Detecting and Locating the Site of Local Relapse Using 18F-PSMA-1007 Imaging After Primary Treatment of 135 Prostate Cancer Patients-Potential Impact on PSMA-Guided Radiation Therapy.

PURPOSE: Due to limited imaging options, the visualization of a local relapse of prostate cancer used to pose a considerable challenge. However, since the integration of 18F-PSMA-1007-PET/CT into the clinic, a relapsed tumor can now easily be detected by hybrid imaging. The present study aimed to evaluate and map the allocate relapse in a large cohort of prostate cancer patients focusing on individual patient management conclusions for radiation therapy. PROCEDURES: The current study included 135 men with prostate cancer after primary treatment who underwent 18F-PSMA-1007-PET/CT due to biochemical relapse detecting a local relapse. Imaging data were reassessed and analyzed with regard to relapse locations. For the correlation of tumor foci with clinical data, we used binary logistic regression models as well as the Kruskal-Wallis test and Mann-Whitney test. RESULTS: In total, 69.6% of all patients (mean age: 65 years) underwent prostatectomy while 30.4% underwent radiation therapy. PET imaging detected most frequently a unifocal relapse (72.6%). There was a statistically significantly higher rate of ipsilateral cases among the relapsed tumors. Comparing both treatment approaches, tumors relapsed most commonly within the posterior region after surgery and transition/peripheral zone after radiation therapy, respectively. CONCLUSIONS: The present study confirms that 18F-PSMA-1007-PET/CT is highly suitable for the localization and allocation of a local relapse in patients with prostate cancer. The data enable further optimizing dose prescriptions and target volume delineations of radiation therapy in the future.

Magnetic resonance imaging-guided transurethral ultrasound ablation of prostate tissue in patients with localized prostate cancer: single-center evaluation of 6-month treatment safety and functional outcomes of intensified treatment parameters.

OBJECTIVES: To evaluate the effect of intensified treatment parameters on safety, functional outcomes, and PSA after MR-Guided Transurethral Ultrasound Ablation (TULSA) of prostatic tissue. PATIENTS AND METHODS: Baseline and 6-month follow-up data were collected for a single-center cohort of the multicenter Phase I (n = 14/30 at 3 sites) and Pivotal (n = 15/115 at 13 sites) trials of TULSA in men with localized prostate cancer. The Pivotal study used intensified treatment parameters (increased temperature and spatial extent of ablation coverage). The reporting site recruited the most patients to both trials, minimizing the influence of physician experience on this comparison of adverse events, urinary symptoms, continence, and erectile function between subgroups of both studies. RESULTS: For Phase I and TACT patients, median age was 71.0 and 67.0 years, prostate volume 41.0 and 44.5 ml, and PSA 6.7 and 6.7 ng/ml, respectively. All 14 Phase I patients had low-risk prostate cancer, whereas 7 of 15 TACT patients had intermediate-risk disease. Baseline IIEF, IPSS, quality of life, and pad use were similar between groups. Pad use at 1 month and quality of life at 3 months favored Phase I patients. At 6 months, there were no significant differences in functional outcomes or adverse events. CONCLUSION: TULSA demonstrated acceptable clinical safety in Phase I trial. Intensified treatment parameters in the TACT Pivotal trial increased ablation coverage from 90 to 98% of the prostate without affecting 6-month adverse events or functional outcomes. Long-term follow-up and 12-month biopsies are needed to evaluate oncological safety.

Twelve-month prostate volume reduction after MRI-guided transurethral ultrasound ablation of the prostate.

PURPOSE: To quantitatively assess 12-month prostate volume (PV) reduction based on T2-weighted MRI and immediate post-treatment contrast-enhanced MRI non-perfused volume (NPV), and to compare measurements with predictions of acute and delayed ablation volumes based on MR-thermometry (MR-t), in a central radiology review of the Phase I clinical trial of MRI-guided transurethral ultrasound ablation (TULSA) in patients with localized prostate cancer. MATERIALS AND METHODS: Treatment day MRI and 12-month follow-up MRI and biopsy were available for central radiology review in 29 of 30 patients from the published institutional review board-approved, prospective, multi-centre, single-arm Phase I clinical trial of TULSA. Viable PV at 12 months was measured as the remaining PV on T2-weighted MRI, less 12-month NPV, scaled by the fraction of fibrosis in 12-month biopsy cores. Reduction of viable PV was compared to predictions based on the fraction of the prostate covered by the MR-t derived acute thermal ablation volume (ATAV, 55°C isotherm), delayed thermal ablation volume (DTAV, 240 cumulative equivalent minutes at 43°C thermal dose isocontour) and treatment-day NPV. We also report linear and volumetric comparisons between metrics. RESULTS: After TULSA, the median 12-month reduction in viable PV was 88%. DTAV predicted a reduction of 90%. Treatment day NPV predicted only 53% volume reduction, and underestimated ATAV and DTAV by 36% and 51%. CONCLUSION: Quantitative volumetry of the TULSA phase I MR and biopsy data identifies DTAV (240 CEM43 thermal dose boundary) as a useful predictor of viable prostate tissue reduction at 12 months. Immediate post-treatment NPV underestimates tissue ablation. KEY POINTS: • MRI-guided transurethral ultrasound ablation (TULSA) achieved an 88% reduction of viable prostate tissue volume at 12 months, in excellent agreement with expectation from thermal dose calculations. • Non-perfused volume on immediate post-treatment contrast-enhanced MRI represents only 64% of the acute thermal ablation volume (ATAV), and reports only 60% (53% instead of 88% achieved) of the reduction in viable prostate tissue volume at 12 months. • MR-thermometry-based predictions of 12-month prostate volume reduction based on 240 cumulative equivalent minute thermal dose volume are in excellent agreement with reduction in viable prostate tissue volume measured on pre- and 12-month post-treatment T2w-MRI.

Incidental appendectomy during robotic laparoscopic prostatectomy-safe and worth to perform?

PURPOSE: The purpose of this study is to investigate the safety and patients' benefit of incidental appendectomy during robot-assisted laparoscopic radical prostatectomy (RALRP). METHODS: Fifty-three patients, who had incidental appendectomy during RALRP between January 2012 and March 2014, were enrolled to this study. To evaluate the safety of the procedure, following parameters were evaluated: patient age, duration of surgery, perioperative complications (classified by Clavien-Dindo), time to bowel movement, and length of hospital stay. Furthermore, intraoperative visual appearance, location, and histopathological evaluation of the appendix were evaluated. Data was analyzed by descriptive statistics. RESULTS: Mean age of patients was 61 years, the average hospital stay 5 days. No perioperative complications occurred. The appendix was unsuspicious in 39 patients (73.6%); 14 patients (26.4%) had macroscopically signs of inflammation. Of the 53 resected appendixes, the histopathological evaluation showed 33 (62.2%) inconspicuous appendices, 11 (20.8%) post-inflammatory changes, 4 (7.5%) with chronical signs of inflammation and 3 (5.7%) with signs of acute inflammation. In 2 patients (3.8%), low-grade mucinous neoplasms were found in the specimens. CONCLUSIONS: Incidental appendectomy during RALRP is a feasible procedure. With regard to inflammation and neoplastic changes, incidental appendectomy can be considered for patients scheduled for robot-assisted prostate surgery.

A prospective randomized controlled trial for assessment of perineal hydrodissection technique for nervesparing robot assisted radical prostatectomy.

BACKGROUND: This study prospectively evaluated the safety and efficacy of perineal hydrodissection in robot assisted nervesparing prostatectomy. METHODS: Patients were randomized for perineal, ultrasound guided hydrodissection (HD) before radical prostatectomy and compared with standard treatment (ST). Follow-up was done every 3 months, including erectile function (IIEF5-score), reported grade of erection, ability for sexual intercourse, continence, PSA. RESULTS: 21 patients were enrolled to this prospective study, 10 for ST and 11 for HD. No significant differences in demographic and preoperative oncological data between both groups were identified. Blood loss and time for surgery did not differ significantly. HD resulted in 66% (4/6) rate of positive surgical margins (PSM) in pT3 tumors vs 50% in ST (1/2; P = 0.67). Follow-up revealed higher IIEF scores, better ability for sexual intercourse and early continence in HD. CONCLUSIONS: Erectile function after radical prostatectomy was improved by perineal hydrodissection in this proof of principal study. However, careful patient selection and further studies are needed as perineal hydrodissection could result in increased positive surgical margins in pT3a tumors.

[Level IV inferior vena cava tumor thrombus : A rare diagnosis in patients with renal cell carcinoma]. / Level-IV-Cavathrombus : Eine seltene Diagnose bei Patienten mit Nierenzellkarzinom.

Renal cell carcinoma in combination with a supradiaphragmatic tumor thrombus is a rare tumor entity. Radical surgery including nephrectomy and thrombectomy is still considered standard treatment. The extent of the tumor thrombus should be preoperatively evaluated by MRI and TEE. An interdisciplinary team is important for surgery planning and realization. Despite the known risks of an operation, a longer overall survival is achieved.

Quality of life and functional outcome after infravesical desobstruction and HIFU treatment for localized prostate cancer.

BACKGROUND: To evaluate quality of life, functional and oncological outcome after infravesical desobstruction and HIFU treatment for localized prostate cancer. METHODS: One hundred thirty-one patients, treated with TURP and HIFU in a single institution were followed up for oncological and functional outcome. Oncological outcome was quantified by biochemical recurrence free survival using the Stuttgart and Phoenix criteria. Quality of life was assessed by usage of standardized QLQ-C30 and QLQ-PR25 questionnaires. In addition, functional questionnaires such as IPSS and IIEF-5 were used. Complications were assessed by the Clavien-Dindo classification. RESULTS: One hundred thirty-one patients with a mean age of 72.8 years (SD: 6.0) underwent HIFU for prostate cancer (29.0% low risk, 58.8% intermediate risk, 12.2% high risk). PSA nadir was 0.6 ng/ml (SD: 1.2) after a mean of 4.6 months (SD: 5.7). Biochemical recurrence free survival defined by Stuttgart criteria was 73.7%, 84.4% and 62.5% for low-, intermediate- and high-risk patients after 22.2 months. Complications were grouped according to Clavien-Dindo and occurred in 10.7% (grade II) and 11.5% (grade IIIa) of cases. 35.1% of patients needed further treatment for bladder neck stricture. Regarding incontinence, 14.3%, 2.9% and 0% of patients had de novo urinary incontinence grade I°, II° and III° and 3.8% urge incontinence due to HIFU treatment. Patients were asked for the ability to have intercourse: 15.8%, 58.6% and 66.7% of patients after non-, onesided and bothsided nervesparing procedure were able to obtain sufficient erection for intercourse, respectively. Regarding quality of life, mean global health score according to QLQ-C30 was 69.4%. CONCLUSION: HIFU treatment for localized prostate cancer shows acceptable oncological safety. Quality of life after HIFU is better than in the general population and ranges within those of standard treatment options compared to literature. HIFU seems a safe valuable treatment alternative for patients not suitable for standard treatment.

Further reduction of disqualification rates by additional MRI-targeted biopsy with transperineal saturation biopsy compared with standard 12-core systematic biopsies for the selection of prostate cancer patients for active surveillance.

BACKGROUND: Active surveillance (AS) is commonly based on standard 10-12-core prostate biopsies, which misclassify ~50% of cases compared with radical prostatectomy. We assessed the value of multiparametric magnetic resonance imaging (mpMRI)-targeted transperineal fusion-biopsies in men under AS. METHODS: In all, 149 low-risk prostate cancer (PC) patients were included in AS between 2010 and 2015. Forty-five patients were initially diagnosed by combined 24-core systematic transperineal saturation biopsy (SB) and MRI/transurethral ultrasound (TRUS)-fusion targeted lesion biopsy (TB). A total of 104 patients first underwent 12-core TRUS-biopsy. All patients were followed-up by combined SB and TB for restratification after 1 and 2 years. All mpMRI examinations were analyzed using PIRADS. AS was performed according to PRIAS-criteria and a NIH-nomogram for AS-disqualification was investigated. AS-disqualification rates for men initially diagnosed by standard or fusion biopsy were compared using Kaplan-Meier estimates and log-rank tests. Differences in detection rates of the SB and TB components were evaluated with a paired-sample analysis. Regression analyses were performed to predict AS-disqualification. RESULTS: A total of, 48.1% of patients diagnosed by 12-core TRUS-biopsy were disqualified from AS based on the MRI/TRUS-fusion biopsy results. In the initial fusion-biopsy cohort, upgrading occurred significantly less frequently during 2-year follow-up (20%, P<0.001). TBs alone were significantly superior compared with SBs alone to detect Gleason-score-upgrading. NPV for Gleason-upgrading was 93.5% for PIRADS⩽2. PSA level, PSA density, NIH-nomogram, initial PIRADS score (P<0.001 each) and PIRADS-progression on consecutive MRI (P=0.007) were significant predictors of AS-disqualification. CONCLUSIONS: Standard TRUS-biopsies lead to significant underestimation of PC under AS. MRI/TRUS-fusion biopsies, and especially the TB component allow more reliable risk classification, leading to a significantly decreased chance of subsequent AS-disqualification. Cancer detection with mpMRI alone is not yet sensitive enough to omit SB on follow-up after initial 12-core TRUS-biopsy. After MRI/TRUS-fusion biopsy confirmed AS, it may be appropriate to biopsy only those men with suspected progression on MRI.

Predictive factors for immediate continence after radical prostatectomy.

PURPOSE: To identify predictive factors for immediate continence after radical prostatectomy. PATIENTS AND METHODS: A total of 1553 patients underwent radical prostatectomy in a single institution (670 RRP, 883 RARP), had complete perioperative data and follow-up for urinary continence and were included in this prospective analysis. Immediate continence was defined as no pad usage after catheter removal. Evaluated parameters included age, body mass index, ECOG performance status, erectile function, prostate volume, PSA, Gleason score, tumor stage and D'Amico risk groups, as well as surgical approach (RRP, RARP), surgeon volume, nerve-sparing, lymphadenectomy, blood transfusions and duration of catheterization. RESULTS: A total of 240 men (15.5 %) did not require any pads 1 day or later after removal of the transurethral catheter. Correlation of parameters with immediate continence revealed significance for age (p < 0.001), ECOG-score (p = 0.025), erectile function (p = 0.001), nerve-sparing (p = 0.022), Gleason score (p = 0.002) and surgeon volume (p ≤ 0.022). Multivariate analyses identified IIEF-score >21 (p = 0.031), ECOG (p < 0.05), bilateral nerve-sparing (p = 0.049), Gleason score <3 + 4 (p ≤ 0.028), less blood transfusion (p ≤ 0.044) and surgeon volume (p ≤ 0.042) as the remaining prognostic parameters for immediate continence after radical prostatectomy. The type of surgical approach (robotic vs. open radical prostatectomy) did not yield significant influence. CONCLUSION: Evaluating continence in a contemporary prospective cohort revealed 15.5 % of patients never requiring a pad postoperatively. Predictive parameters for immediate continence were erectile function, ECOG, bilateral nerve-sparing, less blood transfusion and Gleason score. Furthermore, the surgeon's experience but not his operative technique had a significant impact on immediate postoperative continence.

[Intratumoral heterogeneity in renal cell carcinoma. Molecular basis and translational implications]. / Intratumorale Heterogenität des Nierenzellkarzinoms. Molekulare Grundlagen und translationale Implikationen.

Advanced clear cell renal cell carcinoma is characterized by extensive intratumoral genomic heterogeneity and branched as well as convergent evolutionary traits with genomically different subclones evolving in parallel in the same tumor. Distinct driver mutations can be found in spatially separated subclones, which may hinder the development of novel targeted therapies. However, truncal mutations of the VHL tumor suppressor gene and chromosome 3p loss were ubiquitously detected and will hence continue to be a focus of future drug development. Nevertheless, genomic instability, enhanced tumor genome plasticity and intratumoral heterogeneity are likely to represent major challenges towards biomarker development and personalized patient care.

[Navigation in urological surgery: Possibilities and limits of current techniques]. / Navigierte urologische Chirurgie : Möglichkeiten und Grenzen aktueller Technik.

Surgical navigation describes the concept of real-time processing and presentation of preoperative and intraoperative data from different sources to intraoperatively provide surgeons with additional cognitive support. Imaging methods such as 3D ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT) and data from optical, electromagnetic or mechanical tracking methods are used. The resulting information of the navigation system will be presented by the means of visual methods. Mostly virtual reality or augmented reality visualization is used. There are different guidance systems for various disciplines introduced. Mostly it operates on rigid structures (bone, brain). For soft tissue navigation motion compensation and deformation detection are necessary. Therefore, marker-based tracking methods are used in several urological application examples; however, the systems are often still under development and have not yet arrived in the clinical routine.

[Structure of biobanks for urological research]. / Struktur von Biobanken für die urologische Forschung.

Biomedical research plays an important role in the development of novel diagnostic procedures, drugs and treatment strategies with regard to cancerous and chronic inflammatory diseases. Biobanks are essential tools in this process. The complex structures and benefits of biobanks are presented in this article.

[Management of prostate cancer in the elderly]. / Management des Prostatakarzinoms in hohem Alter.

The management of prostate cancer in elderly patients is a topic of controversial discussion. The current guidelines recommend diagnosis and treatment of prostate cancer only in patients with a life expectancy of more than 10 years. Especially in elderly patients pre-existing comorbidities play a crucial role in life expectancy. In clinical practice mostly patient age alone is considered for the treatment decision; however, a guideline-based therapy of prostate cancer should also be offered to elderly patients. The treatment decision should be based on patient general health status and the oncological risk. The patient individual health status can be determined on the basis of comorbidities present and patient nutritional and performance status. For an optimal therapy regime the oncological risk has to be considered in treatment decisions. The aim of this article is to give an overview of risk stratification and treatment options for localized and metastatic prostate cancer in elderly patients.

Endogenous BTG2 expression stimulates migration of bladder cancer cells and correlates with poor clinical prognosis for bladder cancer patients.

BACKGROUND: The B-cell translocation gene 2 (BTG2) is considered to act as a tumour-suppressor gene because of its antiproliferative and antimigratory activities. Higher levels of BTG2 expression in tumour cells have been linked to a better clinical outcome for several cancer entities. Here, we investigated the expression and function of BTG2 in bladder cancer. METHODS: The expression of BTG2 in bladder cancer cells was silenced by RNA interference. Cell motility was investigated by wound healing and Boyden chamber assays. The protein expression of BTG2 in bladder cancer was studied by immunohistochemistry. RESULTS: We observed that targeted suppression of BTG2 by RNA interference did not result in growth stimulation but led to a substantial inhibition of bladder cancer cell motility. Tissue microarray analyses of bladder cancer cystectomy specimens revealed that higher BTG2 expression levels within the tumours correlated strongly with a decreased cancer-specific survival for bladder cancer patients. CONCLUSION: These results indicate that endogenous BTG2 expression contributes to the migratory potential of bladder cancer cells. Moreover, high levels of BTG2 in bladder cancers are linked to decreased cancer-specific survival. These findings question the conception that BTG2 generally acts as a tumour suppressor and typically represents a favourable clinical marker for cancer patients.

[Conservative management of postoperative urinary incontinence in men]. / Konservative Therapie der postoperativen Harninkontinenz des Mannes.

Urinary incontinence in men most commonly occurs after radical prostatectomy. Of these patients, 3-23% remain incontinent a year after prostatectomy. Data on conservative therapy for postoperative incontinence is contradictory. Nonetheless, conservative treatment strategies must generally be attempted before any operative technique. Early pelvic floor muscle training with or without biofeedback therapy and duloxetine seem to have a positive effect on continence. Further randomised controlled studies are necessary to accurately assess other conservative therapeutic options such as extracorporeal magnetic innervation and electrical stimulation therapy.

[Infiltrating perineal and scrotal inflammation: rare cutaneous manifestation of familial Mediterranean fever or acne inversa?]. / Einschmelzende Entzündungen perineal und skrotal : Seltene kutane Manifestation bei Familiärem Mittelmeerfieber oder Acne inversa?

Familial Mediterranean fever (FMF) can present cutaneous symptoms. In the reported case, infiltrating perineal and scrotal inflammation were attributed to FMF and treated by systemic medication with colchicine. The poor outcome of this conservative approach and pathognomonic axillary dermatological findings allowed the diagnosis of acne inversa to be made. Knowledge of this clinical picture possibly including genital manifestations is crucial, as early excision of all affected regions is the therapy of choice that enables healing.