High-intensity focused ultrasound with visually directed power adjustment for focal treatment of localized prostate cancer: systematic review and meta-analysis.

PURPOSE: To characterize patient outcomes following visually directed high-intensity focused ultrasound (HIFU) for focal treatment of localized prostate cancer. METHODS: We performed a systematic review of cancer-control outcomes and complication rates among men with localized prostate cancer treated with visually directed focal HIFU. Study outcomes were calculated using a random-effects meta-analysis model. RESULTS: A total of 8 observational studies with 1,819 patients (median age 67 years; prostate-specific antigen 7.1 mg/ml; prostate volume 36 ml) followed over a median of 24 months were included. The mean prostate-specific antigen nadir following visually directed focal HIFU was 2.2 ng/ml (95% CI 0.9-3.5 ng/ml), achieved after a median of 6 months post-treatment. A clinically significant positive biopsy was identified in 19.8% (95% CI 12.4-28.3%) of cases. Salvage treatment rates were 16.2% (95% CI 9.7-23.8%) for focal- or whole-gland treatment, and 8.6% (95% CI 6.1-11.5%) for whole-gland treatment. Complication rates were 16.7% (95% CI 9.9-24.6%) for de novo erectile dysfunction, 6.2% (95% CI 0.0-19.0%) for urinary retention, 3.0% (95% CI 2.1-3.9%) for urinary tract infection, 1.9% (95% CI 0.1-5.3%) for urinary incontinence, and 0.1% (95% CI 0.0-1.4%) for bowel injury. CONCLUSION: Limited evidence from eight observational studies demonstrated that visually directed HIFU for focal treatment of localized prostate cancer was associated with a relatively low risk of complications and acceptable cancer control over medium-term follow-up. Comparative, long-term safety and effectiveness results with visually directed focal HIFU are lacking.

PI-QUAL version 2: an update of a standardised scoring system for the assessment of image quality of prostate MRI.

Multiparametric MRI is the optimal primary investigation when prostate cancer is suspected, and its ability to rule in and rule out clinically significant disease relies on high-quality anatomical and functional images. Avenues for achieving consistent high-quality acquisitions include meticulous patient preparation, scanner setup, optimised pulse sequences, personnel training, and artificial intelligence systems. The impact of these interventions on the final images needs to be quantified. The prostate imaging quality (PI-QUAL) scoring system was the first standardised quantification method that demonstrated the potential for clinical benefit by relating image quality to cancer detection ability by MRI. We present the updated version of PI-QUAL (PI-QUAL v2) which applies to prostate MRI performed with or without intravenous contrast medium using a simplified 3-point scale focused on critical technical and qualitative image parameters. CLINICAL RELEVANCE STATEMENT: High image quality is crucial for prostate MRI, and the updated version of the PI-QUAL score (PI-QUAL v2) aims to address the limitations of version 1. It is now applicable to both multiparametric MRI and MRI without intravenous contrast medium. KEY POINTS: High-quality images are essential for prostate cancer diagnosis and management using MRI. PI-QUAL v2 simplifies image assessment and expands its applicability to prostate MRI without contrast medium. PI-QUAL v2 focuses on critical technical and qualitative image parameters and emphasises T2-WI and DWI.

Global Variation in Magnetic Resonance Imaging Quality of the Prostate.

Background High variability in prostate MRI quality might reduce accuracy in prostate cancer detection. Purpose To prospectively evaluate the quality of MRI scanners taking part in the quality control phase of the global PRIME (Prostate Imaging Using MRI ± Contrast Enhancement) trial using the Prostate Imaging Quality (PI-QUAL) standardized scoring system, give recommendations on how to improve the MRI protocols, and establish whether MRI quality could be improved by these recommendations. Materials and Methods In the prospective clinical trial (PRIME), for each scanner, centers performing prostate MRI submitted five consecutive studies and the MRI protocols (phase I). Submitted data were evaluated in consensus by two expert genitourinary radiologists using the PI-QUAL scoring system that evaluates MRI diagnostic quality using five points (1 and 2 = nondiagnostic; 3 = sufficient; 4 = adequate, 5 = optimal) between September 2021 and August 2022. Feedback was provided for scanners not achieving a PI-QUAL 5 score, and centers were invited to resubmit new imaging data using the modified protocol (phase II). Descriptive comparison of outcomes was made between the MRI scanners, feedback provided, and overall PI-QUAL scores. Results In phase I, 41 centers from 18 countries submitted a total of 355 multiparametric MRI studies from 71 scanners, with nine (13%) scanners achieving a PI-QUAL score of 3, 39 (55%) achieving a score of 4, and 23 (32%) achieving a score of 5. Of the 48 (n = 71 [68%]) scanners that received feedback to improve, the dynamic contrast-enhanced sequences were those that least adhered to the Prostate Imaging Reporting and Data System, version 2.1, criteria (44 of 48 [92%]), followed by diffusion-weighted imaging (20 of 48 [42%]) and T2-weighted imaging (19 of 48 [40%]). In phase II, 36 centers from 17 countries resubmitted revised studies, resulting in a total of 62 (n = 64 [97%]) scanners with a final PI-QUAL score of 5. Conclusion Substantial variation in global prostate MRI acquisition parameters as a measure of quality was observed, particularly with DCE sequences. Basic evaluation and modifications to MRI protocols using PI-QUAL can lead to substantial improvements in quality. Clinical trial registration no. NCT04571840 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Almansour and Chernyak in this issue.

Regional Histopathology and Prostate MRI Positivity: A Secondary Analysis of the PROMIS Trial.

Background The effects of regional histopathologic changes on prostate MRI scans have not been accurately quantified in men with an elevated prostate-specific antigen (PSA) level and no previous biopsy. Purpose To assess how Gleason grade, maximum cancer core length (MCCL), inflammation, prostatic intraepithelial neoplasia (PIN), or atypical small acinar proliferation within a Barzell zone affects the odds of MRI visibility. Materials and Methods In this secondary analysis of the Prostate MRI Imaging Study (PROMIS; May 2012 to November 2015), consecutive participants who underwent multiparametric MRI followed by a combined biopsy, including 5-mm transperineal mapping (TPM), were evaluated. TPM pathologic findings were reported at the whole-prostate level and for each of 20 Barzell zones per prostate. An expert panel blinded to the pathologic findings reviewed MRI scans and declared which Barzell areas spanned Likert score 3-5 lesions. The relationship of Gleason grade and MCCL to zonal MRI outcome (visible vs nonvisible) was assessed using generalized linear mixed-effects models with random intercepts for individual participants. Inflammation, PIN, and atypical small acinar proliferation were similarly assessed in men who had negative TPM results. Results Overall, 161 men (median age, 62 years [IQR, 11 years]) were evaluated and 3179 Barzell zones were assigned MRI status. Compared with benign areas, the odds of MRI visibility were higher when a zone contained cancer with a Gleason score of 3+4 (odds ratio [OR], 3.1; 95% CI: 1.9, 4.9; P < .001) or Gleason score greater than or equal to 4+3 (OR, 8.7; 95% CI: 4.5, 17.0; P < .001). MCCL also determined visibility (OR, 1.24 per millimeter increase; 95% CI: 1.15, 1.33; P < .001), but odds were lower with each prostate volume doubling (OR, 0.7; 95% CI: 0.5, 0.9). In men who were TPM-negative, the presence of PIN increased the odds of zonal visibility (OR, 3.7; 95% CI: 1.5, 9.1; P = .004). Conclusion An incremental relationship between cancer burden and prostate MRI visibility was observed. Prostatic intraepithelial neoplasia contributed to false-positive MRI findings. ClinicalTrials.gov registration no. NCT01292291 © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Harmath in this issue.

Evaluation of Outcomes Following Focal Ablative Therapy for Treatment of Localized Clinically Significant Prostate Cancer in Patients >70 Years: A Multi-institute, Multi-energy 15-Year Experience.

PURPOSE: In older patients who do not wish to undergo watchful waiting, focal therapy could be an alternative to the more morbid radical treatment. We evaluated the role of focal therapy in patients 70 years and older as an alternative management modality. MATERIALS AND METHODS: A total of 649 patients across 11 UK sites receiving focal high-intensity focused ultrasound or cryotherapy between June 2006 and July 2020 reported within the UK-based HEAT (HIFU Evaluation and Assessment of Treatment) and ICE (International Cryotherapy Evaluation) registries were evaluated. Primary outcome was failure-free survival, defined by need for more than 1 focal reablation, progression to radical treatment, development of metastases, need for systemic treatment, or prostate cancer-specific death. This was compared to the failure-free survival in patients undergoing radical treatment via a propensity score weighted analysis. RESULTS: Median age was 74 years (IQR: 72, 77) and median follow-up 24 months (IQR: 12, 41). Sixty percent had intermediate-risk disease and 35% high-risk disease. A total of 113 patients (17%) required further treatment. Sixteen had radical treatment and 44 required systemic treatment. Failure-free survival was 82% (95% CI: 76%-87%) at 5 years. Comparing patients who had radical therapy to those who had focal therapy, 5-year failure-free survival was 96% (95% CI: 93%-100%) and 82% (95% CI: 75%-91%) respectively (P < .001). Ninety-three percent of those in the radical treatment arm had received radiotherapy as their primary treatment with its associated use of androgen deprivation therapy, thereby leading to potential overestimation of treatment success in the radical treatment arm, especially given the similar metastases-free and overall survival rates seen. CONCLUSIONS: We propose focal therapy to be an effective management option for the older or comorbid patient who is unsuitable for or not willing to undergo radical treatment.

Picture Perfect: The Status of Image Quality in Prostate MRI.

Magnetic resonance imaging is the gold standard imaging modality for the diagnosis of prostate cancer (PCa). Image quality is a fundamental prerequisite for the ability to detect clinically significant disease. In this critical review, we separate the issue of image quality into quality improvement and quality assessment. Beginning with the evolution of technical recommendations for scan acquisition, we investigate the role of patient preparation, scanner factors, and more advanced sequences, including those featuring Artificial Intelligence (AI), in determining image quality. As means of quality appraisal, the published literature on scoring systems (including the Prostate Imaging Quality score), is evaluated. Finally, the application of AI and teaching courses as ways to facilitate quality assessment are discussed, encouraging the implementation of future image quality initiatives along the PCa diagnostic and monitoring pathway. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Quantification of Prostate Cancer Metabolism Using 3D Multiecho bSSFP and Hyperpolarized [1-13 C] Pyruvate: Metabolism Differs Between Tumors of the Same Gleason Grade.

BACKGROUND: Three-dimensional (3D) multiecho balanced steady-state free precession (ME-bSSFP) has previously been demonstrated in preclinical hyperpolarized (HP) 13 C-MRI in vivo experiments, and it may be suitable for clinical metabolic imaging of prostate cancer (PCa). PURPOSE: To validate a signal simulation framework for the use of sequence parameter optimization. To demonstrate the feasibility of ME-bSSFP for HP 13 C-MRI in patients. To evaluate the metabolism in PCa measured by ME-bSSFP. STUDY TYPE: Retrospective single-center cohort study. PHANTOMS/POPULATION: Phantoms containing aqueous solutions of [1-13 C] lactate (2.3 M) and [13 C] urea (8 M). Eight patients (mean age 67 ± 6 years) with biopsy-confirmed Gleason 3 + 4 (n = 7) and 4 + 3 (n = 1) PCa. FIELD STRENGTH/SEQUENCES: 1 H MRI at 3 T with T2 -weighted turbo spin-echo sequence used for spatial localization and spoiled dual gradient-echo sequence used for B0 -field measurement. ME-bSSFP sequence for 13 C MR spectroscopic imaging with retrospective multipoint IDEAL metabolite separation. ASSESSMENT: The primary endpoint was the analysis of pyruvate-to-lactate conversion in PCa and healthy prostate regions of interest (ROIs) using model-free area under the curve (AUC) ratios and a one-directional kinetic model (kP ). The secondary objectives were to investigate the correlation between simulated and experimental ME-bSSFP metabolite signals for HP 13 C-MRI parameter optimization. STATISTICAL TESTS: Pearson correlation coefficients with 95% confidence intervals and paired t-tests. The level of statistical significance was set at P < 0.05. RESULTS: Strong correlations between simulated and empirical ME-bSSFP signals were found (r > 0.96). Therefore, the simulation framework was used for sequence optimization. Whole prostate metabolic HP 13 C-MRI, observing the conversion of pyruvate into lactate, with a temporal resolution of 6 seconds was demonstrated using ME-bSSFP. Both assessed metrics resulted in significant differences between PCa (mean ± SD) (AUC = 0.33 ± 012, kP  = 0.038 ± 0.014) and healthy (AUC = 0.15 ± 0.10, kP  = 0.011 ± 0.007) ROIs. DATA CONCLUSION: Metabolic HP 13 C-MRI in the prostate using ME-bSSFP allows for differentiation between aggressive PCa and healthy tissue. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Accurate diagnosis of prostate cancer by combining Proclarix with magnetic resonance imaging.

OBJECTIVES: To assess of the clinical performance of Proclarix® (a novel Conformité Européenne [CE]-marked biomarker test aiding in the identification of clinically significant prostate cancer [csPCa]) alone or in combination with multiparametric magnetic resonance imaging (mpMRI) to predict csPCa (International Society of Urological Pathology Grade Group ≥2). PATIENTS AND METHODS: The study included blood samples from 721 men undergoing mpMRI followed by biopsy at University College London, London, and Vall d'Hebron University Hospital, Barcelona. Samples were tested blindly. The Proclarix-MRI model combining prostate volume, Proclarix and mpMRI results was trained using the UCL cohort (n = 159) and validated in the Vall d'Hebron cohort (n = 562). Its diagnostic performance was established in correlation to biopsy outcome and compared to available clinical parameters and risk calculators. RESULTS: Clinical performance of the Proclarix-MRI model in the validation cohort did not significantly differ from the training cohort and resulted in a sensitivity for csPCa of 90%, 90% negative predictive value and 66% positive predictive value. The Proclarix-MRI score's specificity (68%) was significantly (P < 0.001) better than the MRI-European Randomized study of Screening for Prostate Cancer risk score (51%), Proclarix (27%) or mpMRI (28%) alone. In addition, Proclarix by itself was found to be useful in the MRI Prostate Imaging-Reporting and Data System (PI-RADS) score 3 subgroup by outperforming prostate-specific antigen density in terms of specificity (25% vs 13%, P = 0.004) at 100% sensitivity. CONCLUSION: When combined with mpMRI and prostate volume, Proclarix reliably predicted csPCa and ruled out men with no or indolent cancer. A large reduction of two thirds of unneeded biopsies was achieved. Proclarix can further be used with high confidence to reliably detect csPCa in men with an indeterminate PI-RADS score 3 mpMRI. Despite these encouraging results, further validation is needed.

External validation of a risk model predicting failure of salvage focal ablation for prostate cancer.

OBJECTIVES: To externally validate a published model predicting failure within 2 years after salvage focal ablation in men with localised radiorecurrent prostate cancer using a prospective, UK multicentre dataset. PATIENTS AND METHODS: Patients with biopsy-confirmed ≤T3bN0M0 cancer after previous external beam radiotherapy or brachytherapy were included from the FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial (NCT01883128; 2014-2018; six centres), and from the high-intensity focussed ultrasound (HIFU) Evaluation and Assessment of Treatment (HEAT) and International Cryotherapy Evaluation (ICE) UK-based registries (2006-2022; nine centres). Eligible patients underwent either salvage focal HIFU or cryotherapy, with the choice based predominantly on anatomical factors. Per the original multivariable Cox regression model, the predicted outcome was a composite failure outcome. Model performance was assessed at 2 years post-salvage with discrimination (concordance index [C-index]), calibration (calibration curve and slope), and decision curve analysis. For the latter, two clinically-reasonable risk threshold ranges of 0.14-0.52 and 0.26-0.36 were considered, corresponding to previously published pooled 2-year recurrence-free survival rates for salvage local treatments. RESULTS: A total of 168 patients were included, of whom 84/168 (50%) experienced the primary outcome in all follow-ups, and 72/168 (43%) within 2 years. The C-index was 0.65 (95% confidence interval 0.58-0.71). On graphical inspection, there was close agreement between predicted and observed failure. The calibration slope was 1.01. In decision curve analysis, there was incremental net benefit vs a 'treat all' strategy at risk thresholds of ≥0.23. The net benefit was therefore higher across the majority of the 0.14-0.52 risk threshold range, and all of the 0.26-0.36 range. CONCLUSION: In external validation using prospective, multicentre data, this model demonstrated modest discrimination but good calibration and clinical utility for predicting failure of salvage focal ablation within 2 years. This model could be reasonably used to improve selection of appropriate treatment candidates for salvage focal ablation, and its use should be considered when discussing salvage options with patients. Further validation in larger, international cohorts with longer follow-up is recommended.

Promoting the use of the PI-QUAL score for prostate MRI quality: results from the ESOR Nicholas Gourtsoyiannis teaching fellowship.

OBJECTIVES: The Prostate Imaging Quality (PI-QUAL) score is a new metric to evaluate the diagnostic quality of multiparametric magnetic resonance imaging (MRI) of the prostate. This study assesses the impact of an intervention, namely a prostate MRI quality training lecture, on the participant's ability to apply PI-QUAL. METHODS: Sixteen participants (radiologists, urologists, physicists, and computer scientists) of varying experience in reviewing diagnostic prostate MRI all assessed the image quality of ten examinations from different vendors and machines. Then, they attended a dedicated lecture followed by a hands-on workshop on MRI quality assessment using the PI-QUAL score. Five scans assessed by the participants were evaluated in the workshop using the PI-QUAL score for teaching purposes. After the course, the same participants evaluated the image quality of a new set of ten scans applying the PI-QUAL score. Results were assessed using receiver operating characteristic analysis. The reference standard was the PI-QUAL score assessed by one of the developers of PI-QUAL. RESULTS: There was a significant improvement in average area under the curve for the evaluation of image quality from baseline (0.59 [95 % confidence intervals: 0.50-0.66]) to post-teaching (0.96 [0.92-0.98]), an improvement of 0.37 [0.21-0.41] (p < 0.001). CONCLUSIONS: A teaching course (dedicated lecture + hands-on workshop) on PI-QUAL significantly improved the application of this scoring system to assess the quality of prostate MRI examinations. KEY POINTS: • A significant improvement in the application of PI-QUAL for the assessment of prostate MR image quality was observed after an educational intervention. • Appropriate training on image quality can be delivered to those involved in the acquisition and interpretation of prostate MRI. • Further investigation will be needed to understand the impact on improving the acquisition of high-quality diagnostic prostate MR examinations.

Multiparametric ultrasound versus multiparametric MRI to diagnose prostate cancer (CADMUS): a prospective, multicentre, paired-cohort, confirmatory study.

BACKGROUND: Multiparametric MRI of the prostate followed by targeted biopsy is recommended for patients at risk of prostate cancer. However, multiparametric ultrasound is more readily available than multiparametric MRI. Data from paired-cohort validation studies and randomised, controlled trials support the use of multiparametric MRI, whereas the evidence for individual ultrasound methods and multiparametric ultrasound is only derived from case series. We aimed to establish the overall agreement between multiparametric ultrasound and multiparametric MRI to diagnose clinically significant prostate cancer. METHODS: We conducted a prospective, multicentre, paired-cohort, confirmatory study in seven hospitals in the UK. Patients at risk of prostate cancer, aged 18 years or older, with an elevated prostate-specific antigen concentration or abnormal findings on digital rectal examination underwent both multiparametric ultrasound and multiparametric MRI. Multiparametric ultrasound consisted of B-mode, colour Doppler, real-time elastography, and contrast-enhanced ultrasound. Multiparametric MRI included high-resolution T2-weighted images, diffusion-weighted imaging (dedicated high B 1400 s/mm2 or 2000 s/mm2 and apparent diffusion coefficient map), and dynamic contrast-enhanced axial T1-weighted images. Patients with positive findings on multiparametric ultrasound or multiparametric MRI underwent targeted biopsies but were masked to their test results. If both tests yielded positive findings, the order of targeting at biopsy was randomly assigned (1:1) using stratified (according to centre only) block randomisation with randomly varying block sizes. The co-primary endpoints were the proportion of positive lesions on, and agreement between, multiparametric MRI and multiparametric ultrasound in identifying suspicious lesions (Likert score of ≥3), and detection of clinically significant cancer (defined as a Gleason score of ≥4 + 3 in any area or a maximum cancer core length of ≥6 mm of any grade [PROMIS definition 1]) in those patients who underwent a biopsy. Adverse events were defined according to Good Clinical Practice and trial regulatory guidelines. The trial is registered on ISRCTN, 38541912, and ClinicalTrials.gov, NCT02712684, with recruitment and follow-up completed. FINDINGS: Between March 15, 2016, and Nov 7, 2019, 370 eligible patients were enrolled; 306 patients completed both multiparametric ultrasound and multiparametric MRI and 257 underwent a prostate biopsy. Multiparametric ultrasound was positive in 272 (89% [95% CI 85-92]) of 306 patients and multiparametric MRI was positive in 238 patients (78% [73-82]; difference 11·1% [95% CI 5·1-17·1]). Positive test agreement was 73·2% (95% CI 67·9-78·1; κ=0·06 [95% CI -0·56 to 0·17]). Any cancer was detected in 133 (52% [95% CI 45·5-58]) of 257 patients, with 83 (32% [26-38]) of 257 being clinically significant by PROMIS definition 1. Each test alone would result in multiparametric ultrasound detecting PROMIS definition 1 cancer in 66 (26% [95% CI 21-32]) of 257 patients who had biopsies and multiparametric MRI detecting it in 77 (30% [24-36]; difference -4·3% [95% CI -8·3% to -0·3]). Combining both tests detected 83 (32% [95% CI 27-38]) of 257 clinically significant cancers as per PROMIS definition 1; of these 83 cancers, six (7% [95% CI 3-15]) were detected exclusively with multiparametric ultrasound, and 17 (20% [12-31]) were exclusively detected by multiparametric MRI (agreement 91·1% [95% CI 86·9-94·2]; κ=0·78 [95% CI 0·69-0·86]). No serious adverse events were related to trial activity. INTERPRETATION: Multiparametric ultrasound detected 4·3% fewer clinically significant prostate cancers than multiparametric MRI, but it would lead to 11·1% more patients being referred for a biopsy. Multiparametric ultrasound could be an alternative to multiparametric MRI as a first test for patients at risk of prostate cancer, particularly if multiparametric MRI cannot be carried out. Both imaging tests missed clinically significant cancers detected by the other, so the use of both would increase the detection of clinically significant prostate cancers compared with using each test alone. FUNDING: The Jon Moulton Charity Trust, Prostate Cancer UK, and UCLH Charity and Barts Charity.

Geographic Variability, Time Trends and Association of Preoperative Magnetic Resonance Imaging with Surgical Outcomes for Elderly United States Men with Prostate Cancer: A Surveillance, Epidemiology, and End Results-Medicare Analysis.

PURPOSE: Our goal was to assess patterns of adoption and population-level outcomes of prostate magnetic resonance imaging (MRI) and association with surgical outcomes across a sample of U.S. elderly. MATERIALS AND METHODS: This population-based retrospective study used Surveillance Epidemiology, and End Results-Medicare linked data from 2003-2016 to identify men receiving prostatectomy for prostate cancer. We characterized the proportion of men receiving preoperative MRI in each year and in each hospital referral region (HRR). A 2-stage instrumental variable analysis was performed to assess the association of preoperative MRI with margin status, surgical complications and further cancer-directed therapies. RESULTS: A total of 19,369 men received prostatectomy in 72 HRRs; the mean age was 70.2 years (SD 3.2). The proportion of men receiving a preoperative MRI increased from 2.9% to 28.2% over the study period and ranged from 0.0% to 28.8% in the different HRRs. In our instrumental variable analysis, preoperative MRI was associated with lower odds of positive surgical margin (OR 0.84, 95% CI 0.72-0.97, p=0.01) lower odds of blood transfusions at 30 and 90 days (OR 0.56, 95% CI 0.38-0.83, p=0.003 and OR 0.58, 95% CI 0.41-0.84, p=0.004) but higher odds of further treatments (OR 1.49, 95% CI 1.32-1.70, p <0.001). CONCLUSIONS: Given that a minority of men receive presurgical MRIs with marked geographic variability, the association of MRI with lower odds of positive surgical margin suggests that efforts to support the dissemination of prostate MRI may improve surgical outcomes-but may come with a tendency for more resource-intensive cancer care overall.

Inter-reader agreement of the PI-QUAL score for prostate MRI quality in the NeuroSAFE PROOF trial.

OBJECTIVES: The Prostate Imaging Quality (PI-QUAL) score assesses the quality of multiparametric MRI (mpMRI). A score of 1 means all sequences are below the minimum standard of diagnostic quality, 3 implies that the scan is of sufficient diagnostic quality, and 5 means that all three sequences are of optimal diagnostic quality. We investigated the inter-reader reproducibility of the PI-QUAL score in patients enrolled in the NeuroSAFE PROOF trial. METHODS: We analysed the scans of 103 patients on different MR systems and vendors from 12 different hospitals. Two dedicated radiologists highly experienced in prostate mpMRI independently assessed the PI-QUAL score for each scan. Interobserver agreement was assessed using Cohen's kappa with standard quadratic weighting (κw) and percent agreement. RESULTS: The agreement for each single PI-QUAL score was strong (κw = 0.85 and percent agreement = 84%). A similar agreement (κw = 0.82 and percent agreement = 84%) was observed when the scans were clustered into three groups (PI-QUAL 1-2 vs PI-QUAL 3 vs PI-QUAL 4-5). The agreement in terms of diagnostic quality for each single sequence was highest for T2-weighted imaging (92/103 scans; 89%), followed by dynamic contrast-enhanced sequences (91/103; 88%) and diffusion-weighted imaging (80/103; 78%). CONCLUSION: We observed strong reproducibility in the assessment of PI-QUAL between two radiologists with high expertise in prostate mpMRI. At present, PI-QUAL offers clinicians the only available tool for evaluating and reporting the quality of prostate mpMRI in a systematic manner but further refinements of this scoring system are warranted. KEY POINTS: • Inter-reader agreement for each single Prostate Imaging Quality (PI-QUAL) score (i.e., PI-QUAL 1 to PI-QUAL 5) was strong, with weighted kappa = 0.85 (95% confidence intervals: 0.51 - 1) and percent agreement = 84%. • Interobserver agreement was strong when the scans were clustered into three groups according to the ability (or not) to rule in and to rule out clinically significant prostate cancer (i.e., PI-QUAL 1-2 vs PI-QUAL 3 vs PI-QUAL 4-5), with weighted kappa = 0.82 (95% confidence intervals: 0.68 - 0.96) and percent agreement = 84%. • T2-weighted acquisitions were the most compliant with the Prostate Imaging Reporting and Data System (PI-RADS) v. 2.0 technical recommendations and were the sequences of highest diagnostic quality for both readers in 95/103 (92%) scans, followed by dynamic contrast enhanced acquisition with 81/103 (79%) scans and lastly by diffusion-weighted imaging with 79/103 (77%) scans.

MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis.

BACKGROUND: Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. METHODS: In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. RESULTS: A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). CONCLUSIONS: The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .).

Is the Toxicity of Salvage Prostatectomy Related to the Primary Prostate Cancer Therapy Received?

PURPOSE: To compare the toxicity profile and oncological outcome of salvage radical prostatectomy following focal therapy versus salvage radical prostatectomy after radiation therapies (external beam radiation therapy or brachytherapy). MATERIALS AND METHODS: Data concerning all men undergoing salvage radical prostatectomy for recurrent prostate cancer after either focal therapy, external beam radiation therapy or brachytherapy were retrospectively collected from 4 high volume surgical centers. The primary outcome measure of the study was toxicity of salvage radical prostatectomy characterized by any 30-day postoperative Clavien-Dindo complication rate, 12-month continence rate and 12-month potency rate. The secondary outcome was oncological outcome after salvage radical prostatectomy including positive margin rate and 12-month biochemical recurrence rate. Biochemical recurrence was estimated using Kaplan-Meier methods and significant differences were calculated using a log rank test. Median followup was 29.5 months. RESULTS: Between April 2007 and September 2018, 185 patients underwent salvage radical prostatectomy of whom 95 had salvage radical prostatectomy after focal therapy and 90 had salvage radical prostatectomy after radiation therapy (external beam radiation therapy or brachytherapy). Salvage radical prostatectomy after radiation therapy was associated with a significantly higher 30-day Clavien-Dindo I-IV complication rate (34% vs 5%, p <0.001). At 12 months following surgery, patients undergoing salvage radical prostatectomy after focal therapy had significantly better continence (83% pad-free vs 49%) while potency outcomes were similar (14% vs 11%). Men undergoing salvage radical prostatectomy after radiation therapy had a significantly higher stage and grade of disease together with a higher positive surgical margin rate (37% vs 13%, p=0.001). The 3-year biochemical recurrence after focal therapy was 35% compared to 32% after radiation therapy (p=0.76). In multivariable analysis, men undergoing salvage radical prostatectomy after focal therapy experienced a higher risk of biochemical recurrence (HR 0.36, 95% CI 0.16-0.82, p=0.02). CONCLUSIONS: This multicenter study demonstrates the toxicity of salvage radical prostatectomy in terms of perioperative complications and long-term urinary continence recovery is dependent on initial primary prostate cancer therapy received with men undergoing salvage radical prostatectomy after focal therapy experiencing lower postoperative complication rates and better urinary continence outcomes.

Prostate Radiofrequency Focal Ablation (ProRAFT) Trial: A Prospective Development Study Evaluating a Bipolar Radiofrequency Device to Treat Prostate Cancer.

PURPOSE: We determined the early efficacy of bipolar radiofrequency ablation with a coil design for focal ablation of clinically significant localized prostate cancer visible at multiparametric magnetic resonance imaging. MATERIALS AND METHODS: A prospective IDEAL phase 2 development study (Focal Prostate Radiofrequency Ablation, NCT02294903) recruited treatment-naïve patients with a single focus of significant localized prostate cancer (Gleason 7 or 4 mm or more of Gleason 6) concordant with a lesion visible on multiparametric magnetic resonance imaging. Intervention was a focal ablation with a bipolar radiofrequency system (Encage™) encompassing the lesion and a predefined margin using nonrigid magnetic resonance imaging-ultrasound fusion. Primary outcome was the proportion of men with absence of significant localized disease on biopsy at 6 months. Trial followup consisted of serum prostate specific antigen, multiparametric magnetic resonance imaging at 1 week, and 6 and 12 months post-ablation. Validated patient reported outcome measures for urinary, erectile and bowel functions, and adverse events monitoring system were used. Analyses were done on a per-protocol basis. RESULTS: Of 21 patients recruited 20 received the intervention. Baseline characteristics were median age 66 years (IQR 63-69) and preoperative median prostate specific antigen 7.9 ng/ml (5.3-9.6). A total of 18 patients (90%) had Gleason 7 disease with median maximum cancer 7 mm (IQR 5-10), for a median of 2.8 cc multiparametric magnetic resonance imaging lesions (IQR 1.4-4.8). Targeted biopsy of the treated area (median number of cores 6, IQR 5-8) showed absence of significant localized prostate cancer in 16/20 men (80%), concordant with multiparametric magnetic resonance imaging. There was a low profile of side effects at patient reported outcome measures analysis and there were no serious adverse events. CONCLUSIONS: Focal therapy of significant localized prostate cancer associated with a magnetic resonance imaging lesion using bipolar radiofrequency showed early efficacy to ablate cancer with low rates of genitourinary and rectal side effects.

Conspicuity of prostate cancer on multiparametric magnetic resonance imaging: A cross-disciplinary translational hypothesis.

Pre-biopsy multiparametric magnetic resonance imaging (mpMRI) has transformed the risk stratification and diagnostic approach for suspected prostate cancer. The majority of clinically significant prostate cancers are visible on pre-biopsy mpMRI, however, there are a subset of significant tumors that are not detected by mpMRI. The radiobiological mechanisms underpinning mpMRI-visibility and invisibility of these cancers remain uncertain. Emerging evidence suggests that mpMRI-visible tumors are enriched with molecular features associated with increased disease aggressivity and poor clinical prognosis, which is supported by short-term endpoints, such as biochemical recurrence following surgery. Furthermore, at the histopathological level, mpMRI-visible tumors appear to exhibit increased architectural and vascular density compared to mpMRI-invisible disease. It seems probable that the genomic, pathological, radiological, and clinical features of mpMRI-visible and mpMRI-invisible prostate cancers are interrelated. Here, we propose a novel cross-disciplinary theory that links genomic and molecular evidence with cellular and histopathological appearances, elucidating both the mpMRI visibility and clinical status of significant prostate cancer.

Outcomes of the RAFT trial: robotic surgery after focal therapy.

OBJECTIVES: To report toxicity of treatment observed in men participating in the Robotic surgery After Focal Therapy (RAFT) clinical trial. PATIENTS AND METHODS: Men were eligible for this prospective single group interventional study if they had histologically confirmed recurrent/residual prostate adenocarcinoma following primary FT. The short-form Expanded Prostate Cancer Index Composite (EPIC-26) measured prior to salvage robotic prostatectomy (S-RARP) and 3-monthly post-operatively together with Clavien-Dindo complications (I-IV). Secondary outcomes included biochemical recurrence-free survival (BCFS) following surgery and need for salvage treatment after surgery. This study is registered with ClinicalTrials.gov NCT03011606. RESULTS: Twenty-four men were recruited between February 2016 and September 2018. 1 patient withdrew from the trial after consenting and before S-RARP. 23 men completed 12-month post S-RARP follow-up. Median EPIC-26 urinary continence scores initially deteriorated after 3 months (82.4 vs 100) but there was no statistically significant difference from baseline at 12 months (100 vs 100, P = 0.31). Median lower urinary tract symptom scores improved after 12 months compared to baseline (93.8 vs 87.5, P = 0.01). At 12 months, 19/23 (83%) were pad-free and 22/23 (96%) required 0/1 pads. Median sexual function subscale scores deteriorated and remained low at 12 months (22.2 vs 58.3, P < 0.001). Utilising a minimally important difference of nine points, at 12 months after surgery 17/23 (74%) reported urinary continence to be 'better' or 'not different' to pre-operative baseline. The corresponding figure for sexual function (utilising a minimally important difference of 12 points) was 7/23 (30%). There was no statistically significant difference on median bowel/hormonal subscale scores. Only a single patient had a post-operative complication (Clavien-Dindo Grade I). BCFS at 12 months after surgery was 82.6% (95% confidence interval [CI]: 60.1-93.1%) while 4/23 (17%) received salvage radiation. CONCLUSIONS: The RAFT clinical trial suggests toxicity of surgery after FT is low, with good urinary function outcomes, albeit sexual function deteriorated overall. Oncological outcomes at 12 months appear acceptable.

Role of MRI for the detection of prostate cancer.

The use of multiparametric MRI has been hastened under expanding, novel indications for its use in the diagnostic and management pathway of men with prostate cancer. This has helped drive a large body of the literature describing its evolving role over the last decade. Despite this, prostate cancer remains the only solid organ malignancy routinely diagnosed with random sampling. Herein, we summarize the components of multiparametric MRI and interpretation, and present a critical review of the current literature supporting is use in prostate cancer detection, risk stratification, and management.

Focal HIFU therapy for anterior compared to posterior prostate cancer lesions.

OBJECTIVE: To compare cancer control in anterior compared to posterior prostate cancer lesions treated with a focal HIFU therapy approach. MATERIALS AND METHODS: In a prospectively maintained national database, 598 patients underwent focal HIFU (Sonablate®500) (March/2007-November/2016). Follow-up occurred with 3-monthly clinic visits and PSA testing in the first year with PSA, every 6-12 months with mpMRI with biopsy for MRI-suspicion of recurrence. Treatment failure was any secondary treatment (ADT/chemotherapy, cryotherapy, EBRT, RRP, or re-HIFU), tumour recurrence with Gleason ≥ 3 + 4 on prostate biopsy without further treatment or metastases/prostate cancer-related mortality. Cases with anterior cancer were compared to those with posterior disease. RESULTS: 267 patients were analysed following eligibility criteria. 45 had an anterior focal-HIFU and 222 had a posterior focal-HIFU. Median age was 64 years and 66 years, respectively, with similar PSA level of 7.5 ng/ml and 6.92 ng/ml. 84% and 82%, respectively, had Gleason 3 + 4, 16% in both groups had Gleason 4 + 3, 0% and 2% had Gleason 4 + 4. Prostate volume was similar (33 ml vs. 36 ml, p = 0.315); median number of positive cores in biopsies was different in anterior and posterior tumours (7 vs. 5, p = 0.009), while medium cancer core length, and maximal cancer percentage of core were comparable. 17/45 (37.8%) anterior focal-HIFU patients compared to 45/222 (20.3%) posterior focal-HIFU patients required further treatment (p = 0.019). CONCLUSION: Treating anterior prostate cancer lesions with focal HIFU may be less effective compared to posterior tumours.