[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.

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.

[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.

[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.

Comparison of transrectal prostate biopsy results with histology of transurethral resection of the prostate in men undergoing high-intensity focused ultrasound.

INTRODUCTION: The aim of our study was to evaluate the significance of transurethral resection of the prostate (TURP) to detect prostate cancer (PCa). A comparison was performed of the TURP specimens of patients undergoing high-intensity focused ultrasound (HIFU) with the core biopsies. MATERIALS AND METHODS: TURP before undergoing HIFU therapy was performed in 106 patients without neoadjuvant treatment. The resected tissue was subjected to histopathological evaluation and compared to the histological results of transrectal prostate biopsy. RESULTS: Cancer was detected in the resected tissue of 69 patients (65%). A positive correlation of the amount of resected tissue and detection of PCa could be demonstrated in a multivariate analysis. CONCLUSIONS: With a rate of 65% PCa detected by TURP, our data provide evidence that TURP might be suitable to detect PCa in a small group of selected patients with continuously rising PSA levels and several negative biopsies. On the other hand, these data underline/reinforce the necessity to treat the whole gland using modern treatment modalities such as HIFU and cryotherapy.

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.

[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.

[Thulium:YAG vaporesection of the prostate. First results]. / Thulium:YAG-Vaporesektion der Prostata. Erste Erfahrungen und Ergebnisse.

OBJECTIVES: Laser treatment of benign prostatic hyperplasia has been introduced. The thulium:YAG (Tm:YAG) laser combines the advantages of established laser systems. This study reports the preliminary results of vaporesection of the prostate, using this 2-microm continuous wave (cw) laser. MATERIAL AND METHODS: A total of 54 consecutive patients were treated with the Tm:YAG laser. The outcomes measured were resection time, catheter time, improvement in urinary flow rate (Q(max)), and post-voiding residual urine (PVR). International Prostate Symptom Score (IPSS) and Quality of Life Index (QoL) were recorded. RESULTS: The mean age was 61 years. Mean prostate volume was 30.3 cc. Average resection time was 52 min. Catheter time was 1.7 days. Qmax significantly improved from 4.2 to 20.9 ml on average. PVR decreased from 86 to 16 ml. IPSS and QoL score improved from 19.8 to 6.5 and 4 to 1, respectively. No patient required re-hospitalization. Transfusions were not necessary. CONCLUSIONS: These preliminary results indicate that Tm:YAG vaporesection of the prostate is safe and efficient. The 18-month follow-up data showed major improvement in voiding symptoms and QoL. Longer follow-up is needed to prove durability of these promising results.

[Bladder preservation or initial cystectomy in T1G3 bladder cancer: which parameters help in therapeutic decision-making?]. / Organ erhaltende Therapie oder initiale Zystektomie beim T1G3-Harnblasenkarzinom: Welche Faktoren helfen bei der Therapieentscheidung?

PURPOSE: T1G3 bladder cancers show the clinical and biological behaviour of muscle invasive tumours with progression rates of about 30%. While radical cystectomy in some cases is indicated, other patients can achieve healing with organ preservation. We present a study analysing the influence of the risk factors multifocality, tumour diameter >or= 3 cm and associated carcinoma in situ (Cis) on the outcome of initial T1G3 bladder cancers treated in various ways. MATERIALS AND METHODS: Of 223 patients with initial T1G3 bladder cancer, 125 patients underwent transurethral resection of the tumour (TURB), second resection and adjuvant bacille Calmette-Guérin (BCG) instillations (TURB group), 98 patients chose initial radical cystectomy (CX group). RESULTS: Median follow-up times were 56 months (TURB group) and 51 months (CX group). 5- and 10-year survival rates (82% and 65% in TURB group vs. 75% and 48% in CX group) did not show statistically significant differences. In Cox regression analysis no single risk factor showed a prognostic value. While in TURB group the combination of all risk factors (multifocality, tumour diameter >or= 3 cm and associated carcinoma in situ) was associated with a statistically significantly lower survival rate, the same combination in the CX group was not oncologically relevant. CONCLUSIONS: While initial T1G3 bladder cancer with up to two risk factors after organ-preserving therapy is not associated with a lower tumour specific survival rate in comparison to radical cystectomy, patients with a combination of the three analysed risk factors would profit by an early radical cystectomy.

[New polymorphisms in the PSA promoter in patients with prostate carcinoma]. / Neue polymorphismen im PSA-promoter bei prostatakrebs.

INTRODUCTION: PSA is still the most important parameter in the diagnosis and follow-up of prostate cancer. We searched for single nucleotide polymorphisms (SNP) in four different parts of the PSA promoter, which harbour binding sites for major transcriptional regulators using PCR-based combined SSCP and sequence analysis. MATERIALS AND METHODS: Lymphocyte DNA samples from 279 prostate cancer patients and 55 age-matched controls were subjected to SSCP analysis after PCR amplification of four approximately 200-bp fragments selected to contain the known AREs I-III or the transcriptional start site, respectively. Conspicuous PCR fragments with variant SSCP patterns were subsequently cloned and sequenced. Computer-assisted comparison with published sequences of the promoter region was performed to reveal polymorphic sites. RESULTS: In 66.6 % of the carcinoma cases DNA displayed polymorphisms in ARE I-, whereas the benign cases showed this SNP only in 14.5 %. This difference was highly significant (p < 0.0001). In addition, we found novel SNPs with lower frequency at positions - 179, - 230, - 233 (ARE I) and - 356 (ARE II). CONCLUSION: The present study confirmed that the otherwise already described polymorphism in the position - 158 is highly significantly more frequent in prostate cancer patients than in the control group. There is no significant correlation to the clinical stage of the disease. Furthermore we described for the first time four rare, previously unknown polymorphisms.

Acupuncture for pain in extracorporeal shockwave lithotripsy.

BACKGROUND AND PURPOSE: In most cases, analgesia is required for extracorporeal shockwave lithotripsy (SWL) treatment. Commonly, a combination of a sedative and a synthetic opioid is used, with a wide range of undesirable side effects. To provide an alternative analgesic especially for outpatients, we performed a prospective trial investigating the usefulness of acupuncture. PATIENTS AND METHODS: A series of 90 patients were included in the study, 49% of whom presented with renal calculi and 10% with proximal-, 10% with middle-, and 31% with distal-ureteral stones. Pain control was performed by acupuncture in the traditional Asian method. The intensity of pain and patient satisfaction were assessed a visual analog scale (VAS). Patients with previous SWL under conventional analgesia also were asked about differences in pain and satisfaction. RESULTS: No significant side effects occurred. The median pain score on the VAS was 2/10 (interquartile range 1). Six patients (6.6%) specified a pain intensity of >4, and in 4 patients (4.4%), a conventional analgesic had to be given to finish SWL. The median satisfaction level was 2/5 (interquartile range 1). Nearly all (93.4%) of the patients would opt again for acupuncture in case of repeated SWL. CONCLUSION: In many patients, acupuncture achieves satisfactory pain control for SWL. Further randomized multi-institutional studies are needed to confirm this conclusion.

Suitability of external fixators for use in the tropics.

External fixation systems proved to decrease the osteomyelitis rate in patients in the tropics compared with internal stabilization. This study was designed to show how external fixators being used for treatment of patients in industrial countries compare with cheap alternatives regarding their suitability for the application in tropical countries. Eleven external fixation systems were compared for stability, cost, weight, variability, handling, and capability of being produced locally. Stiffness, slipping moment, and irreversible deformation were determined in material testing machines. The technically best fixators are expensive and cannot be manufactured locally. The inexpensive constructs lack variability and stability. When cost is not a problem, the Synthes model is recommended. With some restrictions in mechanical stability and variability, the Pfeifer Fixator II and a wooden model offer inexpensive and locally producible alternatives. These results may help to select an external fixation device to meet local needs and possibilities in tropical countries.