Publications by authors named "Shonit Punwani"

156 Publications

Which Prostate Cancers are Undetected by Multiparametric Magnetic Resonance Imaging in Men with Previous Prostate Biopsy? An Analysis from the PICTURE Study.

Eur Urol Open Sci 2021 Aug 15;30:16-24. Epub 2021 Jun 15.

Department of Urology, Imperial College Healthcare NHS Trust, London, UK.

Background: Multiparametric magnetic resonance imaging (mpMRI) has improved risk stratification for suspected prostate cancer in patients following prior biopsy. However, not all significant cancers are detected by mpMRI. The PICTURE study provides the ideal opportunity to investigate cancer undetected by mpMRI owing to the use of 5 mm transperineal template mapping (TTPM) biopsy.

Objective: To summarise attributes of cancers systematically undetected by mpMRI in patients with prior biopsy.

Design Setting And Participants: PICTURE was a paired-cohort confirmatory study in which men requiring repeat biopsy underwent mpMRI followed by TTPM biopsy.

Outcome Measurements And Statistical Analysis: Attributes were compared between cancers detected and undetected by mpMRI at the patient level. Four predefined histopathological thresholds were used as the target condition for TTPM biopsy. Application of prostate-specific antigen density (PSAD) was explored.

Results And Limitations: When nonsuspicious mpMRI was defined as Likert score 1-2, 2.9% of patients (3/103; 95% confidence interval [CI] 0.6-8.3%) with definition 1 disease (Gleason ≥ 4 + 3 of any length or maximum cancer core length [MCCL] ≥ 6 mm of any grade) had their cancer not detected by mpMRI. This proportion was 6.5% (11/168; 95% CI 3.3-11%) for definition 2 disease (Gleason ≥ 3 + 4 of any length or MCCL ≥ 4 mm of any grade), 4.8% (7/146; 95% CI 2.0-9.6%) for any amount of Gleason ≥ 3 + 4 cancer, and 9.3% (20/215; 95% CI 5.8-14%) for any cancer. Definition 1 cancers undetected by mpMRI had lower overall Gleason score ( = 0.02) and maximum Gleason score ( = 0.01) compared to cancers detected by mpMRI. Prostate cancers undetected by mpMRI had shorter MCCL than cancers detected by mpMRI for every cancer threshold: definition 1, 6 versus 8 mm ( = 0.02); definition 2, 5 versus 6 mm ( = 0.04); any Gleason ≥ 3 + 4, 5 versus 6 mm ( = 0.03); and any cancer, 3 versus 5 mm ( = 0.0009). A theoretical PSAD threshold of 0.15 ng/ml/ml reduced the proportion of patients with undetected disease on nonsuspicious mpMRI to 0% (0/105; 95% CI 0-3.5%) for definition 1, 0.58% (1/171; 95% CI 0.01-3.2%) for definition 2, and 0% (0/146) for any Gleason ≥ 3 + 4.

Conclusions: Few significant cancers are undetected by mpMRI in patients requiring repeat prostate biopsy. Undetected tumours are of lower overall and maximum Gleason grade and shorter cancer length compared to cancers detected by mpMRI.

Patient Summary: In patients with a previous prostate biopsy, magnetic resonance imaging (MRI) overlooks few prostate cancers, and these tend to be smaller and less aggressive than cancer that is detected.
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http://dx.doi.org/10.1016/j.euros.2021.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277581PMC
August 2021

Emerging methods for prostate cancer imaging: evaluating cancer structure and metabolic alterations more clearly.

Mol Oncol 2021 Jul 30. Epub 2021 Jul 30.

UCL Centre for Medical Imaging, London, UK.

Imaging plays a fundamental role in all aspects of the cancer management pathway. However, conventional imaging techniques are largely reliant on morphological and size descriptors that have well-known limitations, particularly when considering targeted-therapy response monitoring. Thus, new imaging methods have been developed to characterise cancer and are now routinely implemented, such as diffusion-weighted imaging, dynamic contrast enhancement, positron emission technology (PET) and magnetic resonance spectroscopy. However, despite the improvement these techniques have enabled, limitations still remain. Novel imaging methods are now emerging, intent on further interrogating cancers. These techniques are at different stages of maturity along the biomarker pathway and aim to further evaluate the cancer microstructure (vascular, extracellular and restricted diffusion for cytometry in tumours) magnetic resonance imaging (MRI), luminal water fraction imaging] as well as the metabolic alterations associated with cancers (novel PET tracers, hyperpolarised MRI). Finally, the use of machine learning has shown powerful potential applications. By using prostate cancer as an exemplar, this Review aims to showcase these potentially potent imaging techniques and what stage we are at in their application to conventional clinical practice.
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http://dx.doi.org/10.1002/1878-0261.13071DOI Listing
July 2021

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

Eur Radiol 2021 Jul 29. Epub 2021 Jul 29.

Department of Radiology, University College London Hospital NHS Foundation Trust, London, UK.

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.
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http://dx.doi.org/10.1007/s00330-021-08169-1DOI Listing
July 2021

Artificial Intelligence Compared to Radiologists for the Initial Diagnosis of Prostate Cancer on Magnetic Resonance Imaging: A Systematic Review and Recommendations for Future Studies.

Cancers (Basel) 2021 Jul 1;13(13). Epub 2021 Jul 1.

Centre for Medical Imaging, Division of Medicine, Bloomsbury Campus, University College London, London WC1E 6DH, UK.

Computer-aided diagnosis (CAD) of prostate cancer on multiparametric magnetic resonance imaging (mpMRI), using artificial intelligence (AI), may reduce missed cancers and unnecessary biopsies, increase inter-observer agreement between radiologists, and alleviate pressures caused by rising case incidence and a shortage of specialist radiologists to read prostate mpMRI. However, well-designed evaluation studies are required to prove efficacy above current clinical practice. A systematic search of the MEDLINE, EMBASE, and arXiv electronic databases was conducted for studies that compared CAD for prostate cancer detection or classification on MRI against radiologist interpretation and a histopathological reference standard, in treatment-naïve men with a clinical suspicion of prostate cancer. Twenty-seven studies were included in the final analysis. Due to substantial heterogeneities in the included studies, a narrative synthesis is presented. Several studies reported superior diagnostic accuracy for CAD over radiologist interpretation on small, internal patient datasets, though this was not observed in the few studies that performed evaluation using external patient data. Our review found insufficient evidence to suggest the clinical deployment of artificial intelligence algorithms at present. Further work is needed to develop and enforce methodological standards, promote access to large diverse datasets, and conduct prospective evaluations before clinical adoption can be considered.
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http://dx.doi.org/10.3390/cancers13133318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268820PMC
July 2021

Computer-aided diagnosis of prostate cancer using multiparametric MRI and clinical features: A patient-level classification framework.

Med Image Anal 2021 10 29;73:102153. Epub 2021 Jun 29.

Biomedical Engineering & Imaging Sciences School, King's College London, UK.

Computer-aided diagnosis (CAD) of prostate cancer (PCa) using multiparametric magnetic resonance imaging (mpMRI) is actively being investigated as a means to provide clinical decision support to radiologists. Typically, these systems are trained using lesion annotations. However, lesion annotations are expensive to obtain and inadequate for characterizing certain tumor types e.g. diffuse tumors and MRI invisible tumors. In this work, we introduce a novel patient-level classification framework, denoted PCF, that is trained using patient-level labels only. In PCF, features are extracted from three-dimensional mpMRI and derived parameter maps using convolutional neural networks and subsequently, combined with clinical features by a multi-classifier support vector machine scheme. The output of PCF is a probability value that indicates whether a patient is harboring clinically significant PCa (Gleason score ≥3+4) or not. PCF achieved mean area under the receiver operating characteristic curves of 0.79 and 0.86 on the PICTURE and PROSTATEx datasets respectively, using five-fold cross-validation. Clinical evaluation over a temporally separated PICTURE dataset cohort demonstrated comparable sensitivity and specificity to an experienced radiologist. We envision PCF finding most utility as a second reader during routine diagnosis or as a triage tool to identify low-risk patients who do not require a clinical read.
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http://dx.doi.org/10.1016/j.media.2021.102153DOI Listing
October 2021

Utility of diffusion MRI characteristics of cervical lymph nodes as disease classifier between patients with head and neck squamous cell carcinoma and healthy volunteers.

NMR Biomed 2021 Jul 8:e4587. Epub 2021 Jul 8.

Centre for Medical Imaging, University College London, London, UK.

Diffusion MRI characteristics assessed by apparent diffusion coefficient (ADC) histogram analysis in head and neck squamous cell carcinoma (HNSCC) have been reported as helpful in classifying tumours based on diffusion characteristics. There is little reported on HNSCC lymph nodes classification by diffusion characteristics. The aim of this study was to determine whether pretreatment nodal microstructural diffusion MRI characteristics can classify diseased nodes of patients with HNSCC from normal nodes of healthy volunteers. Seventy-nine patients with histologically confirmed HNSCC prior to chemoradiotherapy, and eight healthy volunteers, underwent diffusion-weighted (DW) MRI at a 1.5-T MR scanner. Two radiologists contoured lymph nodes on DW (b = 300 s/m ) images. ADC, distributed diffusion coefficient (DDC) and alpha (α) values were calculated by monoexponential and stretched exponential models. Histogram analysis metrics of drawn volume were compared between patients and volunteers using a Mann-Whitney test. The classification performance of each metric between the normal and diseased nodes was determined by receiver operating characteristic (ROC) analysis. Intraclass correlation coefficients determined interobserver reproducibility of each metric based on differently drawn ROIs by two radiologists. Sixty cancerous and 40 normal nodes were analysed. ADC histogram analysis revealed significant differences between patients and volunteers (p ≤0.0001 to 0.0046), presenting ADC distributions that were more skewed (1.49 for patients, 1.03 for volunteers; p = 0.0114) and 'peaked' (6.82 for patients, 4.20 for volunteers; p = 0.0021) in patients. Maximum ADC values exhibited the highest area under the curve ([AUC] 0.892). Significant differences were revealed between patients and volunteers for DDC and α value histogram metrics (p ≤0.0001 to 0.0044); the highest AUC were exhibited by maximum DDC (0.772) and the 25th percentile α value (0.761). Interobserver repeatability was excellent for mean ADC (ICC = 0.88) and the 25th percentile α value (ICC = 0.78), but poor for all other metrics. These results suggest that pretreatment microstructural diffusion MRI characteristics in lymph nodes, assessed by ADC and α value histogram analysis, can identify nodal disease.
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http://dx.doi.org/10.1002/nbm.4587DOI Listing
July 2021

Prostate MRI quality: a critical review of the last 5 years and the role of the PI-QUAL score.

Br J Radiol 2021 Jul 8:20210415. Epub 2021 Jul 8.

Department of Radiology, University College London Hospital NHS Foundation Trust, London, UK.

There is increasing interest in the use of multiparametric magnetic resonance imaging (mpMRI) in the prostate cancer pathway. The European Association of Urology (EAU) and the British Association of Urological Surgeons (BAUS) now advise mpMRI prior to biopsy, and the Prostate Imaging Reporting and Data System (PI-RADS) recommendations set out the minimal technical requirements for the acquisition of mpMRI of the prostate.The widespread and swift adoption of this technique has led to variability in image quality. Suboptimal image acquisition reduces the sensitivity and specificity of mpMRI for the detection and staging of clinically significant prostate cancer.This critical review outlines the studies aimed at improving prostate MR quality that have been published over the last 5 years. These span from the use of specific MR sequences, magnets and coils to patient preparation. The rates of adherence of prostate mpMRI to technical standards in different cohorts across the world are also discussed.Finally, we discuss the first standardised scoring system ( Prostate Imaging Quality, PI-QUAL) that has been created to evaluate image quality, although further iterations of this score are expected in the future.
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http://dx.doi.org/10.1259/bjr.20210415DOI Listing
July 2021

Tumour growth rates of prostate cancer during active surveillance: is there a difference between MRI-visible low and intermediate-risk disease?

Br J Radiol 2021 Jul 8:20210321. Epub 2021 Jul 8.

Department of Radiology, University College London Hospital NHS Foundation Trust, London, UK.

Objectives: The aim of this study was to evaluate the changes in lesion volume on serial multiparametric magnetic resonance (mpMRI) during active surveillance for prostate cancer.

Methods: A total of 160 patients with a targeted biopsy-confirmed visible lesion on mpMRI, stratified by low- and intermediate-risk disease (Gleason Grade Group 1 vs Gleason Grade Group 2), were analysed. The % change per year was calculated using the formula: .

Results: There was no significant difference in the annual median percentage change between Gleason Grade Group 1 (18%) and Gleason Grade Group 2 (23%) disease (p = 0.16), and between ≤ 10% (23%) and > 10% (22%) of Gleason pattern 4 (p = 0.78).Assuming a spherical lesion, these changes corresponded to annual increases in mean tumour diameter of 6% and 7% for Gleason Grade Group 1 and Gleason Grade Group 2 respectively, which may be less than the interscan variability of serial mpMRI.

Conclusion: In an active surveillance cohort, we did not see a significant difference in the annual growth rate of Gleason Grade Group 1 and 2 tumours.

Advances In Knowledge: In patients on active surveillance, the measured growth rates for visible tumours in Gleason Grade Groups 1 and 2 were similar. The annual growth rate was small in most cases and this may have implications for the MRI follow-up interval in active surveillance.
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http://dx.doi.org/10.1259/bjr.20210321DOI Listing
July 2021

Texture Analysis of Fractional Water Content Images Acquired during PET/MRI: Initial Evidence for an Association with Total Lesion Glycolysis, Survival and Gene Mutation Profile in Primary Colorectal Cancer.

Cancers (Basel) 2021 May 31;13(11). Epub 2021 May 31.

Research Department of Imaging, Division of Medicine, University College London (UCL), London WC1E 6BT, UK.

To assess the capability of fractional water content (FWC) texture analysis (TA) to generate biologically relevant information from routine PET/MRI acquisitions for colorectal cancer (CRC) patients. Thirty consecutive primary CRC patients (mean age 63.9, range 42-83 years) prospectively underwent FDG-PET/MRI. FWC tumor parametric images generated from Dixon MR sequences underwent TA using commercially available research software (TexRAD). Data analysis comprised (1) identification of functional imaging correlates for texture features (TF) with low inter-observer variability (intraclass correlation coefficient: ICC > 0.75), (2) evaluation of prognostic performance for FWC-TF, and (3) correlation of prognostic imaging signatures with gene mutation (GM) profile. Of 32 FWC-TF with ICC > 0.75, 18 correlated with total lesion glycolysis (TLG, highest: r = -0.547, = 0.002). Using optimized cut-off values, five MR FWC-TF identified a good prognostic group with zero mortality (lowest: = 0.017). For the most statistically significant prognostic marker, favorable prognosis was significantly associated with a higher number of GM per patient (medians: 7 vs. 1.5, = 0.009). FWC-TA derived from routine PET/MRI Dixon acquisitions shows good inter-operator agreement, generates biological relevant information related to TLG, GM count, and provides prognostic information that can unlock new clinical applications for CRC patients.
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http://dx.doi.org/10.3390/cancers13112715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199380PMC
May 2021

Understanding PI-QUAL for prostate MRI quality: a practical primer for radiologists.

Insights Imaging 2021 May 1;12(1):59. Epub 2021 May 1.

Department of Radiology, University College London Hospital NHS Foundation Trust, London, UK.

Prostate magnetic resonance imaging (MRI) of high diagnostic quality is a key determinant for either detection or exclusion of prostate cancer. Adequate high spatial resolution on T2-weighted imaging, good diffusion-weighted imaging and dynamic contrast-enhanced sequences of high signal-to-noise ratio are the prerequisite for a high-quality MRI study of the prostate. The Prostate Imaging Quality (PI-QUAL) score was created to assess the diagnostic quality of a scan against a set of objective criteria as per Prostate Imaging-Reporting and Data System recommendations, together with criteria obtained from the image. The PI-QUAL score is a 1-to-5 scale where a score of 1 indicates that all MR sequences (T2-weighted imaging, diffusion-weighted imaging and dynamic contrast-enhanced sequences) are below the minimum standard of diagnostic quality, a score of 3 means that the scan is of sufficient diagnostic quality, and a score of 5 implies that all three sequences are of optimal diagnostic quality. The purpose of this educational review is to provide a practical guide to assess the quality of prostate MRI using PI-QUAL and to familiarise the radiologist and all those involved in prostate MRI with this scoring system. A variety of images are also presented to demonstrate the difference between suboptimal and good prostate MR scans.
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http://dx.doi.org/10.1186/s13244-021-00996-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088425PMC
May 2021

Evaluation of PSA and PSA Density in a Multiparametric Magnetic Resonance Imaging-Directed Diagnostic Pathway for Suspected Prostate Cancer: The INNOVATE Trial.

Cancers (Basel) 2021 Apr 20;13(8). Epub 2021 Apr 20.

Centre for Medical Imaging, University College London, London WC1E 6BT, UK.

: To assess the clinical outcomes of mpMRI before biopsy and evaluate the space remaining for novel biomarkers. The INNOVATE study was set up to evaluate the validity of novel fluidic biomarkers in men with suspected prostate cancer who undergo pre-biopsy mpMRI. We report the characteristics of this clinical cohort, the distribution of clinical serum biomarkers, PSA and PSA density (PSAD), and compare the mpMRI Likert scoring system to the Prostate Imaging-Reporting and Data System v2.1 (PI-RADS) in men undergoing biopsy. : 340 men underwent mpMRI to evaluate suspected prostate cancer. 193/340 (57%) men had subsequent MRI-targeted prostate biopsy. Clinically significant prostate cancer (csigPCa), i.e., overall Gleason ≥ 3 + 4 of any length OR maximum cancer core length (MCCL) ≥4 mm of any grade including any 3 + 3, was found in 96/195 (49%) of biopsied patients. Median PSA (and PSAD) was 4.7 (0.20), 8.0 (0.17), and 9.7 (0.31) ng/mL (ng/mL/mL) in mpMRI scored Likert 3,4,5 respectively for men with csigPCa on biopsy. The space for novel biomarkers was shown to be within the group of men with mpMRI scored Likert3 (178/340) and 4 (70/350), in whom an additional of 40% (70/178) men with mpMRI-scored Likert3, and 37% (26/70) Likert4 could have been spared biopsy. PSAD is already considered clinically in this cohort to risk stratify patients for biopsy, despite this 67% (55/82) of men with mpMRI-scored Likert3, and 55% (36/65) Likert4, who underwent prostate biopsy had a PSAD below a clinical threshold of 0.15 (or 0.12 for men aged <50 years). Different thresholds of PSA and PSAD were assessed in mpMRI-scored Likert4 to predict csigPCa on biopsy, to achieve false negative levels of ≤5% the proportion of patients whom who test as above the threshold were unsuitably high at 86 and 92% of patients for PSAD and PSA respectively. When PSA was re tested in a sub cohort of men repeated PSAD showed its poor reproducibility with 43% (41/95) of patients being reclassified. After PI-RADS rescoring of the biopsied lesions, 66% (54/82) of the Likert3 lesions received a different PI-RADS score. : The addition of simple biochemical and radiological markers (Likert and PSAD) facilitate the streamlining of the mpMRI-diagnostic pathway for suspected prostate cancer but there remains scope for improvement, in the introduction of novel biomarkers for risk assessment in Likert3 and 4 patients, future application of novel biomarkers tested in a Likert cohort would also require re-optimization around Likert3/PI-RADS2, as well as reproducibility testing.
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http://dx.doi.org/10.3390/cancers13081985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074769PMC
April 2021

Update from the ReIMAGINE Prostate Cancer Screening Study NCT04063566: Inviting Men for Prostate Cancer Screening Using Magnetic Resonance Imaging.

Eur Urol Focus 2021 May 23;7(3):503-505. Epub 2021 Apr 23.

UCL Division of Surgical & Interventional Sciences, University College London, London, UK; Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK.

ReIMAGINE Screening is a single-centre study assessing the feasibility of biparametric magnetic resonance imaging as a screening tool for prostate cancer. The study outcomes will take us a step towards more accurate and less harmful prostate cancer screening.
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http://dx.doi.org/10.1016/j.euf.2021.03.027DOI Listing
May 2021

Standardisation of prostate multiparametric MRI across a hospital network: a London experience.

Insights Imaging 2021 Apr 20;12(1):52. Epub 2021 Apr 20.

Centre for Medical Imaging, University College London, 2nd Floor Charles Bell House, 43-45 Foley Street, London, W1W 7TS, UK.

Objectives: National guidelines recommend prostate multiparametric (mp) MRI in men with suspected prostate cancer before biopsy. In this study, we explore prostate mpMRI protocols across 14 London hospitals and determine whether standardisation improves diagnostic quality.

Methods: An MRI physicist facilitated mpMRI set-up across several regional hospitals, working together with experienced uroradiologists who judged diagnostic quality. Radiologists from the 14 hospitals participated in the assessment and optimisation of prostate mpMRI image quality, assessed according to both PiRADSv2 recommendations and on the ability to "rule in" and/or "rule out" prostate cancer. Image quality and sequence parameters of representative mpMRI scans were evaluated across 23 MR scanners. Optimisation visits were performed to improve image quality, and 2 radiologists scored the image quality pre- and post-optimisation.

Results: 20/23 mpMRI protocols, consisting of 111 sequences, were optimised by modifying their sequence parameters. Pre-optimisation, only 15% of T2W images were non-diagnostic, whereas 40% of ADC maps, 50% of high b-value DWI and 41% of DCE-MRI were considered non-diagnostic. Post-optimisation, the scores were increased with 80% of ADC maps, 74% of high b-value DWI and 88% of DCE-MRI to be partially or fully diagnostic. T2W sequences were not optimised, due to their higher baseline quality scores.

Conclusions: Targeted intervention at a regional level can improve the diagnostic quality of prostate mpMRI protocols, with implications for improving prostate cancer detection rates and targeted biopsies.
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http://dx.doi.org/10.1186/s13244-021-00990-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058121PMC
April 2021

F-FDG PET/MRI for staging and interim response assessment in pediatric and adolescent Hodgkin lymphoma: a prospective study with F-FDG PET/CT as reference standard.

J Nucl Med 2021 Feb 19. Epub 2021 Feb 19.

University College London Hospital - department of Radiology, United Kingdom.

Treatment regimens for pediatric Hodgkin's lymphoma (HL) depend on accurate staging and treatment response assessment, based on accurate disease distribution and metabolic activity depiction. With the aim of radiation dose reduction, we compared the diagnostic performance of F-FDG PET/MR to a F-FDG PET/CT reference standard for staging and response assessment. Twenty-four patients (mean age 15.4 years, range 8-19.5 years) with histologically proven HL were prospectively and consecutively recruited in 2015 and 2016, undergoing both F-FDG PET/CT and F-FDG PET/MRI at initial staging (N = 24) and at response assessment (N = 21). Diagnostic accuracy of F-FDG PET/MRI for both nodal and extra-nodal disease was compared to F-FDG PET/CT, which was considered as the reference standard. Discrepancies were retrospectively classified as perceptual or technical errors and F-FDG PET/MRI and F-FDG PET/CT were corrected by removing perceptual error. Agreement with Ann-Arbor staging and Deauville grading was also assessed. For nodal and extranodal sites combined, corrected staging F-FDG PET/MRI sensitivity was 100% (95% confidence interval (CI) 96.7%-100%), specificity 99.5% (95%CI 98.3%-99.9%). Corrected response assessment F-FDG PET/MRI sensitivity was 83.3% (95%CI 36.5%-99.1%), specificity 100% (95%CI 99.2%-100%). Modified Ann-Arbor staging agreement between F18-FDG PET/CT and F-FDG PET/MRI was perfect (k = 1.0, = 0.000). Deauville grading agreement between F-FDG PET/MRI and F-FDG PET/CT was excellent (k = 0.835, = 0.000). F-FDG PET/MRI is a promising alternative to F-FDG PET/CT for staging and response assessment in children with Hodgkin lymphoma.
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http://dx.doi.org/10.2967/jnumed.120.260059DOI Listing
February 2021

Long-term biopsy outcomes in prostate cancer patients treated with external beam radiotherapy: a systematic review and meta-analysis.

Prostate Cancer Prostatic Dis 2021 Sep 8;24(3):612-622. Epub 2021 Feb 8.

Centre for Medical Imaging, University College London, London, UK.

Background: Biopsy after external beam radiotherapy (EBRT) for localised prostate cancer (PCa) is an infrequently used but potentially valuable technique to evaluate local recurrence and predict long-term outcomes.

Methods: We performed a meta-analysis of studies until March 2020 where a post-EBRT biopsy was performed on patients with low-to intermediate risk PCa, according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The primary outcome was the aggregate post-EBRT positive biopsy rate (≥2 years after EBRT) and the associated odds ratio (OR) of a positive biopsy on biochemical failure (BCF), distant metastasis-free survival (DMFS) and prostate cancer-specific mortality (PCSM). A sensitivity analysis was performed which examined biopsy rate as a function of post-EBRT biopsy protocol, PCa risk, ADT usage and radiation dose.

Results: A total of 22 studies were included, of which 10 were randomised controlled trials and 12 were cohort studies. Nine out of the 22 studies used dosing regimens consistent with the 2020 NCCN radiotherapy guidelines. The weighted-average positive biopsy rate across all 22 studies was 32% (95%-CI: 25-39%, n = 3017). In studies where post-treatment biopsy was part of the study protocol, the rate was 35% (95%-CI: 21-38%, n = 2450). In the subgroup of studies that conformed to the 2020 NCCN radiotherapy guidelines, this rate was 22% (95% CI: 19-41%, n = 832). Patients with positive biopsy had a 10-fold higher odds of developing BCF (OR of 10.3, 95%-CI: 3.7-28.7, p < 0.00001), 3-fold higher odds of developing distant metastasis (OR 3.1, 95%-CI: 2.1-4.7, p < 0.00001) and 5-fold higher odds of dying from their PCa (OR 5.1, 95%-CI: 2.6-10, p < 0.00001).

Conclusion: A positive biopsy after EBRT is associated with a poor prognosis compared to a negative biopsy. The post-EBRT positive biopsy rate is an important measure which provides additional insight when comparing EBRT to other treatment modalities for PCa.
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http://dx.doi.org/10.1038/s41391-021-00323-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384630PMC
September 2021

Whole Body 3.0 T Magnetic Resonance Imaging in Lymphomas: Comparison of Different Sequence Combinations for Staging Hodgkin's and Diffuse Large B Cell Lymphomas.

J Pers Med 2020 Dec 16;10(4). Epub 2020 Dec 16.

Centre for Medical Imaging, University College London, 2nd Floor Charles Bell House, 43-45 Foley Street, London W1W 7TS, UK.

To investigate the diagnostic value of different whole-body magnetic resonance imaging (WB-MRI) protocols for staging Hodgkin and diffuse-large B-cell lymphomas (HL and DLBCL), twenty-two patients (M/F 12/10, median age 32, range 22-87, HL/DLBCL 14/8) underwent baseline WB-MRI and F-2-fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography (PET) fused with computed tomography (CT) scan F-FDG-PET-CT. The 3.0 T WB-MRI was performed using pre-contrast modified Dixon (mDixon), T2-weighted turbo-spin-echo (TSE), diffusion-weighted-imaging (DWI), dynamic-contrast-enhanced (DCE) liver/spleen, contrast-enhanced (CE) lung MRI and CE whole-body mDixon. WB-MRI scans were divided into: (1) "WB-MRI ": whole-body DWI + in-phase mDixon (2) "WB-MRI ": whole-body T2-TSE (3) "WB-MRI ": whole-body CE mDixon + DCE liver/spleen and CE lung mDixon (4) "WB-MRI All ": the entire protocol. Two radiologists evaluated WB-MRIs at random, independently and then in consensus. Two nuclear-medicine-physicians reviewed F-FDG PET-CT in consensus. An enhanced-reference-standard (ERS) was derived using all available baseline and follow-up imaging. The sensitivity and specificity of WB-MRI protocols for nodal and extra-nodal staging was derived against the ERS. Agreement between the WB-MRI protocols and the ERS for overall staging was assessed using kappa statistic. For consensus WB-MRI, the sensitivity and specificity for nodal staging were 75%, 98% for WB-MRI , 76%, 98% for WB-MRI , 83%, 99% for WB-MRI and 87%, 100% for WB-MRI . The sensitivity and specificity for extra-nodal staging were 67% 100% for WB-MRI , 89%, 100% for WB-MRI , 89%, 100% for WB-MRI and 100%, 100% for the WB-MRI . The consensus WB-MRI read had perfect agreement with the ERS for overall staging [kappa = 1.00 (95% CI: 1.00-1.00)]. The best diagnostic performance is achieved combining all available WB-MRI sequences.
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http://dx.doi.org/10.3390/jpm10040284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765916PMC
December 2020

A critical evaluation of visual proportion of Gleason 4 and maximum cancer core length quantified by histopathologists.

Sci Rep 2020 10 14;10(1):17177. Epub 2020 Oct 14.

Department of Urology, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.

Gleason score 7 prostate cancer with a higher proportion of pattern 4 (G4) has been linked to genomic heterogeneity and poorer patient outcome. The current assessment of G4 proportion uses estimation by a pathologist, with a higher proportion of G4 more likely to trigger additional imaging and treatment over active surveillance. This estimation method has been shown to have inter-observer variability. Fifteen patients with Prostate Grade Group (GG) 2 (Gleason 3 + 4) and fifteen patients with GG3 (Gleason 4 + 3) disease were selected from the PROMIS study with 192 haematoxylin and eosin-stained slides scanned. Two experienced uropathologists assessed the maximum cancer core length (MCCL) and G4 proportion using the current standard method (visual estimation) followed by detailed digital manual annotation of each G4 area and measurement of MCCL (planimetric estimation) using freely available software by the same two experts. We aimed to compare visual estimation of G4 and MCCL to a pathologist-driven digital measurement. We show that the visual and digital MCCL measurement differs up to 2 mm in 76.6% (23/30) with a high degree of agreement between the two measurements; Visual gave a median MCCL of 10 ± 2.70 mm (IQR 4, range 5-15 mm) compared to digital of 9.88 ± 3.09 mm (IQR 3.82, range 5.01-15.7 mm) (p = 0.64) The visual method for assessing G4 proportion over-estimates in all patients, compared to digital measurements [median 11.2% (IQR 38.75, range 4.7-17.9%) vs 30.4% (IQR 18.37, range 12.9-50.76%)]. The discordance was higher as the amount of G4 increased (Bias 18.71, CI 33.87-48.75, r 0.7, p < 0.0001). Further work on assessing actual G4 burden calibrated to clinical outcomes might lead to the use of differing G4 thresholds of significance if the visual estimation is used or by incorporating semi-automated methods for G4 burden measurement.
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http://dx.doi.org/10.1038/s41598-020-73524-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561724PMC
October 2020

False Positive Multiparametric Magnetic Resonance Imaging Phenotypes in the Biopsy-naïve Prostate: Are They Distinct from Significant Cancer-associated Lesions? Lessons from PROMIS.

Eur Urol 2021 01 10;79(1):20-29. Epub 2020 Oct 10.

UCL Division of Surgery & Interventional Science, University College London, London, UK; Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK.

Background: False positive multiparametric magnetic resonance imaging (mpMRI) phenotypes prompt unnecessary biopsies. The Prostate MRI Imaging Study (PROMIS) provides a unique opportunity to explore such phenotypes in biopsy-naïve men with raised prostate-specific antigen (PSA) and suspected cancer.

Objective: To compare mpMRI lesions in men with/without significant cancer on transperineal mapping biopsy (TPM).

Design, Setting, And Participants: PROMIS participants (n=235) underwent mpMRI followed by a combined biopsy procedure at University College London Hospital, including 5-mm TPM as the reference standard. Patients were divided into four mutually exclusive groups according to TPM findings: (1) no cancer, (2) insignificant cancer, (3) definition 2 significant cancer (Gleason ≥3+4 of any length and/or maximum cancer core length ≥4mm of any grade), and (4) definition 1 significant cancer (Gleason ≥4+3 of any length and/or maximum cancer core length ≥6mm of any grade).

Outcome Measurements And Statistical Analysis: Index and/or additional lesions present in 178 participants were compared between TPM groups in terms of number, conspicuity, volume, location, and radiological characteristics.

Results And Limitations: Most lesions were located in the peripheral zone. More men with significant cancer had two or more lesions than those without significant disease (67% vs 37%; p< 0.001). In the former group, index lesions were larger (mean volume 0.68 vs 0.50 ml; p< 0.001, Wilcoxon test), more conspicuous (Likert 4-5: 79% vs 22%; p< 0.001), and diffusion restricted (mean apparent diffusion coefficient [ADC]: 0.73 vs 0.86; p< 0.001, Wilcoxon test). In men with Likert 3 index lesions, logPSA density and index lesion ADC were significant predictors of definition 1/2 disease in a logistic regression model (mean cross-validated area under the receiver-operator characteristic curve: 0.77 [95% confidence interval: 0.67-0.87]).

Conclusions: Significant cancer-associated MRI lesions in biopsy-naïve men have clinical-radiological differences, with lesions seen in prostates without significant disease. MRI-calculated PSA density and ADC could predict significant cancer in those with indeterminate MRI phenotypes.

Patient Summary: Magnetic resonance imaging (MRI) lesions that mimic prostate cancer but are, in fact, benign prompt unnecessary biopsies in thousands of men with raised prostate-specific antigen. In this study we found that, on closer look, such false positive lesions have different features from cancerous ones. This means that doctors could potentially develop better tools to identify cancer on MRI and spare some patients from unnecessary biopsies.
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http://dx.doi.org/10.1016/j.eururo.2020.09.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772750PMC
January 2021

Natural history of prostate cancer on active surveillance: stratification by MRI using the PRECISE recommendations in a UK cohort.

Eur Radiol 2021 Mar 30;31(3):1644-1655. Epub 2020 Sep 30.

Division of Surgery & Interventional Science, University College London, 3rd Floor, Charles Bell House, 43-45 Foley St., London, W1W 7TS, UK.

Objectives: The PRECISE recommendations for magnetic resonance imaging (MRI) in patients on active surveillance (AS) for prostate cancer (PCa) include repeated measurement of each lesion, and attribution of a PRECISE radiological progression score for the likelihood of clinically significant change over time. We aimed to compare the PRECISE score with clinical progression in patients who are managed using an MRI-led AS protocol.

Methods: A total of 553 patients on AS for low- and intermediate-risk PCa (up to Gleason score 3 + 4) who had two or more MRI scans performed between December 2005 and January 2020 were included. Overall, 2161 scans were retrospectively re-reported by a dedicated radiologist to give a PI-RADS v2 score for each scan and assess the PRECISE score for each follow-up scan. Clinical progression was defined by histological progression to ≥ Gleason score 4 + 3 (Gleason Grade Group 3) and/or initiation of active treatment. Progression-free survival was assessed using Kaplan-Meier curves and log-rank test was used to assess differences between curves.

Results: Overall, 165/553 (30%) patients experienced the primary outcome of clinical progression (median follow-up, 74.5 months; interquartile ranges, 53-98). Of all patients, 313/553 (57%) did not show radiological progression on MRI (PRECISE 1-3), of which 296/313 (95%) had also no clinical progression. Of the remaining 240/553 patients (43%) with radiological progression on MRI (PRECISE 4-5), 146/240 (61%) experienced clinical progression (p < 0.0001). Patients with radiological progression on MRI (PRECISE 4-5) showed a trend to an increase in PSA density.

Conclusions: Patients without radiological progression on MRI (PRECISE 1-3) during AS had a very low likelihood of clinical progression and many could avoid routine re-biopsy.

Key Points: • Patients without radiological progression on MRI (PRECISE 1-3) during AS had a very low likelihood of clinical progression and many could avoid routine re-biopsy. • Clinical progression was almost always detectable in patients with radiological progression on MRI (PRECISE 4-5) during AS. • Patients with radiological progression on MRI (PRECISE 4-5) during AS showed a trend to an increase in PSA density.
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http://dx.doi.org/10.1007/s00330-020-07256-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880925PMC
March 2021

Prostate cancer measurements on serial MRI during active surveillance: it's time to be PRECISE.

Br J Radiol 2020 Dec 21;93(1116):20200819. Epub 2020 Sep 21.

Division of Surgery & Interventional Science, University College London, London, UK.

Objective: The PRECISE criteria for reporting multiparametric MRI in patients on active surveillance (AS) for prostate cancer (PCa) score the likelihood of clinically significant change over time using a 1-5 scale, where 4 or 5 indicates radiological progression. According to the PRECISE recommendations, the index lesion size can be reported using different definitions of volume (planimetry or ellipsoid formula) or by measuring one or two diameters. We compared different measurements using planimetry as the reference standard and stratified changes according to the PRECISE scores.

Methods: We retrospectively analysed 196 patients on AS with PCa confirmed by targeted biopsy who had two MR scans (baseline and follow-up). Lesions were measured on weighted imaging (WI) according to all definitions. A PRECISE score was assessed for each patient.

Results: The ellipsoid formula exhibited the highest correlation with planimetry at baseline (ρ = 0.97) and follow-up (ρ = 0.98) imaging, compared to the biaxial measurement and single maximum diameter. There was a significant difference ( < 0.001) in the yearly percentage volume change between radiological regression/stability (PRECISE 2-3) and progression (PRECISE 4-5) for planimetry (39.64%) and for the ellipsoid formula (46.78%).

Conclusion: The ellipsoid formula could be used to monitor tumour growth during AS. Evidence of a significant yearly percentage volume change between radiological regression/stability (PRECISE 2-3) and progression (PRECISE 4-5) has been also observed.

Advances In Knowledge: The ellipsoid formula is a reasonable surrogate for planimetry in capturing tumour volume changes on WI in patients on imaging-led AS. This is also associated with radiological changes using the PRECISE recommendations.
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http://dx.doi.org/10.1259/bjr.20200819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716009PMC
December 2020

Update on Multiparametric Prostate MRI During Active Surveillance: Current and Future Trends and Role of the PRECISE Recommendations.

AJR Am J Roentgenol 2021 04 3;216(4):943-951. Epub 2021 Feb 3.

Division of Surgery & Interventional Science, University College London, 3rd Fl, Charles Bell House, 43-45 Foley St, London, UK, W1W 7TS.

Active surveillance for low-to-intermediate risk prostate cancer is a conservative management approach that aims to avoid or delay active treatment until there is evidence of disease progression. In recent years, multiparametric MRI (mpMRI) has been increasingly used in active surveillance and has shown great promise in patient selection and monitoring. This has been corroborated by publication of the Prostate Cancer Radiologic Estimation of Change in Sequential Evaluation (PRECISE) recommendations, which define the ideal reporting standards for mpMRI during active surveillance. The PRECISE recommendations include a system that assigns a score from 1 to 5 (the PRECISE score) for the assessment of radiologic change on serial mpMRI scans. PRECISE scores are defined as follows: a score of 3 indicates radiologic stability, a score of 1 or 2 denotes radiologic regression, and a score of 4 or 5 indicates radiologic progression. In the present study, we discuss current and future trends in the use of mpMRI during active surveillance and illustrate the natural history of prostate cancer on serial scans according to the PRECISE recommendations. We highlight how the ability to classify radiologic change on mpMRI with use of the PRECISE recommendations helps clinical decision making.
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http://dx.doi.org/10.2214/AJR.20.23985DOI Listing
April 2021

An optimized and highly repeatable MRI acquisition and processing pipeline for quantitative susceptibility mapping in the head-and-neck region.

Magn Reson Med 2020 12 3;84(6):3206-3222. Epub 2020 Jul 3.

Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom.

Purpose: Quantitative Susceptibility Mapping (QSM) is an emerging technique sensitive to disease-related changes including oxygenation. It is extensively used in brain studies and has increasing clinical applications outside the brain. Here we present the first MRI acquisition protocol and QSM pipeline optimized for the head-and-neck region together with a repeatability analysis performed in healthy volunteers.

Methods: We investigated both the intrasession and the intersession repeatability of the optimized method in 10 subjects. We also implemented two, Tikhonov-regularisation-based susceptibility calculation techniques that were found to have higher contrast-to-noise than existing methods in the head-and-neck region. Repeatability was evaluated by calculating the distributions of susceptibility differences between repeated scans and the corresponding minimum detectable effect sizes (MDEs).

Results: Deep brain regions had higher QSM repeatability than neck regions. As expected, intrasession repeatability was generally better than intersession repeatability. Susceptibility maps calculated using projection onto dipole fields for background field removal were more repeatable than using the Laplacian boundary value method in the head-and-neck region. Small (short-axis diameter <5 mm) lymph nodes had the lowest repeatability (MDE = 0.27 ppm) as imperfect segmentation included some of the surrounding paramagnetic fatty fascia, highlighting the importance of accurate region delineation. MDEs in the larger lymph nodes (0.16 ppm), submandibular glands (0.10 ppm), and especially the parotid glands (0.06 ppm) were much lower, comparable to those of the brain regions.

Conclusions: The high repeatability of the acquisition and pipeline optimized for QSM will facilitate clinical studies in the head-and-neck region.
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http://dx.doi.org/10.1002/mrm.28377DOI Listing
December 2020

Noninvasive diffusion magnetic resonance imaging of brain tumour cell size for the early detection of therapeutic response.

Sci Rep 2020 06 8;10(1):9223. Epub 2020 Jun 8.

Centre for Advanced Biomedical Imaging, University College London, London, UK.

Cancer cells differ in size from those of their host tissue and are known to change in size during the processes of cell death. A noninvasive method for monitoring cell size would be highly advantageous as a potential biomarker of malignancy and early therapeutic response. This need is particularly acute in brain tumours where biopsy is a highly invasive procedure. Here, diffusion MRI data were acquired in a GL261 glioma mouse model before and during treatment with Temozolomide. The biophysical model VERDICT (Vascular Extracellular and Restricted Diffusion for Cytometry in Tumours) was applied to the MRI data to quantify multi-compartmental parameters connected to the underlying tissue microstructure, which could potentially be useful clinical biomarkers. These parameters were compared to ADC and kurtosis diffusion models, and, measures from histology and optical projection tomography. MRI data was also acquired in patients to assess the feasibility of applying VERDICT in a range of different glioma subtypes. In the GL261 gliomas, cellular changes were detected according to the VERDICT model in advance of gross tumour volume changes as well as ADC and kurtosis models. VERDICT parameters in glioblastoma patients were most consistent with the GL261 mouse model, whilst displaying additional regions of localised tissue heterogeneity. The present VERDICT model was less appropriate for modelling more diffuse astrocytomas and oligodendrogliomas, but could be tuned to improve the representation of these tumour types. Biophysical modelling of the diffusion MRI signal permits monitoring of brain tumours without invasive intervention. VERDICT responds to microstructural changes induced by chemotherapy, is feasible within clinical scan times and could provide useful biomarkers of treatment response.
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http://dx.doi.org/10.1038/s41598-020-65956-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280197PMC
June 2020

Negative Predictive Value of Multiparametric Magnetic Resonance Imaging in the Detection of Clinically Significant Prostate Cancer in the Prostate Imaging Reporting and Data System Era: A Systematic Review and Meta-analysis.

Eur Urol 2020 09 20;78(3):402-414. Epub 2020 May 20.

Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.

Context: Prebiopsy multiparametric magnetic resonance imaging (mpMRI) is increasingly used in prostate cancer diagnosis. The reported negative predictive value (NPV) of mpMRI is used by some clinicians to aid in decision making about whether or not to proceed to biopsy.

Objective: We aim to perform a contemporary systematic review that reflects the latest literature on optimal mpMRI techniques and scoring systems to update the NPV of mpMRI for clinically significant prostate cancer (csPCa).

Evidence Acquisition: We conducted a systematic literature search and included studies from 2016 to September 4, 2019, which assessed the NPV of mpMRI for csPCa, using biopsy or clinical follow-up as the reference standard. To ensure that studies included in this analysis reflect contemporary practice, we only included studies in which mpMRI findings were interpreted according to the Prostate Imaging Reporting and Data System (PIRADS) or similar Likert grading system. We define negative mpMRI as either (1) PIRADS/Likert 1-2 or (2) PIRADS/Likert 1-3; csPCa was defined as either (1) Gleason grade group ≥2 or (2) Gleason grade group ≥3. We calculated NPV separately for each combination of negative mpMRI and csPCa.

Evidence Synthesis: A total of 42 studies with 7321 patients met our inclusion criteria and were included for analysis. Using definition (1) for negative mpMRI and csPCa, the pooled NPV for biopsy-naïve men was 90.8% (95% confidence interval [CI] 88.1-93.1%). When defining csPCa using definition (2), the NPV for csPCa was 97.1% (95% CI 94.9-98.7%). Calculation of the pooled NPV using definition (2) for negative mpMRI and definition (1) for csPCa yielded the following: 86.8% (95% CI 80.1-92.4%). Using definition (2) for both negative mpMRI and csPCa, the pooled NPV from two studies was 96.1% (95% CI 93.4-98.2%).

Conclusions: Multiparametric MRI of the prostate is generally an accurate test for ruling out csPCa. However, we observed heterogeneity in the NPV estimates, and local institutional data should form the basis of decision making if available.

Patient Summary: The negative predictive values should assist in decision making for clinicians considering not proceeding to biopsy in men with elevated age-specific prostate-specific antigen and multiparametric magnetic resonance imaging reported as negative (or equivocal) on Prostate Imaging Reporting and Data System/Likert scoring. Some 7-10% of men, depending on the setting, will miss a diagnosis of clinically significant cancer if they do not proceed to biopsy. Given the institutional variation in results, it is of upmost importance to base decision making on local data if available.
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http://dx.doi.org/10.1016/j.eururo.2020.03.048DOI Listing
September 2020

The Role of Percentage of Prostate-specific Antigen Reduction After Focal Therapy Using High-intensity Focused Ultrasound for Primary Localised Prostate Cancer. Results from a Large Multi-institutional Series.

Eur Urol 2020 08 19;78(2):155-160. Epub 2020 May 19.

Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK; Division of Surgery and Interventional Science, University College London, London, UK.

Focal therapy (FT) for prostate cancer (PCa) is emerging as a novel therapeutic approach for patients with low- to intermediate-risk disease, in order to provide acceptable oncological control, whilst avoiding the side effects of radical treatment. Evidence regarding the ideal follow-up strategy and the significance of prostate-specific antigen (PSA) kinetics after treatment is needed. In this study, we aimed to assess the value of the percentage of PSA reduction (%PSA reduction) after FT in predicting the likelihood of any additional treatment or any radical treatment. We retrospectively analysed a multicentre cohort of 703 men receiving FT for low- and intermediate-risk PCa. Overall, the rates of any additional treatment and any radical treatment were 30% and 13%, respectively. The median follow-up period was 41 mo. The median %PSA reduction after FT was 73%. At Cox multivariable analysis, %PSA reduction was an independent predictor of any additional treatment (hazard ratio [HR]: 0.96; p < 0.001) and radical treatment (HR: 0.97; p < 0.001) after FT. For %PSA reduction of>90%, the probability of any additional treatment within 5 yr was 20%. Conversely, for %PSA reduction of <10%, the probability of receiving any additional treatment within 5 yr was roughly 70%. This study is the first to assess the role of %PSA reduction in the largest multicentre cohort of men receiving FT for PCa. Given the lack of standardised follow-up strategies in the FT field, the use of the %PSA reduction should be considered. PATIENT SUMMARY: The percentage of prostate-specific antigen reduction is a useful tool to assess men following focal therapy (FT). It can assist the urologist in setting up an appropriate follow-up and during post-FT patient counselling.
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http://dx.doi.org/10.1016/j.eururo.2020.04.068DOI Listing
August 2020

What Type of Prostate Cancer Is Systematically Overlooked by Multiparametric Magnetic Resonance Imaging? An Analysis from the PROMIS Cohort.

Eur Urol 2020 08 1;78(2):163-170. Epub 2020 May 1.

UCL Division of Surgery & Interventional Science, University College London, London, UK; Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK.

Background: All risk stratification strategies in cancer overlook a spectrum of disease. The Prostate MR Imaging Study (PROMIS) provides a unique opportunity to explore cancers that are overlooked by multiparametric magnetic resonance imaging (mpMRI).

Objective: To summarise attributes of cancers that are systematically overlooked by mpMRI.

Design, Setting, And Participants: PROMIS tested performance of mpMRI and transrectal ultrasonography (TRUS)-guided biopsy, using 5 mm template mapping (TPM) biopsy as the reference standard.

Outcome Measurements And Statistical Analysis: Outcomes were overall and maximum Gleason scores, maximum cancer core length (MCCL), and prostate-specific antigen density (PSAD). Cancer attributes were compared between cancers that were overlooked and those that were detected.

Results And Limitations: Of men with cancer, 7% (17/230; 95% confidence interval [CI] 4.4-12%) had significant disease overlooked by mpMRI according to definition 1 (Gleason ≥ 4 + 3 of any length or MCCL ≥ 6 mm of any grade) and 13% (44/331; 95% CI 9.8-17%) according to definition 2 (Gleason ≥ 3 + 4 of any length or MCCL ≥ 4 mm). In comparison, TRUS-guided biopsy overlooked 52% (119/230; 95% CI 45-58%) of significant disease by definition 1 and 40% (132/331; 95% CI 35-45%) by definition 2. Prostate cancers undetected by mpMRI had significantly lower overall and maximum Gleason scores (p = 0.0007; p < 0.0001) and shorter MCCL (median difference: 3 mm [5 vs 8 mm], p < 0.0001; 95% CI 1-3) than cancers that were detected. No tumours with overall Gleason score > 3 + 4 (Gleason Grade Groups 3-5; 95% CI 0-6.4%) or maximum Gleason score > 4 + 3 (Gleason Grade Groups 4-5; 95% CI 0-8.0%) on TPM biopsy were undetected by mpMRI. Application of a PSAD threshold of 0.15 reduced the proportion of men with undetected cancer to 5% (12/230; 95% CI 2.7-8.9%) for definition 1 and 9% (30/331; 95% CI 6.2-13%) for definition 2. Application of a PSAD threshold of 0.10 reduced the proportion of men with undetected disease to 3% (6/230; 95% CI 1.0-5.6%) for definition 1 cancer and to 3% (11/331; 95% CI 1.7-5.9%) for definition 2 cancer. Limitations were post hoc analysis and uncertain significance of undetected lesions.

Conclusions: Overall, a small proportion of cancers are overlooked by mpMRI, with estimates ranging from 4.4% (lower boundary of 95% CI for definition 1) to 17% (upper boundary of 95% CI for definition 2). Prostate cancers undetected by mpMRI are of lower grade and shorter length than cancers that are detected.

Patient Summary: Prostate cancers that are undetected by magnetic resonance imaging (MRI) are smaller and less aggressive than those that are detected, and none of the most aggressive cancers are overlooked by MRI.
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http://dx.doi.org/10.1016/j.eururo.2020.04.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397509PMC
August 2020
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