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Purpose Due to the tissue preserving approach of focal therapy (FT), local cancer relapse can occur. Uncertainty exists regarding triggers and outcome of salvage strategies. Methods Patients with biopsy-proven prostate cancer (PCa) after FT for localized PCa from 2011 to 2020 at eight tertiary referral hospitals in Germany that underwent salvage radical prostatectomy (S-RP), salvage radiotherapy (S-RT) or active surveillance (AS) were reported. Prostate specific antigen (PSA) changes, suspicious lesions on mpMRI and histopathological findings on biopsy were analyzed. A multivariable regression model was created for adverse pathological findings (APF) at S-RP specimen. Kaplan–Meier curves were generated to determine oncological outcomes. Results A total of 90 men were included. Cancer relapse after FT was detected at a median of 12 months (IQR 9–16). Of 50 men initially under AS 13 received S-RP or S-RT. In total, 44 men underwent S-RP and 13 S-RT. At cancer relapse 17 men (38.6%) in the S-RP group [S-RT n = 4 (30.8%); AS n = 3 (6%)] had ISUP > 2. APF (pT ≥ 3, ISUP ≥ 3, pN + or R1) were observed in 23 men (52.3%). A higher ISUP on biopsy was associated with APF [p = 0.006 (HR 2.32, 97.5% CI 1.35–4.59)] on univariable analysis. Progression-free survival was 80.4% after S-RP and 100% after S-RT at 3 years. Secondary therapy-free survival was 41.7% at 3 years in men undergoing AS. Metastasis-free survival was 80% at 5 years for the whole cohort. Conclusion With early detection of cancer relapse after FT S-RP and S-RT provide sufficient oncologic control at short to intermediate follow-up. After AS, a high secondary-therapy rate was observed.

Objective To assess the efficacy of irreversible electroporation (IRE) ablation of pT1a renal cell carcinoma (RCC) in the first prospective, monocentric phase 2a pilot ablate-and-resect study (Irreversible Electroporation of Kidney Tumors Before Partial Nephrectomy [IRENE] trial). It has been postulated that focal IRE can bring about complete ablation of soft-tissue tumors with protection of healthy peritumoral tissue and anatomic structures. Patients and Methods The first 7 study patients with biopsy-proven pT1a RCC (15-39 mm) underwent IRE. Percutaneous computed tomography-guided IRE was performed with electrocardiographic triggering under general anesthesia and deep muscle paralysis with 3-6 monopolar electrodes positioned within the renal tumor. Twenty-eight days later, the tumor region was completely resected to confirm tumor destruction pathologically. Individual results for these patients are displayed, described, and discussed. Results Technical feasibility was attained in all patients, but electrode placement and ablation were complex, with a mean overall procedure time of 129 minutes. There were no major complications. Partial kidney resection was performed in 5 patients, and radical nephrectomy was performed in 2 patients because of central tumor location and ablation areas. Resections revealed by tumor, node, and metastasis classification of the International Union for Cancer Control 2017 no residual tumor as complete ablation in 4 cases (ypT0V0N0Pn0R0) and microscopic residual tumor cells as incomplete ablation in the other 3 cases (ypT1aV0N0Pn0R1). Conclusion Renal percutaneous IRE appears to be a safe treatment for pT1a RCC but requires substantial procedural effort. Resection specimens of the ablation zone revealed a high rate of microscopic incomplete ablation 4 weeks after IRE. According to these initial study results, curative, kidney-sparing ablation of T1a RCC appears possible but needs technical improvement to ensure complete ablation.

Eine gut hundertjahrige Periode, in der die Vorsteherdruse nur als Ganzes betrachtet und behandelt wurde, geht gerade voruber. Eine hochauflosende Bildgebung liefert endlich tiefe Detailinformationen, neue Therapieformen konnen kleinste Ziele anvisieren. Dem lange bestehenden Patientenwunsch nach individueller „nichtinvasiver“ Diagnostik und Therapie von Prostataerkrankungen kann nun mit wirklich dazu passenden Konzepten geantwortet werden. Die klinische Verarbeitung und Anwendung der enormen Informationsfulle als individualisiertes Gesamtkonzept fur den Patienten erfordern allerdings ein interdisziplinar eng verzahntes Raderwerk, welches herkommliche Sprechstunden in jeder Hinsicht uberfordert. Es ist Zeit fur neue Konstrukte! Das Dienstleistungsprinzip einer einseitig gerichteten Befund- oder Therapieanforderung an den Urologen, Radiologen oder Strahlentherapeuten ist uberholt, diese interdisziplinaren Partner gehoren nun zu einem gleichrangigen „Managementteam Prostata“.

Purpose : Many virtual and augmented reality systems have been proposed to support renal interventions. This paper reviews such systems employed in the treatment of renal cell carcinoma and renal stones. Methods : A systematic literature search was performed. Inclusion criteria were virtual and augmented reality systems for radical or partial nephrectomy and renal stone treatment, excluding systems solely developed or evaluated for training purposes. Results : In total, 52 research papers were identified and analyzed. Most of the identified literature (87%) deals with systems for renal cell carcinoma treatment. About 44% of the systems have already been employed in clinical practice, but only 20% in studies with ten or more patients. Main challenges remaining for future research include the consideration of organ movement and deformation, human factor issues, and the conduction of large clinical studies. Conclusion : Augmented and virtual reality systems have the potential to improve safety and outcomes of renal interventions. In the last ten years, many technical advances have led to more sophisticated systems, which are already applied in clinical practice. Further research is required to cope with current limitations of virtual and augmented reality assistance in clinical environments.

The aim of the study was to establish the setup and workflow for delivering focal MRI-guided high-dose-rate (HDR) brachytherapy for prostate cancer (PCA) and to assess patient comfort and safety aspects of MRI-guided single-fraction HDR. Patients with histologically proven focal low- to intermediate-risk PCA with a single PIRADS 4/5 lesion were treated with percutaneous interstitial HDR brachytherapy in a single fraction with a minimum dose for the gross tumor volume of 20 Gy while sparing the organ at risk (OAR). Using a 3T-MRI, brachytherapy catheters were placed transgluteal in freehand technique. No antibiotic therapy or general analgesics were administered. Patient data, procedure time, patient discomfort, and complications were recorded. Quarterly PSA controls, biannual follow-up imaging, and annual re-biopsy were planned. So far, 9 patients were successfully treated and followed for 6 months. Mean intervention time was 34 min. Using the VAS scale, the pain reported for the intervention ranged from 2 to 3. Short-term follow-up showed no acute genitourinary or gastrointestinal toxicity so far. None of the patients displayed signs of infection. PSA levels in all patients decreased significantly. On follow up no residual PCA was detected treated region so far. PSA levels in all patients decreased significantly. On follow-up, no residual PCA was detected so far. MR-guided single-fraction focal HDR brachytherapy for localized PCA is feasible as well as safe for the individual patient. Catheters can be placed accurately and maximum therapeutic dose distribution can be restricted to the tumor. Countersigning the minimally invasive character of the procedure, no general anesthesia or antibiosis is necessary. • MR-guided focal HDR brachytherapy allows an accurate placement of catheters with maximum therapeutic dose distribution restricted to the tumor. • No major anesthesia or antibiosis is necessary emphasizing the minimal invasive character of the procedure. • Patients with low- and intermediate-risk prostate carcinoma in particular may benefit to halt disease progression whereas treatment-related morbidity is reduced compared with radical therapy.

Purpose To investigate focal therapy using High Intensity Focused Ultrasound (HIFU) for the treatment of localized prostate cancer (CaP), we analyzed the safety and complications of this procedure. Methods Patients (pts) eligible for this multicenter prospective cohort study suffered from low to intermediate risk localized CaP with no prior treatment. After tumor identification on multiparametric MRI and in prostate biopsy, the lesions were treated with HIFU observing a safety margin of 8 to 10 mm. Adverse events (AE) after 30 and 90 days, as well as the required interventions were assessed and stratified for treatment localizations. Results Of the 98 men included in the study in two European centers, 35 (35.7%) experienced AEs in the first 30 days after HIFU intervention with Clavien-Dindo grade ≤ II: 15 pts (15.3%) had a postoperative urinary tract infection and 26 pts (26.5%) a urinary retention. Four pts (4.1%) underwent subsequent intervention (Clavien-Dindo grade IIIa/b). The number of late postoperative complications occurring between 30 and 90 days after intervention was low (2.0%). The highest complication rate was associated with tumors located at the anterior base (50.0%). The inclusion of the urethra in the ablation zone led to AEs in 20 out of 41 cases (48.8%) and represented a significant risk factor for complications within 30 days (odds ratio = 2.53; 95% confidence interval: 1.08–5.96; P = 0.033). Conclusions Focal therapy of CaP lesions with a robotic HIFU-probe is safe and renders an acceptable rate of minor early AEs. The inclusion of the urethra in the ablation zone leads to an increase in early complications and should be avoided whenever possible.

Individualized and accurate segmentations of the prostate are essential for diagnosis as well as therapy planning in prostate cancer (PCa). Most of the previously proposed prostate segmentation approaches rely purely on axial MRI scans, which suffer from low out-of-plane resolution. We propose a method that makes use of sagittal and coronal MRI scans to improve the accuracy of segmentation. These scans are typically acquired as standard of care for PCa staging, but are generally ignored by the segmentation algorithms. Our method is based on a multi-stream 3D convolutional neural network for the automatic extraction of isotropic high resolution segmentations from MR images. We evaluated segmentation performance on an isotropic high resolution ground truth (n = 40 subjects). The results show that the use of multi-planar volumes for prostate segmentation leads to improved segmentation results not only for the whole prostate (92.1% Dice similarity coefficient), but also in apex and base regions.

Irreversible electroporation (IRE) is a new potential ablation modality for small renal masses. Animal experiments have shown preservation of the urine-collecting system (UCS). The purpose of this clinical study was to perform the first evaluation and comparison of IRE’s effects on the renal UCS by using urinary cytology, magnetic-resonance imaging, and resection histology in men after IRE of pT1a renal-cell carcinoma (RCC). Seven patients with biopsy-proven RCC pT1a cN0cM0 underwent IRE in a phase 2a pilot ablate-and-resect study (IRENE trial). A contrast-enhanced, diffusion-weighted MRI and urinary cytology was performed 1 day before and 2, 7, and 27 days after IRE. Twenty-eight days after IRE the tumour region was completely resected surgically. Technical feasibility was demonstrated in all patients. In all cases, MRI revealed complete coverage of the tumour area by the ablation zone with degenerative change. The urographic late venous MRI phase (urogram scans) demonstrated normal morphological appearances. Urine cytology showed a temporary vacuolisation of the cyto- and caryoplasmas after IRE. Whereas the urothelium showed signs of regeneration 28 days after IRE-ablation, the tumour and parenchyma below it showed necrosis and permanent tissue destruction. Renal percutaneous IRE appears to be a safe treatment for pT1a RCC. The preservation of the UCS with unaltered normal morphology as well as urothelial regeneration and a phenomenon (new in urinary cytology) of temporary degeneration with vacuolisation of detached transitional epithelium cells were demonstrated in this clinical pilot study.

Background: Docetaxel plus prednisone is a standard treatment for castration-resistant prostate cancer. Cyclophosphamide may be an effective combination partner. Methods: This randomised, multicentre, phase II trial compared the combination therapy of docetaxel plus prednisone plus cyclophosphamide with the standard therapy of docetaxel plus prednisone. Results: Thirty-three patients received six 3-week treatment cycles (in total 171 cycles). During treatment, an adequate decline in prostate-specific antigen was seen in both groups (p = 0.068) without between-group differences (p = 0.683). No relevant differences between within-group changes were observed for blood pressure, weight, pain score, laboratory variables or quality of life. There were no serious side effects apart from leucopenia requiring treatment (docetaxel + prednisone + cyclophosphamide arm) and no drug-related withdrawals; all three fatalities were considered to be cancer related. Conclusions: The oncological effectiveness and tolerability of docetaxel plus prednisone were supported; an additional effect of cyclophosphamide was not detected. However, the small number of patients and short observation period restrict the generalisability of the results.

INTRODUCTION: Lymph node involvement (LNI) in prostate cancer with a Gleason score (GS) 6 or less is very rare and some authors have concluded that pelvic lymph node dissection (PLND) can regularly be omitted if the GS of the needle biopsy (NB) specimen is ≤ 6. Objective of our study was to analyze data from a multicenter cohort regarding the incidence of LNI in GS ≤ 6 prostate cancer. METHODS: Data was obtained from the onlinedatabase www.prostata-ca.net. Descriptive statistics were calculated using SPSS 22. RESULTS: 9,511 Patients had been treated by RP and PLND in the years 1994 to 2015. While 3,513 (36.9%) were initially diagnosed with a GS ≤ 6 by NB, only 1,831 (19.3%) actually had a GS ≤ 6 in the RP specimen. Significant upgrading (GS ≤ 6 to GS ≥ 7) occurred in 1,984 (20.8%) of all cases. LNI was present in 944 cases (9.9%) overall. Prevalence of LNI in patients with a GS ≤ 6 in the NB specimen was 2.4% compared to 0.2% if the GS ≤ 6 was confirmed in the RP specimen. CONCLUSIONS: LNI in low grade prostate cancer is rare (3 cases, 0.2%). However, 81 patients with LNI showed a GS ≥ 7 at final diagnosis, but were initially graded as GS ≤ 6 in the NB specimen. Significant undergrading of the NB specimen was common and occurred in more than half of all patients with a GS ≤ 6 in the biopsy. Our study demonstrates that, especially outside of highly specialized centers, undergrading of NB specimen is still common and the malignant potential of some cancers is thus discovered only after RP and PLND. More reliable tools for pretreatment riskstratification are warranted. Treated by RP + PLND 9,511 Initial PSA: Median (Mean) ng/ml PSA > 10 ng/ml 103 missing 8.05 (12.31) 3,553 (37.8%) Clinical Stage: cT1 cT2 cT3/4 505 missing 5,300 (58.8%) 3,340 (37.1%) 366 (4.1%) Gleason score NB Gleason ≤ 6 Gleason 7 Gleason ≥ 8 3,513 (36.9%) 4,224 (44.4%) 1,774 (18.7%) Gleason score RP Gleason ≤ 6 Gleason 7 Gleason 8 1,831 (19.3%) 6,000 (63.1%) 1,680 (17.7%) Grade-shift NB-RPE No Grade-Shift Upgrading total Downgrading total Upgrading GS ≤ 6 to ≥ 7 5,525 (58.1%) 2,802 (29.5%) 1,184 (12.4%) 1,984 (20.8%) LNI No LNI LNI inconclusive 944 (9.9%) 8,399 (88.3%) 168 (1.7%) Pathological stage pT1 pT2 pT3/pT4 24 missing 16 (0,2%) 5,715 (60.2%) 3,756 (39.6%) Abstract ID: 15-2961 GS NB ≤ 6 Total 3,513 LNI 83 GS RP ≤ 6 GS RP = 7 GS RP ≥ 8 1,529 (43.5%) 1,822 (51.7%) 162 (4.6%) 2 (2.4%) 59 (71.1%) 22 (26.5%) Upgrading 2,110 (60.1%) 82 (98.8%) Downgrading 137 (3.9%) 1 (1.2%) Sign. Up. 1,984 (56.5%) 81 (97.6%) primary treatment cases: 18,311 no GS of RP: 3,455 no RP: 554 14,302 treated by RP and GS available no GS of NB available: 1,437 12,865 with GS of RP and NB available PLND inconclusive: 1,156 PLND: 9,515 implausible data: 4 9,511 cases for data analysis

Background: Patients with advanced renal cell cancer (RCC) have a poor prognosis not least because of resistance towards standard drugs (SoC). Recently, pronounced intratumoral heterogeneity (ITH) in RCC was shown. We were interested whether this ITH is a potential cause for treatment failure. We developed a large panel of patient-derived xenograft (PDX) models from RCC, including subsets of models from different regions of one individual tumor. The PDX models were evaluated for response to SoC. To better understand correlations between inter- and intratumoral heterogeneity and treatment response, tumor models were panel sequenced and expression profiled. Methods: Specimens from primary and metastatic RCCs were collected from consenting patients and transplanted into mice. Tumor engraftment was monitored for up to 4 months. Tumor sections were examined histopathologically to assess concordance between patient tumor and model and were stained for RCC specific markers (Pax2, Pax8, CD31, and RCC). Stable growing PDX were treated with SoC (sunitinib, sorafenib, bevacizumab and everolimus). Global gene expression was analyzed in primary tumors and PDX models using microarrays (Affymetrix). In addition, sequence variations (Illumina NGS cancer panel) and MET and TERT gene copy numbers were analyzed in PDX models. Results: A panel of 34 RCC PDX models was established from more than 200 patient samples. Among these, 13 models were derived from different tumor regions of three advanced tumors. Original patient tumor and PDX showed a very similar and characteristic RCC histopathology. Inter- and intratumoral heterogeneity was preserved for several passages. We treated all PDX with standard targeted drugs and observed response rates comparable to results from clinical trials. One out of 8 regions obtained from one aggressive RCC clearly differentiated in regard to its response to bevacizumab and sunitinib. Genomic analysis revealed that this region has differences in global gene expression and sequence variation pattern. Besides a common MET mutation an additional variation in the HRAS gene was detected. In the whole PDX set we found 34 sequence variations in 20 genes, e.g. ATM, MET, TP53 and VHL and copy number variations in the MET locus. Conclusion: We have shown that PDX derived from distinct regions within one individual tumor exhibit differences in targeted treatment response as well as in genetic profile. These differences and their correlation to their molecular heterogeneity is subject of ongoing investigations to explain failure in treatment response. The available panel of renal cancer PDX provides an excellent source for translational research and for preclinical testing of new drug candidates. Citation Format: Michael Becker, Burkhard Jandrig, Susanne Flechsig, Reiner Zeisig, Daniel Schindele, Martin Schostak, Christian Schmees, Annika Wulf-Goldenberg, Jörg Hennenlotter, Elke Schaeffeler, Matthias Schwab, Arnulf Stenzl, Jens Bedke, Jens Hoffmann. Intratumoral heterogeneity of renal cancer is related to differences in drug response and development of therapy resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1843. doi:10.1158/1538-7445.AM2017-1843

Introduction.Mondor's disease of the penis is an uncommon condition characterized by thrombosis or thrombophlebitis involving the superficial dorsal veins. An accompanied lymphangitis is discussed. There is typical self-limiting clinical course.Case Presentation.This paper firstly reports a secondary abscess formation of the preputial leaf two weeks after penile Mondor's disease and subcutaneous lymphangitis as complication of excessive sexual intercourse of a 44-year-old man. Sexual transmitted diseases could be excluded. Lesions healed up completely under abscess drainage, antibiotic, and anti-inflammatory medication.Conclusion.Previous reports in the literature include several entities of the penile Mondor's disease. Our patient is very unusual in that he presented with a secondary preputial abscess formation due to superficial thrombophlebitis, subcutaneous lymphangitis, and local bacterial colonisation. Abscess drainage plus antiphlogistic and antibiotic medication is the treatment of choice.