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Objective To determine whether multiparametric magnetic resonance imaging (mp-MRI) has a role in reducing the uncertainty in risk stratification by transrectal ultrasound (TRUS) biopsy, using histology at transperineal template-guided prostate mapping (TPM) biopsy as the reference test. Materials and methods Overall, 194 patients underwent TRUS biopsy, who were followed up in less than 18 months by means of (a) mp-MRI with pelvic phased array using T2-weighted, diffusion-weighted and dynamic contrast-enhanced sequences and (b) TPM biopsy. Of those patients, low risk on TRUS biopsy was defined in 4 different ways—(a) definition 1: Gleason 3+3 (any cancer core length) ( n = 137), (b) definition 2: maximum cancer core length (MCCL)<50% (any Gleason score) ( n = 62), (c) definition 3: Gleason 3+3 and MCCL<50% ( n = 52), and (d) definition 4: Gleason 3+3, MCCL<50%, prostate-specific antigen level<10 ng/ml, and<50% positive cores ( n = 28). Mp-MRI was scored for the likelihood of cancer from 1 (cancer very unlikely) to 5 (cancer very likely). Binary logistic regression analysis was performed to evaluate the association between MRI scores and TPM histology. Results Median prostate-specific antigen level was 7 ng/ml (range: 0.9–29), median time between TRUS biopsy and mp-MRI was 120 days (range: 41–480), and median time between mp-MRI and TPM biopsy was 60 days (range: 1–420). A median of 48 cores (range: 20–118) were taken at TPM biopsy. Gleason score was upgraded in 62 of 137 (45%) patients at TPM biopsy. The negative predictive values of mp-MRI score 1 to 2 for predicting that cancer remained low risk (according to each definition) were 75%, 100%, 83%, and 100% for definitions 1, 2, 3, and 4, respectively. An mp-MRI score of 4 to 5 had positive predictive values for upgrade or upsize of 59%, 67%, 75%, and 69% for definitions 1, 2, 3, and 4, respectively. Conclusion The presence of an mp-MRI lesion in men with low-risk prostate cancer on TRUS biopsy confers, in most patients, a high likelihood that higher-risk disease will be present (either Gleason pattern 4 or a significant cancer burden). Conversely, if a lesion is not seen on mp-MRI, the attribution of low-risk grade or cancer burden is much more likely to be correct. Mp-MRI might therefore be used to triage men for resampling biopsies before entering active surveillance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The current diagnostic and therapeutic strategy for localized prostate cancer is not working. In fact, it is severely flawed and, as such, fraught with controversy. Our current strategy has arisen from the imprecision of our diagnostic pathway. We do not know where the cancer is, so we subject the prostate to randomly placed needles in the hope of hitting the tumor. This leads to overdiagnosis, underdiagnosis, missclassification of risk and overtreatment and undertreatment. If we do find cancer, we usually subject the entire prostate to radiotherapy or surgery, which damages the surrounding structures—neurovascular bundles, external urinary sphincter, rectum, and bladder neck. Multiparametric magnetic resonance imaging, coupled with an intensive sampling strategy (targeted biopsies), might be able to rule out clinically significant lesions with a negative predictive value in the order of 90% to 95%. Focal therapy certainly leads to less genitourinary and rectal side effects. Current data from more than 3,000 men treated internationally show that incontinence after focal therapy is 0% to 5% (radical therapy can lead to incontinence in 15%–20%) whereas erectile dysfunction occurs in 5% to 10% of men with good baseline function (radical therapy rates vary between 30% and 60%). Early to medium cancer control using biopsies after treatment shows between 80% and 90% of patients have a successful treatment, with 10% to 15% of men requiring redo-treatment with minimal additional morbidity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To systematically review erectile function (EF) outcomes following primary whole gland (WG) and focal ablative therapies for localized prostate cancer to ascertain whether the treatment modality or intended treatment volume affects the time taken to recover baseline EF.Method and Materials: A systematic review was performed according to the preferred reporting items for systematic review and meta-analysis statement. Inclusion criteria were men with localized prostate cancer treated with primary, ablative therapy. Primary outcome was the return to baseline EF measured with objective, validated symptoms scores. Secondary outcome was use of phosphodiesterase inhibitors or erectile aids. Meta-analysis was not performed owing to heterogenous outcome measures.Results: Of 222 articles identified in February 2017, 55 studies which reported EF after ablative therapy were identified but only 17 used validated outcome measures and met inclusion criteria. WG cryotherapy was used in 2 studies, WG high-intensity focused ultrasound (HIFU) in 5, focal cryotherapy in 2, focal HIFU in 3, focal phototherapy or laser therapy in 4, vascular-targeted photodynamic therapy in 3, and irreversible electroporation in 2. WG cryotherapy was associated with a significant decline in EF at 6 months with minimal improvement at 36 months. Baseline IIEF-15 of patients undergoing focal HIFU fell 30 points at 1 month but returned to baseline by 6 months. The remaining focal therapies demonstrated minimal or no effect on EF, but the men in these studies had small foci of disease. The review is limited by lack of randomized studies and heterogenous outcome measures.Conclusions: Most studies assessing the outcomes of focal therapy on sexual function were not of high quality, used heterogenous outcomes, and had relatively short follow up, highlighting the need for more robustly designed studies using validated patient reported outcome measures  for comparison. However, FT in general resulted in less effect on EF than WG ablation. [ABSTRACT FROM AUTHOR]

• Radiological staging of prostate cancer with mpMRI leads to a possible Will Rogers phenomenon. • Our modified EAU risk group model that incorporates mpMRI provides a more precise risk stratification. • Predictive models using both DRE and mpMRI have the best predictive value for PFS. 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. 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. 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. 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. [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]

New technologies in prostate cancer are attempting to change the current prostate cancer pathway by aiming to reduce harms while maintaining the benefits associated with screening, diagnosis, and treatment. In this article, we discuss the optimal evaluation that new technologies should undergo to provide level 1 evidence typically required to change the practice. With this in mind, we focus on feasible and pragmatic trials that could be delivered in a timely fashion by many centers while retaining primary outcomes that focus on clinically meaningful outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Focal salvage HIFU is a feasible therapeutic option in some men who have recurrence after primary radiotherapy for prostate cancer. We aimed to determine if multi-parametric quantitative parameters, in addition to clinical factors, might have a role in independently predicting focal salvage HIFU outcomes.Methods: A retrospective registry analysis included 150 consecutive men who underwent focal salvage HIFU (Sonablate500) (2006-2015); 89 had mpMRI available. Metastatic disease was excluded by nodal assessment on pelvic MRI, a radioisotope bone-scan and/or choline or FDG PET/CT scan. All men had mpMRI and either transperineal template prostate mapping biopsy or targeted and systematic TRUS-biopsy. mpMRI included T2-weighted, diffusion-weighted and dynamic contrast-enhancement. Pre-HIFU quantitative mpMRI data was obtained using Horos DICOM Viewer v3.3.5 for general MRI parameters and IB DCE v2.0 plug-in. Progression-free survival (PFS) was defined by biochemical failure and/or positive localized or distant imaging results and/or positive biopsy and/or systemic therapy and/or metastases/prostate cancer-specific death. Potential predictors of PFS were analyzed by univariable and multivariable Cox-regression.Results: Median age at focal salvage HIFU was 71 years (interquartile range [IQR] 65-74.5) and median PSA pre-focal salvage treatment was 5.8ng/ml (3.8-8). Median follow-up was 35 months (23-47) and median time to failure was 15 months (7.8-24.3). D-Amico low, intermediate and high-risk disease was present in 1% (1/89), 40% (36/89) and 43% (38/89) prior to focal salvage HIFU (16% missing data). 56% (50/89) failed by the composite outcome. A total of 22 factors were evaluated on univariable and 8 factors on multivariable analysis. The following quantitative parameters were included: Ktrans, Kep, Ve, Vp, IS, rTTP and TTP. On univariable analysis, PSA, prostate volume at time of radiotherapy failure and Ve (median) value were predictors for failure. Ve represents extracellular fraction of the whole tissue volume. On multivariable analysis, only Ve (median) value remained as an independent predictor.Conclusions: One pharmacokinetic quantitative parameter based on DCE sequences seems to independently predict failure following focal salvage HIFU for radio-recurrent prostate cancer. This likely relates to the tumor microenvironment producing heat-sinks which counter the heating effect of HIFU. Further validation in larger datasets and evaluating mechanisms to reduce heat-sinks are required. [ABSTRACT FROM AUTHOR]

Introduction: The urological community's opinion over focal therapy (FT) for prostate cancer (PCa) has never been assessed. Our aim was to investigate the current opinion on FT in the European urological community.Methods: A 25-item questionnaire was devised according to the Cherries checklist and distributed through SurveyMonkey using a web link from November 2016 to October 2017. After a pilot validation (n = 40 urologists), the survey was sent through EAU and 9 other national European urological societies mailing list. Twitter was also used.Results: We received 484 replies from 51 countries. Almost half (44.8%, n = 217) stated FT would represent a step forward, and 52.0% (n = 252) would suggest FT to a patient. Almost three-quarters (70.8%, n = 343) agreed FT will become a standard option after improvements in patient selection (n = 66) or when its effectiveness will be proven (n = 78), or both (n = 199). Most frequently used definition of FT was treatment of all significant (life-threatening) cancer foci whilst leaving untreated the rest of the gland (39.3%, n = 190). FT use was considered as an alternative to whole-gland treatments by 29.7% (n = 144), and to AS by 25.0% (n = 121). On multivariate analysis, FT availability and publications were associated with a positive opinion on FT. Conversely, attending International congresses, treating high PCa volumes and high percentages of high-risk PCa was associated with a negative opinion.Conclusions: FT is considered as an attractive option for PCa treatment by the European urological community sampled by our survey. FT availability positively influences these thoughts. The present survey suggests whilst some early adopters already embraced FT, the relative majority of the urological community is prone to embrace FT in the near future, once current areas of debate are solved. [ABSTRACT FROM AUTHOR]

Purpose: Patient selection for focal salvage remains difficult. Therefore, we developed and internally validated prediction models for biochemical failure (BF) and a composite endpoint (CE) following focal salvage high intensity focused ultrasound (HIFU) for radiorecurrent prostate cancer.Materials and Methods: A prospective HIFU registry identified 150 cases (November 2006-August 2015). Recurrence was assessed with multiparametric magnetic resonance imaging (MRI) combined with template prostate mapping biopsies, targeted biopsies, or systematic transrectal ultrasound-guided biopsies. Metastatic disease was ruled out with a positron emission tomography-computed tomography and a bone scan. Focal salvage HIFU consisted of quadrant-ablation, hemi-ablation, or index-lesion ablation. Cox-regression was used for BF (Phoenix-definition) and CE (BF/MRI+/biopsies+/local or systemic treatment/metastases+/prostate cancer specific mortality+). Internal validation was performed using bootstrap resampling (500 datasets) after which C-statistic and hazard ratios were adjusted. Models were calibrated and risk scores created.Results: Median follow-up was 35 months (interquartile range: 22-52). Median biochemical disease-free survival (DFS) was 33 months (95% CI: 23-45). Median CE-free survival was 24 months (95% CI: 21-35). After multivariable analysis, DFS interval after primary radiotherapy, presalvage prostate-specific antigen (PSA), PSA-doubling time, prostatic volume, and T-stage (both MRI based) predicted BF. For the CE, PSA-doubling time was not predictive but additionally, primary Gleason score was. The adjusted C-statistics were 0.68 and 0.64 for BF and CE, respectively. Calibration was accurate until 48 months. The risk scores showed 3 groups, with biochemical DFS of 60%, 35%, and 7% and CE-free survival of 40%, 24%, and 0% at 4 years.Conclusion: Our model, once externally validated, could allow for better selection of patients for focal salvage HIFU. [ABSTRACT FROM AUTHOR]

Objectives: Targeted biopsy based on cognitive or software magnetic resonance imaging (MRI) to transrectal ultrasound registration seems to increase the detection rate of clinically significant prostate cancer as compared with standard biopsy. However, these strategies have not been directly compared against an accurate test yet. The aim of this study was to obtain pilot data on the diagnostic ability of visually directed targeted biopsy vs. software-based targeted biopsy, considering transperineal template mapping (TPM) biopsy as the reference test.Methods and Materials: Prospective paired cohort study included 50 consecutive men undergoing TPM with one or more visible targets detected on preoperative multiparametric MRI. Targets were contoured on the Biojet software. Patients initially underwent software-based targeted biopsies, then visually directed targeted biopsies, and finally systematic TPM. The detection rate of clinically significant disease (Gleason score ≥3+4 and/or maximum cancer core length ≥4mm) of one strategy against another was compared by 3×3 contingency tables. Secondary analyses were performed using a less stringent threshold of significance (Gleason score ≥4+3 and/or maximum cancer core length ≥6mm).Results: Median age was 68 (interquartile range: 63-73); median prostate-specific antigen level was 7.9ng/mL (6.4-10.2). A total of 79 targets were detected with a mean of 1.6 targets per patient. Of these, 27 (34%), 28 (35%), and 24 (31%) were scored 3, 4, and 5, respectively. At a patient level, the detection rate was 32 (64%), 34 (68%), and 38 (76%) for visually directed targeted, software-based biopsy, and TPM, respectively. Combining the 2 targeted strategies would have led to detection rate of 39 (78%). At a patient level and at a target level, software-based targeted biopsy found more clinically significant diseases than did visually directed targeted biopsy, although this was not statistically significant (22% vs. 14%, P = 0.48; 51.9% vs. 44.3%, P = 0.24). Secondary analysis showed similar results. Based on these findings, a paired cohort study enrolling at least 257 men would verify whether this difference is statistically significant.Conclusion: The diagnostic ability of software-based targeted biopsy and visually directed targeted biopsy seems almost comparable, although utility and efficiency both seem to be slightly in favor of the software-based strategy. Ongoing trials are sufficiently powered to prove or disprove these findings. [ABSTRACT FROM AUTHOR]