Correction to: The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

In multivariate analysis, GS of the regular prostatectomy specimen was the only statistically significant parameter for pT2R1 prostate cancer.

[Importance of magnetic resonance imaging/ultrasound-guided fusion biopsy for the detection and monitoring of prostate cancer]. / Stellenwert der MRT/Ultraschall-Fusionsbiopsie für die Detektion und Verlaufskontrolle des Prostatakarzinoms.

The use of multiparametric magnetic resonance imaging (mpMRI) is becoming increasingly more important for the primary diagnostics of prostate cancer (PCa) and for monitoring under active surveillance. Current studies confirmed that the use of mpMRI can increase the detection of clinically significant PCa and reduce the detection rate of insignificant PCa as well as the rate of unnecessary biopsies. The information from mpMRI can be cognitively used for in-bore biopsy and using fusion biopsy systems. There are no clear recommendations on the access approach for fusion biopsy (e. g. transrectal or perineal), whereby higher rates of rectal bleeding and infections have been described for transrectal access compared to perineal access. The increasing rate of antibiotic resistance as well as restricted indications for the use of quinolones are a major challenge for transrectal biopsy.

[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.

[High intensity focused ultrasound (HIFU) : Importance in the treatment of prostate cancer]. / Hochintensiver fokussierter Ultraschall (HIFU) : Stellenwert bei der Therapie des Prostatakarzinoms.

BACKGROUND: High intensity focused ultrasound (HIFU) has been used since the beginning of the 1990s as an alternative treatment for prostate cancer. OBJECTIVE: Overview of the current status and critical review of the different indications for HIFU in the treatment of prostate cancer. MATERIAL AND METHODS: Review of the current literature on the indications, side effects, oncologic results and current guideline recommendations. RESULTS: The principle of HIFU is based on high energy sound waves, which lead to coagulation necrosis at the focal point. It can be applied for different indications: complete ablation of prostatic tissue is attempted in whole gland HIFU in the primary treatment of localized prostate cancer. There are several case series in the current literature with a maximum median follow-up of 8.1 years. The main side effect is the formation of bladder neck sclerosis. A further indication is for salvage HIFU in patients with localized recurrent prostate cancer after radiotherapy. This is a high-risk procedure due to increased risk of incontinence and formation of rectourethral fistula. Focal therapy is an innovative field aiming at partial prostate gland ablation with HIFU thereby reducing side effects. Technical improvements in HIFU enable treatment planning with fusion of multiparametric magnetic resonance imaging (mpMRI). Due to the experimental character, this should only be carried out within clinical trials. DISCUSSION: Due to a lack of prospective randomized trials and limited long-term results, whole gland HIFU is considered differently in the guidelines of European countries. Focal therapy is still experimental and should only be carried out 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.

[Management of ureteral strictures and hydronephrosis]. / Management von Harnleiterstrikturen und Harnstauung.

Patients who develop hydronephrosis due to an acute cause often have colic-like pain but hydronephrosis secondary to a chronic cause is often asymptomatic. Ureteral obstruction can be due to a variety of intrinsic and extrinsic causes, such as trauma, radiation, iatrogenic injury, urolithiasis, malignancies and congenital causes. Management planning is dictated by the underlying cause, patient comorbidity and life expectancy. Malignant ureteral obstructions can be managed with segmental metal stents with advantages in the quality of life and provide an alternative to long-term treatment with a DJ stent. Endoscopic balloon dilatation and endoureterotomy are options for benign ureteral strictures up to 2 cm in length. For longer benign strictures there are a number of reconstructive techniques, which can also be performed by laparoscopic or robot-assisted approaches at specialized centers.

[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.

The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

PURPOSE: To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy. METHODS: A multicenter data analysis of 956 patients with pT2R1N0/Nx tumors was performed. Patients underwent radical prostatectomy between 1994 and 2009. No patients received neoadjuvant or adjuvant therapy. All prostate specimens were re-evaluated according to a well-defined protocol. The association of pathological and clinical features, in regard to BCR, was calculated using various statistical tests. RESULTS: With a mean follow-up of 48 months, BCR was found in 25.4 %. In univariate analysis, multiple parameters such as tumor volume, PSA, Gleason at positive margin were significantly associated with BCR. However, in multivariate analysis, Gleason score (GS) of the prostatectomy specimen was the only significant parameter for BCR. Median time to recurrence for GS ≤ 6 was not reached; 5-year BCR-free survival was 82 %; and they were 127 months and 72 % for GS 3+4, 56 months and 54 % for GS 4 + 3, and 27 months and 32 % for GS 8-10. The retrospective approach is a limitation of our study. CONCLUSIONS: Our study provides data on the BCR in pT2R1-PCa without adjuvant/neoadjuvant therapy and thus a rationale for an individual's risk stratification. The data support patients and physicians in estimating the individual risk and timing of BCR and thus serve to personalize the management in pT2R1-PCa.

[Laparascopic radical prostatectomy]. / Laparoskopische radikale Prostatektomie.

BACKGROUND: Since its initial description 20 years ago, laparoscopic radical prostatectomy (LRP) is now a standard treatment option for localized prostate cancer. However, in recent years robot-assisted laparoscopic radical prostatectomy (RALP) has been gradually replacing LRP, despite high costs incurred with RALP. OBJECTIVES: The purpose of this work was to determine the oncological outcomes of LRP from selected series with a follow-up of around 10 years and to compare oncological and functional outcomes between LRP and RALP. MATERIAL AND METHODS: The outcomes of a case series of LRP with a median follow-up of at least 3 years were reviewed. In addition, the outcomes of comparative studies between LRP and RALP were reviewed. RESULTS: The first case series of LRP with follow-ups of 10 years after LRP are available and show favorable oncologic outcomes. Current data show that RALP offers superior functional results (recovery of erectile function) following bilateral nerve sparing when compared to LRP. CONCLUSION: The first review a few years ago showed comparable oncologic and functional outcomes between open prostatectomy, LRP, and RALP. Recent data from comparative studies show superiority of RALP over LRP for potency following bilateral nerve sparing. The potency outcomes between LRP and RALP are, however, similar following wide excision of both neurovascular bundles. Therefore, both treatment options can be recommended for the treatment of localized PC.

[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.

Utility of immunohistochemistry markers in the interpretation of post-high-intensive focussed ultrasound prostate biopsy cores.

PURPOSE: To overcome the difficulties in the interpretation of postoperative tumor obtaining biopsy cores for patients who treated their prostate cancer with high-intensity focussed ultrasound (HIFU) therapy. METHODS: The H&E slides of 58 patients with residual prostate cancer after HIFU treatment were systematically reviewed. Correlation between the pathologist's findings and immunohistochemical expression of MIB-1, alpha-Methyl-Co-Racemase and 34ßE-12 staining was analyzed. RESULTS: Mean time from treatment to biopsy was 40.2 (8-208) weeks. The expert review of the H&E slides identified 40 patients with viable carcinoma in the post-HIFU biopsy cores. 18 patients were revised to necrosis-only-tumors. These biopsies were performed not later than 16 weeks after HIFU treatment (median 10.9 weeks, range 8-14). Both MIB-1 and AMACR staining displayed significant differential expression in viable carcinoma (p < 0.001) compared to necrosis tumors. Referring to viable carcinoma tissue, AMACR staining index was significantly rising, the longer treatment dated back from biopsy (p < 0.002). In this context, 34-ß-E12 stained negative through all tumor areas and positive in the majority (85%) of the surrounding non-neoplastic epithelium. CONCLUSIONS: AMACR and MIB-1 reliably differentiate viable carcinoma from a process of ongoing irreversible necrosis in early post-HIFU prostate biopsy cores and therefore proposed-in addition with 34 beta-E12-as useful markers exposing suspicious tumor foci in difficult cases.

[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.

First results of endocavity evaluation of the microvascularization of malignant prostate tumors using contrast enhanced ultrasound (CEUS) including perfusion analysis: first results.

AIM: Detection of prostate cancer lesions using transrectal contrast enhanced ultrasound (CEUS) of the prostate utilizing quantitative perfusion analysis. METHOD: 20 patients (mean age 63 years, 47-71) with biopsy proven prostate cancer underwent transrectal ultrasound (TRUS) prior to radical prostatectomy by 2 experienced examiners using a multifrequency endocavitary probe (5-9 MHZ, LOGIQ E9, GE Healthcare, Chalfont St Giles, UK) to detect cancer-suspect lesions. CEUS was performed dynamically up to 3 Min after bolus injections of 2.4 ml SonoVue® (BRACCO, Italy). Digital cine loops were analyzed by an independent blinded examiner using perfusion quantification software with colour-coded parametric images in order to define suspect regions based on the perfusion-related parameters early wash in rate (WIR), mean transit time (MTT) and rise time (RT). The results of CEUS perfusion analysis were compared with the histopathology after surgery, obtained from whole mount sections. RESULTS: After prostatectomy and histopathology, 34 prostate cancer foci were found in 20 patients. In 30/34 cases an early enhancement within the tumor was detected by CEUS perfusion analysis without early wash out. By evaluating the MTT and RT tumor detection was possible in 29/34 and 25/34 cases. The highest detection rate of prostate cancers was obtained by analysis of early contrast enhancement (priot to the normal prostate parenchyma), with a sensitivity of 88%, specificity 100%, NPP 60%, PPV 90%, in clinically suspicious cases with good correlation to the postoperative histopathological findings (r = 0.728). CONCLUSION: This pilot study demonstrates, that quantitaive analysis of perfusion parameters obtained with transrectal CEUS could be helpful for characterization of neoplastic microcirculation of prostate cancer, for preoperative localization of cancer-suspect areas and for therapy guidance and management.

[HIFU in salvage treatment of patients with prostate cancer after primary external radiation therapy--status 2012]. / HIFU in der Salvage Behandlung von Patienten mit Prostatakarzinom-Rezidiv nach primärer externer Bestrahlungstherapie - Status 2012.

BACKGROUND: Patients with (local) recurrence of prostate cancer after radiation therapy face the question of the appropriate diagnostic and possible therapeutic options. Many patients in this setting receive palliative androgen deprivation therapy alone, with arguable impact on overall cancer survival. In the case of an isolated local recurrence, salvage prostatectomy represents a potentially curative therapeutic option, albeit with a high complication rate. Alternatively, these patients can be offered a local treatment with salvage HIFU therapy. MATERIAL AND METHODS: Salvage HIFU therapy is based on the thermal ablation of tissue through high-intensity focused ultrasound. In addition, the formation of microbubbles (cavitation) and their implosion lead to an enhancement of tissue ablation. RESULTS: The results of 6 monocentric studies (2004-2011) with an overall number of 408 patients (22-167 patients) are presented and critically reviewed. The median follow-up was 18.71 months (7.4-39). The 3-year progression free survival (PFS) varied from 25% (D'Amico high risk) to 53% (D'Amico low-risk), the 5-year overall survival was 90%. The rate of urinary incontinence varied between 7 and 60% in all grades (grade III urinary incontinence 0-9.5%). In 22 cases surgical incontinence treatment was performed. 53 patients developed a urethral stricture or stenosis leading to surgical treatment. Urethral-rectal fistulae were seen in 0-7%. CONCLUSIONS: The current data on salvage HIFU can be evaluated as insufficient. The main criticisms can be seen in the lack of randomization, the monocentric and retrospective analyses of the data, the heterogeneous stratification of risk groups as well as inadequate definition of postinterventional treatment failure. The studies indicate that salvage HIFU therapy leads to a mid-term overall survival with complication rates that are comparable to those of other local salvage therapies. Randomized multicentric studies are needed to further validate the results of salvage HIFU therapy.

Complete high-intensity focused ultrasound in prostate cancer: outcome from the @-Registry.

BACKGROUND: To analyze data on patients with localized prostate cancer who were treated with complete high-intensity focused ultrasound (HIFU) prospectively captured within a voluntary HIFU user database (@-Registry). METHODS: The @-Registry includes data from consecutive patients treated with Ablatherm (EDAP-TMS) HIFU at nine European Centres during the period 1994 and 2009. For this analysis, the data repository was reviewed for information on patients with localized prostate cancer (T1 -- T2) treated with complete (whole-gland) HIFU on the basis of an anterior-posterior prostate height of ≤24 mm and a treated volume >120% of the prostate volume. Patients were regularly followed with PSA measurement and biopsy. Biochemical failure was defined for this study as PSA nadir +2 ngml(-1) (Phoenix definition). Disease-free survival was based on a biopsy, retreatment and biochemical data. Patients were risk group-stratified using the D'Amico classification system. RESULTS: The median follow-up was 2.8 years for the 356 patients included in the analysis. The majority could be classified as either low (44.9%) or intermediate risk (39.6%); 14.6% patients were classified as high risk. The median (mean, s.d.) PSA nadir was 0.11 ng ml(-1) (0.78 and 3.6), achieved at a mean (s.d.) of 14.4 (11.6) weeks after HIFU. Follow-up biopsies on 226/356 (63.5%) patients revealed an overall negative biopsy rate of 80.5% (182/226); there was no statistically significant difference in positive biopsy rate by risk group-stratification. Actuarial freedom from biochemical recurrence at 5 and 7 years according to the Phoenix definition was 85% and 79%, respectively. Disease-free progression rates at 5 and 7 years were 64% and 54%, respectively. CONCLUSIONS: Whole-gland prostate HIFU as primary monotherapy for localized prostate cancer achieves a recurrence-free survival in short-term analysis as assessed by prostate biopsy and serum PSA endpoints in a majority of patients.