Background Positive surgical margins after radical prostatectomy (RP) are an imperfect surrogate of residual tumor and do not reliably identify men who will experience biochemical recurrence (BCR). Promoter hypermethylation of retinoic acid receptor beta gene ( RARB ) is a frequent epigenetic alteration in prostate cancer (PCa). We evaluated whether intraoperative sampling of the prostatic fossa with quantitative methylation-specific PCR (qMSP) for RARB improves prediction of BCR compared with conventional histology and margin status. Methods In a dual-centre study, 176 men with biopsy-proven PCa undergoing open or robot-assisted RP had nine standardized biopsies (sites A–I) taken from the prostatic fossa before vesicourethral anastomosis; 32 cystectomy patients served as cancer-free controls. Each fossa biopsy was split for routine histology and qMSP analysis of RARB ( MYOD1 as internal control). Clinicopathologic data and PSA follow-up were prospectively recorded. BCR was defined per German S3 guideline thresholds. Statistical testing included Pearson’s χ², Fisher’s exact, McNemar, and Mann–Whitney U tests (two-sided, α = 0.05). Results Median age was 65 years; median diagnostic PSA 7.15 ng/ml. On specimen assessment, 130 men were R0 and 46 R1. Among 164 fossa samples with benign histology, 96 (59%) were RARB -positive by qMSP; among 12 histologically malignant fossa samples, 9 (75%) were RARB -positive (Table 1). RARB hypermethylation associated significantly with surgical margin status (p < 0.0001) and with BCR (p = 0.039), but not with T-stage or initial PSA; associations by ISUP grade showed a trend for ≥ 3 (p = 0.090) and significance for ≥ 4 (p = 0.029). All 160 control-fossa samples were RARB -negative, while 20 prostate cancer tissue controls were RARB -positive. During a median 60-month follow-up (n = 152), 32 men (21%) developed BCR. In the BCR subset suitable for analysis (n = 27), fossa histology was positive in 3 (11%), specimen margin status was positive in 13 (48%), and RARB was positive in 23 (85%). For predicting BCR, RARB analysis outperformed margin status and fossa histology (each p < 0.001; McNemar where applicable). Conclusions Intraoperative prostatic fossa biopsies analyzed for RARB promoter hypermethylation detect molecular residual disease that is frequently missed by routine histology and provide superior prediction of BCR compared with surgical margin status. RARB methylation may enable earlier, biologically informed selection for adjuvant or early salvage radiotherapy while avoiding overtreatment in molecularly negative patients. Prospective validation and integration with multivariable models are warranted.

Radical prostatectomy is a standard treatment for prostate cancer, yet about 30

ObjectiveTo assess the potential for molecular staging in biopsies of the prostatic fossa after radical prostatectomy (RP) by searching for occult tumour cells through analysis of glutathione S‐transferase P1 (GSTP1) methylation status.Patients and MethodsWe analysed 2446 biopsies: 2286 biopsies from a group of 254 patients with clinically organ‐confined prostate cancer who underwent RP and 160 biopsies from a control group of 32 patients. After prostate gland excision, biopsies were obtained from defined areas of the prostatic fossa and bisected for histopathological and molecular genetics analyses. Results were related to clinicopathological data including tumour stage, lymph node status, resection status, tumour grading, initial PSA level, and biochemical recurrence.ResultsIn total, 34 patients (13.4%) had at least one core positive for the GSTP1 promoter hypermethylation, six of whom (17.6%) were characterised as having a clinically localised tumour stage (pT2, pN0) and 28 (82.4%) as an advanced tumour stage (≥pT3 and/or pN1). GSTP1 promoter hypermethylation significantly correlated with tumour stage (P < 0.001), International Society of Urological Pathology grading (P = 0.001), lymph node status (P < 0.001), surgical margin status (P < 0.001), and biochemical recurrence (P = 0.001). Furthermore, in 46 patients (18.1%) further analysis led to a down‐ or upgrading of conventional surgical margin status. Classical R‐status (margins of the specimen) is significantly superior to histological sampling from the fossa (P = 0.006) but not to GSTP1 analysis from the fossa (P = 0.227).ConclusionFor the detection of residual tumour in the fossa after RP in order to better predict recurrence, molecular GSTP1 promoter hypermethylation has some value; however, the classical R‐status (margins of the specimen) is simpler and more widely applicable with similar results.

OBJECTIVE To assess the efficacy of irreversible electroporation (IRE) ablation of pT1a renal cell carcinoma (RCC) in the first prospective, monocentric phase 2a pilot ablate-and-resect study (Irreversible Electroporation of Kidney Tumors Before Partial Nephrectomy [IRENE] trial). It has been postulated that focal IRE can bring about complete ablation of soft-tissue tumors with protection of healthy peritumoral tissue and anatomic structures. PATIENTS AND METHODS The first 7 study patients with biopsy-proven pT1a RCC (15-39 mm) underwent IRE. Percutaneous computed tomography-guided IRE was performed with electrocardiographic triggering under general anesthesia and deep muscle paralysis with 3-6 monopolar electrodes positioned within the renal tumor. Twenty-eight days later, the tumor region was completely resected to confirm tumor destruction pathologically. Individual results for these patients are displayed, described, and discussed. RESULTS Technical feasibility was attained in all patients, but electrode placement and ablation were complex, with a mean overall procedure time of 129 minutes. There were no major complications. Partial kidney resection was performed in 5 patients, and radical nephrectomy was performed in 2 patients because of central tumor location and ablation areas. Resections revealed by tumor, node, and metastasis classification of the International Union for Cancer Control 2017 no residual tumor as complete ablation in 4 cases (ypT0V0N0Pn0R0) and microscopic residual tumor cells as incomplete ablation in the other 3 cases (ypT1aV0N0Pn0R1). CONCLUSION Renal percutaneous IRE appears to be a safe treatment for pT1a RCC but requires substantial procedural effort. Resection specimens of the ablation zone revealed a high rate of microscopic incomplete ablation 4 weeks after IRE. According to these initial study results, curative, kidney-sparing ablation of T1a RCC appears possible but needs technical improvement to ensure complete ablation. (C) 2017 Elsevier Inc.

Objectives: Magnetic resonance imaging/transrectal ultrasound (MRI/TRUS) fusion-guided focal high intensity focused ultrasound (HIFU) therapy of the prostate has recently been developed as a selective HIFU-therapy technique to enable targeted ablation of prostate cancer. Here we report a series of patients treated with focal HIFU therapy, discuss its potential pitfalls, and address controversies concerning the indications. Materials and Methods: This single-center prospective study reports outcomes of patients treated from September 2014 to March 2016. Follow-up was a minimum of 12 months. MRI/TRUS-fusion-guided HIFU was performed under general anesthesia using the Focal One device (EDAP, France). A control biopsy at 12 months was taken using the MRI/TRUS-fusion biopsy platform ArtemisTM (Eigen, California) combining targeted and systematic cores. Prostate-specific antigen (PSA) changes from baseline, patient-reported outcome measures, and complications using the Clavien Dindo classification system are also reported. Results: Twenty-four patients (PSA < 10 ng/ml, n = 17 Gleason 3+3, n = 7 Gleason 3+4) with either unifocal or bifocal prostate imaging reporting and data system (PI-RADS) 3-5 lesions (n = 19) or without a PI-RADS lesion (n = 5) were treated. Nineteen patients underwent focal HIFU, five patients zonal HIFU. Of the 20 patients that had biopsies at 12 months, 8 patients had a positive biopsy within the ablation zone (overall cancer free rate: 60%). Using different definitions of clinically significant cancer, the cancer-free rate for the ablation zone varies between 75% and 95%. Four of the eight patients (all persistent Gleason 3+4 or upgrading to 4+3) underwent a radical whole gland salvage therapy. Patient-reported outcome measures showed no significant decrease in urinary continence (expanded prostate cancer index composite-26 urinary incontinence: P = 0.080), but there was a reduction in potency (International index of erectile function in preoperatively potent patients: median decrease of 2 points to a median of 19 points at 12 months; 95% confidence interval: 15.79-22.21; P = 0.044). Only one complication > grade II occurred. Conclusions: Targeted MRI/TRUS fusion-guided focal HIFU allows local tumor ablation, but is not free from limitations. The procedure has good functional outcomes and a quick recovery. Multicenter trials with more patients are required to determine the procedure's role in the prostate cancer therapy algorithm. (C) 2018 Elsevier Inc. All rights reserved.

The aim of our study was (1) to establish an in-bore targeted biopsy of suspicious prostate lesions, avoiding bowel penetration using a transgluteal approach and (2) to assess operator setup, patient comfort and safety aspects in the clinical setting for freehand real-time MR-guidance established for percutaneous procedures in an open MR-scanner.

The target of focal therapy (FT) in prostate cancer (PC) is partial treatment of the prostate aiming at preserving surrounding anatomical structures. The intention is to minimize typical side effects of radical treatment options combined with local tumor control. Numerous established and new technologies are used. Results of published studies showed a good safety profile, few side effects and good preservation of functional results. Oncologic long-term data are lacking so far. Photodynamic therapy (PDT) is the only technology that has been studied in a published prospective randomized trial. The FT is challenged by the multifocality of PC; therefore, the quality of prostate biopsy, histopathological assessment as well as imaging are of paramount importance. Multiparametric magnetic resonance imaging (MRI) has gained increasing importance. The FT is experimental and should only be offered within clinical trials.

Eine gut hundertjährige Periode, in der die Vorsteherdrüse nur als Ganzes betrachtet und behandelt wurde, geht gerade vorüber. Eine hochauflösende Bildgebung liefert endlich tiefe Detailinformationen, neue Therapieformen können kleinste Ziele anvisieren. Dem lange bestehenden Patientenwunsch nach individueller „nichtinvasiver“ Diagnostik und Therapie von Prostataerkrankungen kann nun mit wirklich dazu passenden Konzepten geantwortet werden. Die klinische Verarbeitung und Anwendung der enormen Informationsfülle als individualisiertes Gesamtkonzept für den Patienten erfordern allerdings ein interdisziplinär eng verzahntes Räderwerk, welches herkömmliche Sprechstunden in jeder Hinsicht überfordert. Es ist Zeit für neue Konstrukte! Das Dienstleistungsprinzip einer einseitig gerichteten Befund- oder Therapieanforderung an den Urologen, Radiologen oder Strahlentherapeuten ist überholt, diese interdisziplinären Partner gehören nun zu einem gleichrangigen „Managementteam Prostata“.

Es existieren zahlreiche Systeme zur MRT/TRUS-fusionierten Biopsie der Prostata. Insgesamt liegt ausreichend Literatur zur Fusionsbiopsie vor, die einen Vorteil bei der Tumordetektion und der Diagnosequalität gegenüber der Randombiopsie belegt. Der Nutzen der Systeme im Rahmen der fokalen Therapie des Prostatakarzinoms (PC) ist unklar.

If technically feasible, organ-preservation is indicated for T1 renal cell carcinoma (RCC), since partial nephrectomy (PN) is equivalent to radical nephrectomy with regard to tumor-specific survival and probably achieves better overall survival. Treatment results of a training clinic were assessed with regard to guideline adherence and treatment quality.

Purpose Irreversible electroporation (IRE) is a new potential ablation modality for small renal masses. Animal experiments have shown preservation of the urine-collecting system (UCS). The purpose of this clinical study was to perform the first evaluation and comparison of IRE's effects on the renal UCS by using urinary cytology, magnetic-resonance imaging, and resection histology in men after IRE of pT1a renal-cell carcinoma (RCC). Methods Seven patients with biopsy-proven RCC pT1a cN0cM0 underwent IRE in a phase 2a pilot ablate-and-resect study (IRENE trial). A contrast-enhanced, diffusion-weighted MRI and urinary cytology was performed 1 day before and 2, 7, and 27 days after IRE. Twenty-eight days after IRE the tumour region was completely resected surgically. Results Technical feasibility was demonstrated in all patients. In all cases, MRI revealed complete coverage of the tumour area by the ablation zone with degenerative change. The urographic late venous MRI phase (urogram scans) demonstrated normal morphological appearances. Urine cytology showed a temporary vacuolisation of the cyto- and caryoplasmas after IRE. Whereas the urothelium showed signs of regeneration 28 days after IRE-ablation, the tumour and parenchyma below it showed necrosis and permanent tissue destruction. Conclusions Renal percutaneous IRE appears to be a safe treatment for pT1a RCC. The preservation of the UCS with unaltered normal morphology as well as urothelial regeneration and a phenomenon (new in urinary cytology) of temporary degeneration with vacuolisation of detached transitional epithelium cells were demonstrated in this clinical pilot study.

Purpose: We evaluated focal therapy with high intensity focused ultrasound hemiablation in a prospective trial. Materials and Methods: We performed a prospective, multicenter, single arm study in patients with unilateral low/intermediate risk prostate cancer who were treated from April 2013 through March 2016 in Germany in AUO (Arbeitsgemeinschaft Urologische Onkologie) Study Protocol AP 68/11. Unilateral prostate cancer was assessed by transrectal ultrasound guided biopsy and multiparametric magnetic resonance imaging. Hemiablation was done using the Ablatherm (R) or the Focal One (R) device. The oncologic outcome was assessed by the salvage treatment rate, multiparametric magnetic resonance imaging and rebiopsy at 12 months. Functional outcome, quality of life, anxiety and depression were measured by validated questionnaires at baseline and every 3 months. Results: Of the 54 recruited patients 51 completed 12-month or greater visits. Mean +/- SD followup was 17.4 +/- 4.5 months. Mean prostate specific antigen decreased from 6.2 +/- 2.0 to 2.9 +/- 1.9 ng/ml at 12 months (p < 0.001). Biopsy at 12 months was positive for any prostate cancer and for clinically significant prostate cancer in 13 (26.5%) and 4 (8.2%) of the 49 patients, respectively. Posttreatment multiparametric magnetic resonance imaging had limited 25% sensitivity for clinically significant prostate cancer. Ten patients (19.6%) underwent salvage treatment. Potency was maintained in 21 of the 30 men who were potent preoperatively. There was no increase in incontinence. Quality of life, anxiety and depression did not change postoperatively. The study was limited by a short followup and the lack of a control arm. Conclusions: Focal therapy hemiablation is safe with little alteration of functional outcome. The oncologic outcome is acceptable on short-term followup. Followup multiparametric magnetic resonance imaging performed poorly and should not replace repeat biopsy. Focal therapy has no impact on posttreatment anxiety and depression.

Ziel der fokalen Therapie (FT) des Prostatakarzinoms (PC) ist eine Teilbehandlung der Prostata unter Schonung der angrenzenden Strukturen. Dadurch sollen typische Nebenwirkungen radikaler Therapieoptionen bei gleichzeitiger Tumorkontrolle minimiert werden. Zahlreiche etablierte und neue Technologien kommen dazu zum Einsatz. Ergebnisse zahlreicher Fallserien belegen ein geringes Nebenwirkungsspektrum bei guten funktionellen Ergebnissen. Onkologische Langzeitergebnisse liegen bislang nicht vor.

Introduction: Transurethral resection risks excessive absorption of irrigating fluid with potentially severe or life-threatening consequences. We determined the amount of absorbed saline irrigation fluid during photoselective vaporisation of the prostate (PVP) and bipolar transurethral resection of the prostate (bTURP). Patients and Methods: Patients at our institution treated by one of these methods were monitored by the alcometric method: ethanol is added to the irrigation fluid and blood alcohol is measured with a breathalyser. Various possible correlations were investigated. Results: Data from 71 patients (36 PVP, 35 bTURP) were analysed. Detection of any absorption was more frequent under bTURP (71% of patients) than under PVP (39%; p = 0.006). Absorption in the volume range 500-1,000 ml was conspicuously more frequent in the bTURP procedure than in PVP. Conclusions: Presence of absorption was more frequent under bTURP than under PVP. However, high-volume absorption was more frequent during bTURP than in PVP.

PURPOSE:To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS:A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS:Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION:Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

Irreversible electroporation (IRE), a new tissue ablation procedure available since 2007, could meet the requirements for ideal focal therapy of prostate cancer with its postulated features, especially the absence of a thermal ablation effect. Thus far, there is not enough evidence of its effectiveness or adverse effects to justify its use as a definitive treatment option for localized prostate cancer. Moreover, neither optimal nor individual treatment parameters nor uniform endpoints have been defined thus far. No advantages over established treatment procedures have as yet been demonstrated. Nevertheless, IRE is now being increasingly applied for primary prostate cancer therapy outside clinical trials, not least through active advertising in the lay press. This review reflects the previous relevant literature on IRE of the prostate or prostate cancer and shows why we should not adopt IRE as a routine treatment modality at this stage.