Search

Background: The IP1-PROSTAGRAM study showed that a short, non-contrast MRI detected more significant cancers with similar rates of biopsy compared to PSA. Herein, we compare the expected and perceived burden of PSA, MRI and ultrasound as screening tests., Methods: IP1-PROSTAGRAM was a prospective, population-based, paired screening study of 408 men conducted at seven UK primary care practices and two imaging centres. The screening tests were serum PSA, non-contrast MRI and ultrasound. If any test was screen-positive, a prostate biopsy was performed. Participants completed an Expected Burden Questionnaire (EBQ) and Perceived Burden Questionnaire (PBQ) before and after each screening test., Results: The overall level of burden for MRI and PSA was minimal. Few men reported high levels of anxiety, burden, embarrassment or pain following either MRI or PSA. Participants indicated an overall preference for MRI after completing all screening tests. Of 408 participants, 194 (47.5%) had no preference, 106 (26.0%) preferred MRI and 79 (19.4%) preferred PSA. This indicates that prior to screening, participants preferred MRI compared to PSA (+6.6%, 95% CI 4.4-8.4, p = 0.02) and after completing screening, the preference for MRI was higher (+21.1%, 95% CI 14.9-27.1, p < 0.001). The proportion of participants who strongly agreed with repeating the test was 50.5% for ultrasound, 65% for MRI and 68% for PSA. A larger proportion of participants found ultrasound anxiety-inducing, burdensome, embarrassing and painful compared to both MRI and PSA., Conclusions: Prostagram MRI and PSA are both acceptable as screening tests among men aged 50-69 years. Both tests were associated with minimal amounts of anxiety, burden, embarrassment and pain. The majority of participants preferred MRI over PSA and ultrasound., Registration: This study was registered on clinicaltrials.gov at https://clinicaltrials.gov/ct2/show/NCT03702439 ., (© 2023. The Author(s).)

Background: The use of prostate-specific antigen (PSA) testing to screen for prostate cancer has been fraught with under- and overdiagnosis. Short, noncontrast magnetic resonance imaging (MRI) might detect more grade group ≥2 cancers with similar rates of biopsy., Objective: To evaluate strategies that combined PSA and MRI to select men based in the community for a prostate biopsy., Design, Setting, and Participants: IP1-PROSTAGRAM was a prospective, population-based, paired cohort study of 408 men aged 50-69 yr conducted at seven UK primary care practice and two imaging centres (from October 10, 2018 to May 15, 2019)., Intervention: All participants underwent screening with a PSA test, MRI (T2-weighted and diffusion), and transrectal ultrasound (b-mode and elastography). If any test was screen positive, a systematic 12-core biopsy was performed. Additional image-fusion targeted biopsies were taken if the MRI or ultrasound was positive., Outcome Measurements and Statistical Analysis: We conducted an analysis, set out in the statistical plan a priori, comparing 13 different pathways including PSA-alone, MRI-alone, and a range of PSA thresholds and MRI scores. The performance of each pathway was evaluated focusing on the trade-offs between biopsy referral rates and detection of grade group ≥2 cancers. A targeted biopsy was performed only where the PROSTAGRAM MRI showed a lesion score of 3, 4, or 5., Results and Limitations: The standard PSA pathway (PSA ≥3 ng/ml + systematic biopsy) would lead to 10% of men being referred for a biopsy and a 1.0% detection rate of grade group ≥2 cancers. Pathways that relied on MRI alone set at a threshold score of 3 for a biopsy led to higher biopsy rates, but with benefit of high cancer detection rates. The pathway that combined an initial low PSA threshold (≥1.0 ng/ml) and MRI score ≥4 accurately identified a high rate of grade group ≥2 cancers (2.5%, 95% confidence interval 1.3-4.6) while recommending fewer patients for a biopsy (7.1%, 95% confidence interval 4.9-10.2). The results are pertinent to only one screening round, the impact of repeat screening rounds is not evaluated, and the required MRI capacity is currently lacking., Conclusions: Our results highlight the trade-off that exists between reducing excessive numbers of biopsies and maintaining grade group ≥2 cancer detection rates. A pathway that combines PSA ≥1 ng/ml and MRI score ≥4 maintains the detection of grade group ≥2 cancers while recommending fewer men for biopsies and would be the preferred strategy to evaluate in future studies at the first screening round., Patient Summary: The IP1-PROSTAGRAM study shows that PROSTAGRAM magnetic resonance imaging in men with a prostate-specific antigen level of ≥1.0 ng/ml could be a promising pathway to evaluate in future screening trials., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: We aimed to test whether the current practice of using mpMRI stage might lead to a Will Rogers phenomenon with a stage migration compared to DRE in men undergoing radical prostatectomy., Material and Methods: A total of 572 consecutive patients who underwent radical prostatectomy at a single institution (2007-2017) were included. Clinical stage using digital rectal examination was determined on table by the operating surgeon; mpMRI and pathological stage were recorded after tumor board review. Progression-free survival (PFS) was defined as no rising PSA, no adjuvant/salvage treatment, and no metastases or mortality. PFS was compared between groups and a model incorporating mpMRI into the EAU risk groups was created., Results: Median age was 63 years (IQR 58.5-67) and median PSA was 8.9 ng/ml (IQR 6.5-13.2). Using DRE stage, 20% were NCCN low risk, 43% were intermediate, and 37% high. Median follow-up was 48 months (IQR 22-73). Estimated PFS at 1, 3, and 5 years was 75%, 59%, and 54%, respectively. When comparing PFS between DRE and mpMRI stages, patients deemed T1 (P < 0.01) or T3 (P = 0.03) by mpMRI showed better outcomes than patients staged T1 or T3 by DRE. On univariable analysis lower risk for failure was seen for MRI T1 disease (HR 0.10 95%, CI 0.01-0.73, P = 0.02) or MRI T3 (HR 0.70, CI 0.51-0.97, P = 0.03). On multivariable analysis, only MRI T1 remained a significant predictor (HR 0.08, 95% CI 0.01-0.59, P = 0.01). The subsequent, modified EAU risk model using both DRE and mpMRI performed significantly better than the DRE model., Conclusion: PFS based on mpMRI is not the same as DRE staging. Current risk groups which use DRE should be used with caution in whom local stage is based on mpMRI. Our modified EAU-risk categories can provide greater accuracy., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Novel screening tests used to detect a target condition are compared against either a reference standard or other existing screening methods. However, as it is not always possible to apply the reference standard on the whole population under study, verification bias is introduced. Statistical methods exist to adjust estimates to account for this bias. We extend common methods to adjust for verification bias when multiple tests are compared to a reference standard using data from a prospective double blind screening study for prostate cancer., Methods: Begg and Greenes method and multiple imputation are extended to include the results of multiple screening tests which determine condition verification status. These two methods are compared to the complete case analysis using the IP1-PROSTAGRAM study data. IP1-PROSTAGRAM used a paired-cohort double-blind design to evaluate the use of imaging as alternative tests to screen for prostate cancer, compared to a blood test called prostate specific antigen (PSA). Participants with positive imaging (index) and/or PSA (control) underwent a prostate biopsy (reference standard)., Results: When comparing complete case results to Begg and Greenes and methods of multiple imputation there is a statistically significant increase in the specificity estimates for all screening tests. Sensitivity estimates remained similar across the methods, with completely overlapping 95% confidence intervals. Negative predictive value (NPV) estimates were higher when adjusting for verification bias, compared to complete case analysis, even though the 95% confidence intervals overlap. Positive predictive value (PPV) estimates were similar across all methods., Conclusion: Statistical methods are required to adjust for verification bias in accuracy estimates of screening tests. Expanding Begg and Greenes method to include multiple screening tests can be computationally intensive, hence multiple imputation is recommended, especially as it can be modified for low prevalence of the target condition., (© 2022. The Author(s).)

Importance: Screening for prostate cancer using prostate-specific antigen (PSA) testing can lead to problems of underdiagnosis and overdiagnosis. Short, noncontrast magnetic resonance imaging (MRI) or transrectal ultrasonography might overcome these limitations., Objective: To compare the performance of PSA testing, MRI, and ultrasonography as screening tests for prostate cancer., Design, Setting, and Participants: This prospective, population-based, blinded cohort study was conducted at 7 primary care practices and 2 imaging centers in the United Kingdom. Men 50 to 69 years of age were invited for prostate cancer screening from October 10, 2018, to May 15, 2019., Interventions: All participants underwent screening with a PSA test, MRI (T2 weighted and diffusion), and ultrasonography (B-mode and shear wave elastography). The tests were independently interpreted without knowledge of other results. Both imaging tests were reported on a validated 5-point scale of suspicion. If any test result was positive, a systematic 12-core biopsy was performed. Additional image fusion-targeted biopsies were performed if the MRI or ultrasonography results were positive., Main Outcomes and Measures: The main outcome was the proportion of men with positive MRI or ultrasonography (defined as a score of 3-5 or 4-5) or PSA test (defined as PSA ≥3 μg/L) results. Key secondary outcomes were the number of clinically significant and clinically insignificant cancers detected if each test was used exclusively. Clinically significant cancer was defined as any Gleason score of 3+4 or higher., Results: A total of 2034 men were invited to participate; of 411 who attended screening, 408 consented to receive all screening tests. The proportion with positive MRI results (score, 3-5) was higher than the proportion with positive PSA test results (72 [17.7%; 95% CI, 14.3%-21.8%] vs 40 [9.9%; 95% CI, 7.3%-13.2%]; P < .001). The proportion with positive ultrasonography results (score, 3-5) was also higher than the proportion of those with positive PSA test results (96 [23.7%; 95% CI, 19.8%-28.1%]; P < .001). For an imaging threshold of score 4 to 5, the proportion with positive MRI results was similar to the proportion with positive PSA test results (43 [10.6%; 95% CI, 7.9%-14.0%]; P = .71), as was the proportion with positive ultrasonography results (52 [12.8%; 95% CI, 9.9%-16.5%]; P = .15). The PSA test (≥3 ng/mL) detected 7 clinically significant cancers, an MRI score of 3 to 5 detected 14 cancers, an MRI score of 4 to 5 detected 11 cancers, an ultrasonography score of 3 to 5 detected 9 cancer, and an ultrasonography score of 4 to 5 detected 4 cancers. Clinically insignificant cancers were diagnosed by PSA testing in 6 cases, by an MRI score of 3 to 5 in 7 cases, an MRI score of 4 to 5 in 5 cases, an ultrasonography score of 3 to 5 in 13 cases, and an ultrasonography score of 4 to 5 in 7 cases., Conclusions and Relevance: In this cohort study, when screening the general population for prostate cancer, MRI using a score of 4 or 5 to define a positive test result compared with PSA alone at 3 ng/mL or higher was associated with more men diagnosed with clinically significant cancer, without an increase in the number of men advised to undergo biopsy or overdiagnosed with clinically insignificant cancer. There was no evidence that ultrasonography would have better performance compared with PSA testing alone.

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., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: We determined whether prostate specific antigen criteria after focal high intensity focused ultrasound to treat prostate cancer could diagnose treatment failure., Materials and Methods: A total of 598 patients in a prospectively maintained national database underwent focal high intensity focused ultrasound with a Sonablate® 500 device from March 2007 to November 2016. Followup consisted of 3-month clinic visits and prostate specific antigen testing in year 1 with prostate specific antigen measurement every 6 to 12 months and multiparametric magnetic resonance imaging with biopsy for magnetic resonance imaging suspicious for recurrence. Treatment failure was considered any secondary treatment, tumor recurrence with Gleason 3 + 4 or greater disease on prostate biopsy without further treatment or metastasis and/or prostate cancer related mortality. To diagnose failure we evaluated a series of nadir + x thresholds with x values of 0.1 to 2.0 ng/ml., Results: Median patient age was 65 years (IQR 60-71) and the median Gleason score was 7 (range 6-9). Gleason 3 + 4 or greater disease was present in 80% of cases. Tumors were radiologically staged as T1c-T2c in 522 of the 596 patients (88%) and as T3a/b in 74 (12.4%). Baseline median prostate specific antigen was 7.80 ng/ml (IQR 5.96-10.45) in failed cases and 6.77 ng/ml (IQR 2.65-9.71) in cases without failure. Optimal performance according to the Youden index to indicate the most appropriate nadir + x at all analyzed time points at 3-month intervals showed that nadir + 1.0 ng/ml would have 27.3% to 100% sensitivity and 39.4% to 85.6% specificity depending on the time of evaluation in the first 3 years. Nadir + 1.5 ng/ml showed 18.2% to 100% sensitivity and 60.6% to 91.8% specificity with nadir + 2.0 ng/ml leading to similar sensitivity and specificity ranges. Nadir + 1.0 ng/ml at 12 months and nadir + 1.5 ng/ml at 24 and 36 months had 100% sensitivity and 96.1% to 100% negative predictive value., Conclusions: Following focal high intensity focused ultrasound a prostate specific antigen nadir of 1.0 ng/ml at 12 months and 1.5 ng/ml at 24 to 36 months might be used to triage men requiring magnetic resonance imaging and biopsy. These data need prospective validation.

Objective: To determine whether indeterminate (Likert-score 3/5) peripheral zone (PZ) multiparametric MRI (mpMRI) studies are classifiable by prostate-specific antigen (PSA), PSA density (PSAD), Prostate Imaging Reporting And Data System version 2 (PI-RADS&#95;v2) rescoring and morphological MRI features., Methods: Men with maximum Likert-score 3/5 within their PZ were retrospectively selected from 330 patients who prospectively underwent prostate mpMRI (3 T) without an endorectal coil, followed by 20-zone transperineal template prostate mapping biopsies ＋/- focal lesion-targeted biopsy. PSAD was calculated using pre-biopsy PSA and MRI-derived volume. Two readers A and B independently assessed included men with both Likert-assessment and PI-RADS&#95;v2. Both readers then classified mpMRI morphological features in consensus. Men were divided into two groups: significant cancer (≥ Gleason 3 ＋ 4) or insignificant cancer (≤ Gleason 3 ＋ 3)/no cancer. Comparisons between groups were made separately for PSA & PSAD using Mann-Whitney test and morphological descriptors with Fisher's exact test. PI-RADS&#95;v2 and Likert-assessment were descriptively compared and percentage inter-reader agreement calculated., Results: 76 males were eligible for PSA & PSAD analyses, 71 for PI-RADS scoring, and 67 for morphological assessment (excluding significant image artefacts). Unlike PSA (p = 0.915), PSAD was statistically different (p = 0.004) between the significant [median: 0.19 ng ml - 2 (interquartile range: 0.13-0.29)] and non-significant/no cancer [median: 0.13 ng ml - 2 (interquartile range: 0.10-0.17)] groups. Presence of mpMRI morphological features was not significantly different between groups. Subjective Likert-assessment discriminated patients with significant cancer better than PI-RADS&#95;v2. Inter-reader percentage agreement was 83% for subjective Likert-assessment and 56% for PI-RADS&#95;v2., Conclusion: PSAD may categorize presence of significant cancer in patients with Likert-scored 3/5 PZ mpMRI findings. Advances in knowledge: PSAD may be used in indeterminate PZ mpMRI to guide decisions between biopsy vs monitoring.

Introduction: Focal therapy for localized prostate cancer has the potential for oncological control without the side effects of radical therapies. However, there is currently no validated method for monitoring treatment success. We assessed the diagnostic performance of prostate-specific antigen (PSA) parameters and MRI compared to histological outcomes following focal therapy., Patients and Methods: Patients from 3 Ethics Review Board approved prospective studies of focal high intensity-focused ultrasound (HIFU) (Sonablate 500) for localized prostate cancer (T1c-T3a, Gleason grade≤4+3, and PSA≤20). Post-HIFU PSA nadir, 6-month PSA, PSA density, and early (<3wk) and late (6mo) MRI (T2-weighted, dynamic contrast-enhanced±diffusion-weighted) was assessed for predictive accuracy of cancer on postoperative biopsy, using receiver operating characteristic (ROC) analysis and sensitivity, specificity, and positive and negative predictive estimates. ROC areas for MRI and PSA were compared. Calculations for statistical significance (P≤0.05) were obtained in a subset of patients comparing area under ROC for 6-month MRI and PSA criteria, across 4 different histological definitions of disease significance., Results: Of 118 men, 111 underwent at least 1 postoperative biopsy (median 6 cores), with an overall positive biopsy rate of 37% (41/118), over a mean follow-up period of 716 days post-HIFU. Areas under ROC for early and late MRI were (depending on definition of significant disease) 0.65 to 0.76 and 0.77 to 0.85, respectively, with sensitivity, specificity, and negative predictive values of 68% to 91%, 52% to 55%, and 85% to 98% (early MRI), and 63% to 80%, 67% to 73%, and 86% to 97% (late MRI). The area under the ROC curve was statistically significantly higher for late MRI than 6 months and nadir PSA for residual disease >3mm or any Gleason 4 tumor., Conclusions: Early and late MRI performed better than PSA measurements in the detection of residual tumor after focal therapy., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Background: Focal therapy as a treatment option for localized prostate cancer (PCa) is an increasingly popular and rapidly evolving field., Objective: To gather expert opinion on patient selection, interventions, and meaningful outcome measures for focal therapy in clinical practice and trial design., Design, Setting, and Participants: Fifteen experts in focal therapy followed a modified two-stage RAND/University of California, Los Angeles (UCLA) Appropriateness Methodology process. All participants independently scored 246 statements prior to rescoring at a face-to-face meeting. The meeting occurred in June 2013 at the Royal Society of Medicine, London, supported by the Wellcome Trust and the UK Department of Health., Outcome Measurements and Statistical Analysis: Agreement, disagreement, or uncertainty were calculated as the median panel score. Consensus was derived from the interpercentile range adjusted for symmetry level., Results and Limitations: Of 246 statements, 154 (63%) reached consensus. Items of agreement included the following: patients with intermediate risk and patients with unifocal and multifocal PCa are eligible for focal treatment; magnetic resonance imaging-targeted or template-mapping biopsy should be used to plan treatment; planned treatment margins should be 5mm from the known tumor; prostate volume or age should not be a primary determinant of eligibility; foci of indolent cancer can be left untreated when treating the dominant index lesion; histologic outcomes should be defined by targeted biopsy at 1 yr; residual disease in the treated area of ≤3 mm of Gleason 3+3 did not need further treatment; and focal retreatment rates of ≤20% should be considered clinically acceptable but subsequent whole-gland therapy deemed a failure of focal therapy. All statements are expert opinion and therefore constitute level 5 evidence and may not reflect wider clinical consensus., Conclusions: The landscape of PCa treatment is rapidly evolving with new treatment technologies. This consensus meeting provides guidance to clinicians on current expert thinking in the field of focal therapy., Patient Summary: In this report we present expert opinion on patient selection, interventions, and meaningful outcomes for clinicians working in focal therapy for prostate cancer., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Unfortunately, the noble aims of the Melbourne Consensus statement on the early detection of prostate cancer lack rigour, failing to take into account the breadth of evidence in this field; as a result, they fall disappointingly short of providing clarity on this important issue.

Purpose: To assess the performance of multiparametric magnetic resonance imaging (mp-MRI) in patients with previous negative transrectal ultrasound (TRUS) guided prostate biopsy., Materials and Methods: Fifty-four patients with at least 1 previous negative TRUS prostate biopsy underwent mp-MRI in the form of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging. This was followed by transperineal template systematic prostate biopsies. Analysis was done based on 2 sectors per prostate, right and left (108 sectors out of 54 prostates). mp-MRI was scored using an ordinal scale 1 to 5 based on the suspicion of the presence of clinically significant disease. We used 6 different definitions for clinically significant disease and tested the performance of mp-MRI at each single definition., Results: Median age was 64 (range, 39-75), median PSA level was 10 (range, 2-23), and median number of biopsies was 45 (range, 21-137). Cancer of any volume and any grade was detected in 34 of 54 (63%) patients. mp-MRI accuracy at detection of clinically significant cancer using University College London (UCL) definition 2 (any Gleason score of 4 or maximum cancer core length of ≥ 4 mm or both) showed sensitivity of 76%, specificity of 42%, positive predictive value of 38%, and negative predictive value of 79%. For a different definition of significant tumor (UCL definition 1; dominant Gleason score 4 or maximum cancer core length ≥ 6 mm or both), the sensitivity was 90%, specificity 42%, positive predictive value 26%, and negative predictive value 95%., Conclusions: mp-MRI showed good performance at both detection and ruling out clinically significant disease, according to the definition used. mp-MRI can then be used as a triage test in the population with persistently elevated or rising PSA levels to select patients that can avoid unnecessary prostate biopsy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

ContextActive surveillance (AS) is an alternative to initial radical treatment of low-risk prostate cancer (PCa). Current criteria for selection and follow-up incorrectly exclude some patients eligible for AS and misclassify some who actually harbour significant disease. Better prediction of cancer behaviour at diagnosis would allow less strict monitoring and may improve acceptance of AS.ObjectiveTo review and critically analyse the literature on the value of novel clinical tools for patient selection and monitoring on AS.Evidence acquisitionA comprehensive search of the PubMed database until July 10, 2013, was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis statement guidelines. Studies assessing novel markers and diagnostics for patient selection for AS and follow-up during AS were included. Studies analysing only classic clinical parameters used in current protocols (prostate-specific antigen, prostate volume, number of (positive) prostate biopsies, percentage malignant tissue, Gleason score) were excluded. This review focuses only on the AS setting and not on predicting insignificant disease in general.Evidence synthesisOf 787 studies on AS, 30 were included in this review: 14 on magnetic resonance imaging (MRI), 5 on serum markers, 5 on urinary markers, 4 on histopathology markers, and 2 on germline genetic markers. Several of these markers improve the prediction of tumour volume, tumour grade, or time to active treatment. MRI has a high specificity for low-risk PCa; new serum markers are associated with unfavourable disease. In none of the studies was the new marker used as the primary decision tool. Long-term outcome measures such as mortality were not assessed. The definition of indolent PCa is disputable.ConclusionsImaging and serum markers may improve future patient selection for AS and follow-up during AS. Prospective studies should aim to further evaluate the clinical utility of these new markers with respect to longer term outcomes of AS.Patient summaryWe searched the literature for articles reporting new ways to safely monitor low-risk prostate cancer for patients who have not had radical treatment. We found 30 articles. The most promising tools appear to be magnetic resonance imaging scans and various new blood markers. These may be used in the future within active surveillance regimens.

Objectives: To assess change in functional outcomes after a second focal high‐intensity focused ultrasonography (HIFU) treatment compared with outcomes after one focal HIFU treatment. Patients and Methods: In this multicentre study (2005–2016), 821 men underwent focal HIFU for localized non‐metastatic prostate cancer. The patient‐reported outcome measures of International Prostate Symptom Score (IPSS), pad usage and erectile function (EF) score were prospectively collected for up to 3 years. To be included in the study, completion of at least one follow‐up questionnaire was required. The primary outcome was comparison of change in functional outcomes between baseline and follow‐up after one focal HIFU procedure vs after a second focal HIFU procedure, using IPSS, Expanded Prostate Cancer Index Composite (EPIC) and International Index of Erectile Function (IIEF) questionnaires. Results: Of 821 men, 654 underwent one focal HIFU procedure and 167 underwent a second focal HIFU procedure. A total of 355 (54.3%) men undergoing one focal HIFU procedure and 65 (38.9%) with a second focal HIFU procedure returned follow‐up questionnaires, respectively. The mean age and prostate‐specific antigen level were 66.4 and 65.6 years, and 7.9 and 8.4 ng/mL, respectively. After one focal HIFU treatment, the mean change in IPSS was −0.03 (P = 0.02) and in IIEF (EF score) it was −0.4 (P = 0.02) at 1–2 years, with no subsequent decline. Absolute rates of erectile dysfunction increased from 9.9% to 20.8% (P = 0.08), leak‐free continence decreased from 77.9% to 72.8% (P = 0.06) and pad‐free continence from 98.6% to 94.8% (P = 0.07) at 1–2 years, respectively. IPSS prior to second focal HIFU treatment compared to baseline IPSS prior to first focal HIFU treatment was lower by −1.3 (P = 0.02), but mean IPSS change was +1.4 at 1–2 years (P = 0.03) and +1.2 at 2–3 years (P = 0.003) after the second focal HIFU treatment. The mean change in EF score after the second focal HIFU treatment was −0.2 at 1–2 years (P = 0.60) and −0.5 at 2–3 years (P = 0.10), with 17.8% and 6.2% of men with new erectile dysfunction. The rate of new pad use was 1.8% at 1–2 years and 2.6% at 2–3 years. Conclusion: A second focal HIFU procedure causes minor detrimental effects on urinary function and EF. These data can be used to counsel patients with non‐metastatic prostate cancer prior to considering HIFU therapy. [ABSTRACT FROM AUTHOR]

Objective: To compare the clinical validity and utility of Likert assessment and the Prostate Imaging Reporting and Data System (PI‐RADS) v2 in the detection of clinically significant and insignificant prostate cancer. Patients and Methods: A total of 489 pre‐biopsy multiparametric magnetic resonance imaging (mpMRI) scans in consecutive patients were subject to prospective paired reporting using both Likert and PI‐RADS v2 by expert uro‐radiologists. Patients were offered biopsy for any Likert or PI‐RADS score ≥4 or a score of 3 with PSA density ≥0.12 ng/mL/mL. Utility was evaluated in terms of proportion biopsied, and proportion of clinically significant and insignificant cancer detected (both overall and on a 'per score' basis). In those patients biopsied, the overall accuracy of each system was assessed by calculating total and partial area under the receiver‐operating characteristic (ROC) curves. The primary threshold of significance was Gleason ≥3 + 4. Secondary thresholds of Gleason ≥4 + 3, Ahmed/UCL1 (Gleason ≥4 + 3 or maximum cancer core length [CCL] ≥6 or total CCL≥6) and Ahmed/UCL2 (Gleason ≥3 + 4 or maximum CCL ≥4 or total CCL ≥6) were also used. Results: The median (interquartile range [IQR]) age was 66 (60–72) years and the median (IQR) prostate‐specific antigen level was 7 (5–10) ng/mL. A similar proportion of men met the biopsy threshold and underwent biopsy in both groups (83.8% [Likert] vs 84.8% [PI‐RADS v2]; P = 0.704). The Likert system predicted more clinically significant cancers than PI‐RADS across all disease thresholds. Rates of insignificant cancers were comparable in each group. ROC analysis of biopsied patients showed that, although both scoring systems performed well as predictors of significant cancer, Likert scoring was superior to PI‐RADS v2, exhibiting higher total and partial areas under the ROC curve. Conclusions: Both scoring systems demonstrated good diagnostic performance, with similar rates of decision to biopsy. Overall, Likert was superior by all definitions of clinically significant prostate cancer. It has the advantages of being flexible, intuitive and allowing inclusion of clinical data. However, its use should only be considered once radiologists have developed sufficient experience in reporting prostate mpMRI. [ABSTRACT FROM AUTHOR]

Objective: To report medium‐term oncological outcomes in men receiving primary focal treatment with high‐intensity focused ultrasonography (HIFU) for prostate cancer (PCa). Patients and Methods: Consecutive patients with PCa treated with primary focal HIFU at two centres by six treating clinicians were assessed. Patients were submitted to either focal ablation or hemi‐ablation using HIFU (Sonablate 500). The primary objective of the study was to assess medium‐term oncological outcomes, defined as overall survival, freedom from biopsy failure, freedom from any further treatment and freedom from radical treatment after focal HIFU. The secondary objective was to evaluate the changes in pathological features among patients treated with focal HIFU over time. We also assessed the relationship between year of surgery and 5‐year retreatment probability. Results: A total of 1032 men treated between November 2005 and October 2017 were assessed. The median age was 65 years and median prostate‐specific antigen level was 7 ng/mL. The majority of patients had a Gleason score of 3 + 4 or above (80.3%). The median (interquartile range) follow‐up was 36 (14–64) months. The overall survival rates at 24, 60 and 96 months were 99%, 97% and 97%, respectively. Freedom from biopsy failure, defined as absence of Gleason 3 + 4 disease, was 84%, 64% and 54% at 24, 60 and 96 months. Freedom from any further treatment was 85%, 59% and 46% at 24, 60 and 96 months, respectively. Approximately 70% of patients who were retreated received a second focal treatment. Freedom from radical treatment was 98%, 91% and 81% at 24, 60 and 96 months. During the study period, we observed an increase in the proportion of patients undergoing focal HIFU with Gleason 3 + 4 disease and with T2 stage disease as defined by multiparametric magnetic resonance imaging. Finally, there was a reduction over time in the proportion of patients undergoing re‐treatment within 5 years of first treatment. Conclusions: Focal HIFU for PCa is a feasible therapeutic strategy, with acceptable survival and oncological results and a reduction in the 5‐year retreatment rates over the last decade. Re‐do focal treatment is a feasible technique whose functional and oncological outcomes have still to be evaluated. [ABSTRACT FROM AUTHOR]

Purpose Transperineal template prostate mapping biopsy is an increasingly used method of procuring tissue from men with suspected prostate cancer. We report patient related outcome measures and adverse events in men in the PICTURE trial (ClinicalTrials.gov NCT01492270) who underwent this diagnostic test. Materials and Methods A total of 249 men underwent multiparametric magnetic resonance imaging followed by transperineal template prostate mapping biopsy as a validation study. Functional outcomes before and after transperineal template prostate mapping were prospectively collected and recorded with questionnaires, including the I-PSS (International Prostate Symptom Score), the I-PSS-QoL (Quality of Life), the IIEF-15 (International Index of Erectile Function-15) and the EPIC (Expanded Prostate Cancer Index Composite) urinary function. Results Mean age was 62 years, median prostate specific antigen was 6.8 ng/ml and median gland size was 37 ml. At transperineal template prostate mapping biopsy a median of 49 cores (IQR 40–55) were taken. Mean time to complete the post-procedure patient related outcome measure questionnaires was 46 days. Adverse events included post-procedure acute urinary retention in 24% of patients, rectal pain in 26% and perineal pain in 41%. Transperineal template prostate mapping biopsy resulted in a statistically significant increase in scores on the I-PSS from 10.9 to 11.8 (p = 0.024) and the I-PSS-QoL from 1.57 to 1.76 (p = 0.03). The IIEF-15 erectile function score decreased by 23.2% from 47.7 to 38.7 (p <0.001). Significant deterioration was noted in all 5 of IIEF-15 functional domains, including erectile and orgasmic function, sexual desire, and intercourse and overall satisfaction (p <0.001). EPIC urinary scores showed no overall change from baseline. Conclusions Transperineal template prostate mapping biopsy causes a high urinary retention rate and a detrimental impact on genitourinary functional outcomes, including deterioration in urinary flow and sexual function. Our findings can be used to ensure adequate counseling about transperineal template prostate mapping biopsies. The results point to a need for strategies such as multiparametric magnetic resonance imaging and targeted biopsies to minimize the harms of transperineal template prostate mapping biopsy. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine the ability of the ratio of free to total prostate-specific antigen and prostate-specific antigen density to predict the presence of clinically significant prostate cancer on template biopsies. The value of these tests may be underestimated as they were previously validated against sextant transrectal biopsy of the prostate, which has been proved to miss a large proportion of significant prostate cancers. The ability of these tests to specifically detect clinically significant cancers has not previously been studied. Patients and methods: A retrospective analysis was performed of patients undergoing transperineal template biopsy who also had free to total prostate-specific antigen and prostate-specific antigen density. Receiver-operating characteristic analysis was performed to determine the comparative utility of each test in the detection of all cancers as well as clinically significant cancers, by means of the area under the curve. Results: Data from 293 patients were analysed. Prostate cancer was detected in 72% of patients, of which 62% of this group had clinically significant disease. Receiver-operating characteristic analysis demonstrated the superiority of prostate-specific antigen density and free to total prostate-specific antigen over standard prostate-specific antigen in the overall detection of cancer (area under the curve 0.662 and 0.674 vs 0.534, p=0.003 and 0.02 respectively). Both tests were even more effective in the detection of clinically significant cancers (area under the curve 0.755 and 0.715 vs 0.572, p<0.0001 and 0.009 respectively). Conclusion: The free to total prostate-specific antigen and prostate-specific antigen density both appear to perform well at detecting clinically significant prostate cancer in our population of men undergoing template biopsy. The potential role of these inexpensive tests should not be overlooked as they may be of value when deciding which patients require biopsy following an initial magnetic resonance imaging scan and also for those on surveillance protocols. [ABSTRACT FROM AUTHOR]

Purpose: Multiparametric magnetic resonance imaging can be used to guide prostate biopsy by targeting biopsies to areas in the prostate at high risk for cancer. We compared the detection of clinically significant and insignificant cancer by transperineal magnetic resonance imaging targeted biopsy and transperineal template guided prostate biopsy. Materials and Methods: A total of 182 men with a lesion suspicious for cancer on multiparametric magnetic resonance imaging underwent transperineal magnetic resonance imaging targeted biopsy using a cognitive registration technique, followed by systematic transperineal template guided prostate biopsy. The primary outcome was the detection rate of clinically significant prostate cancer. Clinical significance was defined using maximum cancer core length 4 mm or greater and/or Gleason grade 3 + 4 or greater (University College London definition 2). We secondarily evaluated other commonly used thresholds of clinically significant disease, including maximum cancer core length 6 mm or greater and/or Gleason grade 4 + 3 or greater, maximum cancer core length 3 mm or greater and/or Gleason grade 3 + 4 or greater, and maximum cancer core length 2 or greater mm and/or Gleason grade 3 + 4 or greater. Strategies were statistically compared with the McNemar test. Results: Mean ± SD patient age was 63.3 ± 7.2 years. Median prostate specific antigen was 6.7 ng/ml (IQR 4.7–10.0). Clinically significant cancer was detected by magnetic resonance imaging targeted biopsy and template guided prostate biopsy in 103 (57%) and 113 of the 182 men (62%) (p = 0.174), and clinically insignificant cancer was detected in 17 (9.3%) and 31 (17.0%), respectively (p = 0.024). Conclusions: Prostate biopsy targeted to suspicious lesions on multiparametric magnetic resonance imaging has encouraging rates of detection of clinically significant cancer while also decreasing the detection rate of clinically insignificant cancer. This is achieved with fewer biopsy cores than for systematic template guided biopsy. Further prospective, multicenter, comparative trials of the performance of targeting strategies are needed to consider magnetic resonance imaging targeted biopsy an alternative to conventional systematic biopsy. [Copyright &y& Elsevier]

Prostate cancer is an important health problem. More than 40 000 incident cases of prostate cancer and more than 10 000 prostate cancer related deaths occur each year in the United Kingdom. Prevention, detection, and treatment of localized prostate cancer remain controversial. Although screening for prostate cancer with serum prostate specific antigen (PSA) testing is not approved in the UK, informal screening is common and has led to a threefold increase in the incidence of prostate cancer. In the United States, since the introduction of PSA screening more than 1.3 million men have been diagnosed with prostate cancer and one million of these have undergone treatment. We update a previous review, highlighting new findings that deal with clinical questions and future research needs for the prevention, detection, and treatment of clinically localized prostate cancer. INSETS: Prostate cancer screening messages for men;A PATIENT¿S PERSPECTIVE. [ABSTRACT FROM AUTHOR]

Purpose: Active surveillance is increasingly recommended to reduce overtreatment in men with favorable risk prostate cancer. A repeat confirmatory biopsy has become the standard recommendation for these men to increase the precision of this risk attribution. We investigate the usefulness of this approach by comparing the current practice standard, repeat transrectal ultrasound biopsy, with template prostate mapping. Materials and Methods: A total of 124 men who were attributed a favorable risk prostate cancer status based on transrectal ultrasound guided biopsy and who were considering a policy of active surveillance underwent combined transrectal ultrasound biopsy and template prostate mapping as a confirmatory strategy. Maximum Gleason grade and disease burden were compared between the 2 confirmatory tests. Results: Depending on the definition used between 8% and 22% of men had prostate cancer reclassified as clinically important by repeat transrectal ultrasound biopsy whereas template guided prostate mapping reclassified the disease in 41% to 85% of the men. Repeat transrectal ultrasound biopsy failed to detect up to 80% of clinically important cancers detected by the reference standard. The sensitivity of repeat transrectal ultrasound biopsy to identify clinically important disease varied from 9% to 24% with the negative predictive value ranging from 23% to 60%. Conclusions: When applied to a population of men initially deemed to have favorable risk prostate cancer, transrectal ultrasound biopsy will miss a large proportion of clinically important cancers compared to template guided prostate mapping. The usefulness of repeat transrectal ultrasound biopsy in ruling out clinically important prostate cancer needs to be reconsidered. [Copyright &y& Elsevier]

Summary: Background: Radical whole-gland therapy can lead to significant genitourinary and rectal side-effects for men with localised prostate cancer. We report on whether selective focal ablation of unifocal and multifocal cancer lesions can reduce this treatment burden. Methods: Men aged 45–80 years were eligible for this prospective development study if they had low-risk to high-risk localised prostate cancer (prostate specific antigen [PSA] ≤15 ng/mL, Gleason score ≤4 + 3, stage ≤T2), with no previous androgen deprivation or treatment for prostate cancer, and who could safely undergo multiparametric MRI and have a general anaesthetic. Patients received focal therapy using high-intensity focused ultrasound, delivered to all known cancer lesions, with a margin of normal tissue, identified on multiparametric MRI, template prostate-mapping biopsies, or both. Primary endpoints were adverse events (serious and otherwise) and urinary symptoms and erectile function assessed using patient questionnaires. Analyses were done on a per-protocol basis. This study is registered with ClinicalTrials.gov, number NCT00561314. Findings: 42 men were recruited between June 27, 2007, and June 30, 2010; one man died from an unrelated cause (pneumonia) 3 months after treatment and was excluded from analyses. After treatment, one man was admitted to hospital for acute urinary retention, and another had stricture interventions requiring hospital admission. Nine men (22%, 95% CI 11–38) had self-resolving, mild to moderate, intermittent dysuria (median duration 5·0 days [IQR 2·5–18·5]). Urinary debris occurred in 14 men (34%, 95% CI 20–51), with a median duration of 14·5 days (IQR 6·0–16·5). Urinary tract infection was noted in seven men (17%, 95% CI 7–32). Median overall International Index of Erectile Function-15 (IIEF-15) scores were similar at baseline and at 12 months (p=0·060), as were median IIEF-15 scores for intercourse satisfaction (p=0·454), sexual desire (p=0·644), and overall satisfaction (p=0·257). Significant deteriorations between baseline and 12 months were noted for IIEF-15 erectile (p=0·042) and orgasmic function (p=0·003). Of 35 men with good baseline function, 31 (89%, 95% CI 73–97) had erections sufficient for penetration 12 months after focal therapy. Median UCLA Expanded Prostate Cancer Index Composite (EPIC) urinary incontinence scores were similar at baseline as and 12 months (p=0·045). There was an improvement in lower urinary tract symptoms, assessed by International Prostate Symptom Score (IPSS), between baseline and 12 months (p=0·026), but the IPSS-quality of life score showed no difference between baseline and 12 months (p=0·655). All 38 men with no baseline urinary incontinence were leak-free and pad-free by 9 months. All 40 men pad-free at baseline were pad-free by 3 months and maintained pad-free continence at 12 months. No significant difference was reported in median Trial Outcomes Index scores between baseline and 12 months (p=0·113) but significant improvement was shown in median Functional Assessment of Cancer Therapy (FACT)-Prostate (p=0·045) and median FACT-General scores (p=0·041). No histological evidence of cancer was identified in 30 of 39 men biopsied at 6 months (77%, 95% CI 61–89); 36 (92%, 79–98) were free of clinically significant cancer. After retreatment in four men, 39 of 41 (95%, 95% CI 83–99) had no evidence of disease on multiparametric MRI at 12 months. Interpretation: Focal therapy of individual prostate cancer lesions, whether multifocal or unifocal, leads to a low rate of genitourinary side-effects and an encouraging rate of early absence of clinically significant prostate cancer. Funding: Medical Research Council (UK), Pelican Cancer Foundation, and St Peters Trust. [Copyright &y& Elsevier]

Abstract: Background: Multiparametric magnetic resonance imaging (mpMRI) may have a role in detecting clinically significant prostate cancer in men with raised serum prostate-specific antigen levels. Variations in technique and the interpretation of images have contributed to inconsistency in its reported performance characteristics. Objective: Our aim was to make recommendations on a standardised method for the conduct, interpretation, and reporting of prostate mpMRI for prostate cancer detection and localisation. Design, setting, and participants: A consensus meeting of 16 European prostate cancer experts was held that followed the UCLA-RAND Appropriateness Method and facilitated by an independent chair. Measurement: Before the meeting, 520 items were scored for “appropriateness” by panel members, discussed face to face, and rescored. Results and limitations: Agreement was reached in 67% of 260 items related to imaging sequence parameters. T2-weighted, dynamic contrast-enhanced, and diffusion-weighted MRI were the key sequences incorporated into the minimum requirements. Consensus was also reached on 54% of 260 items related to image interpretation and reporting, including features of malignancy on individual sequences. A 5-point scale was agreed on for communicating the probability of malignancy, with a minimum of 16 prostatic regions of interest, to include a pictorial representation of suspicious foci. Limitations relate to consensus methodology. Dominant personalities are known to affect the opinions of the group and were countered by a neutral chairperson. Conclusions: Consensus was reached on a number of areas related to the conduct, interpretation, and reporting of mpMRI for the detection, localisation, and characterisation of prostate cancer. Before optimal dissemination of this technology, these outcomes will require formal validation in prospective trials. [Copyright &y& Elsevier]

Simple Summary: International guidelines recommend multiparametric magnetic resonance imaging (mpMRI) of the prostate for use by radiologists to identify lesions containing clinically significant prostate cancer, prior to confirmatory biopsy. Automatic assessment of prostate mpMRI using artificial intelligence algorithms holds a currently unrealized potential to improve the diagnostic accuracy achievable by radiologists alone, improve the reporting consistency between radiologists, and enhance reporting quality. In this work, we introduce AutoProstate: a deep learning-powered framework for automatic MRI-based prostate cancer assessment. In particular, AutoProstate utilizes patient data and biparametric MRI to populate an automatic web-based report which includes segmentations of the whole prostate, prostatic zones, and candidate clinically significant prostate cancer lesions, and in addition, several derived characteristics with clinical value are presented. Notably, AutoProstate performed well in external validation using the PICTURE study dataset, suggesting value in prospective multicentre validation, with a view towards future deployment into the prostate cancer diagnostic pathway. Multiparametric magnetic resonance imaging (mpMRI) of the prostate is used by radiologists to identify, score, and stage abnormalities that may correspond to clinically significant prostate cancer (CSPCa). Automatic assessment of prostate mpMRI using artificial intelligence algorithms may facilitate a reduction in missed cancers and unnecessary biopsies, an increase in inter-observer agreement between radiologists, and an improvement in reporting quality. In this work, we introduce AutoProstate, a deep learning-powered framework for automatic MRI-based prostate cancer assessment. AutoProstate comprises of three modules: Zone-Segmenter, CSPCa-Segmenter, and Report-Generator. Zone-Segmenter segments the prostatic zones on T2-weighted imaging, CSPCa-Segmenter detects and segments CSPCa lesions using biparametric MRI, and Report-Generator generates an automatic web-based report containing four sections: Patient Details, Prostate Size and PSA Density, Clinically Significant Lesion Candidates, and Findings Summary. In our experiment, AutoProstate was trained using the publicly available PROSTATEx dataset, and externally validated using the PICTURE dataset. Moreover, the performance of AutoProstate was compared to the performance of an experienced radiologist who prospectively read PICTURE dataset cases. In comparison to the radiologist, AutoProstate showed statistically significant improvements in prostate volume and prostate-specific antigen density estimation. Furthermore, AutoProstate matched the CSPCa lesion detection sensitivity of the radiologist, which is paramount, but produced more false positive detections. [ABSTRACT FROM AUTHOR]

To determine whether indeterminate (Likert-score 3/5) peripheral zone (PZ) multiparametric MRI (mpMRI) studies are classifiable by prostate-specific antigen (PSA), PSA density (PSAD), Prostate Imaging Reporting And Data System version 2 (PI-RADS_v2) rescoring and morphological MRI features. Men with maximum Likert-score 3/5 within their PZ were retrospectively selected from 330 patients who prospectively underwent prostate mpMRI (3 T) without an endorectal coil, followed by 20-zone transperineal template prostate mapping biopsies ＋/- focal lesion-targeted biopsy. PSAD was calculated using pre-biopsy PSA and MRI-derived volume. Two readers A and B independently assessed included men with both Likert-assessment and PI-RADS_v2. Both readers then classified mpMRI morphological features in consensus. Men were divided into two groups: significant cancer (≥ Gleason 3 ＋ 4) or insignificant cancer (≤ Gleason 3 ＋ 3)/no cancer. Comparisons between groups were made separately for PSA & PSAD using Mann–Whitney test and morphological descriptors with Fisher's exact test. PI-RADS_v2 and Likert-assessment were descriptively compared and percentage inter-reader agreement calculated. 76 males were eligible for PSA & PSAD analyses, 71 for PI-RADS scoring, and 67 for morphological assessment (excluding significant image artefacts). Unlike PSA (p = 0.915), PSAD was statistically different (p = 0.004) between the significant [median: 0.19 ng ml–2 (interquartile range: 0.13–0.29)] and non-significant/no cancer [median: 0.13 ng ml–2 (interquartile range: 0.10–0.17)] groups. Presence of mpMRI morphological features was not significantly different between groups. Subjective Likert-assessment discriminated patients with significant cancer better than PI-RADS_v2. Inter-reader percentage agreement was 83% for subjective Likert-assessment and 56% for PI-RADS_v2. PSAD may categorize presence of significant cancer in patients with Likert-scored 3/5 PZ mpMRI findings. PSAD may be used in indeterminate PZ mpMRI to guide decisions between biopsy vs monitoring. [ABSTRACT FROM AUTHOR]

Multiparametric magnetic resonance imaging (MP-MRI) is established in the diagnosis of prostate cancer, but the need for enhanced sequences has recently been questioned. To assess whether dynamic contrast-enhanced imaging (DCE) improves accuracy over T2 and diffusion sequences. PROMIS was a multicentre, multireader trial, with, in this part, 497 biopsy-naïve men undergoing standardised 1.5T MP-MRI using T2, diffusion, and DCE, followed by a detailed transperineal prostate mapping (TPM) biopsy at 5 mm intervals. Likert scores of 1–5 for the presence of a significant tumour were assigned in strict sequence, for (1) T2 + diffusion and then (2) T2 + diffusion + dynamic contrast-enhanced images. For the primary analysis, the primary PROMIS outcome measure (Gleason score ≥4 + 3 or ≥6 mm maximum cancer length) on TPM was used, and an MRI score of ≥3 was considered positive. Sensitivity without and with DCE was 94% and 95%, specificity 37% and 38%, positive predictive value 51% and 51%, and negative predictive value 90% and 91%, respectively (p > 0.05 in each case). The number of patients avoiding biopsy (scoring 1–2) was similar (123/497 vs 121/497, p = 0.8). The number of equivocal scores (3/5) was slightly higher without DCE (32% vs 28% p = 0.031). The proportion of MRI equivocal (3/5) and positive (4–5) cases showing significant tumours were similar (23% and 71% vs 20% and 69%). No cases of dominant Gleason 4 or higher were missed with DCE, compared with a single case with T2 + diffusion-weighted imaging. No attempt was made to correlate lesion location on MRI and histology, which may be considered a limitation. Radiologists were aware of the patient's prostate-specific antigen. Contrast adds little when MP-MRI is used to exclude significant prostate cancer. An intravenous injection of contrast may not be necessary when magnetic resonance imaging is used as a test to rule out significant tumours in the prostate. The addition of dynamic contrast-enhanced imaging did not offer a statistically significant improvement in diagnostic accuracy compared with T2 + diffusion sequences alone, although there was a marginal reduction of equivocal (3/5) magnetic resonance imaging results. [ABSTRACT FROM AUTHOR]

• A novel patient-level classification framework, PCF, for clinically significant prostate cancer, trained using patient-level labels only. • PCF extracts features from three-dimensional multiparametric MRI and derived parameter maps using convolutional neural networks, and subsequently combines extracted MRI features with clinical features using a multi-classifier support vector machine scheme. • PCF achieved a mean area under the receiver operating characteristic curve of 0.79 on the PICTURE study dataset and 0.86 on the publicly available PROSTATEx dataset, using five-fold cross-validation. • Clinical evaluation over a temporally separated PICTURE study cohort demonstrated comparable sensitivity and specificity to a radiologist with over 10 years' experience in reading prostate MRI. • Prostate-specific antigen density in conjunction with MRI features improved classification performance. [Display omitted] 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. [ABSTRACT FROM AUTHOR]

: 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. : 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). : 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. : 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%). : 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. : 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. Depending on definition of "negative multiparametric magnetic resonance imaging" and "clinically significant prostate cancer", the negative predictive value ranged from 84% to 97%, suggesting that it is a reliable test to rule out clinically significant prostate cancer. [ABSTRACT FROM AUTHOR]

Focal cryotherapy can be used to treat patients with clinically significant nonmetastatic prostate cancer to reduce side effects. Early-medium-term cancer control and functional outcomes. A prospective registry-based case series of 122 consecutive patients undergoing focal cryotherapy between October 1, 2013, and November 30, 2016, in five UK centres. Median follow-up was 27.8 mo [interquartile range (IQR) 19.5–36.7]. A total of 35 patients (28.7%) had National Comprehensive Cancer Network (NCCN) high risk and 87 (71.3%) had intermediate risk disease. Risk and zonal stratification included multiparametric magnetic resonance imaging (mpMRI) with targeted and systematic biopsies, or transperineal mapping biopsies. Focal cryoablation of MR-visible tumours. Follow-up involved prostate-specific antigen (PSA) monitoring, mpMRI, and for-cause biopsies. Primary outcome was failure-free survival (FFS), defined as transition to radical, whole-gland, or systemic therapy, or metastases/death. Secondary outcomes included adverse events and functional outcomes. A total of 80 (65.6%) had anterior ablation, 23 (19.7%) combined posterior and anterior ablation, and two (1.6%) posterior ablation alone (SeedNet or Visual-ICE, BTG plc). Median age was 68.7 yr (IQR 64.9–73.8) and preoperative PSA 10.8 ng/ml (IQR 7.8–15.6). Overall FFS at 3 yr was 90.5% [95% confidence interval (CI) 84.2–97.3]. When stratified for the NCCN risk group, 3-yr outcomes were 84.7% (95% CI 71.4–100) in high risk and 93.3% (95% CI 86.8–100) in intermediate risk. At last follow-up, incontinence defined as any pad use was 0/69 (0%) and erectile dysfunction (defined as erections insufficient for penetration) was 5/31 (16.1%). Limitations include lack of long-term outcomes. Focal cryotherapy primarily for anterior intermediate and high-risk prostate cancer results in good rates of cancer control and low rates of treatment-related side effects. In this multicentre study of 122 patients undergoing focal cryotherapy for medium- to high-risk prostate cancer, at 3 yr, no patient died from their cancer whilst failure-free survival, was approximately 90%. None of the patients needed pads for managing urine leakage, although 16% had erection problems. Focal cryotherapy used primarily for anterior intermediate and high-risk prostate cancer results in good rates of cancer control and low rates of treatment-related side effects in the medium term. [ABSTRACT FROM AUTHOR]

Abstract Background Clinically significant nonmetastatic prostate cancer (PCa) is currently treated using whole-gland therapy. This approach is effective but can have urinary, sexual, and rectal side effects. Objective To report on 5-yr PCa control following focal high-intensity focused ultrasound (HIFU) therapy to treat individual areas of cancer within the prostate. Design, setting, and participants This was a prospective study of 625 consecutive patients with nonmetastatic clinically significant PCa undergoing focal HIFU therapy (Sonablate) in secondary care centres between January 1, 2006 and December 31, 2015. A minimum of 6-mo follow-up was available for599 patients. Intermediate- or high-risk PCa was found in 505 patients (84%). Intervention Disease was localised using multiparametric magnetic resonance imaging (mpMRI) combined with targeted and systematic biopsies, or transperineal mapping biopsies. Areas of significant disease were treated. Follow-up included prostate-specific antigen (PSA) measurement, mpMRI, and biopsies. Outcome measurements and statistical analysis The primary endpoint, failure-free survival (FFS), was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality. Results and limitations The median follow-up was 56 mo (interquartile range [IQR] 35–70). The median age was 65 yr (IQR 61–71) and median preoperative PSA was 7.2 ng/ml (IQR 5.2–10.0). FFS was 99% (95% confidence interval [CI] 98–100%) at 1 yr, 92% (95% CI 90–95%) at 3 yr, and 88% (95% 85–91%) at 5 yr. For the whole patient cohort, metastasis-free, cancer-specific, and overall survival at 5 yr was 98% (95% CI 97–99%), 100%, and 99% (95% CI 97–100%), respectively. Among patients who returned validated questionnaires, 241/247 (98%) achieved complete pad-free urinary continence and none required more than 1 pad/d. Limitations include the lack of long-term follow-up. Conclusions Focal therapy for select patients with clinically significant nonmetastatic prostate cancer is effective in the medium term and has a low probability of side effects. Patient summary In this multicentre study of 625 patients undergoing focal therapy using high-intensity focused ultrasound (HIFU), failure-free survival, metastasis-free survival, cancer-specific survival, and overall survival were 88%, 98%, 100%, and 99%, respectively. Urinary incontinence (any pad use) was 2%. Focal HIFU therapy for patients with clinically significant prostate cancer that has not spread has a low probability of side effects and is effective at 5 yr. Take Home Message Our study shows that at median follow-up of approximately 5 yr after focal high-intensity focused ultrasound, nine out of ten patients with predominantly intermediate- or high-risk prostate cancer are able to avoid surgery, radiotherapy, and systemic therapy. Prostate cancer–specific survival was 100%. There was a low probability of urinary incontinence (2%), erectile dysfunction (15%), and rectal side effects (rare). [ABSTRACT FROM AUTHOR]

Background High-intensity focused ultrasound (HIFU) is a minimally-invasive treatment for nonmetastatic prostate cancer. Objective To report medium-term outcomes in men receiving primary whole-gland HIFU from a national multi-centre registry cohort. Design, setting, and participants Five-hundred and sixty-nine patients at eight hospitals were entered into an academic registry. Intervention Whole-gland HIFU (Sonablate 500) for primary nonmetastatic prostate cancer. Redo-HIFU was permitted as part of the intervention. Outcome measurements and statistical analysis Our primary failure-free survival outcome incorporated no transition to any of the following: (1) local salvage therapy (surgery or radiotherapy), (2) systemic therapy, (3) metastases, or (4) prostate cancer-specific mortality. Secondary outcomes included adverse events and genitourinary function. Results and limitations Mean age was 65 yr (47–87 yr). Median prostate-specific antigen was 7.0 ng/ml (interquartile range 4.4–10.2). National Comprehensive Cancer Network low-, intermediate-, and high-risk disease was 161 (28%), 321 (56%), and 81 (14%), respectively. One hundred and sixty three of 569 (29%) required a total of 185 redo-HIFU procedures. Median follow-up was 46 (interquartile range 23–61) mo. Failure-free survival at 5 yr after first HIFU was 70% (95% confidence interval [CI]: 64–74). This was 87% (95% CI: 78–93), 63% (95% CI: 56–70), and 58% (95% CI: 32–77) for National Comprehensive Cancer Network low-, intermediate-, and high-risk groups, respectively. Fifty eight of 754 (7.7%) had one urinary tract infection, 22/574 (2.9%) a recurrent urinary tract infection, 22/754 (3%) epididymo-orchitis, 227/754 (30%) endoscopic interventions, 1/754 (0.13%) recto-urethral fistula, and 1/754 (0.13%) osteitis pubis. Of 206 known to be pad-free pre-HIFU, 183/206 (88%) remained pad free, and of 236 with good baseline erectile function, 91/236 (39%) maintained good function. The main limitation is lack of long-term data. Conclusions Whole-gland HIFU is a repeatable day-case treatment that confers low rates of urinary incontinence. Disease control at a median of just under 5 yr of follow-up demonstrates its potential as a treatment for nonmetastatic prostate cancer. Endoscopic interventions and erectile dysfunction rates are similar to other whole-gland treatments. Patient summary In this report we looked at the 5-yr outcomes following whole-gland high-intensity focused ultrasound treatment for prostate cancer and found that cancer control was acceptable with a low risk of urine leakage. However, risk of erectile dysfunction and further operations was similar to other whole-gland treatments like surgery and radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose We evaluated the prostate cancer detection with transperineal template-guided mapping biopsy in patients with elevated prostate-specific antigen and negative magnetic resonance imaging (MRI)−guided biopsy. Materials and methods Totally 75 patients underwent transperineal template-guided mapping biopsy for prior negative MRI−guided (cognitive registration) biopsy during April 2013 to August 2014. Primary objective was to report clinically significant cancer detection in this cohort of patients. Significant cancer was defined using varying thresholds of MCL or Gleason grade 3+4 or greater or both. Cancers with more than 80% of positive core length anterior to the level of urethra were termed anterior zone cancer. Secondary objective was to evaluate the potential clinical and radiological predictors for significant cancer detection. Results The mean age was 61.6±6.5 years and median prostate-specific antigen was 10.4 ng/dl (7.9−18) with a mean MRI target size of 7.2 mm (4−11). Transperineal template-guided mapping biopsy identified cancer in 36% (27/75) patients and 66.6% (18/27) of them were anterior zone cancers. The rates of detection of clinically significant and insignificant cancer according to the several definitions used range from 22.7% to 30.7% and 5.3% to 13.3%, respectively. Multivariate analysis did not identify any predictors for finding clinically significant and anterior cancers in this group of patients. Conclusion Transperineal template-guided mapping biopsy appears to be an excellent biopsy protocol for downstream management following negative MRI−guided biopsy. Most of the cancers detected were predominantly anterior tumors. [ABSTRACT FROM AUTHOR]