Postoperative change in Gleason score of prostate cancer in fusion targeted biopsy: a matched pair analysis.

OBJECTIVE: To evaluate if MRI/ultrasound fusion based targeted biopsy (FBx) leads to a reduced rate of change in Gleason score (GS) compared to prostatectomy specimen. METHODS: The histopathological findings of the biopsy of the prostate and the radical prostatectomy (RP) specimen of 210 patients who were referred to our hospital between 2012 and 2017 were compared retrospectively in this study. One hundred and five patients who underwent FBx combined with ultrasound-guided 12-core biopsy of the prostate (SBx) were matched with 105 patients who underwent SBx only. This study evaluated the rate of up- or downgrading in the RP specimen in both groups and compared the results via matched pair analysis. RESULTS: Concordance in Gleason grade group (GGG) was found in 52/105 patients (49.5%) in SBx and in 49/105 patients (46.7%) with FBx (p = 0.679). The rate of downgrading was statistically significant (p = 0.014) and was higher in the FBx group (14/105 patients, 13.3%) than in the SBx group (4/105 patients, 3.8%). A higher rate of upgrading was seen in SBx (49/105 patients; 46.7%) compared to FBx (42/105 patients; 40%), with no statistical significance (p = 0.331). The change in GGG from biopsy to final pathology in patients with GGG 1 and 2 at biopsy level was not statistically significant (p = 0.168). CONCLUSION: FBx does not decrease the rate of upgrading between biopsy and final pathology in RP specimens. Our results indicate that FBx tends to overestimate the final GGG compared to SBx.

Detection of Gleason 6 prostate cancer in patients with clinically significant prostate cancer on multiparametric magnetic resonance imaging.

INTRODUCTION: Multiparametric-Magnetic Resonance Imaging (mpMRI)-Ultrasound fusion guided biopsy (Fbx) has emerged as the new standard of risk stratification for prostate cancer (PCa) with superior detection rates of clinically significant PCa than randomized biopsy. In the present study, we evaluated patients with suspicion of clinically significant PCa on mpMRI, but histopathologically proven Gleason 6 PCa in Fbx. MATERIAL AND METHODS: Between 2015 and 2019, 849 patients underwent Fbx and concurrent systematic 12-core biopsy at our department. 234 patients were diagnosed with Gleason 6 PCa in either mpMRI-targeted and/or concurrent systematic biopsy. Patients were analyzed regarding PSA, mpMRI findings according to PI-RADS classification, histopathological results of Fbx and systematic 12-core biopsy. 99/234 patients were also analyzed in regards of histopathology of the whole-mount specimen of subsequent radical prostatectomy (RP). RESULTS: In 131/234 patients (56%), Gleason 6 PCa was detected in the mpMRI target. In 103/234 patients (44%), Gleason 6 PCa was detected in the concurrent systematic 12-core biopsy with negative mpMRI-targeted biopsy. Men with evidence of Gleason 6 in the mpMRI target had significantly higher amounts of overall positive biopsies (median 4 vs. 2, p < 0.001) and higher maximum tumor infiltration per biopsy core (30% vs. 20%, p < 0.001) compared to men with negative mpMRI-targeted biopsy. Detection of Gleason 6 in mpMRI Target lesions correlated significantly with the PI-RADS score (p < 0.001). Patients with positive mpMRI-target had significantly higher tumor infiltration in whole-mount specimen after prostatectomy (20% vs. 15%, p = 0.0026) compared to men without detection of Gleason 6 in mpMRI-targeted biopsy but in additional systematic biopsy. CONCLUSION: Detection of Gleason 6 PCa in mpMRI-targeted biopsy indicates higher tumor burden compared to detection of Gleason 6 PCa in concurrent systematic biopsy and negative mpMRI-targeted biopsy.

Follow-up after focal therapy of the prostate with high intensity focused ultrasound (HIFU) using contrast enhanced ultrasound (CEUS) in combination with MRI image fusion.

INTRODUCTION: Focal therapy (FT) of the prostate for low risk prostate cancer (PCa) is an alternative to traditional definite treatment options like external beam radiotherapy or radical prostatectomy. However, follow up after FT is still challenging and is subject to current studies. Significance of imaging after FT such as multiparametric MRI (mpMRI) is currently not well established. In this study, we aimed to evaluate the efficacy of alternative imaging during the follow up of low risk PCa treated with focal HIFU therapy using CEUS and image fusion. MATERIALS AND METHODS: Retrospective single arm study in patients with uni- or bilateral, low or intermediate risk prostate cancer treated with HIFU at our institution between October 2016 and January 2018. CEUS in combination with image fusion using an axial T2-weighted MRI sequence was performed during follow up 3, 6, 9 and 12 months after the therapy. RESULTS: 4 consecutive patients with Gleason score (GS) 6 and 4 patients with GS 7a prostate cancer were included in the study. Hemiablation was performed in 7 patients with unilateral tumor. One patient underwent whole gland treatment due to histological proven bilateral PCa. Mean patient age at time of therapy was 70.3 (54-83) years and mean Prostate-specific antigen (PSA) level prior treatment was 7.8 ng/ml (2.1-14.4), after 3 months mean PSA level was 3.9 ng/ml (0.1-7.2), after 6 months 3.5 ng/ml (0.2-6.0), after 9 months 3.1 ng/ml (0.2-6.8) and 3.3 ng/ml (0.2-6.1) after 12 months. CEUS showed no signs of microvascularisation after 3, 6, 9 and 12 months in the ablated zone. 3 months posttreatment the necrotic tissue was still visible in the B-mode scan, although with no signs of vascularization performing CEUS. After 6 months the ablated side of the prostate was almost completely atrophic. And after 9 months the necrotic tissue was completely resolved. Between 9 and 12 months no changes in microvascularisation and perfusion could be shown. CONCLUSIONS: MpMRI/CEUS image fusion is a cost-effective and feasible technique to monitor the perfusion of the ablation zone after focal therapy of the prostate.

[Active surveillance of prostate cancer : An update]. / Active Surveillance beim Prostatakarzinom : Ein Update.

Prostate cancer is a heterogeneous disease. In cases of low-risk prostate cancer, active surveillance represents an attractive alternative treatment. Significant complications of a definitive treatment can therefore be delayed or completely avoided. Despite strict inclusion criteria for active surveillance, the diagnosis of low-risk prostate cancer can be inaccurate and there is therefore a risk of missing the optimal point in time for definitive treatment. Multimodal diagnostics and continuous aftercare are therefore crucial.

Medium-term Follow-up of Vascular-targeted Photodynamic Therapy of Localized Prostate Cancer Using TOOKAD Soluble WST-11 (Phase II Trials).

BACKGROUND AND OBJECTIVE: To assess the medium-term tumor control in patients with localized prostate cancer (PCa) treated with vascular-targeted photodynamic (VTP) therapy with TOOKAD Soluble WST11 (VTP) and to assess the medium-term tolerability of the treatment. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: During the clinical phase II studies, 68 patients were treated with VTP under optimal treatment conditions (WST11 at 4mg/kg, light energy at 200J/cm, and a light density index ≥1) and have been included in a 3.5-yr follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Post-interventional visits were scheduled every 6 mo and conducted as per local standard practice in each study center. Cancer-free status was assessed by means of prostate-specific antigen kinetics, multiparametric magnetic resonance imaging and/or prostate biopsies. RESULTS AND LIMITATIONS: At the end of the 3.5-yr follow-up, overall successful focal ablation was achieved for 51 patients (75%). Cancer was identified in the untreated lobe in 17 patients (25%). In total, 34 patients (50%) were cancer-free in both the prostate lobes. In case of recurrent/persistent malignancy, the Gleason score remained consistent or changed at the maximum by one point (upgrading by 1 Gleason point to 3+4 for eight patients and 4+3 for two patients). There were 64 related adverse events (AEs): 48% were Clavien grade I, 47% were grade II, and 5% were grade III. There were no Clavien grade IV and V AEs. Limitations included small sample size and heterogeneity in the follow-up for some centers. CONCLUSIONS: VTP is a safe and efficient treatment and represents an alternative option for localized low-risk PCa management over the medium term. Precise diagnostic methods and imaging tools are thereby essential requirements to ensure safe and complete targeted therapy. PATIENT SUMMARY: In this report, we looked at the medium-term outcomes of focal photodynamic therapy for early-stage prostate cancer. We found that this form of treatment is efficient and might have the potential to become a therapeutic option for low-risk cancer. Effectiveness depends on precise diagnostic methods, such as magnetic resonance imaging and accurate biopsy.

Comparison of PIRADS 3 lesions with histopathological findings after MRI-fusion targeted biopsy of the prostate in a real world-setting.

INTRODUCTION: We aimed to evaluate whether PIRADS 3 lesions in multiparametric MRI (mpMRI) represent a significant risk of prostate cancer (PCa) in a real-world setting of different referring radiologic institutes. MATERIALS AND METHODS: Between May 2015 and October 2017, a total of 408 patients were referred to our clinic for MRI-ultrasound fusion targeted biopsy of the prostate (FusPbx) due to suspected prostate cancer. In all patients, preoperatively an mpMRI of the prostate was performed by altogether 62 different radiologic institutes. Prostate lesions were classified according to the PIRADS system. A PIRADS 3 lesion was diagnosed in 41 patients. FusPbx was performed transrectally using a Philips EPIQ 7 (Philips Medical Systems, Bothell, WA) scanner with plane wise fusion of ultrasound and MRI image data. In addition to FusPbx in each patient a randomized 12-core transrectal ultrasound guided biopsy (USPbx) was performed. RESULTS: Mean PSA Level was 9.5 ng/ml (range: 1- 26 ng/ml), mean patients age was 66.1 years (48.6- 80.4). In 11/41 patients (26.8%) prostate cancer was diagnosed by FusPbx of the PIRADS 3 lesion. In the target lesion PCa was classified as Gleason Score 3+3 in 5 patients, as 3+4 in 3, 4+3 in 1, 4+4 in 1 and 4+5 in 1 patient. In patients with negative FusPbx USPbx revealed PCa in another 7 patients (17.1%). In 5 of these GS 3+3 PCa was found, in another 2 patients GS 3+4 PCa. CONCLUSIONS: PIRADS 3 lesion indicates an equivocal likelihood of significant prostate cancer. In our series the overall PCa detection rate was 26.8% and 14.6% for clinically significant cancer in PIRADS 3 lesions. This evokes the question, if PIRADS 3 lesions could be surveilled only. The findings should be confirmed in a larger series.

MRI-TRUS fusion biopsy of the prostate: Quality of image fusion in a clinical setting.

INTRODUCTION: Prostate cancer (PCa) is one of the most common malignancies in men. The diagnostic standard to confirm prostate cancer is the transrectal ultrasound-guided biopsy. However, this procedure is associated with the underdetection of clinically significant prostate cancer and therefore needs to be improved. In the last years MRI fusion based targeted biopsy gained importance as consequence. In this study, we evaluated the quality of MRI ultrasound image fusion and evaluated factors influencing the image fusion quality. This was done by comparing fusion quality with the histopathological findings in the defined MRI target on the one hand and the PIRADS score on the other hand. MATERIALS AND METHODS: Single arm study including patients with elevated prostate specific antigen (PSA) and a multiparametric MRI showing a suspicious lesion underwent a MRI fusion targeted biopsy at our institution. MRI fusion targeted biopsy and an additional 12-core transrectal ultrasound (TRUS) guided biopsy was performed using the Philips Percunav device (Philips Medical Systems, Bothell, WA). The fusion accuracy was rated by two experienced clinicians (1 radiologist, 18 years of experience, 1 urologist, 5 years of experience) using a five-point rank scale (1 = best) and comparing the result with the histological findings in the target and the PIRADS score. RESULTS: The detection rate of clinically significant cancer (Gleason 7a or greater) by MRI-ultrasound fusion targeted biopsy was 58.6% (17/29) compared to 50% (19/38) in the standard transrectal ultrasound-guided approach. PCa was found in 36.4% (4/11 patients) of patients with a PIRADS 3 lesion, in 57.7% (15/26 patients) of patients with a PIRADS 4 lesion. In 76.9% (10/13 patients) of patients with a PIRADS 5 lesion PCa was diagnosed. No statistical significance was found comparing the quality of registration either with the PIRADS (p = 0.7873) nor with the Gleason score (p = 0.4376). The study is limited by the small number of patients. CONCLUSIONS: MRI fusion based targeted biopsy improves the identification of clinical significant cancer. The Gleason score of detected PCa is not influenced by the quality of fusion.

Contrast enhanced ultrasound (CEUS) with MRI image fusion for monitoring focal therapy of prostate cancer with high intensity focused ultrasound (HIFU)1.

INTRODUCTION: Reduced acceptance of radical prostatectomy in patients with low risk or intermediate risk prostate cancer has significantly changed treatment strategies in prostate cancer (PCa) during the last years. Focal therapy of the prostate with high intensity focused ultrasound (HIFU) is an organ-preserving treatment for prostate cancer with less impairment of health-related quality of life. Follow-up after HIFU therapy by imaging modalities remains a major problem as eg. MRI performs poorly. Contrast enhanced ultrasound (CEUS) allows to monitor the vascular architecture of organs non-invasively. However, only limited data are available using CEUS to define successful and complete HIFU treatment of the prostate. In this study, we aimed to evaluate short-term image findings using CEUS and image fusion before and after HIFU treatment. MATERIALS AND METHODS: Prospective single arm study in patients with uni- or bilateral, low or intermediate risk prostate cancer or recurrent cancer after radiotherapy treated with HIFU at our institution between October 2016 and November 2017. HIFU hemiablation or whole gland treatment was performed using the Focal One® device. PCa was diagnosed either by multiparametric magnetic resonance imaging (mpMRI) followed by MRI fusion based targeted biopsy combined with 12 core transrectal ultrasound (TRUS) guided biopsy or 12 core random biopsy only. Monitoring of the target region before, immediately and 24 hours after the ablation was done by CEUS in combination with image fusion using an axial T2-weighted MRI sequence. RESULTS: 6 consecutive patients with Gleason score (GS) 6, 5 patients with GS 7a prostate cancer and one patient with biochemical recurrence after radiotherapy were included in the study. Three patients underwent whole gland treatment due to histological proven bilateral PCa or recurrent PCa after radiotherapy. Hemiablation was performed in 9 patients with unilateral tumor and no PIRADS 4 or 5 lesion in the contralateral lobe. Median patient age was 69.8 years and median PSA (prostate-specific antigen) level was 8.4 ng/ml. CEUS showed markedly reduced microbubbles in the ablated area, the prostate capsule still showed signs of perfusion. The study is limited by the short follow up and small number of patients. CONCLUSIONS: CEUS examination showed a reduction of microcirculation in the treated area immediately after the treatment and 24 hours later. The combination of CEUS and image fusion seems to be helpful for detecting the PCa target lesion and monitor the success of HIFU ablation treatment. Evidence for image findings after HIFU-therapy are rare. Further studies on this topic are needed.

[Stricture of the vesicourethral anastomosis after radical prostatectomy]. / Die Striktur der vesikourethralen Anastomose nach radikaler Prostatektomie.

BACKGROUND: The development of a stricture of the vesicourethral anastomosis is a serious complication after radical prostatectomy. Strictures occur in 5-8% of patients after radical prostatectomy. SYMPTOMS: Usually the clinical symptoms include an irritative and obstructive component similar to benign prostatic hyperplasia. In rare cases, patients suffer from partial or complete stress incontinence as a result of the anastomotic stricture. DIAGNOSTICS: The diagnostic workup is similar to the procedure for urethral strictures. In addition to uroflowmetry, a cystourethrogram (CUG) or, if necessary, a micturating cystourethrogram (MCU) can be performed. A urethrocystoscopy can be performed to ensure the diagnosis. THERAPY: In most cases, endoscopic procedures were performed for treatment. Beside a transurethral dilation of the stricture or the Sachse urethrotomy, the most common procedure is transurethral resection to treat the stricture. However, all procedures are associated with a high recurrence rate. In recurrent strictures, open surgical procedures, usually a perineal reanastomosis, should performed early. CONCLUSION: Endourological procedures like transurethral resection are a good treatment option, but due to the high recurrence rates, open surgical procedures should be discussed and if necessary should be performed early.

Risks and benefits of pelvic lymphadenectomy in octogenarians undergoing radical cystectomy due to urothelial carcinoma of the bladder.

OBJECTIVES: According to current guidelines, radical cystectomy (RC) should be combined with an extended pelvic lymphadenectomy (PLND) as therapeutic and staging instrument. Objective of this study was to analyze the influence of PLND on survival rates and complication rates in a selected group of elderly patients with a minimum age of 80 years. MATERIALS AND METHODS: In this single-center retrospective analysis, we evaluated 102 patients who underwent RC due to UCB from 2004 to 2015 at our institution. In 74 patients (73%), RC was combined with PLND; in 28 cases (27%), RC was performed without PLND. Impact of PLND on cancer specific survival (CSS), overall survival (OS) and progression-free survival (PFS) was analyzed using log-rank test and COX regression model. RESULTS: In univariate analysis of the data, we were not able to show a significant impact of PLND on CSS (p = 0.606), OS (p = 0.979) or PFS (p = 0.883). Also in multivariate analysis of the data, we were not able to identify PLND as an independent prognostic parameter on survival rates of patients undergoing RC, neither for CSS (p = 0.912) nor OS (p = 0.618) or PFS (p = 0.900). CONCLUSIONS: Our small and single-center study was not able to demonstrate a significant independent influence of PLND on CSS, OS and PFS in octogenarians undergoing RC due to UCB. There is no doubt that RC should usually be combined with PLND, but the results of this small data set with a selected patient cohort indicate that RC without PLND might be an option in selected cases of elderly patients.

[Urinary tract infections in children]. / Harnwegsinfekte bei Kindern.

Urinary tract infections (UTI) are the most common bacterial infections in children. The symptoms are not very specific and range from abdominal pain, poor feeding to nocturnal urinary incontinence. The technique of collecting urine plays an important role for securing the diagnosis. The best way to obtain urine in non-toilet-trained children is catheterization or suprapubic bladder aspiration. In toilet-trained children midstream urine is an acceptable alternative after cleaning the foreskin or labia. In the case of an infection a prompt empirical antibiotic therapy is necessary to reduce the risk of parenchymal scarring of the kidneys. There are different approaches to diagnose vesicoureteral reflux in different countries. The commonly used standard approach in Germany is voiding cystourethrography. In the case of reflux dimercaptosuccinic acid (DMSA) scintigraphy should be performed additionally to exclude renal scarring (bottom-up approach).

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

BACKGROUND: Prostate cancer (PCa) is the most common cancer in men, which is increasingly diagnosed at a localized stage due to the widespread use of PSA (prostate-specific antigen)-screening. METHOD: Traditionally, definite treatment options for PCa include radical prostatectomy, external beam radiotherapy, or brachytherapy. However, treatment-related side effects such as urinary incontinence and erectile dysfunction are common. Alternatively, national and international guidelines recommend active surveillance (AS) as a treatment option for low-risk PCa. Organ-preserving surgery is commonly used in other organs, such as organ-conserving surgery for breast cancer. Focal therapy (FT) for PCa may close the gap between radical treatment options and active surveillance while reducing side effects. AIM: This article highlights the current therapy options for FT in Germany including their limitations and perspectives. Currently, different therapy options are available for FT in PCa. However, the use of FT is still embedded in clinical trials and has not been approved for routine use yet. Initial results seem to be promising, but most studies are currently enrolling or have not been published yet.

Impact of preoperative hemoglobin and CRP levels on cancer-specific survival in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder: results of a single-center study.

PURPOSE: Different blood parameters have shown to be associated with patient's oncological outcome. There is only limited knowledge about the prognostic relevance of routine blood parameters in patients undergoing radical cystectomy for transitional cell carcinoma (TCC). Therefore, we retrospectively analyzed the influence of preoperative C-reactive protein (CRP) and hemoglobin (Hb) levels on overall survival (OS) and cancer-specific survival (CSS). MATERIALS AND METHODS: Preoperative CRP and Hb levels were available in 664 patients who underwent RC due to TCC from 2004 to 2013 at our institution. More men than women (77 vs. 23 %) underwent surgery with a median age of 70 years (35-97). Median follow-up time was 24 months (max. 108). Outcome was analyzed using Kaplan-Meier method, log-rank test, and Cox regression models. RESULTS: Median CRP level was 0.5 mg/dl (0.1-28.3), and median Hb level was 13.4 g/dl (6.7-17.9). Patients with CRP value above the median died significantly earlier due to their disease than those with CRP below the median (median CSS 19 vs. 70 months; p < 0.001). Patients with preoperative Hb level below the median had significantly worse outcome than those with Hb level above the median (median CSS 25 vs. 78 months; p < 0.001). In multivariate analysis, CRP and Hb levels were independent prognostic parameters regarding CSS/OS (CRP p = 0.016/p = 0.004; Hb p = 0.006/p = 0.004, respectively). CONCLUSIONS: In our single-center study, preoperative CRP and Hb levels were found to be independent prognostic factors, indicating impaired outcome in patients undergoing RC for TCC. These findings could be used for individual risk stratification and optimization of therapeutic strategies.

[Vesico-ureteral reflux: Diagnosis and treatment recommendations]. / Vesikoureteraler Reflux : Diagnose und Therapieempfehlungen.

BACKGROUND: Vesico-ureteral reflux (VUR) is one of the most common urologic diseases in childhood. About every third child that presents with a urinary tract infection (UTI) has urinary reflux to the ureter or kidney. Demonstration of a backflow of urine into the ureters or kidneys proves vesicoureteral reflux. In unclear cases, a positioned instillation of contrast agent (PIC) cystogram might be performed and is able to prove vesico-ureteral reflux. OBJECTIVES: Since low-grade VUR has a high probability of maturation and self-limitation, infants with VUR should be given prophylactic antibiotics during their first year of life, reevaluating the status of VUR after 12 months. The aim of any treatment is to prevent renal damage. THERAPY: The individual risk of renal scarring is decisive for the choice of adequate therapy. This risk is mainly dependent on reflux grade, age, and gender of the child as well as parental therapy adherence. In principle, therapeutic options include conservative as well as endoscopic or open surgical antireflux therapies. CONCLUSION: Decisions on treatment should be made individually with parents taking into account all the findings available.