Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer.

BACKGROUND: The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN. PATIENTS AND METHODS: Patients received apalutamide (240 mg/day) or placebo plus ADT (1 : 1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation to rPFS (22.7 months' follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months' follow-up) in patients with or without confirmed PSA decline using a landmark analysis, the Kaplan-Meier method, and Cox proportional hazards model. RESULTS: One thousand and fifty-two patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients, respectively. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.25-0.48), rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44), and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P < 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment. CONCLUSIONS: Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.

Plasma tumor gene conversions after one cycle abiraterone acetate for metastatic castration-resistant prostate cancer: a biomarker analysis of a multicenter international trial.

BACKGROUND: Plasma tumor DNA fraction is prognostic in metastatic cancers. This could improve risk stratification before commencing a new treatment. We hypothesized that a second sample collected after one cycle of treatment could refine outcome prediction of patients identified as poor prognosis based on plasma DNA collected pre-treatment. PATIENTS AND METHODS: Plasma DNA [128 pre-treatment, 134 cycle 2 day 1 (C2D1), and 49 progression] from 151 chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC) patients in a phase II study of abiraterone acetate (NCT01867710) were subjected to custom targeted next-generation sequencing covering exons of these genes: TP53, AR, RB1, PTEN, PIK3CA, BRCA1, BRCA2, ATM, CDK12, CHEK2, FANCA HDAC2 and PALB2. We also captured 1500 pan-genome regions enriched for single nucleotide polymorphisms to allow detection of tumor DNA using the rolling B-allele method. We tested associations with overall survival (OS) and progression-free survival (PFS). RESULTS: Plasma tumor DNA detection was associated with shorter OS [hazard ratio (HR): 2.89, 95% confidence intervals (CI): 1.77-4.73, P ≤ 0.0001] and PFS (HR: 2.05; 95% CI: 1.36-3.11, P < 0.001). Using a multivariable model including plasma tumor DNA, patients who had a TP53, RB1 or PTEN gene alteration pre-treatment and at C2D1 had a significantly shorter OS than patients with no alteration at either time point (TP53: HR 7.13, 95% CI 2.37-21.47, P < 0.001; RB1: HR 6.24, 95% CI 1.97-19.73, P = 0.002; PTEN: HR 11.9, 95% CI 3.6-39.34, P < 0.001). Patients who were positive pre-treatment and converted to undetectable had no evidence of a difference in survival compared with those who were undetectable pre-treatment (P = 0.48, P = 0.43, P = 0.5, respectively). Progression samples harbored AR gain in all patients who had gain pre-treatment (9/49) and de novo AR somatic point mutations were detected in 8/49 patients. CONCLUSIONS: Plasma gene testing after one cycle treatment refines prognostication and could provide an early indication of treatment benefit.

The new ISUP 2014/WHO 2016 prostate cancer grade group system: first résumé 5 years after introduction and systemic review of the literature.

PURPOSE: To systematically and comprehensively review and summarize the most recent literature assessing the value of the new grading system introduced by the International Society of Urological Pathology (ISUP) in 2014 and accepted by the World Health Organization (WHO) in 2016. METHODS: A systematic literature search in the PubMed database was performed up to November 2018. Overall, 15 studies in the period from 2016 to 2018 evaluating the new grading system have been selected for evidence synthesis. RESULTS: The main goals of the new ISUP 2014/WHO 2016 grading system were to establish (I) a more accurate and simplified grade stratification, (II) less overtreatment of indolent prostate cancer as well as (III) an improved patient communication. The majority of the studies chose biochemical recurrence as an endpoint for evaluation and statistically assigns the new ISUP 2014/WHO 2016 grading system a higher prognostic accuracy than the former Gleason grading. However, in only a subset of studies it was clearly evident that the historical samples were not only re-grouped according to the new grade groups but also re-graded according to the new histomorphological 2014 ISUP criteria. CONCLUSIONS: The vast majority of the studies support an improved prognostic accuracy of the ISUP 2014/WHO 2016 grade groups and endorse its worldwide application.

Substantial utilization of Facebook, Twitter, YouTube, and Instagram in the prostate cancer community.

PURPOSE: To measure the usage rate of social media (SoMe) resources in the prostate cancer community, we performed a comprehensive quantitative and qualitative assessment of SoMe activity on the topic of PCa on the four most frequented platforms. METHODS: We scanned the SoMe platforms Facebook, Twitter, YouTube, and Instagram for "prostate cancer" as a cross-sectional analysis or during a defined time period. Sources were included if their communication centered on PCa by title and content. We assessed activity measurements for each SoMe source and classified the sources into six functional categories. RESULTS: We identified 99 PCa-related Facebook groups that amassed 31,262 members and 90 Facebook pages with 283,996 "likes". On YouTube, we found 536 PCa videos accounting for 43,966,634 views, 52,655 likes, 8597 dislikes, and 12,393 comments. During a 1-year time period, 32,537 users generated 110,971 tweets on #ProstateCancer on Twitter, providing over 544 million impressions. During a 1-month time period, 638 contributors posted 1081 posts on Instagram, generating over 22,000 likes and 4,748,159 impressions. Among six functional categories, general information/support dominated the SoMe landscape on all SoMe platforms. CONCLUSION: SoMe activity on the topic of PCa on the four most frequented platforms is high. Facebook groups, YouTube videos, and Twitter tweets are mainly used for giving general information on PCa and education. High SoMe utilization in the PCa community underlines its future role for communication of PCa.

Perception of cure in prostate cancer: human-led and artificial intelligence-assisted landscape review and linguistic analysis of literature, social media and policy documents.

BACKGROUND: Understanding stakeholders' perception of cure in prostate cancer (PC) is essential to preparing for effective communication about emerging treatments with curative intent. This study used artificial intelligence (AI) for landscape review and linguistic analysis of definition, context and value of cure among stakeholders in PC. MATERIALS AND METHODS: Subject-matter experts (SMEs) selected cure-related key words using Elicit, a semantic literature search engine, and extracted hits containing the key words from Medline, Sermo and Overton, representing academic researchers, health care providers (HCPs) and policymakers, respectively. NetBase Quid, a social media analytics and natural language processing tool, was used to carry out key word searches in social media (representing the general public). NetBase Quid analysed linguistics of key word-specific hit sets for key word count, geolocation and sentiments. SMEs qualitatively summarised key word-specific insights. Contextual terms frequently occurring with key words were identified and quantified. RESULTS: SMEs identified seven key words applicable to PC (number of acquired hits) across four platforms: Cure (12429), Survivor (6063), Remission (1904), Survivorship (1179), Curative intent (432), No evidence of disease (381) and Complete remission (83). Most commonly used key words were Cure by the general public and HCPs (11815 and 224 hits), Survivorship by academic researchers and Survivor by policymakers (378 hits each). All stakeholders discussed Cure and cure-related key words primarily in early-stage PC and associated them with positive sentiments. All stakeholders defined cure differently but communicated about it in relation to disease measurements (e.g. prostate-specific antigen) or surgery. Stakeholders preferred different terms when discussing cure in PC: Cure (academic researchers), Cure rates (HCPs), Potential cure and Survivor/Survivorship (policymakers) and Cure and Survivor (general public). CONCLUSION: This human-led, AI-assisted large-scale qualitative language-based research revealed that cure was commonly discussed by academic researchers, HCPs, policymakers and the general public, especially in early-stage PC. Stakeholders defined and contextualised cure in their communications differently and associated it with positive value.

Hsa-mir-124-3 CpG island methylation is associated with advanced tumours and disease recurrence of patients with clear cell renal cell carcinoma.

BACKGROUND: Whether methylation of the microRNA (mir)-124-3 CpG island is of relevance for the clinical course of a solid cancer and whether it shows association with clinicopathology or survival of patients with renal cell cancer (RCC) is not known as yet. METHODS: In a cross-sectional study, relative methylation of mir-124-3 was measured in 111 RCC samples and 77 paired normal appearing tissues using quantitative methyl-specific PCR. Results were statistically compared with tumour histology, clinicopathological parameters and disease recurrence. RESULTS: We found tumour-specific hypermethylation of mir-124-3 in samples of RCCs with clear cell histology (ccRCC) compared with paired normal appearing tissues (P<0.0001). Methylation was significantly increased in tumours with state of advanced disease (P<0.0001). Higher relative methylation was associated with worse recurrence-free survival in both univariate (hazard ratio=9.37; P=0.0005) as well as bivariate Cox regression analyses considering age, sex, diameter of tumours and state of advanced disease, metastasis and lymph node metastases as covariates (hazard ratios=5.9-18.2; P-values of 0.0003-0.008). CONCLUSION: We identified mir-124-3 CpG islands (CGI) methylation as a relevant epigenetic mark for ccRCC thus underlining the need for functional studies of potentially affected signalling pathways in kidney tumour models. Methylation of mir-124-3 is suggested as an independent prognosticator for ccRCC.

The use of mannitol in partial and live donor nephrectomy: an international survey.

PURPOSE: Animal studies have shown the potential benefits of mannitol as renoprotective during warm ischemia; it may have antioxidant and anti-inflammatory properties and is sometimes used during partial nephrectomy (PN) and live donor nephrectomy (LDN). Despite this, a prospective study on mannitol has never been performed. The aim of this study is to document patterns of mannitol use during PN and LDN. MATERIALS AND METHODS: A survey on the use of mannitol during PN and LDN was sent to 92 high surgical volume urological centers. Questions included use of mannitol, indications for use, physician responsible for administration, dosage, timing and other renoprotective measures. RESULTS: Mannitol was used in 78 and 64 % of centers performing PN and LDN, respectively. The indication for use was as antioxidant (21 %), as diuretic (5 %) and as a combination of the two (74 %). For PN, the most common dosages were 12.5 g (30 %) and 25 g (49 %). For LDN, the most common doses were 12.5 g (36.3 %) and 25 g (63.7 %). Overall, 83 % of centers utilized mannitol, and two (percent or centers??) utilized furosemide for renoprotection. CONCLUSIONS: A large majority of high-volume centers performing PN and LDN use mannitol for renoprotection. Since there are no data proving its value nor standardized indication and usage, this survey may provide information for a randomized prospective study.

Oncological outcome of primary versus secondary muscle-invasive bladder cancer is comparable after radical cystectomy.

BACKGROUND: High-risk non-muscle-invasive bladder cancer (NMIBC) progressing to muscle-invasive bladder cancer (MIBC) is associated with adverse tumour biology. It is unclear, however, whether outcome of NMIBC progressing to MIBC is adverse compared to primary MIBC and whether NMIBC of higher risk of progression to MIBC is adverse compared to NMIBC of lower risk. OBJECTIVE: Our objective was to assess cancer-specific survival (CSS) following radical cystectomy (RC) for primary MIBC and for NMIBC progressing to MIBC in dependence of EORTC risk score. MATERIALS AND METHODS: Clinical and histopathological characteristics and CSS of 150 patients were assessed. Secondary MIBCs were stratified by EORTC risk score at the last transurethral resection of bladder tumour for NMIBC. RESULTS: CSS did not differ significantly between primary and secondary MIBC (p = 0.521). Secondary MIBC with high EORTC score had significantly shorter CSS compared to secondary MIBC with intermediate EORTC score (p = 0.029). In multivariable analysis, pathological tumour stage (HR = 3.77; p = 0.020) and lymph node stage (HR = 2.34; p = 0.022) were significantly correlated with CSS. CONCLUSION: While the outcome of secondary MIBC is not generally adverse compared to primary MIBC, the EORTC risk score not only reflects high risk of progression of NMIBC to MIBC, but also worse outcome following RC for secondary MIBC. Timely RC should thus be debated in high-risk NMIBC.

Fluorescence-guided laser lithotripsy: Estimation of the potential effectiveness and safety increase based on first clinical data.

In clinically approved laser lithotripsy systems, there is no automatic monitoring of fiber position to date. We investigated whether detecting stone autofluorescence, excited by a green aiming beam, is possible via the fiber during fragmentation by continuously recording the fluorescence signal in 12 ureterosopic lithotripsy procedures. We estimated which threshold the fluorescence signal's amplitude exceeds before laser pulses with visible stone removal by retrospective inspection of the endoscope's video data. For all procedures, blocking the laser when the fluorescence amplitude is below a threshold corresponding to the signal's baseline plus its range (maximum-minimum value) would have been appropriate to suppress ineffective pulses-the energy input could have been reduced by a mean of 14% (1%-29%) without changing the operation time. Ablation of the PTFE coating of the guidewire could have been prevented three times and cutting of a wire of the retrieval basket two times.

Kidney-specific cadherin correlates with the ontogenetic origin of renal cell carcinoma subtypes: an indicator of a malignant potential?

INTRODUCTION AND OBJECTIVES: To evaluate retrospectively kidney-specific cadherin (Ksp-cad) expression in renal cell carcinoma (RCC) subtypes and oncocytoma in correlation with its ontogenetic origin of distal and proximal tubules and to correlate Ksp-cad expression with tumour characteristics. MATERIALS AND METHODS: Membranous and cytoplasmic expression of Ksp-cad was determined in 40 clear cell (ccRCC), 25 papillary (pRCC), 19 chromophobe carcinomas (chRCC), 27 oncocytomas (oncocytomas) (n = 111) and 32 benign kidney parenchyma specimens separated in distal tubules (DT) and proximal tubules (PT) by immunohistochemistry using tissue microarray technique. Staining intensity was quantified as a score ranging from 0 to 12. Comparison of data and correlation with tumour characteristics were done by Wilcoxon/Kruskal-Wallis tests (post hoc Tukey-Kramer analysis). RESULTS: In benign renal tissue, membranous and cytoplasmic expression of Ksp-cad in the DT was significantly higher than that in the PT (12.0 ± 0 vs. 5.2 ± 0.3 and 6.3 ± 0.5 vs. 0.0 ± 0.0, respectively; (P < 0.05)). Membranous KSP-cad expression was significantly higher in chRCC (5.2 ± 0.8) and oncocytomas (3.7 ± 0.4) than that in ccRCC (0.8 ± 0.2) and pRCC (1.4 ± 0.4; P < 0.05), while expression between oncocytomas and chRCC did not differ significantly. In RCC, Ksp-cad expression was significantly associated with higher T stage and the occurrence of synchronous metastasis (P < 0.05). Higher N stages and grading tended to correlate with a lower Ksp-cad expression. CONCLUSIONS: In this cohort, the origin of tumour subtypes-chRCC and oncocytomas develop from DT and ccRCC and pRCC from PT cells-is mirrored by the respective Ksp-cad expression. This raises the question whether DT-derived tumours have a less malignant potential than PT-derived tumours.

Akt signalling parameters are different in oncocytomas compared to renal cell carcinoma.

PURPOSE: Renal oncocytomas are assigned as benign tumours, and their detailed molecular mechanism is poorly characterised. Activation of the PKB/Akt pathway is assumed to contribute to the pathogenesis and progression of malignant disease. For oncocytomas, hardly any data are available for Akt signalling parameters. Aim of the present work was to determine the alterations of Akt parameters PTEN, phosphorylated Akt (p-Akt) and p27(Kip1) in oncocytoma to better understand the dedifferentiation of renal tumours. METHODS: By tissue microarray analysis 15 oncocytoma, 18 clear cell renal cell carcinoma (ccRCC) and the corresponding benign tissue were investigated. Significant expression differences between PTEN, p-Akt and p27(Kip1) were determined by immunohistochemistry using One-way ANOVA with all pairs Tukey-Kramer as post hoc analyses. To investigate Akt parameter interactions in the oncocytoma, linear regression analyses were performed. RESULTS: Expression of all proteins was significantly different between the groups and in all groups the lowest for oncocytoma: PTEN: 32.9 ± 13.0 versus 75.5 ± 8.0 versus 123.7 ± 8.8; p < 0.001 for oncocytoma, benign parenchyma and ccRCC and 2.7 ± 1.2 versus 40.8 ± 9.5 versus 143.6 ± 12.2; p < 0.001 for p27(Kip1). p-Akt expression was significantly different between oncocytoma and ccRCC (67.3 ± 15.7 vs. 144.0 ± 26.6; p < 0.05). CONCLUSION: All three investigated parameters were the lowest in oncocytoma when compared to ccRCC. Expression of PTEN and p27(Kip1) seems to be exceedingly associated with malignant conditions of ccRCC. These findings might contribute to the understanding of tumorous signalling of the PKB/Akt axis in renal tumours.

Waterjet hydrodissection: first experiences and short-term outcomes of a novel approach to bladder tumor resection.

INTRODUCTION: TURB is the standard approach to bladder tumors but suffers from several disadvantages. Waterjet hydrodissection is a new technology for removing superficial tumors in the GI tract promising to preserve the histological structures of biopsy specimens with favorable long-term results as recent studies have shown. The aim of this study was to show the feasibility and applicability of waterjet hydrodissection for removing papillary superficial bladder tumors. MATERIALS AND METHODS: In five patients diagnosed with superficial papillary bladder tumor, transurethral submucosal dissection was conducted using the T-type I-Jet HybridKnife (Erbe, Tuebingen). The resection edges were labeled by means of electrical coagulation with the HybridKnife. Subsequently, a submucosal fluid cushion specific to the tissue layer was formed by the waterjet implementation function of the HybridKnife, thereby elevating the tumorous tissue. The tumor was endoscopically extracted with a retrieval bag. Biopsy specimens of the tumor edges and base were subsequently collected. RESULTS: All tumors could be resected en bloc, and the lamina propria was intact in all specimens, allowing the pathologist to distinguish between superficial and invasive tumors. Pathological analysis confirmed R0 resection in all samples. CONCLUSION: These initial results prove the feasibility of waterjet hydrodissection for removing bladder tumors. In contrast to conventional TURB, this new technique allows the pathologist to assess the entire lamina propria and the resection edges due to the en-bloc resection and to determine invasiveness as well as R0 versus R1 resection. These first results are promising, long-term oncological follow-up, and prospective randomized surveys investigating the recurrence rate have to be evaluated.

Response of renal lesions during systemic treatment with sunitinib in patients with metastatic renal cell carcinoma: a single center experience with 14 patients.

PURPOSE: The tyrosine kinase inhibitor (TKI) sunitinib induces partial remissions (PR) in a substantial proportion of patients with metastatic renal cell carcinoma (mRCC). Only little is known about the activity of sunitinib in renal lesions in patients with metastatic disease, as most patients with synchronous metastases receive palliative nephrectomy. METHODS: Fourteen patients with clear cell mRCC with renal lesions and sunitinib therapy (50 mg OD, 4/2 scheme) were retrieved retrospectively from clinic records. Tumor assessment consisted of CT scans at least every two cycles, analyzed according to RECIST. In 5 of 14 patients, renal tumors were considered as the primary tumor, while the remaining patients had kidney metastases. In total, 65 target lesions were evaluated. RESULTS: The median progression-free survival (PFS) of sunitinib was 8.7 months (range: 2.7-40.2). Median overall survival (OS) from initiation of TKI therapy was 26 months (range: 3-55). Best response according to RECIST consisted of partial remission (PR) in 4 patients, stable disease (SD) in 7 patients, a complete remission (CR) in 1 patient, and 2 patients with progressive disease (PD). Analyzing the response of renal lesions only, 1 patient had PD, 8 patients had SD, 4 patients had PR, and 1 had a CR. Palliative nephrectomy was performed after two courses of sunitinib in 2 patients. CONCLUSIONS: In our cohort, similar responses of renal tumors and peripheral metastases were achieved with sunitinib treatment. Our results support the use of sunitinib to control renal tumor lesions in metastatic patients.

[A retrospective comparison of robotic assisted and conventional laparoscopic pyeloplasty in two centres]. / Retrospektiver Vergleich der roboterassistierten und der laparoskopischen Pyeloplastik an zwei Zentren.

PURPOSE: The aim of this retrospective study was to compare our initial experience with robotic assisted laparoscopic pyeloplasty (R-LPP) with the conventional laparoscopic method (C-LPP). MATERIALS AND METHODS: In the defined period from May 2015 to September 2019, a total of 76 renal pelvic surgeries were performed at two different university clinics. In all, 63 patients who received either L­NBP (n = 27) or R­NBP (n = 36) were considered for data analysis. RESULTS: The median follow-up for C­LPP and R­LPP was 22.5 and 12.7 months, respectively. The statistical analysis of the two groups revealed no statistically significant difference regarding age, body mass index, gender or affected side. The operating time was nonsignificantly shorter in the R­LPP group (180 ± 72 vs. 159 ± 54 min, p = 0.194). There were no statistically significant differences in postoperative pain, complications, average length of stay in hospital (7.48 ± 2.86 vs. 6.33 ± 2.04 days) or success rate. CONCLUSION: This study shows no significant reduction in operating time in the R­LPP group with an equal rate of complications. It could be shown that there is no disadvantage for the patients undergoing R­LPP directly after the implementation of a robotic system.

SAUL, a single-arm study of atezolizumab for chemotherapy-pretreated locally advanced or metastatic carcinoma of the urinary tract: outcomes by key baseline factors, PD-L1 expression and prior platinum therapy.

BACKGROUND: The impact of pretreatment factors on immune checkpoint inhibition in platinum-refractory advanced urothelial cancer (aUC) deserves further evaluation. The aim was to study the association of Bellmunt risk factors, time from last chemotherapy (TFLC), previous therapy and PD-L1 expression with atezolizumab efficacy in platinum-refractory aUC. PATIENTS AND METHODS: This was a post-hoc analysis of patients who had received prior cisplatin or carboplatin in the prospective, single-arm, phase IIIb SAUL study (NCT02928406). Patients were treated with 3-weekly atezolizumab 1200 mg intravenously. The primary outcome was overall survival (OS). Relationships were analysed using Cox regression and long-rank test. RESULTS: Of 997 patients in SAUL, 969 were eligible for this analysis. The number of Bellmunt risk factors was associated with OS (P < 0.001); median OS (mOS) for 0, 1 and 2-3 risk factors was 17.9, 8.9 and 3.3 months, respectively. Significant associations were also observed between OS and TFLC (P < 0.001), programmed death-ligand 1 (PD-L1) expression (P = 0.002), and prior perioperative chemotherapy (P = 0.013); mOS was 6.97 versus 11.63 months for TFLC ≤6 versus >6 months, 7.75 versus 11.6 months for PD-L1 expression on <1% of tumour-infiltrating immune cells (ICs) (IC0)/expression on 1% to <5% of tumour-infiltrating ICs (IC1) versus expression on ≥5% of tumour-infiltrating ICs (IC2/3) and 10.2 versus 7.8 months for prior versus no prior perioperative chemotherapy, respectively. The type of platinum compound and number of previous treatment lines were not associated with outcomes. CONCLUSIONS: Post-platinum atezolizumab is active in aUC, irrespective of previous platinum compound and lines of therapy. Bellmunt risk stratification, PD-L1 expression, TFLC and perioperative chemotherapy were identified as prognostic factors for OS with second-line atezolizumab, indicating the need for novel prognostic signatures for immunotherapy-treated patients with aUC.

[Treatment of metastatic, castration-resistant prostate cancer]. / Therapie des metastasierten kastrationsresistenten Prostatakarzinoms.

BACKGROUND: For many decades metastatic, castration-resistant prostate cancer (mCRPC) was thought to be treatment inaccessible. However, today, five drugs with significant life-prolonging effects are available in Germany, namely abiraterone, enzalutamide, docetaxel, cabazitaxel and radium-223. OBJECTIVE: The different treatment strategies in mCRPC are reviewed. MATERIALS AND METHODS: Landmark trials with supplementary information from Medline and abstracts of international congresses (ASCO; ASCO GU, ESMO) are summarized. RESULTS: The androgen receptor (AR)-targeting agents abiraterone and enzalutamide significantly prolong overall survival before and after docetaxel therapy. In addition, cabazitaxel can be applied secondary to docetaxel. Due to the low affinity of cabazitaxel to p­glycoprotein it remains active even if docetaxel has failed. The α­emitter radium-223 can be considered in third line therapy for symptomatic patients with bone limited disease only. In patients with castration resistance, a short prostate-specific antigen (PSA) doubling time but without metastases in conventional imaging apalutamide, darolutamide and enzalutamide significantly prolong metastasis-free survival. DISCUSSION: Prostate-specific membrane antigen (PSMA)-ligand therapy and novel targeting agents such as PARP inhibitors are promising new therapeutic modalities for mCRPC. Combination treatment strategies with immunotherapy are currently being evaluated in clinical trials. Based on the results of molecular analyses of tumor tissue as well as of circulating tumor cells and DNA, treatment of prostate cancer will be increasingly personalized in the future.

[Rate of thrombosis and bleeding after urological surgery under standardized anticoagulation]. / Thromboserate und Blutungen in der universitären operativen Urologie unter standardisierter Antikoagulation.

BACKGROUND: According to the current definition of the German guideline for prevention of venous thromboembolism, urological surgery includes a high number of high-risk patients. All patients undergoing urological surgery between 2012 and 2016 were analyzed with regard to complications (bleeding or thrombosis). MATERIALS AND METHODS: This study is a retrospective and monocentric cohort study. Included were all patients who underwent surgery between 2012 and 2016 at the Urological Department at the University Hospital of Luebeck. Information was collected relating to anticoagulation, patient-specific and surgery-specific risk factors, and complications. RESULTS: In all, 3609 surgeries were analyzed: 77.8% of patients received no medical prophylaxis, 10.2% received an aggregation inhibitor, and 8.5% synthetic, unfractionated or low molecular weight heparin. Heparin was administered to 80.4% of patients after surgery. During an average hospital stay of 4.5 days, 93.3% of the patients received no change in anticoagulation. Merely 0.8% of all patients suffered from clinical thomboembolic events within 28 days. In contrast the number of bleedings was higher with 20.3% (minor: 4.8%, major: 15.5%). CONCLUSION: We found a slight risk for postoperative thromboembolism (0.8%). The risk for postoperative bleeding in contrast was 20.3%, including 15.5% major bleedings. The results are discussed in relation to the current guidelines.

[The impact of the androgen receptor splice variant AR-V7 on the prognosis and treatment of advanced prostate cancer]. / Bedeutung der Androgenrezeptor-Spleißvariante AR-V7 für Prognose und Therapie des fortgeschrittenen Prostatakarzinoms.

A recently discovered mechanism enabling prostate cancer cells to escape the effects of endocrine therapies consists in the synthesis of C-terminally truncated, constitutively active androgen receptor (AR) splice variants (AR-V). Devoid of a functional C-terminal hormone/ligand binding domain, various AR-Vs are insensitive to therapies targeting the androgen/AR signalling axis. Preliminary studies suggest that AR-V7, the most common AR-V, is a promising predictive tumour marker and a relevant selection marker for the treatment of advanced prostate cancer. This review critically outlines recent advances in AR-V7 diagnostics and presents an overview of current AR-V7 targeted therapies.

[Reports of prostate needle biopsies-what pathologists provide and urologists want]. / Befundbericht zu Prostatastanzbiopsien ­ was Pathologen liefern und Urologen wollen.

BACKGROUND: The prostate biopsy report is key for risk stratification of prostate cancer patients and subsequent therapeutic decision-making. However, due to the inclusion of a multitude of additional parameters its interpretation is becoming more challenging. OBJECTIVES: We aimed to determine how urologists currently interpret prostate biopsy reports, in particular how they consider different histopathological parameters for therapy decision-making. MATERIALS AND METHODS: A survey was sent to all urology practices in Germany with the help of the BDU (Berufsverband der Deutschen Urologen e. V.). In total, there were 106 complete responses that could be included for further analyses. RESULTS: Most urologists consider the number of positive cores and relative tumor burden (%) per core as crucial for the assessment of tumor extension. In case of targeted biopsies, the majority of urologists prefers a separate statement of positive cores per random biopsy scheme and per region of interest, respectively. The core with the highest Gleason score is mostly the basis for therapy decision-making (versus the overall Gleason score). Proportion of Gleason 4 pattern also seems to be critical for prostate cancer management. Only half of the urologists demand reporting of the new ISUP/WHO (International Society of Urological Pathology/World Health Organization) grade groups. Additional parameters claimed are Ki67, prostate-specific membrane antigen status, presence of intraductal or neuroendocrine component of the tumor. CONCLUSIONS: Our survey shows that there is no standardized reporting for prostate biopsies and that the interpretation of prostate biopsy reports varies among urologists. Further studies and guideline recommendations are necessary to establish a standardized reporting scheme for prostate biopsies.