Multiparametric Prostate Magnetic Resonance Imaging and Cognitively Targeted Transperineal Biopsy in Patients With Previous Abdominoperineal Resection and Suspicion of Prostate Cancer.

OBJECTIVE: To report our experience with a combination of prostate magnetic resonance imaging (MRI) and transperineal ultrasound biopsy for evaluating the prostate in patients with elevated prostate-specific antigen (PSA) who have previously undergone abdominoperineal resection (APR). PATIENTS AND METHODS: We reviewed the records of 11 patients with a history of APR and clinical suspicion of prostate cancer due to elevated PSA levels over a 5-year period. All patients underwent multiparametric MRI at our institution prior to biopsy. MR diagnoses were validated either by transperineal ultrasound biopsy (Likert 3-5) guided by visual registration or clinical follow-up >6 months (Likert 1-2). RESULTS: All 7 cases with highly suspicious lesions (Likert 4-5) on MRI demonstrated cancer-1 case of Gleason 3 + 3 and 6 cases of Gleason ≥3 + 4 disease. Two cases with Likert 3 MR lesions revealed benign tissue upon biopsy. Two patients with no suspicious lesions on MRI were followed-up clinically, with PSA levels remaining stable over a mean period of 17.5 months (range 7-28 months). CONCLUSION: The use of prebiopsy multiparametric prostate MRI and subsequent cognitively targeted transperineal biopsy guided by visual registration can aid in the diagnostic pathway of patients with APR and a suspicion of prostate cancer.Author 1 has received a research grant from RWTH Aachen University Hospital (Aachen, Germany). Author 6 acknowledges support from Cancer Research UK, National Institute of Health Research Cambridge Biomedical Research Centre, Cancer Research UK and the Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester and the Cambridge Experimental Cancer Medicine Centre.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.urology.2016.04.03

Repeat prostate biopsy strategies after initial negative biopsy: meta-regression comparing cancer detection of transperineal, transrectal saturation and MRI guided biopsy.

INTRODUCTION: There is no consensus on how to investigate men with negative transrectal ultrasound guided prostate biopsy (TRUS-B) but ongoing suspicion of cancer. Three strategies used are transperineal (TP-B), transrectal saturation (TS-B) and MRI-guided biopsy (MRI-B). We compared cancer yields of these strategies. METHODS: Papers were identified by search of Pubmed, Embase and Ovid Medline. Included studies investigated biopsy diagnostic yield in men with at least one negative TRUS-B and ongoing suspicion of prostate cancer. Data including age, PSA, number of previous biopsy episodes, number of cores at re-biopsy, cancer yield, and Gleason score of detected cancers were extracted. Meta-regression analyses were used to analyse the data. RESULTS: Forty-six studies were included; 12 of TS-B, 14 of TP-B, and 20 of MRI-B, representing 4,657 patients. Mean patient age, PSA and number of previous biopsy episodes were similar between the strategies. The mean number of biopsy cores obtained by TP-B and TS-B were greater than MRI-B. Cancer detection rates were 30·0%, 36·8%, and 37·6% for TS-B, TP-B, and MRI-B respectively. Meta-regression analysis showed that MRI-B had significantly higher cancer detection than TS-B. There were no significant differences however between MRI-B and TP-B, or TP-B and TS-B. In a sensitivity analysis incorporating number of previous biopsy episodes (36 studies) the difference between MRI-B and TP-B was not maintained resulting in no significant difference in cancer detection between the groups. There were no significant differences in median Gleason scores detected comparing the three strategies. CONCLUSIONS: In the re-biopsy setting, it is unclear which strategy offers the highest cancer detection rate. MRI-B may potentially detect more prostate cancers than other modalities and can achieve this with fewer biopsy cores. However, well-designed prospective studies with standardised outcome measures are needed to accurately compare modalities and define an optimum re-biopsy approach

Comparison of initial and tertiary centre second opinion reads of multiparametric magnetic resonance imaging of the prostate prior to repeat biopsy.

OBJECTIVES: To investigate the value of second-opinion evaluation of multiparametric prostate magnetic resonance imaging (MRI) by subspecialised uroradiologists at a tertiary centre for the detection of significant cancer in transperineal fusion prostate biopsy. METHODS: Evaluation of prospectively acquired initial and second-opinion radiology reports of 158 patients who underwent MRI at regional hospitals prior to transperineal MR/untrasound fusion biopsy at a tertiary referral centre over a 3-year period. Gleason score (GS) 7-10 cancer, positive predictive value (PPV) and negative (NPV) predictive value (±95 % confidence intervals) were calculated and compared by Fisher's exact test. RESULTS: Disagreement between initial and tertiary centre second-opinion reports was observed in 54 % of cases (86/158). MRIs had a higher NPV for GS 7-10 in tertiary centre reads compared to initial reports (0.89 ± 0.08 vs 0.72 ± 0.16; p = 0.04), and a higher PPV in the target area for all cancer (0.61 ± 0.12 vs 0.28 ± 0.10; p = 0.01) and GS 7-10 cancer (0.43 ± 0.12 vs 0.2 3 ± 0.09; p = 0.02). For equivocal suspicion, the PPV for GS 7-10 was 0.12 ± 0.11 for tertiary centre and 0.11 ± 0.09 for initial reads; p = 1.00. CONCLUSIONS: Second readings of prostate MRI by subspecialised uroradiologists at a tertiary centre significantly improved both NPV and PPV. Reporter experience may help to reduce overcalling and avoid overtargeting of lesions. KEY POINTS: • Multiparametric MRIs were more often called negative in subspecialist reads (41 % vs 20 %). • Second readings of prostate mpMRIs by subspecialist uroradiologists significantly improved NPV and PPV. • Reporter experience may reduce overcalling and avoid overtargeting of lesions. • Greater education and training of radiologists in prostate MRI interpretation is advised.RWTH Aachen University Hospital (Aachen, Germany), National Institute for Health Research Cambridge Biomedical Research Centre, Cancer Research UK, Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester, Cambridge Experimental Cancer Medicine Centr

Targeted transperineal biopsy of the prostate has limited additional benefit over background cores for larger MRI-identified tumors.

PURPOSE: To compare histological outcomes in patients undergoing MRI-transrectal ultrasound fusion transperineal (MTTP) prostate biopsy and determine the incremental benefit of targeted cores. METHODS: Seventy-six consecutive patients with 89 MRI-identified targets underwent MTTP biopsy. Separate targeted biopsies and background cores were obtained according to a standardized protocol. Target biopsies were considered of added diagnostic value if these cores showed a higher Gleason grade than non-targeted cores taken from the same sector (Group 1, n = 41). Conversely, where background cores demonstrated an equal or higher Gleason grade, target cores were considered to be non-beneficial (Group 2, n = 48). RESULTS: There was no significant difference in age, PSA, prostate volume, time-to-biopsy, and number of cores obtained between the groups. A greater proportion of target cores were positive for cancer (158/228; 69.3 %) compared to background (344/1881; 18.38 %). The median target volume was 0.54 cm(3) for Group 1 (range 0.09-2.79 cm(3)) and 1.65 cm(3) for Group 2 (0.3-9.07 cm(3)), p 1.0 cm.The authors acknowledge research support from Cancer Research UK, National Institute of Health Research Cambridge Biomedical Research Centre, Cancer Research UK and the Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester and the Cambridge Experimental Cancer Medicine Centre.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00345-015-1650-

MRI-derived PRECISE scores for predicting pathologically-confirmed radiological progression in prostate cancer patients on active surveillance

Funder: University of CambridgeAbstract: Objectives: To assess the predictive value and correlation to pathological progression of the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scoring system in the follow-up of prostate cancer (PCa) patients on active surveillance (AS). Methods: A total of 295 men enrolled on an AS programme between 2011 and 2018 were included. Baseline multiparametric magnetic resonance imaging (mpMRI) was performed at AS entry to guide biopsy. The follow-up mpMRI studies were prospectively reported by two sub-specialist uroradiologists with 10 years and 13 years of experience. PRECISE scores were dichotomized at the cut-off value of 4, and the sensitivity, specificity, positive predictive value and negative predictive value were calculated. Diagnostic performance was further quantified by using area under the receiver operating curve (AUC) which was based on the results of targeted MRI-US fusion biopsy. Univariate analysis using Cox regression was performed to assess which baseline clinical and mpMRI parameters were related to disease progression on AS. Results: Progression rate of the cohort was 13.9% (41/295) over a median follow-up of 52 months. With a cut-off value of category ≥ 4, the PRECISE scoring system showed sensitivity, specificity, PPV and NPV for predicting progression on AS of 0.76, 0.89, 0.52 and 0.96, respectively. The AUC was 0.82 (95% CI = 0.74–0.90). Prostate-specific antigen density (PSA-D), Likert lesion score and index lesion size were the only significant baseline predictors of progression (each p < 0.05). Conclusion: The PRECISE scoring system showed good overall performance, and the high NPV may help limit the number of follow-up biopsies required in patients on AS. Key Points: • PRECISE scores 1–3 have high NPV which could reduce the need for re-biopsy during active surveillance. • PRECISE scores 4–5 have moderate PPV and should trigger either close monitoring or re-biopsy. • Three baseline predictors (PSA density, lesion size and Likert score) have a significant impact on the progression-free survival (PFS) time

MRI-derived PRECISE scores for predicting pathologically-confirmed radiological progression in prostate cancer patients on active surveillance

Funder: University of CambridgeAbstract: Objectives: To assess the predictive value and correlation to pathological progression of the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scoring system in the follow-up of prostate cancer (PCa) patients on active surveillance (AS). Methods: A total of 295 men enrolled on an AS programme between 2011 and 2018 were included. Baseline multiparametric magnetic resonance imaging (mpMRI) was performed at AS entry to guide biopsy. The follow-up mpMRI studies were prospectively reported by two sub-specialist uroradiologists with 10 years and 13 years of experience. PRECISE scores were dichotomized at the cut-off value of 4, and the sensitivity, specificity, positive predictive value and negative predictive value were calculated. Diagnostic performance was further quantified by using area under the receiver operating curve (AUC) which was based on the results of targeted MRI-US fusion biopsy. Univariate analysis using Cox regression was performed to assess which baseline clinical and mpMRI parameters were related to disease progression on AS. Results: Progression rate of the cohort was 13.9% (41/295) over a median follow-up of 52 months. With a cut-off value of category ≥ 4, the PRECISE scoring system showed sensitivity, specificity, PPV and NPV for predicting progression on AS of 0.76, 0.89, 0.52 and 0.96, respectively. The AUC was 0.82 (95% CI = 0.74–0.90). Prostate-specific antigen density (PSA-D), Likert lesion score and index lesion size were the only significant baseline predictors of progression (each p < 0.05). Conclusion: The PRECISE scoring system showed good overall performance, and the high NPV may help limit the number of follow-up biopsies required in patients on AS. Key Points: • PRECISE scores 1–3 have high NPV which could reduce the need for re-biopsy during active surveillance. • PRECISE scores 4–5 have moderate PPV and should trigger either close monitoring or re-biopsy. • Three baseline predictors (PSA density, lesion size and Likert score) have a significant impact on the progression-free survival (PFS) time

Investigating the ability of multiparametric MRI to exclude significant prostate cancer prior to transperineal biopsy.

INTRODUCTION: We characterized false negative prostate magnetic resonance imaging (MRI) reporting by using histology derived from MRI-transrectal ultrasound (TRUS)-guided transperineal (MTTP) fusion biopsies. METHODS: In total, 148 consecutive patients were retrospectively reviewed. Men underwent multiparametric MRI (mpMRI), reported by a consultant/attending radiologist in line with European Society of Urogenital Radiology (ESUR) standards. MTTP biopsy of the lesions was performed according to the Ginsburg recommendations. Cases with an MRI-histology mismatch were identified and underwent a second read by an experienced radiologist. A third review was performed with direct histology comparison to determine a true miss from an MRI-occult cancer. Statistical analysis was performed with McNemar's test. RESULTS: False negative lesions were identified in 29 MRI examinations (19.6%), with a total of 46 lesions. Most false negative lesions (21/46) were located in the anterior sectors of the prostate. The second read led to a significant decrease of false-negative lesions with 7/29 further studies identified as positive on a patient-by-patient basis (24.1% of studies, p = 0.016) and 11/46 lesions (23.9%; p = 0.001). Of these, 30 lesions following the first read and 23 lesions after the second read were considered significant cancer according to the University College London criteria. However, on direct comparison with histology, most lesions were MRI occult. CONCLUSION: We demonstrate that MRI can fail to detect clinically relevant lesions. Improved results were achieved with a second read but despite this, a number of lesions remain MRI-occult. Further advances in imaging are required to reduce false negative results.National Institute of Health Research Cambridge Biomedical Research Centre, Cancer Research UK, Cancer Research UK and the Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester, Cambridge Experimental Cancer Medicine CentreThis is the final version of the article. It first appeared from the Canadian Urological Association via http://dx.doi.org/10.5489/cuaj.289

Multicentre evaluation of targeted and systematic biopsies using magnetic resonance and ultrasound image-fusion guided transperineal prostate biopsy in patients with a previous negative biopsy.

OBJECTIVES: To evaluate the detection rates of targeted and systematic biopsies in magnetic resonance imaging (MRI) and ultrasound (US) image-fusion transperineal prostate biopsy for patients with previous benign transrectal biopsies in two high-volume centres. PATIENTS AND METHODS: A two centre prospective outcome study of 487 patients with previous benign biopsies that underwent transperineal MRI/US fusion-guided targeted and systematic saturation biopsy from 2012 to 2015. Multiparametric MRI (mpMRI) was reported according to Prostate Imaging Reporting and Data System (PI-RADS) Version 1. Detection of Gleason score 7-10 prostate cancer on biopsy was the primary outcome. Positive (PPV) and negative (NPV) predictive values including 95% confidence intervals (95% CIs) were calculated. Detection rates of targeted and systematic biopsies were compared using McNemar's test. RESULTS: The median (interquartile range) PSA level was 9.0 (6.7-13.4) ng/mL. PI-RADS 3-5 mpMRI lesions were reported in 343 (70%) patients and Gleason score 7-10 prostate cancer was detected in 149 (31%). The PPV (95% CI) for detecting Gleason score 7-10 prostate cancer was 0.20 (±0.07) for PI-RADS 3, 0.32 (±0.09) for PI-RADS 4, and 0.70 (±0.08) for PI-RADS 5. The NPV (95% CI) of PI-RADS 1-2 was 0.92 (±0.04) for Gleason score 7-10 and 0.99 (±0.02) for Gleason score ≥4 + 3 cancer. Systematic biopsies alone found 125/138 (91%) Gleason score 7-10 cancers. In patients with suspicious lesions (PI-RADS 4-5) on mpMRI, systematic biopsies would not have detected 12/113 significant prostate cancers (11%), while targeted biopsies alone would have failed to diagnose 10/113 (9%). In equivocal lesions (PI-RADS 3), targeted biopsy alone would not have diagnosed 14/25 (56%) of Gleason score 7-10 cancers, whereas systematic biopsies alone would have missed 1/25 (4%). Combination with PSA density improved the area under the curve of PI-RADS from 0.822 to 0.846. CONCLUSION: In patients with high probability mpMRI lesions, the highest detection rates of Gleason score 7-10 cancer still required combined targeted and systematic MRI/US image-fusion; however, systematic biopsy alone may be sufficient in patients with equivocal lesions. Repeated prostate biopsies may not be needed at all for patients with a low PSA density and a negative mpMRI read by experienced radiologists.N. Hansen has received a research grant from RWTH Aachen University Hospital (Aachen, Germany). T. Barrett acknowledges support from Cancer Research UK, National Institute of Health Research Cambridge Biomedical Research Centre, Cancer Research UK and the Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester and the Cambridge Experimental Cancer Medicine Centre. A. Warren acknowledges support from the National Institute for Health Research Cambridge Biomedical Research Centre UK. C. Kastner acknowledges that he has received speaker or mentorship fees from Siemens Healthcare and MedCom GmbH. The Department of Urology, Addenbrooke's Hospital, Cambridge, UK, also received sponsorship of various industry for organising Prostate MRI workshops. B. Hadaschik acknowledges support from the German Research Foundation

Utilizing multi-objective decision support tools for protected area selection

Establishing and maintaining protected areas (PAs) is a key action in delivering post-2020 biodiversity targets. PAs often need to meet multiple objectives, ranging from biodiversity protection to ecosystem service provision and climate change mitigation, but available land and conservation funding is limited. Therefore, optimizing resources by selecting the most beneficial PAs is vital. Here, we advocate for a flexible and transparent approach to selecting PAs based on multiple objectives, and illustrate this with a decision support tool on a global scale. The tool allows weighting and prioritization of different conservation objectives according to user-specified preferences as well as real-time comparison of the outcome. Applying the tool across 1,346 terrestrial PAs, we demonstrate that decision makers frequently face trade-offs among conflicting objectives, e.g., between species protection and ecosystem integrity. Nevertheless, we show that transparent decision support tools can reveal synergies and trade-offs associated with PA selection, thereby helping to illuminate and resolve land-use conflicts embedded in divergent societal and political demands and values.publishedVersio

Diagnostic evaluation of magnetization transfer and diffusion kurtosis imaging for prostate cancer detection in a re-biopsy population.

OBJECTIVE: To evaluate diffusion kurtosis imaging (DKI) and magnetisation transfer imaging (MTI) compared to standard MRI for prostate cancer assessment in a re-biopsy population. METHODS: Thirty-patients were imaged at 3 T including DKI (Kapp and Dapp) with b-values 150/450/800/1150/1500 s/mm2 and MTI performed with and without MT saturation. Patients underwent transperineal biopsy based on prospectively defined MRI targets. Receiver-operating characteristic (ROC) analyses assessed the parameters and Wilcoxon-signed ranked test assessed relationships between metrics. RESULTS: Twenty patients had ≥ 1 core positive for cancer in a total of 26 MRI targets (Gleason 3+3 in 8, 3+4 in 12, ≥ 4+3 in 6): 13 peripheral (PZ) and 13 transition zone (TZ). The apparent diffusion coefficient (ADC) and Dapp were significantly lower and the Kapp and MT ratio (MTR) significantly higher in tumour versus benign tissue (all p ≤ 0.005); ROC values 0.767-1.000. Normal TZ had: lower ADC and Dapp and higher Kapp and MTR compared to normal PZ. MTR showed a moderate correlation to Kapp (r = 0.570) and Dapp (r = -0.537) in normal tissue but a poor correlation in tumours. No parameter separated low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease for either PZ (p = 0.414-0.825) or TZ (p = 0.148-0.825). CONCLUSION: ADC, Dapp, Kapp and MTR all distinguished benign tissue from tumour, but none reliably differentiated low- from high-grade disease. KEY POINTS: • MTR was significantly higher in PZ and TZ tumours versus normal tissue • K app was significantly lower and D app higher for PZ and TZ tumours • There was no incremental value for DKI/MTI over mono-exponential ADC parameters • No parameter could consistently differentiate low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease • Divergent MTR/DKI values in TZ tumours suggests they offer different functional information