Miguel Godinho Ferreira

Index grade group is superior to composite grade group for prediction of biochemical recurrence following radical prostatectomy

Publisher: Elsevier BV

Date: 06-2023

DOI: 10.1016/J.PATHOL.2022.10.012

Focal ablation of apical prostate cancer lesions with irreversible electroporation (IRE)

Publisher: Springer Science and Business Media LLC

Date: 02-06-2020

DOI: 10.1007/S00345-020-03275-Z

Oncological and Quality-of-life Outcomes Following Focal Irreversible Electroporation as Primary Treatment for Localised Prostate Cancer: A Biopsy-monitored Prospective Cohort

Publisher: Elsevier BV

Date: 06-2020

DOI: 10.1016/J.EUO.2019.04.008

Abstract: Focal irreversible electroporation (IRE) can be used to treat men with localised prostate cancer (PCa) with reduced impact on quality of life (QoL). To assess oncological and functional outcomes. To report on a prospective database of patients undergoing primary IRE between February 2013 and August 2018. A minimum of 12-mo follow-up was available for 123 patients. Median follow-up was 36 mo (interquartile range [IQR] 24-52 mo). A total of 112 (91%) patients had National Comprehensive Cancer Network intermediate risk and 11 (9%) had low risk. A total of 12 (9.8%) had International Society of Urological Pathology (ISUP) grade 1, 88 (71.5%) had ISUP 2, and 23 (18.7%) had ISUP 3. Focal IRE ablation of PCa lesions. Follow-up involved serial prostate-specific antigen (PSA), multiparametric magnetic resonance imaging (mpMRI), and transperineal template mapping biopsy (TTMB) at 12 mo. Failure-free survival (FFS) was defined as progression to whole-gland or systemic treatment or metastasis/death. Functional outcomes were assessed. Median age was 68yr (IQR 62-73yr). Median preoperative PSA was 5.7ng/ml (IQR 3.8-8.0ng/ml). On post-treatment TTMB, in-field recurrence was present in 2.7-9.8% of patients. FFS at 3yr was 96.75%, metastasis-free survival 99%, and overall survival 100%. A total of 18 patients required salvage treatment (12 had repeat IRE six had whole-gland treatment). The negative predictive value of mpMRI was 94% and sensitivity 40% for detecting in-field residual disease 6 mo after treatment. Among patients who returned questionnaires, 80/81 (98.8%) remained pad free and 40/53 (76%) had no change in erectile function. Focal IRE in select patients with localised clinically significant PCa has satisfactory short-term oncological outcomes with a minimal impact on patient QoL. In this study, 123 patients underwent focal therapy using irreversible electroporation. Follow-up biopsy was clear of residual disease in 90.2-97.3% of patients. Of patients, 96.75% avoided whole gland treatment at 3yr.

Diagnostic accuracy of

Publisher: Wiley

Date: 09-07-2019

DOI: 10.1111/BJU.14794

Abstract: To evaluate the ability of prostate-specific membrane antigen (PSMA)-positron-emission tomography (PET)/computed tomography (CT) to detect intermediate-grade intra-prostatic prostate cancer (PCa), and to determine if PSMA-PET improves the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI). A total of 56 consecutive patients with International Society of Urological Pathology (ISUP) grade 2-3 PCa after radical prostatectomy, who underwent both mpMRI and PSMA-PET CT (hereafter PSMA-PET) preoperatively, were enrolled in this study. The accuracy of PSMA-PET, mpMRI alone, and the two procedures in combination was analysed for identifying ISUP grades 1-3 within a 12-segment model. The accuracy of a combined predictive model (PSMA-PET and mpMRI) was determined. Receiver-operating characteristic curve analysis to determine the optimal standardized uptake value (SUV On a per-patient basis, the sensitivities for PSMA-PET and mpMRI in identifying ISUP grades 2-3 PCa were 100% and 97%, respectively. Assessing ISUP grade ≥2 PCa using a 12-segment analysis, PSMA-PET demonstrated greater diagnostic accuracy (area under the curve), sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV), with values of 0.91, 88%, 93%, 95% and 85%, respectively, than did mpMRI (Prostate Imaging Reporting and Data System [PI-RADS] 3-5), at 0.79, 68%, 91%, 87%, and 75%, respectively. When used in combination (PSMA-PET and mpMRI PIRADS 4-5), sensitivity, specificity, NPV and PPV were 92%, 90%, 96% and 81%, respectively. The sensitivity for both techniques reduced markedly when assessing ISUP grade 1 PCa (18% for PSMA-PET, 10% for mpMRI). An SUV PSMA-PET is accurate in detecting segments containing intermediate-grade intra-prostatic PCa (ISUP grade ≥ 2), compared with and complementary to mpMRI. By contrast the detection rate for ISUP grade 1 disease for both PSMA-PET and mpMRI was low.

Superior quality of life and improved surgical margins are achievable with robotic radical prostatectomy after a long learning curve: a prospective single-surgeon study of 1552 consecutive cases.

Publisher: Elsevier BV

Date: 03-2013

DOI: 10.1016/J.EURURO.2013.10.030

Abstract: Comparative studies suggest functional and perioperative superiority of robot-assisted radical prostatectomy (RARP) over open radical prostatectomy (ORP). To determine whether high-volume experienced open surgeons can improve their functional and oncologic outcomes with RARP and, if so, how many cases are required to surpass ORP outcomes and reach the learning curve plateau. A prospective observational study compared two surgical techniques: 1552 consecutive men underwent RARP (866) or ORP (686) at a single Australian hospital from 2006 to 2012, by one surgeon with 3000 prior ORPs. Demographic and clinicopathologic data were collected prospectively. The Expanded Prostate Cancer Index Composite quality of life (QoL) questionnaire was administered at baseline, 1.5, 3, 6, 12, and 24 mo. Multivariate linear and logistic regression modelled the difference in QoL domains and positive surgical margin (PSM) odds ratio (OR), respectively, against case number. A total of 1511 men were included in the PSM and 609 in the QoL analysis. RARP sexual function scores surpassed ORP scores after 99 RARPs and increased to a mean difference at 861st case of 11.0 points (95% confidence interval [CI], 5.9-16.1), plateauing around 600-700 RARPs. Early urinary incontinence scores for RARP surpassed ORP after 182 RARPs and increased to a mean difference of 8.4 points (95% CI, 2.1-14.7), plateauing around 700-800 RARPs. The odds of a pT2 PSM were initially higher for RARP but became lower after 108 RARPs and were 55% lower (OR: 0.45 95% CI, 0.22-0.92) by the 866th RARP. The odds of a pT3/4 PSM were initially higher for RARP but decreased, plateauing around 200-300 RARPs with an OR of 1.15 (0.68-1.95) at the 866th RARP. Limitations include single-surgeon data and residual confounding. RARP had a long learning curve with inferior outcomes initially, and then showed progressively superior sexual, early urinary, and pT2 PSM outcomes and similar pT3 PSM and late urinary outcomes. Learning RARP was worthwhile for this high-volume surgeon, but the learning curve may not be justifiable for late-career/low-volume surgeons further studies are needed.

Superior Biochemical Recurrence and Long-term Quality-of-life Outcomes Are Achievable with Robotic Radical Prostatectomy After a Long Learning Curve-Updated Analysis of a Prospective Single-surgeon Cohort of 2206 Consecutive Cases.

Publisher: Elsevier BV

Date: 05-2017

DOI: 10.1016/J.EURURO.2017.11.035

Abstract: Our earlier analysis suggested that robot-assisted radical prostatectomy (RARP) achieved superiority over open radical prostatectomy (ORP) in terms of positive surgical margin (PSM) rates and functional outcomes. With larger s le size and longer follow-up, the objective of this study update is to assess whether our previous findings are upheld and whether the improved PSM rates for RARP after an initial learning curve compared with ORP-as observed in our earlier analysis-ultimately resulted in improved biochemical control. Prospective observational study comparing two surgical techniques 2271 consecutive men underwent RARP (1520) or ORP (751) at a single centre from 2006 to 2016. Demographic and clinicopathological data were prospectively collected. The EPIC-QOL questionnaire was administered at baseline and 1.5, 3, 6, 12, and 24 mo. Multivariate linear regression modelled the difference in quality of life (QOL) domains against case number logistic and Cox regression modelled the differences in PSM and biochemical recurrence (BCR) hazard ratios (HR), respectively. A total of 2206 men were included in BCR/PSM analysis and 1045 consented for QOL analysis. Superior pT2 surgical margins, early and late sexual outcomes, and early urinary outcomes were upheld and became more robust (narrowing of 95% confidence intervals [CIs]). The risk of BCR was initially higher for RARP, improved after 191 RARPs, and was 35% lower (hazard ratio [HR] 0.65, 95% CI 0.47-0.90) at final RARP, plateauing after 226 RARPs. Improved late (12-24 mo) urinary bother scores (adjusted mean difference [AMD]=4.7, 95% CI 1.3-8.0) and irritative-obstructive scores (AMD=3.8, 95% CI 0.9-5.6) at final RARP were demonstrated. Limitations include observational single surgeon data, possible residual confounding, and short follow-up. The results from this updated analysis demonstrate that RARP can be beneficial for patients of high-volume surgeons, although more randomised studies and studies with survival outcomes are needed. Robot-assisted radical prostatectomy was able to improve functional and oncological outcomes in this single surgeon's learning curve.

Multiparametric magnetic resonance imaging guided diagnostic biopsy detects significant prostate cancer and could reduce unnecessary biopsies and over detection: A prospective study

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 07-2014

DOI: 10.1016/J.JURO.2014.01.014

Abstract: Multiparametric magnetic resonance imaging appears to improve prostate cancer detection but prospective studies are lacking. We determined the accuracy of multiparametric magnetic resonance imaging for detecting significant prostate cancer before diagnostic biopsy in men with abnormal prostate specific antigen/digital rectal examination. In this single center, prospective study men older than 40 years with abnormal prostate specific antigen/digital rectal examination and no previous multiparametric magnetic resonance imaging underwent T2-weighted, diffusion-weighted and dynamic contrast enhanced imaging without an endorectal coil. Imaging was allocated alternately to 1.5/3.0 Tesla. Imaging was double reported independently using PI-RADS (Prostate Imaging Reporting and Data System) by specialist radiologists. Transperineal grid directed 30-core biopsy was performed with additional magnetic resonance imaging directed cores for regions of interest outside template locations. Four significant cancer definitions were tested. Chi-square and logistic regression analysis was done. Men undergoing prostatectomy were analyzed. Of the 165 men who enrolled in the study 150 were analyzed. Median age was 62.4 years, median prostate specific antigen was 5.6 ng/ml, 29% of patients had an abnormal digital rectal examination and 88% underwent initial biopsy. Multiparametric magnetic resonance imaging was positive (PI-RADS 3 to 5) in 66% of patients, 61% had prostate cancer and 30% to 41% had significant prostate cancer (definitions 1 to 4). For significant cancer sensitivity was 93% to 96%, specificity was 47% to 53%, and negative and positive predictive values were 92% to 96% and 43% to 57%, respectively (definitions 1 to 4). Radical prostatectomy results in 48 men were similar. Aggregate PI-RADS (4 to 20) performed similarly to overall PI-RADS (1 to 5). Negative and positive predictive values (100% and 71%, respectively) were similar in men at higher risk, defined as prostate specific antigen greater than 10 ng/ml with abnormal digital rectal examination. On multivariate analysis PI-RADS score was associated with significant prostate cancer (p <0.001) but magnet strength was not. Adding PI-RADS to the multivariate model improved the AUC from 0.810 to 0.913 (95% CI 0.038-0.166, p = 0.002). Radiologist agreement was substantial (weighted κ = 0.626). Multiparametric magnetic resonance imaging reported by expert radiologists achieved an excellent negative predictive value and a moderate positive predictive value for significant prostate cancer at 1.5 and 3.0 Tesla.

Combination of Peri-Tumoral and Intra-Tumoral Radiomic Features on Bi-Parametric MRI Accurately Stratifies Prostate Cancer Risk: A Multi-Site Study

Publisher: MDPI AG

Date: 06-08-2020

DOI: 10.3390/CANCERS12082200

Abstract: Background: Prostate cancer (PCa) influences its surrounding habitat, which tends to manifest as different phenotypic appearances on magnetic resonance imaging (MRI). This region surrounding the PCa lesion, or the peri-tumoral region, may encode useful information that can complement intra-tumoral information to enable better risk stratification. Purpose: To evaluate the role of peri-tumoral radiomic features on bi-parametric MRI (T2-weighted and Diffusion-weighted) to distinguish PCa risk categories as defined by D’Amico Risk Classification System. Materials and Methods: We studied a retrospective, HIPAA-compliant, 4-institution cohort of 231 PCa patients (n = 301 lesions) who underwent 3T multi-parametric MRI prior to biopsy. PCa regions of interest (ROIs) were delineated on MRI by experienced radiologists following which peri-tumoral ROIs were defined. Radiomic features were extracted within the intra- and peri-tumoral ROIs. Radiomic features differentiating low-risk from: (1) high-risk (L-vs.-H), and (2) (intermediate- and high-risk (L-vs.-I + H)) lesions were identified. Using a multi-institutional training cohort of 151 lesions (D1, N = 116 patients), machine learning classifiers were trained using peri- and intra-tumoral features in idually and in combination. The remaining 150 lesions (D2, N = 115 patients) were used for independent hold-out validation and were evaluated using Receiver Operating Characteristic (ROC) analysis and compared with PI-RADS v2 scores. Results: Validation on D2 using peri-tumoral radiomics alone resulted in areas under the ROC curve (AUCs) of 0.84 and 0.73 for the L-vs.-H and L-vs.-I + H classifications, respectively. The best combination of intra- and peri-tumoral features resulted in AUCs of 0.87 and 0.75 for the L-vs.-H and L-vs.-I + H classifications, respectively. This combination improved the risk stratification results by 3–6% compared to intra-tumoral features alone. Our radiomics-based model resulted in a 53% accuracy in differentiating L-vs.-H compared to PI-RADS v2 (48%), on the validation set. Conclusion: Our findings suggest that peri-tumoral radiomic features derived from prostate bi-parametric MRI add independent predictive value to intra-tumoral radiomic features for PCa risk assessment.

Medium-term oncological outcomes for extended vs saturation biopsy and transrectal vs transperineal biopsy in active surveillance for prostate cancer.

Publisher: Wiley

Date: 23-10-2014

DOI: 10.1111/BJU.12858

Abstract: To assess, in men undergoing active surveillance (AS) for low-risk prostate cancer, whether saturation or transperineal biopsy altered oncological outcomes, compared with standard transrectal biopsy. Retrospective analysis of prospectively collected data from two cohorts with localised prostate cancer (1998-2012) undergoing AS. Prostate cancer-specific, metastasis-free and treatment-free survival, unfavourable disease and significant cancer at radical prostatectomy (RP) were compared for standard ( 12 core, median 16), and transrectal vs transperineal biopsy, using multivariate analysis. In all, 650 men were included in the analysis with a median (mean) follow-up of 55 (67) months. Prostate cancer-specific, metastasis-free and biochemical recurrence-free survival were 100%, 100% and 99% respectively. Radical treatment-free survival at 5 and 10 years were 57% and 45% respectively (median time to treatment 7.5 years). On Kaplan-Meier analysis, saturation biopsy was associated with increased objective biopsy progression requiring treatment (log-rank P = 0.01). On multivariate Cox proportional hazards analysis, saturation biopsy (hazard ratio 1.68, P < 0.01) but not transperineal approach (P = 0.89) was associated with increased objective biopsy progression requiring treatment. On logistic regression analysis of 179 men who underwent RP for objective progression, transperineal biopsy was associated with lower likelihood of unfavourable RP pathology (odds ratio 0.42, P = 0.03) but saturation biopsy did not alter the likelihood (P = 0.25). Neither transperineal nor saturation biopsy altered the likelihood of significant vs insignificant cancer at RP (P = 0.19 and P = 0.41, respectively). AS achieved satisfactory oncological outcomes. Saturation biopsy increased progression to treatment on AS longer follow-up is needed to determine if this represents beneficial earlier detection of significant disease or over-treatment. Transperineal biopsy reduced the likelihood of unfavourable disease at RP, possibly due to earlier detection of anterior tumours.

Taurine deficiency as a driver of aging

Publisher: American Association for the Advancement of Science (AAAS)

Date: 09-06-2023

DOI: 10.1126/SCIENCE.ABN9257

Abstract: Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.

Median 4‐year outcomes of salvage irreversible electroporation for localized radio‐recurrent prostate cancer

Publisher: Wiley

Date: 03-01-2023

DOI: 10.1111/BJU.15948

Abstract: To evaluate the safety, and short to mid‐term oncological and quality‐of‐life (QoL) outcomes of focal irreversible electroporation (IRE) for radio‐recurrent prostate cancer (PCa) at a median follow‐up of 4 years. This was a single‐centre series of men with biopsy‐proven radio‐recurrent PCa treated with IRE between December 2013 and February 2022, with a minimum follow‐up of 6 months. Follow‐up included magnetic resonance imaging at 6 months, and standard transperineal saturation template biopsies at 12 months. Further biopsies were guided by suspicion on serial imaging or prostate‐specific antigen (PSA) levels. Validated questionnaires were used to measure functional outcomes. Significant local recurrence was defined as any International Society of Urological Pathology (ISUP) score ≥ 2 on biopsies. Progression‐free survival was defined as no signs of local or systemic disease on either imaging or template biopsies, or according to the Phoenix criteria for biochemical recurrence. Final analysis was performed on 74 men with radio‐recurrent PCa (median age 69 years, median PSA level 5.4 ng/mL, 76% ISUP score 2/3). The median (range) follow‐up was 48 (27–68) months. One rectal fistula occurred, and eight patients developed urethral sloughing that resolved with transurethral resection. Among patients who returned questionnaires (30/74, 41%), 93% (28/30) had preserved urinary continence and 23% (7/30) had sustained erectile function at 12‐month follow‐up. Local control was achieved in 57 patients (77%), who needed no further treatment. Biopsy diagnosed 41(55%) patients received follow up template biopsies, in‐field recurrences occurred in 7% (3/41), and out‐field recurrences occurred in 15% of patients (6/41). The metastasis‐free survival rate was 91% (67/74), with a median (interquartile range) time to metastases of 8 (5–27) months. The Kaplan–Meier estimated 5‐year progression‐free survival rate was 60%. These short‐ to mid‐term safety, oncological and QoL outcome data endorse results from smaller series and show the ability of salvage focal IRE to safely achieve oncological control in patients with radio‐recurrent PCa.

Synchronous vs independent reading of prostate‐specific membrane antigen positron emission tomography (PSMA‐PET) and magnetic resonance imaging (MRI) to improve diagnosis of pros

Publisher: Wiley

Date: 05-12-2022

DOI: 10.1111/BJU.15929

Abstract: To identify whether synchronous reading of multiparametric magnetic resonance imaging (mpMRI) and 68 Ga‐PSMA‐11 positron emission tomography (PET)/computed tomography (prostate‐specific membrane antigen [PSMA‐PET]) images can improve diagnostic performance and certainty compared with mpMRI/PSMA‐PET reported independently and synthesized, while also assessing concordance between imaging modalities and agreement with histopathology. This was a retrospective analysis of 100 patients randomly selected from the PRIMARY trial, a prospective Phase II multicentre imaging trial. Three dual‐trained radiologist/nuclear medicine physicians re‐reported the mpMRI and PSMA‐PET both independently and synchronously for the same patients in random order, blinded to previous results. Diagnostic performance was assessed for mpMRI/PSMA‐PET images read synchronously or independently and then synthesized. Agreement between imaging results and histopathology was examined. ‘Concordance’ between imaging modalities was defined as overlapping lesions. Reporting certainty was evaluated by the in idual reporters for each modality. International Society of Urological Pathology Grade Group ≥2 cancer was present in 60% of patients on biopsy. Synchronous reading of mpMRI/PSMA‐PET increased sensitivity compared to mpMRI or PSMA‐PET alone (93% vs 80% vs 88%, respectively), although specificity was not improved (63% vs 58% vs 78%, respectively). No significant difference in diagnostic performance was noted between mpMRI/PSMA‐PET read synchronously and mpMRI or PSMA‐PET reported independently and then synthesized. Most patients had concordant imaging (60%), while others had discordant lesions only (28%) or a mixture (concordant and discordant lesions 12%). When mpMRI/PSMA‐PET findings were concordant and positive, 95% of patients had clinically significant prostate cancer (csPCa). When PSMA‐PET alone was compared to synchronous PSMA‐PET/MRI reads, there was an improvement in reader certainty in 20% of scans. Synchronous mpMRI/PSMA‐PET reading improves reader certainty and sensitivity for csPCa compared to mpMRI or PSMA‐PET alone. However, synthesizing the results of independently read PSMA‐PET and mpMRI reports provided similar diagnostic performance to synchronous PSMA‐PET/MRI reads. This may provide greater flexibility for urologists in terms of referral patterns, reducing healthcare system costs and improving efficiencies in prostate cancer diagnosis.

Irreversible electroporation (IRE): a narrative review of the development of IRE from the laboratory to a prostate cancer treatment

Publisher: Wiley

Date: 05-12-2020

DOI: 10.1111/BJU.14951

Abstract: Whilst whole-gland radical treatment is highly effective for prostate cancer control, it has significant impact on quality of life and is unnecessary 'over-treatment' in many men with screening-detected prostate cancer. Improvements in prostate biopsy and imaging have led to increased interest in partial gland ablation to reduce treatment-related morbidity. Several energies for focal ablation have been trialled. Irreversible electroporation (IRE) is a novel technology that ablates tissue by delivering direct current between electrodes. This narrative review documents the history of electroporation including its scientific basis, early data from pre-clinical animal studies, and contemporary clinical outcomes from the use of IRE in prostate cancer. A literature search using the Medical Literature Analysis and Retrieval System Online (MEDLINE), the Excerpta Medica dataBASE (EMBASE), PubMed and Google Scholar was undertaken to identify historical perspectives and current clinical data relating to IRE for prostate cancer. The history of electroporation and its implementation as a prostate cancer treatment was following the basic scientific principles, in vitro data, then animal studies, and now short- to medium-term clinical cohorts in humans. The results of IRE on >283 patients have been published in several papers, with preserved rates of (pad-free) continence in 91-100% of men and preserved erectile function in 79-100% of men. In-field recurrence rates range from 0% to 33%. The current state of evidence for IRE for the treatment of primary and salvage prostate cancer is considered as Idea, Development, Exploration, Assessment, Long-term follow-up (IDEAL) stage 2B. IRE is a new focal ablative technology for the treatment of localised prostate cancer in carefully selected men. Published cohorts report encouraging short-term oncological and functional outcomes however, longer-term data are needed to validate this treatment before it can be recommended for widespread clinical use.

Focal irreversible electroporation as primary treatment for localized prostate cancer

Publisher: Wiley

Date: 04-09-2017

DOI: 10.1111/BJU.13983

Abstract: To determine the safety, quality of life (QoL) and short-term oncological outcomes of primary focal irreversible electroporation (IRE) for the treatment of localized prostate cancer (PCa), and to identify potential risk factors for oncological failure. Patients who met the consensus guidelines on patient criteria and selection methods for primary focal therapy were eligible for analysis. Focal IRE was performed for organ-confined clinically significant PCa, defined as high-volume disease with Gleason sum score 6 (International Society of Urological Pathology [ISUP] grade 1) or any Gleason sum score of 7 (ISUP grades 2-3). Oncological, adverse event (AE) and QoL outcome data, with a minimum of 6 months' follow-up, were analysed. Patient characteristics and peri-operative treatment variables were compared between patients with and without oncological failure on follow-up biopsy. Wilcoxon's signed rank test, Wilcoxon's rank sum test and the chi-squared test were used to assess statistically significant differences in paired continuous, unpaired continuous and categorical variables respectively. A total of 63 patients met all eligibility criteria and were included in the final analysis. No high-grade AEs occurred. QoL questionnaire analysis demonstrated no significant change from baseline in physical (P = 0.81), mental (P = 0.48), bowel (P = 0.25) or urinary QoL domains (P = 0.41 and P = 0.25), but there was a mild decrease in the sexual QoL domain (median score 66 at baseline vs 54 at 6 months P < 0.001). Compared with baseline, a decline of 70% in prostate-specific antigen level (1.8 ng/mL, interquartile range 0.96-4.8 ng/mL) was seen at 6-12 months. A narrow safety margin (P = 0.047) and system errors (P = 0.010) were identified as potential early risk factors for in-field oncological failure. In-field and whole-gland oncological control on follow-up biopsies was 84% (38/45 patients) and 76% (34/45 patients) this increased to 97% (38/39 patients) and 87% (34/39 patients) when patients treated with a narrow safety margin and system errors were excluded. Our data support the safety and feasibility of focal IRE as a primary treatment for localized PCa with effective short-term oncological control in carefully selected men.

Median 5‐year outcomes of primary focal irreversible electroporation for localised prostate cancer

Publisher: Wiley

Date: 28-12-2022

DOI: 10.1111/BJU.15946

Abstract: To evaluate longer‐term oncological and functional outcomes of focal irreversible electroporation (IRE) as primary treatment for localised clinically significant prostate cancer (csPCa) at a median follow‐up of 5 years (up to 10 years). All patients that underwent focal IRE as primary treatment for localised PCa between February 2013 and August 2021 with a minimum 12 months of follow‐up were analysed. Follow‐up included 6‐month magnetic resonance imaging (MRI) and standardised transperineal saturation template ± targeted biopsies at 12 months, and further biopsies in the case of clinical suspicion on serial imaging and/or prostate‐specific antigen (PSA) levels. Failure‐free survival (FFS) was defined as no progression to radical treatment or nodal/distant disease. Local recurrence was defined as any International Society of Urological Pathology Grade of ≥2 on biopsy. A total of 229 patients were analysed with a median (interquartile range [IQR]) follow‐up of 60 (40–80) months. The median (IQR) age was 68 (64–74) years, the median (IQR) PSA level was 5.9 (4.1–8.2) ng/mL, and 86% harboured intermediate‐risk disease and 7% high‐risk disease. In all, 38 patients progressed to radical treatment (17%), at a median (IQR) of 35 (17–53) months after IRE. Kaplan–Meier FFS rates were 91% at 3 years, 84% at 5 years and 69% at 8 years. Metastasis‐free survival was 99.6% (228/229), PCa‐specific and overall survival were 100% (229/229). Residual csPCa was found in 24% (45/190) during follow‐up biopsy and MRI showed a complete ablation in 82% (186/226). Short‐term urinary continence was preserved (98%, three of 144 at baseline, 99%, one of 131 at 12 months) and erections sufficient for intercourse decreased by 13% compared to baseline (71% to 58%). Longer‐term follow‐up confirms our earlier findings that focal IRE provides acceptable local and distant oncological control in selected men with less urinary and sexual toxicity than radical treatment. Long‐term follow‐up and external validation of these findings, is required to establish this new treatment paradigm as a valid treatment option.

Salvage irreversible electroporation for radio‐recurrent prostate cancer – the prospective FIRE trial

Publisher: Wiley

Date: 09-01-2023

DOI: 10.1111/BJU.15947

Abstract: To prospectively assess the safety, functional‐ and oncological‐outcomes of irreversible electroporation (IRE) as salvage therapy for radio‐recurrent focal prostate cancer in a multicenter setting. Men with focal recurrent PCa after external beam radiation or brachytherapy without metastatic disease on staging imaging and co‐registration between mpMRI and biopsies were prospectively included in this multicenter trial. Adverse events were reported following the Clavien‐Dindo classification. Validated questionnaires were used for patient‐reported functional outcomes. Follow‐up consisted of 3 monthly prostate specific antigen (PSA) levels, a 6‐month mpMRI and standardised transperineal template mapping biopsies at 12‐months. Thereafter follow‐up was guided by MRI and/or PSMA‐PET/CT and PSA. Local recurrence was defined as any ISUP score ≥2 on biopsies. 37 patients were analysed with a median (interquartile range (IQR)) follow up of 29 (22–43) months. Median age was 71 (53–83), median PSA was 3.5 ng/mL (2.7–6.1). 28 (75.5%) patients harboured intermediate risk and 9 patients (24.5%) high risk PCa. Seven patients (19%) reported self‐limiting urgency, frequency, or hematuria (grade 1–2). Seven patients (19%) developed a grade 3 AE urethral sludge requiring transurethral resection. At 12 months post treatment 93% of patients remained continent and erectile function sufficient for intercourse deteriorated from 35% to 15% (4/27). Local control was achieved in 29 patients (78%) and 27 patients (73%) were clear of local and systemic disease. Four (11%) patients had local recurrence only. Six (16%) patients developed metastatic disease with a median time to metastasis of 8 months. The FIRE trial shows that salvage IRE after failed radiation therapy for localised PCa is safe with minimal toxicity, and promising functional and oncological outcomes. Salvage IRE can offer a possible solution for notoriously difficult to manage radio recurrent prostate tumours.

Pair-matched patient-reported quality of life and early oncological control following focal irreversible electroporation versus robot-assisted radical prostatectomy.

Publisher: Springer Science and Business Media LLC

Date: 28-03-2018

DOI: 10.1007/S00345-018-2281-Z

Protocol for the PRIMARY clinical trial, a prospective, multicentre, cross‐sectional study of the additive diagnostic value of gallium‐68 prostate‐specific membrane antigen positron‐emission tomography/computed tomography to multiparametric magnetic resonance imaging in the diagnostic setting for men being investigated for prostate cancer

Publisher: Wiley

Date: 12-02-2020

DOI: 10.1111/BJU.14999

Abstract: Primary objectives: To determine the additive value of gallium‐68 prostate‐specific membrane antigen (PSMA) positron emission topography (PET)/computed tomography (CT) when combined with multiparametric magnetic resonance imaging (mpMRI) detecting clinically significant prostate cancer (csPCa) in men undergoing initial biopsy for suspicion of PCa, and to determine the proportion of men who could have avoided prostate biopsy with positive mpMRI (PI‐RADS ≥3) but negative PSMA‐PET/CT. Secondary objectives: To determine the proportion of men who had csPCa detected only by PSMA‐PET/CT or only by systematic prostate biopsy to compare index lesions by template biopsies vs targeted lesions identified on mpMRI or PSMA‐PET/CT to assess whether there may be health economic benefit or harm if PSMA‐PET/CT is incorporated into the diagnostic algorithm and to develop a nomogram which combines clinical, imaging and biomarker data to predict the likelihood of csPCa. The PRIMARY trial is a multicentre, prospective, cross‐sectional study that meets the criteria for level 1 evidence in diagnostic test evaluation. PRIMARY will investigate if a limited (pelvic‐only) PSMA‐PET/CT in combination with routine mpMRI can reliably discriminate men with csPCa from those without csPCa. We conducted a power calculation based on pilot data and will recruit up to 600 men who will undergo PSMA‐PET/CT (the index test), mpMRI (standard test) and transperineal template + targeted (PSMA‐PET/CT and/or mpMRI) biopsies (reference test). The conduct and reporting of the mpMRI and PSMA‐PET/CT will be blinded to each other. The PRIMARY trial will measure and compare sensitivity, specificity, positive predictive value and negative predictive value of both mpMRI and PSMA‐PET/CT vs targeted prostrate biopsy. The results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of csPCa. Furthermore, we will assess whether there is a health economic benefit in incorporating PSMA‐PET/CT into the diagnostic algorithm. This trial will provide robust prospective data to determine the diagnostic ability of PSMA‐PET/CT used in addition to mpMRI. It will establish if certain patients can avoid biopsy in the investigation of PCa.

Assessment of the Performance of Magnetic Resonance Imaging/Ultrasound Fusion Guided Prostate Biopsy against a Combined Targeted Plus Systematic Biopsy Approach Using 24-Core Transperineal Template Saturation Mapping Prostate Biopsy.

Publisher: Hindawi Limited

Date: 2016

DOI: 10.1155/2016/3794738

Abstract: Objective. To compare the performance of multiparametric resonance imaging/ultrasound fusion targeted biopsy (MRI/US-TBx) to a combined biopsy strategy (MRI/US-TBx plus 24-core transperineal template saturation mapping biopsy (TTMB)). Methods. Between May 2012 and October 2015, all patients undergoing MRI/US-TBx at our institution were included for analysis. Patients underwent MRI/US-TBx of suspicious lesions detected on multiparametric MRI + / - simultaneous TTMB. Subgroup analysis was performed on patients undergoing simultaneous MRI/US-TBx + TTMB. Primary outcome was PCa detection. Significant PCa was defined as ≥Gleason score (GS) 3 + 4 = 7 PCa. McNemar’s test was used to compare detection rates between MRI/US-TBx and the combined biopsy strategy. Results. 148 patients underwent MRI/US-TBx and 80 patients underwent MRI/US-TBx + TTMB. In the MRI/US-TBx versus combined biopsy strategy subgroup analysis ( n = 80 ), there were 55 PCa and 38 significant PCa. The detection rate for the combined biopsy strategy versus MRI/US-TBx for significant PCa was 49% versus 40% ( p = 0.02 ) and for insignificant PCa was 20% versus 10% ( p = 0.04 ), respectively. Eleven cases (14%) of significant PCa were detected exclusively on MRI/US-TBx and 7 cases (8.7%) of significant PCa were detected exclusively on TTMB. Conclusions. A combined biopsy approach (MRI/US-TBx + TTMB) detects more significant PCa than MRI/US-TBx alone however, it will double the detection rate of insignificant PCa.

Feasibility and safety of focal irreversible electroporation as salvage treatment for localized radio-recurrent prostate cancer.

Publisher: Wiley

Date: 19-09-2017

DOI: 10.1111/BJU.13991

Abstract: To evaluate the feasibility, safety, early quality-of-life (QoL) and oncological outcomes of salvage focal irreversible electroporation (IRE) for radio-recurrent prostate cancer (PCa). Patients with localized, radio-recurrent PCa without evidence of metastatic or nodal disease were offered focal IRE according to the consensus guidelines. Patients with a minimum follow-up of 6 months were eligible for analysis. Adverse events were monitored using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0). Patient-reported QoL data were collected at baseline, 6 weeks, 3, 6 and 12 months using the Expanded Prostate Cancer Index Composite (EPIC), the American Urological Association (AUA) symptom score and the 12-item short-from health survey (SF-12) physical and mental component summary questionnaires. Oncological control was evaluated according to serial prostate-specific antigen (PSA), 6-month multiparametric magnetic resonance imaging (mpMRI) and 12-month prostate biopsy. Wilcoxon's signed rank test was used to assess QoL differences over time in paired continuous variables. A total of 18 patients were included in the analysis. The median follow-up was 21 months. No high-grade adverse events (CTCAE >2) or recto-urethral fistulae occurred. No statistically significant declines were observed in QoL outcomes (n = 11) on the EPIC bowel domain (P = 0.29), AUA symptom score (P = 0.77), or the SF-12 physical (P = 0.17) or SF-12 mental component summary (P = 0.77) questionnaires. At 6 months, patients who had undergone salvage therapy experienced a decline in EPIC sexual domain score (median of 38-24 P = 0.028) and urinary domain (median of 96-92 P = 0.074). Pad-free continence and erections sufficient for intercourse were preserved in 8/11 patients and 2/6 patients at 6 months, respectively. The mpMRI was clear in 11/13 patients, with two single out-field lesions (true-positive and false-positive, respectively). The median (interquartile range) nadir PSA was 0.39 (0.04-0.43) μg/L. Three and four patients experienced biochemical failure using the Phoenix and Stuttgart definitions of biochemical failure, respectively. Eight out of 10 of the patients were clear of any PCa on follow-up biopsy, whereas two patients had significant PCa on follow-up biopsy (International Society of Urological Pathology grade 5). Our short-term safety, QoL and oncological control data show that focal IRE is a feasible salvage option for localized radio-recurrent PCa. A prospective multicentre study (FIRE trial) has been initiated that will provide further insight into the ability of focal IRE to obtain oncological control of radio-recurrent PCa with acceptable patient morbidity.

How Does Age Affect Urinary Continence following Robot-Assisted Radical Prostatectomy? A Prospective Multi-Institutional Study Using Independently Collected, Validated Questionnaires

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 05-2022

DOI: 10.1097/JU.0000000000002391

Imaging: MRI improves cost and accuracy of prostate cancer biopsy.

Publisher: Springer Science and Business Media LLC

Date: 08-11-2017

DOI: 10.1038/NRUROL.2017.185

The Diagnostic Performance of Multiparametric Magnetic Resonance Imaging to Detect Significant Prostate Cancer.

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 05-2015

DOI: 10.1016/J.JURO.2015.10.140

Abstract: We assess the accuracy of multiparametric magnetic resonance imaging for significant prostate cancer detection before diagnostic biopsy in men with an abnormal prostate specific antigen/digital rectal examination. A total of 388 men underwent multiparametric magnetic resonance imaging, including T2-weighted, diffusion weighted and dynamic contrast enhanced imaging before biopsy. Two radiologists used PI-RADS to allocate a score of 1 to 5 for suspicion of significant prostate cancer (Gleason 7 with more than 5% grade 4). PI-RADS 3 to 5 was considered positive. Transperineal template guided mapping biopsy of 18 regions (median 30 cores) was performed with additional manually directed cores from magnetic resonance imaging positive regions. The anatomical location, size and grade of in idual cancer areas in the biopsy regions (18) as the primary outcome and in prostatectomy specimens (117) as the secondary outcome were correlated to the magnetic resonance imaging positive regions. Of the 388 men who were enrolled in the study 344 were analyzed. Multiparametric magnetic resonance imaging was positive in 77.0% of patients, 62.5% had prostate cancer and 41.6% had significant prostate cancer. The detection of significant prostate cancer by multiparametric magnetic resonance imaging had a sensitivity of 96%, specificity of 36%, negative predictive value of 92% and positive predictive value of 52%. Adding PI-RADS to the multivariate model, including prostate specific antigen, digital rectal examination, prostate volume and age, improved the AUC from 0.776 to 0.879 (p <0.001). Anatomical concordance analysis showed a low mismatch between the magnetic resonance imaging positive regions and biopsy positive regions (4 [2.9%]), and the significant prostate cancer area in the radical prostatectomy specimen (3 [3.3%]). In men with an abnormal prostate specific antigen/digital rectal examination, multiparametric magnetic resonance imaging detected significant prostate cancer with an excellent negative predictive value and moderate positive predictive value. The use of multiparametric magnetic resonance imaging to diagnose significant prostate cancer may result in a substantial number of unnecessary biopsies while missing a minimum of significant prostate cancers.

Reply to Patrick H. Tuliao and Koon Ho Rha's letter to the editor re: James E. Thompson, Sam Egger, Maret Böhm, et al. Superior quality of life and improved surgical margins are achievable with robotic radical prostatectomy after a long learning curve: a prospective single-surgeon study of 1552 consecutive cases. Eur Urol 2014;65:521-31.

Publisher: Elsevier BV

Date: 06-2014

DOI: 10.1016/J.EURURO.2014.01.021

Salvage robot-assisted radical prostatectomy following focal ablation with irreversible electroporation: feasibility, oncological and functional outcomes

Publisher: Springer Science and Business Media LLC

Date: 02-03-2022

DOI: 10.1186/S12894-022-00978-W

Abstract: To report the feasibility, oncological and functional outcomes of salvage robot-assisted radical prostatectomy (sRARP) for recurrent prostate cancer (PCa) after irreversible electroporation (IRE). This was a retrospective analysis of patients who underwent sRARP by a single high-volume surgeon after IRE treatment in our institution. Surgical complications, oncological and functional outcomes were assessed. 15 patients with at least 12 months follow up were identified out of the 234 men who underwent primary IRE between 2013 and 2019. The median [IQR] age was 68 (62–70) years. The median [IQR] time from focal IRE to sRARP was 42 (21–57) months. There were no rectal, bladder or ureteric injuries. The T-stage was pT2 in 9 (60%) patients and pT3a in 6 (40%) patients. Only one (7%) patient had a positive surgical margin. At a median [IQR] follow up of 22 (16–32) months no patient had a biochemical recurrence (PSA 0.2). All 15 patients were continent (pad-free) by 6 months and 9 (60%) patients had erections sufficient for intercourse with or without PDE5 inhibitors. No predisposing factors were identified for predicting erectile dysfunction after sRARP. In patients with recurrent or residual significant PCa after focal IRE ablation it is feasible to obtain good functional and oncological outcomes with sRARP. Our results demonstrate that good outcomes can be achieved with sRARP, when respecting close monitoring post-IRE, good patient selection and surgical experience. The limitations of this study are that it is a small series, with short follow up and a lack of standardised quality of life instruments.

A multiparametric magnetic resonance imaging-based risk model to determine the risk of significant prostate cancer prior to biopsy.

Publisher: Wiley

Date: 31-03-2017

DOI: 10.1111/BJU.13814

Abstract: To develop and externally validate a predictive model for detection of significant prostate cancer. Development of the model was based on a prospective cohort including 393 men who underwent multiparametric magnetic resonance imaging (mpMRI) before biopsy. External validity of the model was then examined retrospectively in 198 men from a separate institution whom underwent mpMRI followed by biopsy for abnormal prostate-specific antigen (PSA) level or digital rectal examination (DRE). A model was developed with age, PSA level, DRE, prostate volume, previous biopsy, and Prostate Imaging Reporting and Data System (PIRADS) score, as predictors for significant prostate cancer (Gleason 7 with >5% grade 4, ≥20% cores positive or ≥7 mm of cancer in any core). Probability was studied via logistic regression. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap res ling. In all, 393 men had complete data and 149 (37.9%) had significant prostate cancer. While the variable model had good accuracy in predicting significant prostate cancer, area under the curve (AUC) of 0.80, the advanced model (incorporating mpMRI) had a significantly higher AUC of 0.88 (P < 0.001). The model was well calibrated in internal and external validation. Decision analysis showed that use of the advanced model in practice would improve biopsy outcome predictions. Clinical application of the model would reduce 28% of biopsies, whilst missing 2.6% significant prostate cancer. In idualised risk assessment of significant prostate cancer using a predictive model that incorporates mpMRI PIRADS score and clinical data allows a considerable reduction in unnecessary biopsies and reduction of the risk of over-detection of insignificant prostate cancer at the cost of a very small increase in the number of significant cancers missed.

Diagnostic accuracy of multi-parametric MRI and transrectal ultrasound-guided biopsy in prostate cancer.

Publisher: Elsevier BV

Date: 02-2017

DOI: 10.1016/S0140-6736(17)30121-6

Initial multicentre experience of (68)gallium-PSMA PET/CT guided robot-assisted salvage lymphadenectomy: acceptable safety profile but oncological benefit appears limited

Publisher: Wiley

Date: 20-06-2017

DOI: 10.1111/BJU.13919

Abstract: To evaluate the safety and short-term oncological outcomes of Between February 2014 and April 2016, 35 patients across two centres underwent RASND for A total of 58 lesions suspicious for lymph node metastases (LNM) in 35 patients were detected on Although RASND appears safe and feasible, less than half of our cohort had a treatment response, and less than a quarter experienced BCR-free survival at 12-month median follow-up.

Radiomic features for prostate cancer detection on MRI differ between the transition and peripheral zones: Preliminary findings from a multi‐institutional study

Publisher: Wiley

Date: 19-12-2016

DOI: 10.1002/JMRI.25562

MRI improves active surveillance of prostate cancer however biopsy is still crucial.

Publisher: Wiley

Date: 08-2018

DOI: 10.1111/BJU.14424

High prostate‐specific membrane antigen (PSMA) positron emission tomography (PET) maximum standardized uptake value in men with PI‐RADS score 4 or 5 confers a high probability of

Publisher: Wiley

Date: 20-04-2022

DOI: 10.1111/BJU.15736

Radiomic features on MRI enable risk categorization of prostate cancer patients on active surveillance: Preliminary findings

Publisher: Wiley

Date: 22-02-2018

DOI: 10.1002/JMRI.25983

Predicting Low-Risk Prostate Cancer from Transperineal Saturation Biopsies.

Publisher: Hindawi Limited

Date: 2016

DOI: 10.1155/2016/7105678

Abstract: Introduction . To assess the performance of five previously described clinicopathological definitions of low-risk prostate cancer (PC). Materials and Methods . Men who underwent radical prostatectomy (RP) for clinical stage ≤T2, PSA ng/mL, Gleason score PC, diagnosed by transperineal template-guided saturation biopsy were included. The performance of five previously described criteria (i.e., criteria 1–5, criterion 1 stringent (Gleason score 6 + ≤5 mm total max core length PC + ≤3 mm max per core length PC) up to criterion 5 less stringent (Gleason score 6-7 with ≤5% Gleason grade 4) was analysed to assess ability of each to predict insignificant disease in RP specimens (defined as Gleason score ≤6 and total tumour volume .5 mL, or Gleason score 7 with ≤5% grade 4 and total tumour volume .7 mL). Results . 994 men who underwent RP were included. Criterion 4 (Gleason score 6) performed best with area under the curve of receiver operating characteristics 0.792. At decision curve analysis, criterion 4 was deemed clinically the best performing transperineal saturation biopsy-based definition for low-risk PC. Conclusions . Gleason score 6 disease demonstrated a superior trade-off between sensitivity and specificity for clarifying low-risk PC that can guide treatment and be used as reference test in diagnostic studies.

Instituto Gulbenkian De Ciencia

Location: Portugal

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Fundação Champalimaud

Location: Portugal

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CNRS Délégation Régionale Côte D'Azur

Location: France

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University Of Colorado Health Sciences Center

Location: United States of America

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Universidade De Lisboa Faculdade De Ciencias

Location: Portugal

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London Research Institute Clare Hall Laboratories

Location: United Kingdom of Great Britain and Northern Ireland

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London Research Institute

Location: United Kingdom of Great Britain and Northern Ireland

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University Of Manchester, School Of Biological Sciences

Location: United Kingdom of Great Britain and Northern Ireland

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St George Hospital

Location: Australia

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Clinica Alemana

Location: Chile

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University Of New South Wales

Location: Australia

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St. Vincent’s Prostate Cancer Centre

Location: Australia

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University College Hospital

Location: United Kingdom of Great Britain and Northern Ireland

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St George Hospital Sydney New South Wales AU

Location: Australia

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St Vincents Hospital, Private Hospital And Clinic, Sydney

Location: Australia

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Hurstville Private

Location: Australia

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Saint George Private Hospital

Location: Australia

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Australian Prostate Cancer Research Centre

Location: Australia

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Garvan Institute Of Medical Research

Location: Australia

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