Utilization of multiparametric prostate magnetic resonance imaging in clinical practice and focal therapy: report from a Delphi consensus project.

PURPOSE: To codify the use of multiparametric magnetic resonance imaging (mpMRI) for the interrogation of prostate neoplasia (PCa) in clinical practice and focal therapy (FT). METHODS: An international collaborative consensus project was undertaken using the Delphi method among experts in the field of PCa. An online questionnaire was presented in three consecutive rounds and modified each round based on the comments provided by the experts. Subsequently, a face-to-face meeting was held to discuss and finalize the consensus results. RESULTS: mpMRI should be performed in patients with prior negative biopsies if clinical suspicion remains, but not instead of the PSA test, nor as a stand-alone diagnostic tool or mpMRI-targeted biopsies only. It is not recommended to use a 1.5 Tesla MRI scanner without an endorectal or pelvic phased-array coil. mpMRI should be performed following standard biopsy-based PCa diagnosis in both the planning and follow-up of FT. If a lesion is seen, MRI-TRUS fusion biopsies should be performed for FT planning. Systematic biopsies are still required for FT planning in biopsy-naïve patients and for patients with residual PCa after FT. Standard repeat biopsies should be taken during the follow-up of FT. The final decision to perform FT should be based on histopathology. However, these consensus statements may differ for expert centers versus non-expert centers. CONCLUSIONS: The mpMRI is an important tool for characterizing and targeting PCa in clinical practice and FT. Standardization of acquisition and reading should be the main priority to guarantee consistent mpMRI quality throughout the urological community.

[MRI/TRUS fusion-guided prostate biopsy : Value in the context of focal therapy]. / MRT/TRUS-fusionierte Biopsiesysteme : Stellenwert bei der fokalen Therapie des Prostatakarzinoms.

BACKGROUND: Several systems for MRI/TRUS fusion-guided biopsy of the prostate are commercially available. Many studies have shown superiority of fusion systems for tumor detection and diagnostic quality compared to random biopsy. The benefit of fusion systems in focal therapy of prostate cancer (PC) is less clear. OBJECTIVES: Critical considerations of fusion systems for planning and monitoring of focal therapy of PC were investigated. MATERIALS AND METHODS: A systematic literature review of available fusion systems for the period 2013-5/2016 was performed. A checklist of technical details, suitability for special anatomic situations and suitability for focal therapy was established by the German working group for focal therapy (Arbeitskreis fokale und Mikrotherapie). RESULTS: Eight fusion systems were considered (Artemis™, BioJet, BiopSee®, iSR´obot™ Mona Lisa, Hitachi HI-RVS, UroNav and Urostation®). Differences were found for biopsy mode (transrectal, perineal, both), fusion mode (elastic or rigid), navigation (image-based, electromagnetic sensor-based or mechanical sensor-based) and space requirements. DISCUSSION: Several consensus groups recommend fusion systems for focal therapy. Useful features are "needle tracking" and compatibility between fusion system and treatment device (available for Artemis™, BiopSee® and Urostation® with Focal One®; BiopSee®, Hitachi HI-RVS with NanoKnife®; BioJet, BiopSee® with cryoablation, brachytherapy). CONCLUSIONS: There are a few studies for treatment planning. However, studies on treatment monitoring after focal therapy are missing.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project.

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.

[Low dose brachytherapy with seeds--an interdisciplinary therapy alternative to radical prostatectomy]. / LDR-Brachytherapie mit Seeds--eine interdisziplinäre Therapiealternative zur radikalen Prostatektomie.

Prostate cancer is together with the carcinoma of the lung the most common cancer in the western world. Better screening methods especially the introduction of PSA (prostate specific antigen) in the beginning of the 90's has increased the early detection rate. In the United States only 30% of prostate tumors were in their early stages before the introduction of PSA-screening as compared to 60% nowadays. The early detection also increased the rate of younger men amongst these patients. Patient demands have increased with respect to incontinence and impotence especially amongst those young patients. Radical prostatectomy still is the gold standard for therapy of localized prostate cancer. Better operating techniques have decreased the side effect rate of this operations but many patients still do not undergo this operation because they fear these side effects. Originating from the USA the low dose rate brachytherapy (LDR) using permanent seeds had a renaissance in recent years. In 1999 alone more than 40,000 patients were successfully operated using this technique. 10 year data published in 1998 showed similar results as compared to a multitude of radical prostatectomy studies and superior results to most of the published external beam studies with significantly less side effects. In Germany and western Europe more and more centers start with LDR-brachytherapy. In contrary to the U.S. where brachytherapy is mostly performed as an outpatient procedure, nearly all European centers do only inpatient brachytherapy. Only very few centers perform outpatient procedures; the first results are very encouraging showing few complications and a very high standard of quality of the treatment.

Permanent brachytherapy: prostate seed implants as an out-patient treatment.

Upto April 1999 interstitial seed implants were being performed throughout Europe only as an in-patient treatment. Consequently, we questioned whether this same method could be performed as an out-patient treatment without forfeiting the required quality and safety normally observed with in-patients. Since April 1999 we have treated 73 patients with iodine 125 seed implants (RAPID strand). The average patient age was 65 yrs, the average PSA was 11.5 ng/ml, tumor stage was either T1 or T2. All treatments were carried out in general anesthesia under ultrasound and flouroscopy monitoring. Pre- and post implant dosimetry was planned using the Variplan 6.7 computer program (former MMS). All patients tolerated the out-patient treatment very well. The average duration for anesthesia was 76 minutes, total time per patient spent in the center on implant day was 250 minutes. 54 patients were treated with a monotherapy 145 Gy, while 19 patients received external beam radiotherapy (45 Gy) plus the iodine seed boost (100 Gy). Almost 75% of the patients experienced some form of voiding discomfort during the 4-10th post implant week. In the CT post plan dosimetry performed 4 weeks after the implant, 95% of the patients obtained a good coverage of the prostate with the planned prescription dose. Iodine seed implants can be considered a safe out-patient form of treatment with a low complication and morbidity rate and a high standard of quality. The technical improvements in computer dosimetry software, modified application methods, constantly updated equipment and critical quality assessment has lead to improved overall long term results.

The isolated perfused kidney of the pig: new model to evaluate shock wave-induced lesions.

Little is known about the mechanisms and determining factors of shock wave-induced kidney trauma. After classification of the renal lesion in a canine model, we attempted to establish an ex vivo model using the isolated kidney of the pig perfused by Tyrode's solution under physiologic conditions. After shock wave application on the Modulith SL 20, vessel lesions were evaluated by microangiography to determine the size and frequency of dye extravasation in the different areas of the organ. Variation of the focus localization caused different patterns of lesions that characterized the pathway of the shock wave. In particular, constant petechial extravasation in the cortex was observed. The generator voltage correlated with the diameter and the frequency of the lesion area. The number of shock waves primarily affected the incidence of vessel rupture in the regions adjacent to the focal zone. Light microscopy revealed dose-dependent necrosis of tubular cells up to gap-like parenchymal defects. Even after application of the minimal shock wave doses, electron microscopy demonstrated vacuolization of tubular cells in the shock wave focus. Traumatic junctions between capillaries and the tubulur system can explain clinically observed macrohematuria without renal hematomas. With this model, it was possible to evaluate localization and dose dependence of shock wave-induced kidney trauma with high sensitivity and reproducibility. Further advantages of the model were easy availability and the fact that studies on living animals were not necessary. Therefore, standardization and comparison of different lithotripters becomes possible.

Observation of ferroelectric 180° domains by microphotometry of holographic gratings.

A new holographic observation technique for 180° domains is demonstrated with a cerium-doped strontium barium niobate sample containing two antiparallel ferroelectric domains. The method relies on the fact that the phase shift of holographically written refractive-index gratings is +π/2 or -π/2 with respect to the initial light interference pattern depending on the orientation of the domains. As a consequence, readout of these gratings creates at the exit face of the sample new interference patterns shifted by 0 or π with respect to the initial one. These patterns, providing an image of the domain structure, are observed by microscope.

Experimental basis of shockwave-induced renal trauma in the model of the canine kidney.

Using the new electromagnetic shockwave source of the Modulith SL 20 shockwave-induced renal trauma was evaluated by acute and chronic studies in the the canine kidney model. In a further study the electromagnetic shockwave source of the Lithostar Plus Overhead module was tested. Overall, 92 kidneys were exposed to shock waves coupled either by water bath (Modulith lab type) or by water cushion (Modulith prototype, Lithostar Overhead) under ultrasound localization. The generator voltage ranged between 11 and 21 kV, the number of impulses between 25 and 2500. After application of 1500/2500 shocks the extent of the renal lesion depended strictly on the applied generator voltage and was classified into 4 grades: Grade 0, no macroscopic trauma detectable (at 11-12 kV); grade 1, petechial medullary bleeding (at 13 kV); grade 2, cortical hematoma (at 14-16 kV); and grade 3, perirenal hematoma (17-20 kV). Whereas at low and medium energy levels the number of shocks played only a minor role, at maximal generator voltage (20 kV) even 25 impulses induced a grade 2 and 600 shocks a grade 3 lesion, emphasizing the importance of shockwave limitation in the upper energy range. In shockwave-induced renal trauma a vascular lesion was predominant and cellular necrosis was secondary. Coupling with a water cushion resulted in a 15%-20% decrease in the disintegrative and traumatic effect, which was compensated for by increasing the generator voltage by 2 kV. Long-term studies showed complete restitution following grade 1 and 2 trauma, whereas after a grade 3 lesion a small segmental and capsular fibrosis without hyperplasia of the juxtaglomerular apparatus was observed. Based on the characteristic ultrasound pattern found in the first study, the threshold for induction of grade 1 lesion was investigated. With both lithotripters a wide range for induction of a grade 1 lesion (Modulith 234-411, Lithostar Plus 220-740) and also a significant overlapping with grade 0 and 2 lesions was seen at low energy settings (levels 2-4). In contrast, the range of shocks (Modulith 96-150, Lithostar Plus 90-142) and overlapping was minimal when high energy was used (levels 7-9). Finally, the disintegration-trauma coefficient combining the results obtained in a standard stone model with those of the canine kidney model was introduced.