[Focal therapy of prostate cancer]. / Fokale Therapie des Prostatakarzinoms.

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.

[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.

Why we should not routinely apply irreversible electroporation as an alternative curative treatment modality for localized prostate cancer at this stage.

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.

[Focal therapy for small renal masses : Observation, ablation or surgery]. / Fokale Therapie von kleinen Nierentumoren : Beobachtung, Ablation oder Operation.

BACKGROUND: The rising incidence of renal cell carcinoma, its more frequent early detection (stage T1a) and the increasing prevalence of chronic renal failure with higher morbidity and shorter life expectancy underscore the need for multimodal focal nephron-sparing therapy. DISCUSSION: During the past decade, the gold standard shifted from radical to partial nephrectomy. Depending on the surgeon's experience, the patient's constitution and the tumor's location, the intervention can be performed laparoscopically with the corresponding advantages of lower invasiveness. A treatment alternative can be advantageous for selected patients with high morbidity and/or an increased risk of complications associated with anesthesia or surgery. Corresponding risk stratification necessitates previous confirmation of the small renal mass (cT1a) by histological examination of biopsy samples. Active surveillance represents a controlled delay in the initiation of treatment. RESULTS: Percutaneous radiofrequency ablation (RFA) and laparoscopic cryoablation are currently the most common treatment alternatives, although there are limitations particularly for renal tumors located centrally near the hilum. More recent ablation procedures such as high intensity focused ultrasound (HIFU), irreversible electroporation, microwave ablation, percutaneous stereotactic ablative radiotherapy and high-dose brachytherapy have high potential in some cases but are currently regarded as experimental for the treatment of renal cell carcinoma.

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.

[Irreversible electroporation. Current value for focal treatment of prostate cancer]. / Irreversible Elektroporation. Aktueller Stellenwert in der fokalen Therapie des Prostatakarzinoms.

BACKGROUND: Irreversible electroporation (IRE), a new tissue ablation procedure available since 2007, could meet the requirements for ideal focal therapy (FT) with its postulated features, especially the absence of a thermal ablative effect. Thus far, there is no adequate tumor-entity-specific proof of its effectiveness, and its clinical application has hitherto been confined to very small patient cohorts. This also holds true for prostate cancer (PCA). Nevertheless, it is now being increasingly applied outside clinical trials-to a certain extent due to active advertising in the lay press. AIM OF THE STUDY: In this study, current discrepancies between the clinical application and study situation and the approval and market implementation of the procedure are described. The media portrayal of IRE is discussed from different perspectives, particularly with reference to the FT of PCA. This is followed by a final clinical assessment of IRE using the NanoKnife® system. DISCUSSION: Strict requirements govern new drug approvals. According to the German Drug Act (AMG), evidence of additional benefit over existing therapy must be provided through comparative clinical trials. For medicotechnical treatment procedures, on the other hand, such trial-based proof is not required according to the Medical Devices Act (MPG). The use of IRE even outside clinical trials has been actively promoted since the NanoKnife® system was put on the market. This has led to an increase in the number of uncontrolled IRE treatments of PCA in the last 2 years. The patients have to cover the high treatment costs themselves in these cases. If articles in the lay press advertise the procedure with promising but unverified contents, false hopes are raised in those concerned. This is disastrous if it delays the use of truly effective treatment options. CONCLUSION: IRE basically still has high potential for the treatment of malignancies; however, whether it can really be used for FT remains unclear due to the lack of data. This also holds true for the treatment of PCA. Only carefully conducted scientific research studies can clarify the unresolved issues regarding IRE of PCA. The urgently needed development of universally valid treatment standards for IRE is unnecessarily hampered by the flow commercially driven patients.

[Cancer control in focus insights and future perspectives for the focal treatment of prostate cancer]. / Krebskontrolle im Fokus - Einblicke und Ausblicke rund um die fokale Therapie des Prostatakrebses.

Faced with the dilemma of choosing between the extremes of standard whole gland therapy and active surveillance, those affected by prostate cancer have recently been on the lookout for less invasive alternatives. Particularly the question of whether it would be possible in low risk cancer to treat only the tumour itself while sparing the organ has long been considered. This article discusses the pros and cons of focal treatment and elucidates the latest innovative technologies. High overtreatment rates in low-risk patients submitted to standard therapy and considerable technological advances in diagnosis (particularly multiparametric MRI) and therapy are regarded by the authors as key arguments for abandoning complete tumour eradication with its side effects in favour of sufficient local cancer control by focal treatment with better preserved quality of life in suitable cases.

[Focal therapy for prostate cancer in Germany - 2014 status]. / Fokale Therapie des Prostatakarzinoms in Deutschland - Status 2014.

BACKGROUND: In localized low-risk prostate cancer (PCa), there is a therapeutic dilemma between possible overtreatment by one of the standard therapies and potentially insufficient cancer control by active surveillance (AS). Focal therapy (FT) provides an alternative therapeutic option as it aims to preserve the organ and to eliminate the cancer focus at the same time. METHODS: In this article the current state of FT for localized low-risk prostate carcinoma in Germany is described. In addition, criteria that should be used to select patients for FT are proposed. RESULTS: Currently, the effectiveness of FT is under evaluation by two multicenter, prospective studies in Germany: TOOKAD and HEMI. However, localized low-risk prostate carcinoma remains a diagnostic challenge: Multiparametric MRI as well as histopathological second opinion are considered mandatory in addition to transrectal biospy. CONCLUSION: The oncological outcome of both the TOOKAD and HEMI study will be crucial for any form of FT for prostate carcinoma in Germany in the future. However, there is a remarkably high acceptance of FT among patients.

[Focal prostate cancer therapy: capabilities, limitations and prospects]. / Fokale Therapie des Prostatakarzinoms: Möglichkeiten, Limitierungen und Ausblick.

INTRODUCTION: Patients with low-risk prostate cancer (PCa) face the difficult decision between a potential overtreatment by one of the standard therapies and active surveillance (AS) with the potential insecurity regarding cancer control. A focal therapy (FT) implies a treatment of the tumor within the prostate only. METHODS: This review evaluates the current literature and expert opinion of different therapies suited for FT as well as concepts for prostate imaging, biopsy and histopathological evaluation. RESULTS: Currently there is a lack of multicenter, randomized, prospective data on the effectiveness of FT. Nonetheless, the published data indicate a sufficient tumor control with a favorable side effect profile. There are still flaws in the diagnostics with regard to tumor detection and histological evaluation. Multicenter studies are currently recruiting worldwide which will provide new data with a higher level of evidence. CONCLUSION: At present, the effectiveness of FT should not be compared directly to standard radical therapies and FT should only be performed within studies. In cases of cancer progression after FT a salvage treatment should still be possible.

[Economic aspects of the treatment of urinary stones. Results of the German Society for Shock Wave Lithotripsy]. / Okonomische Aspekte der Harnsteintherapie. Ergebnisse des Konsensusmeetings der Deutschen Gesellschaft für Stosswellenlithotrypsie (DGSWL).

Urolithiasis is the disease that leads to the largest number of inpatient treatments in urologic clinics in Germany. It is very important to know the current rules of remuneration for urinary stone therapy and to adjust the relevant clinical pathways. The German Society for Shock Wave Lithotripsy (DGSWL) stressed these economic aspects at its 2009 consensus meeting, since clinical therapy cannot be free of economic restrictions in the long term.

[Results of the randomised phase III study of the German Testicular Cancer Study Group. Retroperitoneal lymphadenectomy versus one cycle BEP as adjuvant therapy for non-seminomatous testicular tumours in clinical stage I]. / Ergebnisse der randomisierten Phase-III-Studie der "German Testicular Cancer Study Group". Retroperitoneale Lymphadenektomie vs. 1 Zyklus PEB als adjuvante Therapie beim nichtseminomatösen Hodentumor im klinischen Stadium I.

OBJECTIVE: As 30% of non-seminomas in clinical stage I will progress during active surveillance, alternative adjuvant strategies of 2 cycles of bleomycin, etoposid, cisplatin (BEP) or nerve sparing retroperitoneal lymphadenectomy (RPLND) can be offered. The risk of relapse is reduced to 2% and 10%, respectively. Without prognostic markers and with lowered toxicity it is postulated that only one cycle of BEP could significantly reduce the recurrence rate in comparison to RPLND. MATERIALS AND METHODS: Between 1996 and 2005, 382 patients were randomly assigned to receive either RPLND (n=191) or 1 cycle of BEP (n=191). In accordance with the protocol, 174 patients were treated with 1 cycle of BEP and 173 underwent RPLND. The primary study end-point was a reduction of recurrence from 10% after RPLND to a maximum of 3% after 1 cycle of BEP. RESULTS: After a mean follow-up of 4.7 years, there were 2 and 13 recurrences in the according-to-protocol population with chemotherapy and surgery, respectively. The difference between chemotherapy (1.15%) and surgery (7.5%) was statistically significant (p=0.0033). The tumor-specific survival was 100%. CONCLUSION: This largest randomized trial investigating treatment strategies in clinical stage I non-seminomas (AUO AH 01/94) showed the superiority of one cycle BEP over RPLND. The data obtained represent the basis for a reduced chemotherapy.

[The future of ESWL]. / Die Zukunft der ESWL.

With the introduction of the Dornier HM3 lithotripter, the successful history of extracorporeal shock wave lithotripsy (ESWL) for noninvasive treatment of urinary stones began about 25 years ago. The development of newer lithotripters has not been able to improve clinical efficacy because the shock wave parameters specifically responsible for stone disintegration or tissue trauma and pain induction have not yet been identified. Actual research in lithotripter technology deals with modification of the focal point. The evolution of endoscopic procedures, ureterorenoscopy, and percutaneous nephrolithotomy took longer but was more successful in terms of clinical efficacy. Nowadays, ESWL or an endoscopic procedure is offered as a reasonable option for most urinary stone cases. Therefore, economic aspects and the surgeon's expertise will become greater factors when a procedure is chosen. ESWL, with or without anaesthesia, will be an inherent part of future treatment modalities for urinary stones.

[New guidelines for urinary stone treatment. Controversy or development?]. / Neue Leitlinien zur Harnsteintherapie. Widerspruch oder Weiterentwicklung?

The new guidelines of the European (EAU), American (AUA), German, and Austrian associations of urology are based on thorough and consistent research and analysis of the published literature. However, the methodology is very diverse. In the case of the EAU-AUA guidelines on ureteral stones, the evidence was generated by a laborious meta-analysis of the entire available published literature on the subject. These guidelines represent the 1A level of evidence. The traditional European guidelines evaluate each statement separately and assign a level of evidence to each. The following aspects are new: the even greater effort to formulate guidelines accompanied by the initiation of international cooperative projects, clarity of presentation and evaluation of the individual statements (including levels of evidence), information on medication-based treatment to facilitate spontaneous passage of ureteral stones as well as stone fragments after extracorporeal shock wave lithotripsy (ESWL), a shift in the value of ESWL and ureterorenoscopy for ureteral stones, retrograde intrarenal surgery for small kidney stones refractory to ESWL or in settings unsuitable for ESWL, the use of laparoscopy in those rare cases that represent an indication for open surgery, and the additional value given to metaphylaxis in diagnosis and therapy. All of the new guidelines take these developments into account, although they differ slightly in the importance they assign to the individual items. The modifications represent the developments secondary to electronic data processing and preparation on the one hand and the rapid development of medical instruments on the other. Although ESWL is still the most important procedure for treating urinary stones, advances in flexible endoscopes, intracorporeal lithotripsy, and extraction instruments have led to a shift in the range of indications. These developments are fully accommodated in the new guidelines.

Study on the prevalence and incidence of urolithiasis in Germany comparing the years 1979 vs. 2000.

OBJECTIVES: In 1979, we conducted a representative study to determine the prevalence and incidence of urolithiasis in Germany. Significant progress in stone therapy and changes in nutritional and environmental factors since then consequently led to a second study in 2001 under the same conditions as in 1979. METHODS: A representative sample of 7500 persons from all over Germany was questioned on the occurrence of urinary stones during their lifetimes (prevalence) and on acute urolithiasis in 2000 (incidence). Additionally, data were collected on urinary stone therapy and metaphylaxis. The current data were then compared with those from 1979. RESULTS: Prevalence has risen from 4% to 4.7% from 1979 to 2001. 9.7% of the 50-64 year old males in 2000 had already had urinary stones (females: 5.9%). The current recurrence rate of urinary stones was estimated to be 42%. In the year 2000, the incidence of urolithiasis in Germany was found to be 1.47% (1979: 0.54%). Over 40% of the stones were passed spontaneously. CONCLUSION: There has been a marked increase in the prevalence and incidence of urolithiasis in Germany within the last 22 years. This probably results from improvements in clinical-diagnostic procedures, changes in nutritional and environmental factors and a general apathy towards metabolic clarification and metaphylaxis.

[Minimally-invasive therapy of urinary stones]. / Interventionelle Therapie von Harnsteinen.

Open surgery was the standard therapy for urinary calculi up to about 30 years ago. This changed upon introduction of extracorporeal shockwave lithotripsy (ESWL) in 1980, a procedure that is now the primary therapy for 70 % of the patients in western countries. Simultaneously, endourological procedures like ureterorenoscopy (URS) and percutaneous nephrolithotripsy (PCNL) have been improved, and now, modern small diameter and highly efficient instruments offer an ideal alternative to shockwave lithotripsy. Today, minimally-invasive stone treatment has replaced open stone surgery almost completely. This article introduces ESWL, URS and PCNL and discusses indications, outcomes and limitations.

[Cystinuria - Cystine Stones: Recommendations for Diagnosis, Therapy and Follow-up]. / Zystinurie - Zystinsteinleiden: Aktuelle Empfehlungen zur Diagnostik, Therapie und Nachsorge.

Cystinuria, an autosomal-recessive disorder, is the cause of 1 - 2 % of all kidney stones observed in adults and about 10 % of those observed in infants. Despite increasing understanding of underlying pathomechanisms, patients still form recurrent stones and have to undergo repeated interventions with increasing risk of renal insufficiency. Dietary and medical metaphylaxis may lower the frequency of recurrent stones but are often not practiced. Regular follow-up examinations and optimal therapy significantly enlarge stone-free intervals. This review offers an overview of the underlying pathogenetic mechanisms as well as guidance for diagnosis, monitoring, metaphylaxis and therapy of cystinuria following the recommendations of the Deutsche Gesellschaft für Urologie (DGU) and the European Association of Urology (EAU).