic malignant lesions ([68Ga]Ga-RM2: mean SUVmax: 5.98 ± 4.13, median: 4.75; [18F]FCH: mean SUVmax: 6.08 ± 2.74, median: 5.5; p = 0.13). CONCLUSIONS: [68Ga]Ga-RM2 showed promising PET tracer for the detection of intraprostatic PCa in a cohort of patients with different risk stratifications. However, significant differences were only found between [68Ga]Ga-RM2 PET-CT and [18F]FCH PET-CT in the intermediate-risk group and [68Ga]Ga-RM2 PET-CT and mpMRT in the high-risk group. In addition, GRP-R-based imaging seems to play a complementary role to choline-based imaging for full characterization of PCa extent and biopsy guidance in low- and intermediate-metastatic-risk PCa patients and has the potential to discriminate them from those at higher risks. KEY POINTS: • [68Ga]Ga-RM2 is a promising PET tracer with a high detection rate for intraprostatic PCa especially in intermediate-risk prostate cancer patients. • GRPr-based imaging seems to play a complementary role to choline-based or PSMA-based PET/CT imaging in selected low- and intermediate-risk PCa patients for better characterization and eventually biopsy guidance of prostate cancer disease.

Prostate MRI percentage tumor involvement or "PI-RADS percent" as a predictor of adverse surgical pathology.

BACKGROUND: This study assesses magnetic resonance imaging (MRI) prostate % tumor involvement or "PI-RADs percent" as a predictor of adverse pathology (AP) after surgery for localized prostate cancer (PCa). Two separate variables, "All PI-RADS percent" (APP) and "Highest PI-RADS percent" (HPP), are defined as the volume of All PI-RADS 3-5 score lesions on MRI and the volume of the Highest PI-RADS 3-5 score lesion each divided by TPV, respectively. METHOD: An analysis was done of an IRB approved prospective cohort of 557 patients with localized PCa who had targeted biopsy of MRI PIRADs 3-5 lesions followed by RARP from April 2015 to May 2020 performed by a single surgeon at a single center. AP was defined as ISUP GGG ≥3, pT stage ≥T3 and/or LNI. Univariate and multivariable analyses were used to evaluate APP and HPP at predicting AP with other clinical variables such as Age, PSA at surgery, Race, Biopsy GGG, mpMRI ECE and mpMRI SVI. Internal and External Validation demonstrated predicted probabilities versus observed probabilities. RESULTS: AP was reported in 44.5% (n = 248) of patients. Multivariable regression showed both APP (odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.04-1.14, p = 0.0007) and HPP (OR: 1.10; 95% CI: 1.04-1.16; p = 0.0007) were significantly associated with AP with individual area under the operating curves (AUCs) of 0.6142 and 0.6229, respectively, and AUCs of 0.8129 and 0.8124 when incorporated in models including preoperative PSA and highest biopsy GGG. CONCLUSIONS: Increasing PI-RADS Percent was associated with a higher risk of AP, and both APP and HPP may have clinical utility as predictors of AP in GGG 1 and 2 patients being considered for AS. PATIENT SUMMARY: Using PIRADs percent to predict AP for presurgical patients may help risk stratification, and for low and low volume intermediate risk patients, may influence treatment decisions.

Detection of Prostate Cancer Using Biparametric Prostate MRI, Radiomics, and Kallikreins: A Retrospective Multicenter Study of Men With a Clinical Suspicion of Prostate Cancer.

BACKGROUND: Accurate detection of clinically significant prostate cancer (csPCa), Gleason Grade Group ≥ 2, remains a challenge. Prostate MRI radiomics and blood kallikreins have been proposed as tools to improve the performance of biparametric MRI (bpMRI). PURPOSE: To develop and validate radiomics and kallikrein models for the detection of csPCa. STUDY TYPE: Retrospective. POPULATION: A total of 543 men with a clinical suspicion of csPCa, 411 (76%, 411/543) had kallikreins available and 360 (88%, 360/411) did not take 5-alpha-reductase inhibitors. Two data splits into training, validation (split 1: single center, n = 72; split 2: random 50% of pooled datasets from all four centers), and testing (split 1: 4 centers, n = 288; split 2: remaining 50%) were evaluated. FIELD STRENGTH/SEQUENCE: A 3 T/1.5 T, TSE T2-weighted imaging, 3x SE DWI. ASSESSMENT: In total, 20,363 radiomic features calculated from manually delineated whole gland (WG) and bpMRI suspicion lesion masks were evaluated in addition to clinical parameters, prostate-specific antigen, four kallikreins, MRI-based qualitative (PI-RADSv2.1/IMPROD bpMRI Likert) scores. STATISTICAL TESTS: For the detection of csPCa, area under receiver operating curve (AUC) was calculated using the DeLong's method. A multivariate analysis was conducted to determine the predictive power of combining variables. The values of P-value < 0.05 were considered significant. RESULTS: The highest prediction performance was achieved by IMPROD bpMRI Likert and PI-RADSv2.1 score with AUC = 0.85 and 0.85 in split 1, 0.85 and 0.83 in split 2, respectively. bpMRI WG and/or kallikreins demonstrated AUCs ranging from 0.62 to 0.73 in split 1 and from 0.68 to 0.76 in split 2. AUC of bpMRI lesion-derived radiomics model was not statistically different to IMPROD bpMRI Likert score (split 1: AUC = 0.83, P-value = 0.306; split 2: AUC = 0.83, P-value = 0.488). DATA CONCLUSION: The use of radiomics and kallikreins failed to outperform PI-RADSv2.1/IMPROD bpMRI Likert and their combination did not lead to further performance gains. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Docetaxel chemotherapy response in PC3 prostate cancer mouse model detected by rotating frame relaxations and water diffusion.

MRI is a common method of prostate cancer diagnosis. Several MRI-derived markers, including the apparent diffusion coefficient (ADC) based on diffusion-weighted imaging, have been shown to provide values for prostate cancer detection and characterization. The hypothesis of the study was that docetaxel chemotherapy response could be picked up earlier with rotating frame relaxation times TRAFF2 and TRAFF4 than with the continuous wave T1ρ , adiabatic T1ρ , adiabatic T2ρ , T1 , T2 or water ADC. Human PC3 prostate cancer cells expressing a red fluorescent protein were implanted in 21 male mice. Docetaxel chemotherapy was given once a week starting 1 week after cell implantation for 10 randomly selected mice, while the rest served as a control group (n = 11). The MRI consisted of relaxation along a fictitious field (RAFF) in the second (RAFF2) and fourth (RAFF4) rotating frames, T1 and T2 , continuous wave T1ρ , adiabatic T1ρ and adiabatic T2ρ relaxation time measurements and water ADC. MRI was conducted at 7 T, once a week up to 4 weeks from cell implantation. The tumor volume was monitored using T2 -weighted MRI and optical imaging. The histology was evaluated after the last imaging time point. Significantly reduced RAFFn, T1ρ, T2ρ and conventional relaxation times 4 weeks after tumor implantation were observed in the treated tumors compared with the controls. The clearest short- and long-term responses were obtained with T1 , while no clear improvement in response to treatment was detected with novel methods compared with conventional methods or with RAFFn compared with all others. The tumor volume decreased after a two-week time point for the treated group and increased significantly in the control group, which was supported by increasing red fluorescent light emission in the control tumors. Decreased relaxation times were associated with successful chemotherapy outcomes. The results indicate altered relaxation mechanisms compared with higher dose chemotherapies previously published.

Prospective comparison of 18F-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer.

PURPOSE: To prospectively compare 18F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa). METHODS: Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent 18F-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used. RESULTS: Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only 18F-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively. CONCLUSION: 18F-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03537391.

Whole Brain Adiabatic T1rho and Relaxation Along a Fictitious Field Imaging in Healthy Volunteers and Patients With Multiple Sclerosis: Initial Findings.

BACKGROUND: In preclinical models of multiple sclerosis (MS), both adiabatic T1rho (T1ρadiab ) and relaxation along a fictitious field (RAFF) imaging have demonstrated potential to noninvasively characterize MS. PURPOSE: To evaluate the feasibility of whole brain T1ρadiab and RAFF imaging in healthy volunteers and patients with MS. STUDY TYPE: Single institutional clinical trial. SUBJECTS: 38 healthy volunteers (24-69 years) and 21 patients (26-59 years) with MS. Five healthy volunteers underwent a second MR examination performed within 8 days. Clinical disease severity (The Expanded Disability Status Scale [EDSS] and The Multiple Sclerosis Severity Score [MSSS]) was evaluated at baseline and 1-year follow-up (FU). FIELD STRENGTH/SEQUENCE: RAFF in second rotating frame of reference (RAFF2) was performed at 3 T using 3D-fast-field echo with magnetization preparation, RF amplitude of 11.74 µT while the corresponding value for T1ρadiab was 13.50 µT. T1 -, T2 -, and FLAIR-weighted images were acquired with reconstruction voxel size 1.0 × 1.0 × 1.0 mm3 . ASSESSMENT: The parametric maps of T1ρadiab and RAFF2 (TRAFF2 ) were calculated using a monoexponential model. Semi-automatic segmentation of MS lesions, white matter (WM), and gray matter (GM), and WM tracks was performed using T1 -, T2 -, and FLAIR-weighted images. STATISTICAL TESTS: Regression analysis was used to evaluate correlation of T1ρadiab and TRAFF2 with age and disease severity while a Friedman test followed by Wilcoxon Signed Rank test for differences between tissue types. Short-term repeatability was evaluated on voxel level. RESULTS: Both T1ρadiab and TRAFF2 demonstrated good short-term repeatability with relative differences on voxel level in the range of 6.1%-11.9%. Differences in T1ρadiab and TRAFF2 between the tissue types in MS patients were significant (P < 0.05). T1ρadiab and TRAFF2 correlated (P < 0.001) with baseline EDSS/MSSM and disease progression at FU (P < 0.001). DATA CONCLUSION: Whole brain T1ρadiab and TRAFF2 at 3 T was feasible with significant differences in T1ρadiab and TRAFF2 values between tissues types and correlation with disease severity. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Added value of systematic biopsy in men with a clinical suspicion of prostate cancer undergoing biparametric MRI-targeted biopsy: multi-institutional external validation study.

PURPOSE: We aimed to develop and externally validate a nomogram based on MRI volumetric parameters and clinical information for deciding when SBx should be performed in addition to TBx in man with suspicious prostate MRI. MATERIALS AND METHODS: Retrospective analyses of single (IMPROD, NCT01864135) and multi-institution (MULTI-IMPROD, NCT02241122) clinical trials. All men underwent a unique rapid biparametric magnetic resonance imaging (IMPROD bpMRI) consisting of T2-weighted imaging and three separate DWI acquisitions. Men with IMPROD bpMRI Likert scores of 3-5 were included. Logistic regression models were developed using IMPROD trial (n = 122) and validated using MULTI-IMPROD trial (n = 262) data. The model's performance was evaluated in the terms of PCa detection with Gleason Grade Group 1 (clinically insignificant prostate cancer, iPCa) and > 1 (clinically significant prostate cancer, csPCa). Net benefits and decision curve analyses (DCA) were compared. Combined biopsies were used for reference. RESULTS: The developed nomogram included age, PSA, prostate volume, MRI suspicion score (IMPROD bpMRI Likert or PIRADsv2.1 score), MRI-suspicion lesion volume percentage, and lesion location. All these variables were significant predictors of csPCa in SBx in multivariable analysis. In the validation cohort (n = 262) using different nomogram cutoffs, 19-43% of men would have avoided SBx while missing 1-4% of csPCa and avoiding detection of 9-20% of iPCa. Similar performance was found for nomograms using IMPROD bpMRI Likert score or v2.1. CONCLUSIONS: The developed nomogram demonstrated potential to select men with a clinical suspicion of PCa who would benefit from performing SBx in addition to TBx. Public access to the nomogram is provided at: https://petiv.utu.fi/multiimprod/ .

Test-retest repeatability of a deep learning architecture in detecting and segmenting clinically significant prostate cancer on apparent diffusion coefficient (ADC) maps.

OBJECTIVES: To evaluate short-term test-retest repeatability of a deep learning architecture (U-Net) in slice- and lesion-level detection and segmentation of clinically significant prostate cancer (csPCa: Gleason grade group > 1) using diffusion-weighted imaging fitted with monoexponential function, ADCm. METHODS: One hundred twelve patients with prostate cancer (PCa) underwent 2 prostate MRI examinations on the same day. PCa areas were annotated using whole mount prostatectomy sections. Two U-Net-based convolutional neural networks were trained on three different ADCm b value settings for (a) slice- and (b) lesion-level detection and (c) segmentation of csPCa. Short-term test-retest repeatability was estimated using intra-class correlation coefficient (ICC(3,1)), proportionate agreement, and dice similarity coefficient (DSC). A 3-fold cross-validation was performed on training set (N = 78 patients) and evaluated for performance and repeatability on testing data (N = 34 patients). RESULTS: For the three ADCm b value settings, repeatability of mean ADCm of csPCa lesions was ICC(3,1) = 0.86-0.98. Two CNNs with U-Net-based architecture demonstrated ICC(3,1) in the range of 0.80-0.83, agreement of 66-72%, and DSC of 0.68-0.72 for slice- and lesion-level detection and segmentation of csPCa. Bland-Altman plots suggest that there is no systematic bias in agreement between inter-scan ground truth segmentation repeatability and segmentation repeatability of the networks. CONCLUSIONS: For the three ADCm b value settings, two CNNs with U-Net-based architecture were repeatable for the problem of detection of csPCa at the slice-level. The network repeatability in segmenting csPCa lesions is affected by inter-scan variability and ground truth segmentation repeatability and may thus improve with better inter-scan reproducibility. KEY POINTS: • For the three ADCm b value settings, two CNNs with U-Net-based architecture were repeatable for the problem of detection of csPCa at the slice-level. • The network repeatability in segmenting csPCa lesions is affected by inter-scan variability and ground truth segmentation repeatability and may thus improve with better inter-scan reproducibility.

Using biomarkers in patients with positive multiparametric magnetic resonance imaging: 4Kscore predicts the presence of cancer outside the index lesion.

OBJECTIVES: To evaluate if the blood biomarker, 4Kscore, in addition to multiparametric magnetic resonance imaging information could identify patients who would benefit from undergoing only a targeted biopsy. METHODS: We retrospectively analyzed a population of 256 men with positive multiparametric magnetic resonance imaging who underwent standard + targeted biopsy at Mount Sinai Hospital, New York, NY, USA. 4Kscore (OPKO Health, Miami, FL, USA) was sampled from all patients before biopsy. Uni- and multivariable binary logistic regression analyses were carried out to predict clinically significant prostate cancer, defined as International Society of Urological Pathology grade group ≥2, in standard biopsy cores. The model with the best area under the curve was selected and internal validation was carried out using the leave-one-out cross-validation. RESULTS: The developed model showed an area under the curve of 0.86. Carrying out only targeted biopsy in patients with a model-derived probability <12.5% resulted in 39.5% (n = 101) fewer standard biopsies and a 33.9% (n = 20) reduction of detecting grade group 1 disease, while missing grade group ≥2 in 5.2% (n = 4) using standard biopsy only and 1.1% (n = 1) using standard biopsy + targeted biopsy. CONCLUSIONS: 4Kscore in combination with multiparametric magnetic resonance imaging can help to reduce unnecessary standard biopsy and decrease detection of clinically insignificant prostate cancer.

Repeatability of radiomics and machine learning for DWI: Short-term repeatability study of 112 patients with prostate cancer.

PURPOSE: To evaluate repeatability of prostate DWI-derived radiomics and machine learning methods for prostate cancer (PCa) characterization. METHODS: A total of 112 patients with diagnosed PCa underwent 2 prostate MRI examinations (Scan1 and Scan2) performed on the same day. DWI was performed using 12 b-values (0-2000 s/mm2 ), post-processed using kurtosis function, and PCa areas were annotated using whole mount prostatectomy sections. A total of 1694 radiomic features including Sobel, Kirch, Gradient, Zernike Moments, Gabor, Haralick, CoLIAGe, Haar wavelet coefficients, 3D analogue to Laws features, 2D contours, and corner detectors were calculated. Radiomics and 4 feature pruning methods (area under the receiver operator characteristic curve, maximum relevance minimum redundancy, Spearman's ρ, Wilcoxon rank-sum) were evaluated in terms of Scan1-Scan2 repeatability using intraclass correlation coefficient (ICC)(3,1). Classification performance for clinically significant and insignificant PCa with Gleason grade groups 1 versus >1 was evaluated by area under the receiver operator characteristic curve in unseen random 30% data split. RESULTS: The ICC(3,1) values for conventional radiomics and feature pruning methods were in the range of 0.28-0.90. The machine learning classifications varied between Scan1 and Scan2 with % of same class labels between Scan1 and Scan2 in the range of 61-81%. Surface-to-volume ratio and corner detector-based features were among the most represented features with high repeatability, ICC(3,1) >0.75, consistently high ranking using all 4 feature pruning methods, and classification performance with area under the receiver operator characteristic curve >0.70. CONCLUSION: Surface-to-volume ratio and corner detectors for prostate DWI led to good classification of unseen data and performed similarly in Scan1 and Scan2 in contrast to multiple conventional radiomic features.

Staging Accuracy of Multiparametric Magnetic Resonance Imaging in Caucasian and African American Men Undergoing Radical Prostatectomy.

PURPOSE: We compared the performance of multiparametric magnetic resonance imaging for the prediction of extraprostatic extension in African American and Caucasian American men and evaluated racial disparities in pathological outcomes after radical prostatectomy. MATERIALS AND METHODS: We identified 975 patients who underwent radical prostatectomy with preoperative multiparametric magnetic resonance imaging between January 2013 and April 2019 at our institution. Multivariable logistic regression analysis was performed predicting pathological extraprostatic extension, high grade prostate cancer (final pathology GGG [Gleason Grade Group] 3 or greater) in the overall population and pathological upgrading (final pathology GGG 3 or greater) in patients with a diagnosis of GGG 1-2 prostate cancer. Adverse pathology was defined as pT3 and/or GGG 3 or greater. RESULTS: A total of 221 (23%) patients were African American. Preoperatively 594 (60.9%) were GGG 1-2 (low risk group) and 381 (39.1%) GGG 3 or greater (high risk group). In the low risk group rates of pathological extraprostatic extension (18% vs 12.8%, p=0.14), adverse pathology (18% vs 13.4%, p=0.2) or upgrading (9.4% vs 12.1%, p=0.4) were similar between races. Similarly, in the high risk group there was no difference in rates of pathological extraprostatic extension. On multivariable analysis multiparametric magnetic resonance imaging predicted the presence of extraprostatic extension (OR 1.80, 95% CI 1.29-2.50) and high grade prostate cancer (OR 1.82, 95% CI 1.25-2.67) on final pathology. Conversely, race did not predict the outcomes of interest (all values p >0.05). Multiparametric magnetic resonance imaging showed comparable sensitivity (22.22% vs 27.84%), specificity (89.2% vs 79.2%), positive predictive value (89.2% vs 83.4%) and negative predictive value (89.2% vs 83.4%) between African American and Caucasian America men, respectively. CONCLUSIONS: The accuracy of multiparametric magnetic resonance imaging in staging prostate cancer was similar in African American and Caucasian American patients and no difference was found between races in pathological outcomes after radical prostatectomy. These findings suggest that access to and use of advanced diagnostic tests may help mitigate prostate cancer racial disparities.

Qualitative and Quantitative Reporting of a Unique Biparametric MRI: Towards Biparametric MRI-Based Nomograms for Prediction of Prostate Biopsy Outcome in Men With a Clinical Suspicion of Prostate Cancer (IMPROD and MULTI-IMPROD Trials).

BACKGROUND: Multiparametric MRI of the prostate has been shown to improve the risk stratification of men with an elevated prostate-specific antigen (PSA). However, long acquisition time, high cost, and inter-center/reader variability of a routine prostate multiparametric MRI limit its wider adoption. PURPOSE: To develop and validate nomograms based on unique rapid biparametric MRI (bpMRI) qualitative and quantitative derived variables for prediction of clinically significant cancer (SPCa). STUDY TYPE: Retrospective analyses of single (IMPROD, NCT01864135) and multiinstitution trials (MULTI-IMPROD, NCT02241122). POPULATION: 161 and 338 prospectively enrolled men who completed the IMPROD and MULTI-IMPROD trials, respectively. FIELD STRENGTH/SEQUENCE: IMPROD bpMRI: 3T/1.5T, T2 -weighted imaging, three separate diffusion-weighted imaging (DWI) acquisitions: 1) b-values 0, 100, 200, 300, 500 s/mm2 ; 2) b values 0, 1500 s/mm2 ; 3) values 0, 2000 s/mm2 . ASSESSMENT: The primary endpoint of the combined trial analysis was the diagnostic accuracy of the combination of IMPROD bpMRI and clinical variables for detection of SPCa. STATISTICAL TESTS: Logistic regression models were developed using IMPROD trial data and validated using MULTI-IMPROD trial data. The model's performance was expressed as the area under the curve (AUC) values for the detection of SPCa, defined as ISUP Gleason Grade Group ≥2. RESULTS: A model incorporating clinical variables had an AUC (95% confidence interval) of 0.83 (0.77-0.89) and 0.80 (0.75-0.85) in the development and validation cohorts, respectively. The corresponding values for a model using IMPROD bpMRI findings were 0.93 (0.89-0.97), and 0.88 (0.84-0.92), respectively. Further addition of the quantitative DWI-based score did not improve AUC values (P < 0.05). DATA CONCLUSION: A prediction model using qualitative IMPROD bpMRI findings demonstrated high accuracy for predicting SPCa in men with an elevated PSA. Online risk calculator: http://petiv.utu.fi/multiimprod/ Level of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1556-1567.

Prediction of biochemical recurrence in prostate cancer patients who underwent prostatectomy using routine clinical prostate multiparametric MRI and decipher genomic score.

BACKGROUND: Biochemical recurrence (BCR) affects a significant proportion of patients who undergo robotic-assisted laparoscopic prostatectomy (RALP). PURPOSE: To evaluate the performance of a routine clinical prostate multiparametric magnetic resonance imaging (mpMRI) and Decipher genomic classifier score for prediction of biochemical recurrence in patients who underwent RALP. STUDY TYPE: Retrospective cohort study. SUBJECTS: Ninety-one patients who underwent RALP performed by a single surgeon, had mpMRI before RALP, Decipher taken from RALP samples, and prostate specific antigen (PSA) follow-up for >3 years or BCR within 3 years, defined as PSA >0.2 mg/ml. FIELD STRENGTH/SEQUENCE: mpMRI was performed at 27 different institutions using 1.5T (n = 10) or 3T scanners and included T2 w, diffusion-weighted imaging (DWI), or dynamic contrast-enhanced (DCE) MRI. ASSESSMENT: All mpMRI studies were reported by one reader using Prostate Imaging Reporting and Data System v. 2.1 (PI-RADsv2.1) without knowledge of other findings. Eighteen (20%) randomly selected cases were re-reported by reader B to evaluate interreader variability. STATISTICAL TESTS: Univariate and multivariate analysis using greedy feature selection and tournament leave-pair-out cross-validation (TLPOCV) were used to evaluate the performance of various variables for prediction of BCR, which included clinical (three), systematic biopsy (three), surgical (six: RALP Gleason Grade Group [GGG], extracapsular extension, seminal vesicle invasion, intraoperative surgical margins [PSM], final PSM, pTNM), Decipher (two: Decipher score, Decipher risk category), and mpMRI (eight: prostate volume, PSA density, PI-RADv2.1 score, MRI largest lesion size, summed MRI lesions' volume and relative volume [MRI-lesion-percentage], mpMRI ECE, mpMRI seminal vesicle invasion [SVI]) variables. The evaluation metric was the area under the curve (AUC). RESULTS: Forty-eight (53%) patients developed BCR. The best-performing individual features with TLPOCV AUC of 0.73 (95% confidence interval [CI] 0.64-0.82) were RALP GGG, MRI-lesion-percentage followed by biopsy GGG (0.72, 0.62-0.82), and Decipher score (0.71, 0.60-0.82). The best performance was achieved by feature selection of Decipher+Surgery and MRI + Surgery variables with TLPOCV AUC of 0.82 and 0.81, respectively DATA CONCLUSION: Relative lesion volume measured on a routine clinical mpMRI failed to outperform Decipher score in BCR prediction. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1075-1085.

Prostate Cancer Risk Stratification in Men With a Clinical Suspicion of Prostate Cancer Using a Unique Biparametric MRI and Expression of 11 Genes in Apparently Benign Tissue: Evaluation Using Machine-Learning Techniques.

BACKGROUND: Accurate risk stratification of men with a clinical suspicion of prostate cancer (cSPCa) remains challenging despite the increasing use of MRI. PURPOSE: To evaluate the diagnostic accuracy of a unique biparametric MRI protocol (IMPROD bpMRI) combined with clinical and molecular markers in men with cSPCa. STUDY TYPE: Prospective single-institutional clinical trial (NCT01864135). SUBJECTS: Eighty men with cSPCa. FIELD STRENGTH/SEQUENCE: 3T, surface array coils. Two T2 -weighted and three diffusion-weighted imaging (DWI) acquisitions: 1) b-values 0, 100, 200, 300, 500 s/mm2 ; 2) b-values 0,1500 s/mm2 ; 3) b-values 0, 2000 s/mm2 . ASSESSMENT: IMPROD bpMRI examinations were qualitatively (IMPROD bpMRI Likert score) and quantitatively (DWI-based Gleason grade score) prospectively reported. Men with IMPROD bpMRI Likert 3-5 had two targeted biopsies followed by 12-core systematic biopsies (SB); those with IMPROD bpMRI Likert 1-2 had only SB. Additionally, 2-core from normal-appearing prostate areas were obtained for the mRNA expression of ACSM1, AMACR, CACNA1D, DLX1, PCA3, PLA2G7, RHOU, SPINK1, SPON2, TMPRSS2-ERG, and TDRD1 measured by quantitative reverse-transcription polymerase chain reaction. STATISTICAL TESTS: Univariate and multivariate analysis using regularized least-squares, feature selection and tournament leave-pair-out cross-validation (TLPOCV), as well as 10 random splits of the data in training-testing sets, were used to evaluate the mRNA, clinical and IMPROD bpMRI parameters in detecting clinically significant prostate cancer (SPCa) defined as Gleason score ≥ 3 + 4. The evaluation metric was the area under the curve (AUC). RESULTS: IMPROD bpMRI Likert demonstrated the highest TLPOCV AUC of 0.92. The tested clinical variables had AUC 0.56-0.73, while the mRNA and additional IMPROD bpMRI parameters had AUC 0.50-0.67 and 0.65-0.89 respectively. The combination of clinical and mRNA biomarkers produced TLPOCV AUC of 0.87, the highest TLPOCV performance without including IMPROD bpMRI Likert. DATA CONCLUSION: The qualitative IMPROD bpMRI Likert score demonstrated the highest accuracy for SPCa detection compared with the tested clinical variables and mRNA biomarkers. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1540-1553.

Validation of IMPROD biparametric MRI in men with clinically suspected prostate cancer: A prospective multi-institutional trial.

BACKGROUND: Magnetic resonance imaging (MRI) combined with targeted biopsy (TB) is increasingly used in men with clinically suspected prostate cancer (PCa), but the long acquisition times, high costs, and inter-center/reader variability of routine multiparametric prostate MRI limit its wider adoption. METHODS AND FINDINGS: The aim was to validate a previously developed unique MRI acquisition and reporting protocol, IMPROD biparametric MRI (bpMRI) (NCT01864135), in men with a clinical suspicion of PCa in a multi-institutional trial (NCT02241122). IMPROD bpMRI has average acquisition time of 15 minutes (no endorectal coil, no intravenous contrast use) and consists of T2-weighted imaging and 3 separate diffusion-weighed imaging acquisitions. Between February 1, 2015, and March 31, 2017, 364 men with a clinical suspicion of PCa were enrolled at 4 institutions in Finland. Men with an equivocal to high suspicion (IMPROD bpMRI Likert score 3-5) of PCa had 2 TBs of up to 2 lesions followed by a systematic biopsy (SB). Men with a low to very low suspicion (IMPROD bpMRI Likert score 1-2) had only SB. All data and protocols are freely available. The primary outcome of the trial was diagnostic accuracy-including overall accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value-of IMPROD bpMRI for clinically significant PCa (SPCa), which was defined as a Gleason score ≥ 3 + 4 (Gleason grade group 2 or higher). In total, 338 (338/364, 93%) prospectively enrolled men completed the trial. The accuracy and NPV of IMPROD bpMRI for SPCa were 70% (113/161) and 95% (71/75) (95% CI 87%-98%), respectively. Restricting the biopsy to men with equivocal to highly suspicious IMPROD bpMRI findings would have resulted in a 22% (75/338) reduction in the number of men undergoing biopsy while missing 4 (3%, 4/146) men with SPCa. The main limitation is uncertainty about the true PCa prevalence in the study cohort, since some of the men may have PCa despite having negative biopsy findings. CONCLUSIONS: IMPROD bpMRI demonstrated a high NPV for SPCa in men with a clinical suspicion of PCa in this prospective multi-institutional clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT02241122.

IMPROD biparametric MRI in men with a clinical suspicion of prostate cancer (IMPROD Trial): Sensitivity for prostate cancer detection in correlation with whole-mount prostatectomy sections and implications for focal therapy.

BACKGROUND: Prostate MRI is increasingly being used in men with a clinical suspicion of prostate cancer (PCa). However, development and validation of methods for focal therapy planning are still lagging. PURPOSE: To evaluate the diagnostic accuracy on lesion, region-of-interest (ROI), and voxel level of IMPROD biparametric prostate MRI (bpMRI) for PCa detection in men with a clinical suspicion of PCa who subsequently underwent radical prostatectomy. STUDY TYPE: Prospective single-institution clinical trial (NCT01864135). POPULATION: Sixty-four men who underwent radical prostatectomy after IMPROD bpMRI performed in prebiopsy settings. FIELD STRENGTH/SEQUENCE: IMPROD bpMRI consisted of T2 -weighted imaging (T2 w) and three separate diffusion-weighted imaging acquisitions with an average acquisition time of 15 minutes. ASSESSMENT: The diagnostic accuracy of prospectively reported manual cancer delineations and regions increased with 3D dilation were evaluated on the voxel level (volume of 1.17 mm3 , 1 mm3 , 125 mm3 ) as well as the 36 ROI level. Only PCa lesions with a diameter ≥ 5 mm or any Gleason Grade 4 were analyzed. All data and protocols are freely available at: http://petiv.utu.fi/improd STATISTICAL TESTS: Sensitivity, specificity, accuracy. RESULTS: In total, 99 PCa lesions were identified. Forty (40%, 40/99) had a Gleason score (GS) of >3 + 4. Twenty-eight PCa lesions (28%, 28/99) were missed by IMPROD bpMRI, three (7.5%, 3/40) with GS >3 + 4. 3D dilation of manual cancer delineations in all directions by ~10-12 mm (corresponding to the Hausdorff distance) was needed to achieve sensitivity approaching 100% on a voxel level. DATA CONCLUSION: IMPROD bpMRI had a high sensitivity on lesion level for PCa with GS >3 + 4. Increasing 3D lesion delineations by ~10-12 mm (corresponding to the Hausdorff distance) was needed to achieve high sensitivity on the voxel level. Such information may help in planning ablation therapies. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1641-1650.