Cytoreductive nephrectomy in metastatic renal cell carcinoma.

BACKGROUND: Nephrectomy is the surgical removal of all or part of a kidney. When the aim of nephrectomy is to reduce tumor burden in people with established metastatic disease, the procedure is called cytoreductive nephrectomy (CN). CN is typically combined with systemic anticancer therapy (SACT). SACT can be initiated before or immediately after the operation or deferred until radiological signs of disease progression. The benefits and harms of CN are controversial. OBJECTIVES: To assess the effects of cytoreductive nephrectomy combined with systemic anticancer therapy versus systemic anticancer therapy alone or watchful waiting in newly diagnosed metastatic renal cell carcinoma. SEARCH METHODS: We performed a comprehensive search in the Cochrane Library, MEDLINE, Embase, Scopus, two trial registries, and other gray literature sources up to 1 March 2024. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated SACT and CN versus SACT alone or watchful waiting. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. Primary outcomes were time to death from any cause and quality of life. Secondary outcomes were time to disease progression, treatment response, treatment-related mortality, discontinuation due to adverse events, and serious adverse events. We performed statistical analyses using a random-effects model. We rated the certainty of evidence using the GRADE approach. MAIN RESULTS: Our search identified 10 records of four unique RCTs that informed two comparisons. In this abstract, we focus on the results for the two primary outcomes. Cytoreductive nephrectomy plus systemic anticancer therapy versus systemic anticancer therapy alone Three RCTs informed this comparison. Due to the considerable heterogeneity when pooling across these studies, we decided to present the results of the prespecified subgroup analysis by type of systemic agent. Cytoreductive nephrectomy plus interferon immunotherapy versus interferon immunotherapy alone CN plus interferon immunotherapy compared with interferon immunotherapy alone probably increases time to death from any cause (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.51 to 0.89; I²= 0%; 2 studies, 326 participants; moderate-certainty evidence). Assuming 820 all-cause deaths at two years' follow-up per 1000 people who receive interferon immunotherapy alone, the effect estimate corresponds to 132 fewer all-cause deaths (237 fewer to 37 fewer) per 1000 people who receive CN plus interferon immunotherapy. We found no evidence to assess quality of life. Cytoreductive nephrectomy plus tyrosine kinase inhibitor therapy versus tyrosine kinase inhibitor therapy alone We are very uncertain about the effect of CN plus tyrosine kinase inhibitor (TKI) therapy compared with TKI therapy alone on time to death from any cause (HR 1.11, 95% CI 0.90 to 1.37; 1 study, 450 participants; very low-certainty evidence). Assuming 574 all-cause deaths at two years' follow-up per 1000 people who receive TKI therapy alone, the effect estimate corresponds to 38 more all-cause deaths (38 fewer to 115 more) per 1000 people who receive CN plus TKI therapy. We found no evidence to assess quality of life. Immediate cytoreductive nephrectomy versus deferred cytoreductive nephrectomy One study evaluated CN followed by TKI therapy (immediate CN) versus three cycles of TKI therapy followed by CN (deferred CN). Immediate CN compared with deferred CN may decrease time to death from any cause (HR 1.63, 95% CI 1.05 to 2.53; 1 study, 99 participants; low-certainty evidence). Assuming 620 all-cause deaths at two years' follow-up per 1000 people who receive deferred CN, the effect estimate corresponds to 173 more all-cause deaths (18 more to 294 more) per 1000 people who receive immediate CN. We found no evidence to assess quality of life. AUTHORS' CONCLUSIONS: CN plus SACT in the form of interferon immunotherapy versus SACT in the form of interferon immunotherapy alone probably increases time to death from any cause. However, we are very uncertain about the effect of CN plus SACT in the form of TKI therapy versus SACT in the form of TKI therapy alone on time to death from any cause. Immediate CN versus deferred CN may decrease time to death from any cause. We found no quality of life data for any of these three comparisons. We also found no evidence to inform any other comparisons, in particular those involving newer immunotherapy agents (programmed death receptor 1 [PD-1]/programmed death ligand 1 [PD-L1] immune checkpoint inhibitors), which have become the backbone of SACT for metastatic renal cell carcinoma. There is an urgent need for RCTs that explore the role of CN in the context of contemporary forms of systemic immunotherapy.

Current perceptions and working time models of female urologists in Germany: results of a large-scale survey.

PURPOSE: Female urologists are distinctly underrepresented in leading positions. The reasons behind this inequity remain unclear, with some suggesting factors such as family responsibilities, part-time work and insufficient mentorship. This study aimed to explore and characterize the working conditions of female urologists in Germany, with a focus on factors influencing the working time model. METHODS: A questionnaire was developed and distributed to 1343 female members of the German Society of Urology between February and March 2022. The survey consisted of 43 questions covering the categories demographics, occupation situation, satisfaction at work, family situation, career aspects and research activity. RESULTS: Of the 487 female German urologists who participated in the survey, 167 (34.3%) worked part-time. Doctors in training were significantly less likely to work part-time than colleagues who had completed their specialist training (p < 0.001). Only 10% of female doctors in training reported working part-time. Similarly, having children (p < 0.001) and engaging in scientific activities (p = 0.03) were independent factors influencing part-time work, with children increasing the likelihood of working part-time as expected, while scientifically active female urologists were more likely to work full-time. CONCLUSION: This study provides the largest survey on the situation of female urologists in German-speaking countries to date. Part-time work during specialist training is rare, while more than 50% of female urologists with children work part-time. With the projected decline in the number of practicing physicians and the increasing demand for medical attention, it is crucial to find ways to retain and support healthcare professionals, particularly female urologists.

Current Role of Multiparametric MRI and MRI Targeted Biopsies for Prostate Cancer Diagnosis in Germany: A Nationwide Survey.

INTRODUCTION: Multiparametric MRI (mpMRI) and MRI targeted biopsies (MRtb) are a new standard in prostate cancer (PCa) screening and diagnosis. Guidelines already include this approach for patients at risk. We aimed to gather information from German urologists about their knowledge, routine use, and attitude toward mpMRI and consecutive biopsy methods. MATERIALS AND METHODS: An anonymous online questionnaire was sent via Survey Monkey to the members of the German Society of Urology (DGU). Statistical analyses were performed using SPSS version 25.0. RESULTS: 496 members with a median age of 48.6 years (±11.7) participated in the survey. The majority rated mpMRI of the prostate as a very useful diagnostic tool (72.7%). MRtb of the prostate was considered as very advantageous (71.5%). MpMRI was used by 95.9%, and 83.2% also recommended MRtb predominantly in clinical institutions. For targeted biopsy, MRI-ultrasound fusion biopsy was clearly favored (75.8%). MpMRI was mostly used in patients with previously negative biopsy (90.9%) and in patients under active surveillance (60.9%). Arguments against the use of prostate mpMRI are costs (84.9%) and/or lack of sufficient radiological infrastructure (17.4%). CONCLUSION: Our data illustrate the meanwhile high acceptance and clinical use of the prostate mpMRI and MRtb in Germany.

Gender-specific outcomes in immune checkpoint inhibitor therapy for advanced or metastatic urothelial cancer: a systematic review and meta-analysis.

PURPOSE: To analyze gender-specific differences in survival parameters in advanced or metastatic urothelial cancer patients undergoing immune checkpoint inhibition. METHODS: The primary aim of this systematic review and meta-analysis was to evaluate gender-specific differences in disease-free (DFS), progression-free (PFS), cancer-specific survival (CSS), event-free survival (EFS), overall survival (OS) and objective response rate (ORR). The sources MEDLINE, Embase and Cochrane Library were systematically searched from January 2010 to June 2022. No restrictions were made concerning language, study region or publication type. A comparison of gender-specific differences in survival parameters was performed using a random-effects meta-analysis. A risk of bias assessment was done using the ROBINS-I tool. RESULTS: Five studies were included. In a random-effect meta-analysis of the studies, PCD4989g and IMvigor 211 with both using atezolizumab, females were more likely to have better objective response rate (ORR) than men (OR 2.24; 95% CI 1.20-4.16; p = 0.0110). In addition, females had a comparable median OS to men (MD 1.16; 95% CI - 3.15-5.46; p = 0.598). In summary, comparing all results, a tendency was seen toward better response rates and survival parameters in female patients. The risk of bias assessment yielded an overall low risk of bias. CONCLUSIONS: There is a tendency toward better outcomes in women for immunotherapy in advanced or metastatic urothelial cancer, but only for the antibody atezolizumab women have a significantly better ORR. Unfortunately, many studies fail to report gender-specific outcomes. Therefore, further research is essential when aiming for individualized medicine. This research should address immunological confounders.

[Factors influencing job satisfaction of female urologists-results of a survey by the German Society of Urology (DGU)]. / Einflussfaktoren für die Berufszufriedenheit von Urologinnen ­ Ergebnisse einer Befragung der Deutschen Gesellschaft für Urologie e. V. (DGU).

INTRODUCTION: Job satisfaction is a valuable good. However, literature on job satisfaction of female and male physicians, especially in the field of urology, is scarce. Therefore, the aim of this study was to evaluate job satisfaction among female members of the German Society of Urology (DGU). MATERIALS AND METHODS: An online questionnaire was sent to 1343 female members of the DGU in Germany, Austria, and Switzerland. The responses of 521 female physicians were statistically analyzed regarding baseline characteristics and in relation to job satisfaction and satisfaction with the choice of specialty. RESULTS: The median age of the participants was 37 (IQR 33; 45) years. While 91% of the respondents were rather or very satisfied with their choice of specialty-urology-only about 54% of the female urologists were satisfied with their job situation. Of the female urologists satisfied (vs. not satisfied) with their professional situation, 95% (vs. 87%) were also satisfied with their choice of urology as their specialty. Satisfaction with the working time model (odds ratio [OR] 9.61) and feeling unequal treatment (OR: 0.18) were independent predictors of satisfaction with the professional situation. CONCLUSION: Considering the increasing proportion of women in the health sector, it is important to identify factors influencing decisions on career and choice of specialty as well as career progression. Achieving career goals, increasing satisfaction with the working time model, and reducing unequal treatment or discrimination are central arguments for sustainably increasing the job satisfaction of female urologists.

[Great potential, little substance : Overview of quality and quantity of urological apps in the German app store]. / Viel Potenzial, wenig Substanz : Eine aktuelle Übersicht über Quantität und Qualität urologischer Apps im deutschen App-Store.

BACKGROUND: The range of medical apps is broad and diverse. The previous evaluations are inconsistent and limited to the respective areas of application. OBJECTIVES: The main objective of this work is to comprehensively present, organize, and evaluate the current range of urological apps with the help of a semi-automatic retrospective app store analysis (SARASA). METHODS: Application of an adaptable method based on filter processes according to predefined criteria by means of SARASA to characterize urological apps from various subject areas in the Apple App Store with subsequent manual filtering and evaluation. RESULTS: From the original list of 34,830 apps in the "Medicine" category of the Apple App Store on 27 September 2021, 3556 apps remained after apps without a German-language store description were removed. 43 subject-specific apps remained for further analysis and description. The number of reviews, rating, topicality, urological issues, technical support and richness of content were taken into account. The two most relevant apps for each topic are presented in detail. CONCLUSION: SARASA offers an easy-to-use method for applying filter processes to identify apps in app stores that meet predefined, formal criteria. The highest number of apps can be classified in categories of patient information and further education and training. An app officially listed by the German Federal Institute for Drugs and Medical Products (BfArM) in the sense of a digital health application (DiGA), the costs of which are reimbursed by the health insurance companies, is available for urology in only one single case. The authors see great potential for future developments in this regard.

Reduced Recurrence Rates Are Associated with Photodynamic Diagnostics Compared to White Light after Extended Transurethral Resection of Bladder Tumors.

One pillar in treating non-muscle-invasive bladder cancer (NMIBC) is the complete and high-quality transurethral resection of the primary tumor (TURBT). However, even after a high-quality primary resection, the residual tumor risk is considerable, thus requiring a re-TURBT. Resections performed with the aid of a photodynamic diagnostics report improved recurrence-free survival rates and increased detection rates of carcinoma in situ (CIS). This monocentric retrospective study reports on patients treated with an extended TURBT procedure using conventional white-light cystoscopy or photodynamic diagnostics (PDD). Only patients undergoing a TURBT resection for their primary tumor were included in the statistical analysis. Recurrence-free survival and overall survival were the clinical endpoints. Mann−Whitney U tests and chi-squared tests were used for descriptive intergroup comparisons. The associations with overall survival and recurrence-free survival were determined by univariate and multivariate analyses. The test results were considered significant when p was < 0.05. In comparison to conventional white-light cystoscopy, PDD increased the detection rates of CIS (p = 0.004) and tumor multifocality (p = 0.005) and led to reduced residual tumor incidence at the primary resection site (p < 0.001). Likewise, tumor recurrence rates were reduced in the PDD cohort (p < 0.001). Patient age and the presence of residual tumor at the primary resection site were identified as independent predictors of overall survival. For recurrence-free survival, only the PDD resection method was an independent predictor (HR = 0.43; p < 0.001). In summary, we demonstrated that the utilization of PDD techniques was associated with improved detection rates of CIS and multifocal tumors and with reduced recurrence rates. The extended resection protocol allowed us to determine that PDD resections lead to a reduced residual tumor rate at the initial resection site. This residual tumor state at the resection site, determined by extended TURBT, became an independent predictor of long-term survival. On the other hand, the PDD technique was confirmed as the only independent predictor of recurrence-free survival.

[Promoting women in urology using the example of habilitation]. / Frauenförderung in der Urologie am Beispiel der Habilitation.

BACKGROUND: The proportion of female urologists is steadily increasing, yet they continue to be underrepresented in academic leadership positions. A postdoctoral lecture qualification (habilitation), which is mandatory for a successful scientific career, is achieved significantly less often by female urologists in Germany than by their male colleagues. OBJECTIVE: To identify factors to effectively promote female urologists into academic leadership positions, the current situation, as well as factors influencing successful habilitation of women who are members of the German Society of Urology (Deutsche Gesellschaft für Urologie [DGU]) were investigated. METHODS: An online questionnaire was distributed to 1343 female members of the DGU in Germany, Austria, and Switzerland. The responses of 521 women were statistically analyzed with respect to baseline characteristics and in relation to research funding. The primary endpoint of our study was the habilitation rate. RESULTS: The average age of the 521 participating female urologists who completed the questionnaire was 37 years (range 21-67 years). Of these, most female physicians were in postgraduate training (n = 168, 32%), worked full-time (n = 324, 62%), and had children (n = 277, 53%). Overall, 359 (69%) of the participants had a PhD and 63 (12%) were still working on their PhD. Thirty (5.8%) female urologists had a habilitation. In univariable logistic regression models, age (odds ratio [OR] 1.06), working time model (part-time OR 0.19), a research fellowship (OR 21.4), release from clinical work for research purposes (OR 13.7), and participation in a funding program (OR 6.9) or mentoring program (OR 7.0) were independent predictors of achieving habilitation. Whether a urologist had children was not an independent predictor of achieving habilitation. In multivariable logistic regression models, age (OR 1.08), and a research fellowship (OR 9.04) were independent predictors of achieving habilitation. CONCLUSIONS: Promoting habilitation among female urologists is required in order to increase the proportion of women in leading academic positions. The results of the data analysis show that the promotion of research fellowships explicitly for women could be a promising approach.

New Oral Antitumor Drugs and Medication Safety in Uro-Oncology: Implications for Clinical Practice Based on a Subgroup Analysis of the AMBORA Trial.

Oral antitumor therapeutics (OAT) bear a high risk for medication errors, e.g., due to drug-drug or drug-food interactions or incorrect drug intake. Advanced age, organ insufficiencies, and polymedication are putting uro-oncological patients at an even larger risk. This analysis sets out to (1) investigate the frequency and relevance of medication errors in patients with prostate cancer or renal cell carcinoma treated with OAT and (2) compile recommendations for clinical practice. This post-hoc subgroup analysis used data collected in the randomized AMBORA trial (2017-2020; DRKS00013271). Clinical pharmacologists/pharmacists conducted advanced medication reviews over 12 weeks after initiation of a new oral regimen and assessed the complete medication process for drug-related problems. Medication errors related to either the OAT, prescribed or prescription-free concomitant medication, or food were classified regarding cause and severity. We identified 67 medication errors in 38 patients within the complete medication within 12 weeks. Thereof, 55% were detected at therapy initiation, 27% were caused by the patients, and 25% were drug-drug or drug-food interactions. Problem-prone issues are summarized in a 'medication safety table' to provide recommendations for clinical practice in uro-oncology. Tailored strategies including intensified care by clinical pharmacologists/pharmacists should be implemented in clinical practice to improve medication safety.

Cell-Free DNA Sequencing Reveals Gene Variants in DNA Damage Repair Genes Associated with Prognosis of Prostate Cancer Patients.

In the present study, we further analyzed the data obtained in our previous study, where we investigated the cell-free DNA (cfDNA) of 34 progressive prostate cancer patients via targeted sequencing. Here, we studied the occurrence and prognostic impact of sequence variants according to their clinical pathological significance (CPS) or their functional impact (FI) in 23 DNA damage repair (DDR) genes with a focus on the ATM serine/threonine kinase gene (ATM). All patients had at least one DDR gene with a CPS or FI variant. Kaplan-Meier analysis indicated that the group with a higher number of CPS variants in DDR genes had a shorter time to treatment change (TTC) compared to the group with a lower number of CPS variants (p = 0.038). Analysis of each DDR gene revealed that CPS variants in the ATM gene and FI variants in the nibrin (NBN) gene showed a shorter TTC (p = 0.034 and p = 0.042). In addition, patients with CPS variants in the ATM gene had shorter overall survival (OS; p = 0.022) and disease-specific survival (DSS; p = 0.010) than patients without these variants. Interestingly, patients with CPS variants in seven DDR genes possessed a better OS (p = 0.008) and DSS (p = 0.009), and patients with FI variants in four DDR genes showed a better OS (p = 0.007) and DSS (p = 0.008). Together, these findings demonstrated that the analysis of cfDNA for gene variants in DDR genes provides prognostic information that may be helpful for future temporal and targeted treatment decisions for advanced PCa patients.

Cell-Free DNA Variant Sequencing Using Plasma and AR-V7 Testing of Circulating Tumor Cells in Prostate Cancer Patients.

Prostate cancer (PCa) is the second most common malignant cancer and is a major cause of morbidity and mortality among men worldwide. There is still an urgent need for biomarkers applicable for diagnosis, prognosis, therapy prediction, or therapy monitoring in PCa. Liquid biopsies, including cell-free DNA (cfDNA) and circulating tumor cells (CTCs), are a valuable source for studying such biomarkers and are minimally invasive. In our study, we investigated the cfDNA of 34 progressive PCa patients, via targeted sequencing, for sequence variants and for the occurrence of CTCs, with a focus on androgen receptor splice variant 7 (AR-V7)-positive CTCs. The cfDNA content was associated with overall survival (OS; p = 0.014), disease-specific survival (DSS; p = 0.004), and time to treatment change (TTC; p = 0.001). Moreover, when considering all sequence variants grouped by their functional impact and allele frequency, a significant association with TTC (p = 0.017) was observed. When investigating only pathogenic or likely pathogenic gene variants, variants of the BRCA1 gene (p = 0.029) and the AR ligand-binding domain (p = 0.050) were associated with a shorter TTC. Likewise, the presence of CTCs was associated with a shorter TTC (p = 0.031). The presence of AR-V7-positive CTCs was associated with TTC (p < 0.001) in Kaplan-Meier analysis. Interestingly, all patients with AR-V7-positive CTCs also carried TP53 point mutations. Altogether, analysis of cfDNA and CTCs can provide complementary information that may support temporal and targeted treatment decisions and may elucidate the optimal choice within the variety of therapy options for advanced PCa patients.

An Easily Expandable Multi-Drug LC-MS Assay for the Simultaneous Quantification of 57 Oral Antitumor Drugs in Human Plasma.

Oral anticancer drugs have led to significant improvements in the treatment of multiple tumor entities. However, in patients undergoing oral antitumor therapy, plasma concentrations are highly variable, resulting in risks of reduced therapeutic effects or an increase in side effects. One important tool to reduce this variability is therapeutic drug monitoring. In this work we describe a method to simultaneously quantify the plasma concentrations of 57 oral antitumor agents. Quantification of these drugs was achieved using liquid chromatography coupled to an Orbitrap mass spectrometer. The method was fully validated according to the FDA guidelines and constitutes a simple and robust way for exposure monitoring of a wide variety of oral anticancer drugs. Applicability to clinical routine was demonstrated by the analysis of 71 plasma samples taken from 39 patients. In summary, this new multi-drug method allows simultaneous quantification of 57 oral antitumor drugs, which can be applied to exposure monitoring in clinical studies, taking into account the broad variety of oral antitumor drugs prescribed in clinical routine.

Development and Usability Analysis of a Multimedia eConsent Solution.

BACKGROUND: More and more medical data is being stored digitally in routine care. The secondary use of patient data is only possible to a limited extent for data protection reasons. In order to enable a long-term and far-reaching use of secondary data, a possible approach is to obtain "broad consent" from patients, e.g. on research projects whose purpose is still unknown at the time of consent. OBJECTIVE: To develop and evaluate an interactive eConsent prototype that presents the extensive contents of the "broad consent" in multimedia form for the purpose of a successful and resource-efficient information and consent process. METHODS: The eConsent prototype was designed on basis of a literature review and in accordance with the goals of the German medical informatics initiative. User tests and subsequent questionnaire surveys using the System Usability Scale (SUS) were carried out with patients from a university hospital to assess the prototype's usability. The study was conducted in a quasi-experimental, one-group posttest-only design. RESULTS: The created interactive prototype can present the contents acoustically and visually and offers the possibility to retrieve additional information. With a SUS score of 84,1/100 the results indicate a very good usability of the prototype. CONCLUSION: The next steps will include further refinements of the prototype based on the feedback received and a subsequent study with a broader user group aimed at introducing an eConsent tool as part of a patient portal.