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The integration of artificial intelligence, particularly Large Language Models (LLMs), has the potential to significantly enhance therapeutic decision-making in clinical oncology. Initial studies across various disciplines have demonstrated that LLM-based treatment recommendations can rival those of multidisciplinary tumor boards (MTBs); however, such data are currently lacking for urological cancers. This preparatory study establishes a robust methodological foundation for the forthcoming CONCORDIA trial, including the validation of the System Causability Scale (SCS) and its modified version (mSCS), as well as the selection of LLMs for urological cancer treatment recommendations based on recommendations from ChatGPT-4 and an MTB for 40 urological cancer scenarios. Both scales demonstrated strong validity, reliability (all aggregated Cohen’s K > 0.74), and internal consistency (all Cronbach’s Alpha > 0.9), with the mSCS showing superior reliability, internal consistency, and clinical applicability (p < 0.01). Two Delphi processes were used to define the LLMs to be tested in the CONCORDIA study (ChatGPT-4 and Claude 3.5 Sonnet) and to establish the acceptable non-inferiority margin for LLM recommendations compared to MTB recommendations. The forthcoming ethics-approved and registered CONCORDIA non-inferiority trial will require 110 urological cancer scenarios, with an mSCS difference threshold of 0.15, a Bonferroni corrected alpha of 0.025, and a beta of 0.1. Blinded mSCS assessments of MTB recommendations will then be compared to those of the LLMs. In summary, this work establishes the necessary prerequisites prior to initiating the CONCORDIA study and validates a modified score with high applicability and reliability for this and future trials.

Abstract Sarcopenia, defined as age-associated loss of skeletal muscle function and muscle mass, is a negative prognostic marker for survival in several tumor entities. However, data evaluating the impact of sarcopenia and fat distribution on penile cancer are rarely described. We performed a retrospective study including 38 patients who were diagnosed with squamous cell carcinoma of the penis. By measuring skeletal muscle mass and fat distribution at axial abdominal computed tomography images at the third lumbar vertebra several body composition parameters including skeletal muscle index (SMI), psoas muscle index (PMI), visceral obesity and visceral-to-subcutaneous fat ratio were determined. Among 38 patients, 26% (n = 10) of the patients with penile cancer were identified as sarcopenic. SMI, age, lymph node metastases, distant metastases and penile cancer of the shaft were identified as significant risk factors for overall survival. PMI and distant metastases were significantly associated with cancer specific survival. None of the analysed adipose tissue parameters could be identified as risk factors for survival in this study. We showed that sarcopenia occurs in a relevant part of patients with penile cancer and is a significant risk factor for overall survival (p = 0.032) and cancer specific survival (p = 0.034) for patients with penile cancer. Regarding fat distribution further studies are needed to evaluate its impact on sarcopenia and survival.

Penile squamous cell carcinoma (pSCC) is a rare malignancy with a global incidence ranging from 0.1 to 0.7 per 100,000 males. Prognosis is generally favorable for localized tumors, but metastatic pSCC remains challenging, with low survival rates. The role of novel biomarkers, such as tumor mutational burden (TMB) and microsatellite instability (MSI), in predicting the response to immune checkpoint inhibitors (ICIs) has been investigated in various cancers. However, MSI has not been observed in pSCC, limiting immunotherapy options for this patient subgroup. Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) are a distinct form of genomic instability associated with deficient MSH3 expression, which has been proposed as a potential biomarker in several cancers. This study investigates EMAST and MSH3 expression in a cohort of 78 pSCC cases using PCR, fragment analysis and immunohistochemistry. For the detection of EMAST, the stability of five microsatellite markers (D9S242, D20S82, MYCL1, D8S321 and D20S85) was analyzed. None of the cases showed an instability. As for MSH3 immunohistochemistry, all analyzable cases showed retained MSH3 expression. These results strongly suggest that neither EMAST nor MSH3 deficiency is involved in the carcinogenesis of pSCC and do not represent reliable predictive biomarkers in this entity. Furthermore, these findings are in full agreement with our previous study showing a very low frequency of MSI and further support the thesis that EMAST and MSI are strongly interconnected forms of genomic instability. Further research is needed to explore novel therapeutic targets and predictive biomarkers for immunotherapy in this patient population.

Objectives: This study examines the impact of temperature variations on out-of-hospital-cardiac-arrests in Germany over a decade (2010–2019). Out-of-hospital-cardiac-arrests affects 164 per 100,000 inhabitants annually in Germany, 11% survive to hospital discharge. The following study investigates days with the following characteristics: summer days, frost days, and high humidity days. Furthermore, the study explores incidence, causes, demographics, and outcomes of out-of-hospital-cardiac-arrests. Methods: Data from the German Resuscitation Registry and Meteorological Service were combined for analysis. The theory posits that temperature and humidity play a significant role in the occurrence and outcomes of out-of-hospital-cardiac-arrests, potentially triggering pre-existing health issues. Results: Findings reveal increased out-of-hospital-cardiac-arrests during frost days (6.39 up to 7.00, p

Recently, the German Federal Institute for Medicines and Medical Products restricted the use of fosfomycin in transrectal biopsy of the prostate (TRBP). Accordingly, the need for other antibiotic agents for prophylaxis in TRBP is urgent since antibiotic prophylaxis is mandatory in accordance with these guidelines. After the restriction of the use of ciprofloxacin, and before the use of fosfomycin in Germany was falsely allowed, amoxicillin/clavulanic acid was evaluated as an alternative for antibiotic prophylaxis in TRBP. Regarding hospitalization for post-interventional infections, 359 patients at the Department of Urology of the University of Regensburg, at Caritas-St. Josef Medical Center as a single center, underwent TRBP between 2 July 2019 and 30 June 2020. Regarding antibiotic prophylaxis, the post-interventional hospitalization rate due to bacterial complications was relevant. Of the 359 patients, 10 (2.8%) had an infection requiring hospitalization post-TRBP. A total of 349 (97.2%) patients had no infection-related hospitalization. This corresponds to an incidence rate of only 2.8%. Referring to the previous infection rates under the now obsolete ciprofloxacin, amoxicillin/clavulanic acid can show a similar, if not tendentially even lower, risk of infection, and so this substance can be an alternative for antibiotic prophylaxis in TRBP. Another advantage is that, according to the WHO’s AWaRe classification, amoxicillin/clavulanic acid is one of the so-called Access antibiotics. This study is limited as rectal swabs and urine cultures were not performed on every patient before TRBP.

Recurrent cystitis in women represents an everyday challenge; however, little to no data regarding this population are available. This study aimed to evaluate this collective with respect to a rational calculated antibiotic therapy. Urine cultures and antibiograms from a urological office were retrospectively evaluated from patient data collected between January 2017 and June 2019. The evaluation was conducted using SPSS ©. In total, 84 female patients, who were aged between 18 and 87 years old (median 60 years), suffered from recurrent cystitis. Escherichia coli was found in 53.9% of cases, Staphylococcus aureus and enterococci were each found in 6.7%, and Proteus spp. and Streptococcus agalactiae were each found in 5.6%. The resistance levels to ciprofloxacin (CIP), trimethoprim–sulfamethoxazole (TRS), nitrofurantoin (NIT), and nitroxoline (NOX) were 18.2%, 30.7%, 16.1%, and 12.5% in the tested cases, respectively. Regarding E. coli, resistance to CIP, TRS, and NIT was found in 17.8%, 25%, and 4.2% of the tested cases, and no resistance to NOX was found. The resistance level to CIP was in a tolerable range of E. coli subgroup. More than a quarter of the bacteria were resistant to TRS. The low resistance rates for NIT and NOX are remarkable, promoting the use of these substances if they are not yet used.

Abstract To determine whether Xpert bladder cancer monitor, a noninvasive PCR-based biomarker test, can predict the need for 2nd transurethral resection of the bladder (TURB) better than clinical assessment. Patients scheduled for TURB were prospectively screened. After initial TURB, patients were assigned to 2nd TURB or follow-up cystoscopy at 3 months (FU) by clinicians’ discretion. Central urine cytology and Xpert monitor tests were performed prior to the 1st TURB and 2nd TURB or FU, respectively. Statistical analysis to compare clinical assessment and Xpert monitor comprised sensitivity (SENS), specificity (SPEC), NPV and PPV. Of 756 screened patients, 171 were included (114 with 2nd TURB, 57 with FU). Residual tumors were detected in 34 patients who underwent 2nd TURB, and recurrent tumors were detected in 2 patients with FU. SENS and SPEC of Xpert monitor were 83.3% and 53.0%, respectively, PPV was 32.6% and NPV was 92.1%. Clinical risk assessment outperformed Xpert monitor. In patients with pTa disease at initial TURB, Xpert monitor revealed a NPV of 96%. Xpert monitor was not superior than clinical assessment in predicting the need for 2nd TURB. It might be an option to omit 2nd TURB for selected patients with pTa disease.

Background: Grade of non–muscle-invasive bladder cancer (NMIBC) is an important prognostic factor for progression. Currently, two World Health Organization (WHO) classification systems (WHO1973, categories: grade 1–3, and WHO2004 categories: papillary urothelial neoplasm of low malignant potential [PUNLMP], low-grade [LG], high-grade [HG] carcinoma) are used. Objective: To ask the European Association of Urology (EAU) and International Society of Urological Pathology (ISUP) members regarding their current practice and preferences of grading systems. Design, setting, and participants: A web-based, anonymous questionnaire with ten questions on grading of NMIBC was created. The members of EAU and ISUP were invited to complete an online survey by the end of 2021. Thirteen experts had previously answered the same questions. Outcome measurements and statistical analysis: The submitted answers from 214 ISUP members, 191 EAU members, and 13 experts were analyzed. Results and limitations: Currently, 53% use only the WHO2004 system and 40% use both systems. According to most respondents, PUNLMP is a rare diagnosis with management similar to Ta-LG carcinoma. The majority (72%) would consider reverting back to WHO1973 if grading criteria were more detailed. Separate reporting of WHO1973-G3 within WHO2004-HG would influence clinical decisions for Ta and/or T1 tumors according the majority (55%). Most respondents preferred a two-tier (41%) or a three-tier (41%) grading system. The current WHO2004 grading system is supported by a minority (20%), whereas nearly half (48%) supported a hybrid three- or four-tier grading system composed of both WHO1973 and WHO2004. The survey results of the experts were comparable with ISUP and EAU respondents. Conclusions: Both the WHO1973 and the WHO2004 grading system are still widely used. Even though opinions on the future of bladder cancer grading were strongly divided, there was limited support for WHO1973 and WHO2004 in their current formats, while the hybrid (three-tier) grading system with LG, HG-G2, and HG-G3 as categories could be considered the most promising alternative. Patient summary: Grading of non–muscle-invasive bladder cancer (NMIBC) is a matter of ongoing debate and lacks international consensus. We surveyed urologists and pathologists of European Association of Urology and International Society of Urological Pathology on their preferences regarding NMIBC grading to generate a multidisciplinary dialogue. Both the “old” World Health Organization (WHO) 1973 and the “new” WHO2004 grading schemes are still used widely. However, continuation of both the WHO1973 and the WHO2004 system showed limited support, while a hybrid grading system composed of both the WHO1973 and the WHO2004 classification system may be considered a promising alternative.

Abstract Background Nectin-4 contributes to tumor proliferation, lymphangiogenesis and angiogenesis in malignant tumors and is an emerging target in tumor therapy. In renal cell carcinoma (RCC) VEGF-directed tyrosine kinase inhibitors and checkpoint inhibitors are currently treatments of choice. Enfortumab vedotin-ejf (EV) is an antibody drug conjugate that targets Nectin-4. The aim of our study was to investigate the expression of Nectin-4 in a large cohort of papillary RCC specimens. Patients and methods Specimens were derived from the PANZAR consortium (Erlangen, Heidelberg, Herne, Homburg, Mainz, Mannheim, Marburg, Muenster, LMU Munich, TU Munich, and Regensburg). Clinical data and tissue samples from n = 190 and n = 107 patients with type 1 and 2 pRCC, respectively, were available. Expression of Nectin-4 was determined by immunohistochemistry (IHC). Results In total, Nectin-4 staining was moderately or strongly positive in of 92 (48.4%) of type 1 and 39 (36.4%) type 2 of pRCC cases. No associations between Nectin-4 expression and age at diagnosis, gender, grading, and TNM stage was found. 5 year overall survival rate was not statistically different in patients with Nectin-4 negative versus Nectin-4 positive tumors for the overall cohort and the pRCC type 2 subgroup, but higher in patient with Nectin-4 positive pRCC type 1 tumors compared to Nectin-4 negative tumors (81.3% vs. 67.8%, p = 0.042). Conclusion Nectin-4 could not be confirmed as a prognostic marker in pRCC in general. Due to its high abundance on pRCC specimens Nectin-4 is an interesting target for therapeutical approaches e.g. with EV. Clinical trials are warranted to elucidate its role in the pRCC treatment landscape.

Purpose Transcutaneous tibial nerve stimulation (TTNS) has proven to be a valuable treatment option for various lower urinary tract conditions, such as overactive bladder syndrome and neurogenic detrusor overactivity. The aim of this study was to investigate acute changes in urodynamic parameters due to bilateral TTNS. Methods Fifty-one patients (18–87 years; 61% female) with various lower urinary tract symptoms were enrolled in this study. They were single-blinded and randomly assigned to receive simultaneous bilateral TTNS either during their first urodynamic examination, followed by a second round using a placebo stimulation technique, or vice versa. Results For subjects without signs of anatomical pathologies, the filling volume at the first desire to void (FDV) increased significantly by 54 mL (interquartile range [IQR], 26–81 mL; P100 mL) increased by 76 mL compared to patients without urinary retention (IQR, 6–166 mL; P=0.03). Conclusions Compared to placebo, simultaneous bilateral TTNS showed significant improvements in bladder functioning, such as delayed FDV, increased maximum cystometric capacity, and reduced urinary retention. Patients with signs of anatomical pathologies did not seem to benefit from TTNS. Further studies need to be conducted to compare the effectiveness of bilateral versus unilateral TTNS.

Abstract Tumor budding is defined as a single cell or a cluster of up to 5 tumor cells at the invasion front. Due to the difficulty of identifying patients at high risk for pT1 non-muscle-invasive bladder cancer (NMIBC) and the difficulties in T1 substaging, tumor budding was evaluated as a potential alternative and prognostic parameter in these patients. Tumor budding as well as growth pattern, invasion pattern and lamina propria infiltration were retrospectively evaluated in transurethral resection of the bladder (TURB) specimens from 92 patients with stage pT1 NMIBC. The presence of tumor budding correlated with multifocal tumors (p = 0.003), discontinuous invasion pattern (p = 0.039), discohesive growth pattern (p

BackgroundPenile cancer represents a rare malignant disease, whereby a small caseload is associated with the risk of inadequate treatment expertise. Thus, we hypothesized that strict guideline adherence might be considered a potential surrogate for treatment quality. This study investigated the influence of the annual hospital caseload on guideline adherence regarding treatment recommendations for penile cancer.MethodsIn a 2018 survey study, 681 urologists from 45 hospitals in four European countries were queried about six hypothetical case scenarios (CS): local treatment of the primary tumor pTis (CS1) and pT1b (CS2); lymph node surgery inguinal (CS3) and pelvic (CS4); and chemotherapy neoadjuvant (CS5) and adjuvant (CS6). Only the responses from 206 head and senior physicians, as decision makers, were evaluated. The answers were assessed based on the applicable European Association of Urology (EAU) guidelines regarding their correctness. The real hospital caseload was analyzed based on multivariate logistic regression models regarding its effect on guideline adherence.ResultsThe median annual hospital caseload was 6 (interquartile range (IQR) 3–9). Recommendations for CS1–6 were correct in 79%, 66%, 39%, 27%, 28%, and 28%, respectively. The probability of a guideline-adherent recommendation increased with each patient treated per year in a clinic for CS1, CS2, CS3, and CS6 by 16%, 7.8%, 7.2%, and 9.5%, respectively (each p < 0.05); CS4 and CS5 were not influenced by caseload. A caseload threshold with a higher guideline adherence for all endpoints could not be perceived. The type of hospital care (academic vs. non-academic) did not affect guideline adherence in any scenario.ConclusionsGuideline adherence for most treatment recommendations increases with growing annual penile cancer caseload. Thus, the results of our study call for a stronger centralization of diagnosis and treatment strategies regarding penile cancer.

Background: Recently, antibiotic resistance rates have risen substantially and care for patients infected with multidrug-resistant organisms (MDRO) has become a common problem in most in – and outpatient settings. The objectives of the study were to compare the awareness, perception, and knowledge of MDRO and rational antibiotic use between physicians from different medical specialties in German hospitals. Methods: A 35-item questionnaire was sent to specialists in internal medicine (internists), gynecologists, urologists, and general surgeons (non-internists) in 18 German hospitals. Likert-scales were used to evaluate awareness and perception of personal performance regarding care for patients infected with MDRO and rational use of antibiotics. Additionally, two items assessing specific knowledge in antibiotic therapy were included. The impact of medical specialty on four predetermined endpoints was assessed by multivariate logistic regression. Results: 43.0% (456/1061) of recipients responded. Both internists and non-internists had low rates of training in antibiotic stewardship. 50.8% of internists and 58.6% of non-internists had attended special training in rational antibiotic use or care for patients infected with MDRO in the 12 months prior to the study. Internists deemed themselves more confidently to choose the indications for screening patients for colonization with methicillin-resistant Staphylococcus aureus (P=0.004) and to initiate adequate infection control measures (P=0.002) than other specialties. However, there was no significant difference between internists and other specialists regarding the two items assessing specific knowledge in antibiotic therapy and infection control. Conclusion: Among the study participants, a considerable need for advanced training in the study subjects was seen, regardless of the medical specialty.

Successful primary closure of classic bladder exstrophy (BE) is crucial for development of bladder capacity and voided continence. It is universally agreed that an intensive pain management including the use of caudal epidural anesthesia is an essential cornerstone for the outcome of this complex surgery. Whether and to what extent pain is caused by structural or functional changes is not yet known. The nerve growth factor (NGF) is regarded as a marker for pain in different bladder disorders. This prospective study investigated the role of histological alterations and NGF in patients with BE including 34 patients with BE and 6 patients with congenital vesicoureterorenal reflux (VUR) who served as controls. Between January 2015 and April 2020 transmural bladder biopsies were taken from the posterior bladder wall during delayed primary bladder closure. The samples were stained for histological evaluation and subjected to immunohistochemistry to analyze NGFR p75. Differences in histological alterations were examined with Fisher's exact test, and Mann-Whitney-U-test was used to compare the NGFR p75 staining intensity between patients with BE and controls. Patients with BE showed significantly more often acute inflammation (p < 0.001), squamous metaplasia (p = 0.002), and cystitis glandularis (p = 0.005) as well as NGFR p75 in the urothelium (p = 0.003) than patients with VUR. A limitation of this study is the small number of participants due to the rare disease entity. Similar to other painful bladder disorders, pain transmission in BE after intitial closure may in part be facilitated by elevated NGF signaling through its receptor.

Objectives Robotic-assisted laparoscopic prostatectomy (RALP) is typically conducted in steep Trendelenburg position (STP). This study investigated the influence of permanent 45° STP and capnoperitoneum on haemodynamic parameters during and after RALP.Design Prospective observational study.Setting Haemodynamic changes were recorded with transpulmonary thermodilution and pulse contour analysis in men undergoing RALP under standardised anaesthesia.Participants Informed consent was obtained from 51 patients scheduled for elective RALP in a University Medical Centre in Germany.Interventions Heart rate, mean arterial pressure, central venous pressure (CVP), Cardiac Index (CI), systemic vascular resistance (SVR), Global End-Diastolic Volume Index (GEDI), global ejection fraction (GEF), Cardiac Power Index (CPI) and stroke volume variation (SVV) were recorded at six time points: 20 min after induction of anaesthesia (T1), after insufflation of capnoperitoneum in supine position (T2), after 30 min in STP (T3), when controlling Santorini’s plexus in STP (T4), before awakening in supine position (T5) and after 45 min in the recovery room (T6). Adverse cardiac events were registered intraoperatively and postoperatively.Results All haemodynamic parameters were significantly changed by capnoperitoneum and STP during RALP and partly normalised at T6. CI, GEF and CPI were highest at T6 (CI: 3.9 vs 2.2 L/min/m²; GEF: 26 vs 22%; CPI: 0.80 vs 0.39 W/m²; p

Background Assessment of the immune status of muscle-invasive bladder cancer (MIBC) has previously shown to be prognostically relevant after treatment with curative intent. We conducted this study to develop a clinically applicable immune gene expression assay to predict prognosis and adjuvant chemotherapy benefit.Patients and methods Gene expression of CD3Z, CD8A and CXCL9, immune cell (IC) populations including stromal tumor infiltrating lymphocytes (sTILs), T-cells, natural killer cells (NK-cells), macrophages, Programmed cell death protein 1 positive (PD-1) IC and tumor subtypes (MD Anderson Cancer Center/MDACC-approach) were assessed in 187 MIBC patients (Comprehensive Cancer Center Erlangen-EMN/CCC-EMN-cohort). A gene expression signature was derived by hierarchical-clustering and validated in The Cancer Genome Atlas (TCGA)-cohort. IC populations in the TCGA cohort were assessed via CIBERSORT. Benefit of platinum-containing adjuvant chemotherapy was assessed in a pooled cohort of 125 patients. Outcome measurements were disease specific survival, disease-free survival and overall survival.Results The gene expression signature of CXCL9, CD3Z and CD8A correlates with quantitative amounts of specific IC populations and sTILs (CCC-EMN: ρ-range: 0.44–0.74; TCGA: ρ-range: 0.56–0.82) and allows stratification of three different inflammation levels (inflamed high, inflamed low, uninflamed). Highly inflamed tumors are preferentially basal subtype and show favorable 5-year survival rates of 67.3% (HR=0.27; CCC-EMN) and 55% (HR=0.41; TCGA). Uninflamed tumors are predominantly luminal subtypes and show low 5-year survival rates of 28% (CCC-EMN) and 36% (TCGA). Inflamed tumors exhibit higher levels of PD-1 and Programmed cell death 1 ligand 1 (PD-L1). Patients undergoing adjuvant platinum-based chemotherapy with ‘inflamed high’ tumors showed a favorable 5-year survival rate of 64% (HR=0.27; merged CCC-EMN and TCGA cohort).Conclusion The gene expression signature of CD3Z, CD8A and CXCL9 can assess the immune status of MIBC and stratify the survival of MIBC patients undergoing surgery and adjuvant platinum-based chemotherapy. Furthermore, the assay can identify patients with immunological hot tumors with particular high expression of PD-L1 potentially suitable for immunotherapy.

Abstract Background To study the expression pattern, localisation and potential clinical significance of aquaporin water channels (AQP) both in prostate cancer (PC) cell lines and in benign and malignant human prostate tissue. Methods The AQP transcript and protein expression of HPrEC, LNCaP, DU-145 and PC3 cell lines was investigated using reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence (IF) microscopy labelling. Immunohistochemistry (IHC) was performed to assess AQP protein expression in surgical specimens of benign prostatic hyperplasia as well as in PC. Tissue mRNA expression of AQPs was quantified by single-step reverse transcriptase quantitative polymerase chain reaction (qPCR). Relative gene expression was determined using the 40-ΔCT method and correlated to clinicopathological parameters. Results Transcripts of AQP 1, 3, 4, 7, 8, 10 and 11 were expressed in all four cell lines, while AQP 9 transcripts were not detected in malignant cell lines. IF microscopy confirmed AQP 3, 4, 5, 7 and 9 protein expression. IHC revealed highly heterogeneous AQP 3 protein expression in PC specimens, with a marked decrease in expression in tumours of increasing malignancy. Loss of AQP 9 was shown in PC specimens. mRNA expression of AQP3 was found to be negatively correlated to PSA levels (ρ = − 0.354; p = 0.013), D’Amico risk stratification (ρ = − 0.336; p = 0.012), ISUP grade (ρ = − 0.321; p = 0.017) and Gleason score (ρ = − 0.342; p = 0.011). Conclusions This is the first study to systematically characterize human prostate cell lines, benign prostatic hyperplasia and PC in relation to all 13 members of the AQP family. Our results indicate the differential expression of several AQPs in benign and malignant prostate tissue. A significant correlation was observed between AQP 3 expression and tumour grade, with progressive loss in more malignant tumours. Taken together, AQPs may play a role in the progression of PC and AQP expression patterns may serve as a prognostic marker.

Abstract Background A multicentre study was conducted to investigate the impact of sarcopenia as an independent predictor of oncological outcome after radical cystectomy for bladder cancer. Methods In total, 500 patients with available digital computed tomography scans of the abdomen obtained within 90 days before surgery were identified. The lumbar skeletal muscle index was measured using pre‐operative computed tomography. Cancer‐specific survival (CSS) and overall survival (OS) were estimated using Kaplan–Meier curves. Predictors of CSS and OS were analysed by univariable and multivariable Cox regression models. Results Based on skeletal muscle index, 189 patients (37.8%) were classified as sarcopenic. Patients with sarcopenia were older compared with their counterparts (P = 0.002), but both groups were comparable regarding to gender, comorbidity, tumor, node, metastasis (TNM) stage, and type of urinary diversion (all P > 0.05). In total, 234 (46.8%) patients died, and of these, 145 (29.0%) died because of urothelial carcinoma of the bladder. Sarcopenic patients had significantly worse 5 year OS (38.3% vs. 50.5%; P = 0.002) and 5 year CSS (49.5% vs. 62.3%; P = 0.016) rates compared with patients without sarcopenia. Moreover, sarcopenia was associated independently with both increased all‐cause mortality (hazard ratio, 1.43; 95% confidence interval 1.09–1.87; P = 0.01) and increased cancer‐specific mortality (hazard ratio, 1.42; 95% confidence interval, 1.00–2.02; P = 0.048). Our results are limited by the lack of prospective frailty assessment. Conclusions Sarcopenia has been shown to be an independent predictor for OS and CSS in a large multicentre study with patients undergoing radical cystectomy for bladder cancer.

Purpose: Smoking represents a primary risk factor for the development of urothelial carcinoma (UC) and a relevant factor impacting UC-specific prognosis. Data on the accordant knowledge of UC-patients in this regard and the significance of physicians in the education of UC-patients is limited. Materials and Methods: Eighty-eight UC-patients were enrolled in a 23-items-survey-study aimed to analyse patient knowledge and awareness of their tumor disease with smoking along with physician smoking cessation counselling. Results: The median age of the study patients was 69 years; 26.1% (n=23), 46.6% (n=41), and 27.3% (n=24), respectively, were non-smokers, previous, and active smokers. Exactly 50% of active smokers reported a previous communication with a physician about the association of smoking and their tumor disease; however, only 25.0% were aware of smoking as main risk factor for UC development. Merely 33% of the active smokers had been prompted directly by their physicians to quit smoking. About 42% of active smokers had received the information that maintaining smoking could result in a tumor-specific impairment of their prognosis. Closely 29% of active and about 5% of previous smokers (during the time-period of active smoking) had been offered support from physicians for smoking cessation. No association was found between smoking anamnesis (p=0.574) and pack-years (p=0.912), respectively, and tumor stage of UC. Conclusions: The results of this study suggest that the medical conversation of physicians with UC-patients about the adverse significance of smoking is limited. Implementation of structured educational programs for smoking cessation may be an opportunity to further enhance comprehensive cancer care.

INTRODUCTION: High-risk non–muscle-invasive bladder cancer (NMIBC) remains challenging given the high probability of progression. Given that the androgen receptor (AR) has been discussed as a possible factor in the development and progression of bladder cancer, we investigated the predictive value of AR in stage pT1 NMIBC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data and AR mRNA expression in 296 patients with stage pT1 NMIBC who underwent a transurethral resection of the bladder. The mRNA expression of the AR transcript variants 1 (AR1) and 2 (AR2) was measured by reverse transcription quantitative real-time polymerase chain reaction. AR expression was also correlated to KRT5 and KRT20 mRNA expression. RESULTS: Kaplan-Meier analysis indicated that high AR1 mRNA expression ≥35.47 is associated with statistically significant better recurrence-free survival (RFS) (P = .0007), progression-free survival (PFS) (P = .0420), and cancer-specific survival (CSS) (P = .0050). Multivariate Cox regression analysis revealed that high AR1 mRNA expression is an independent prognostic marker for RFS (P = .0029) and CSS (P = .0119). Spearman rank correlation revealed a significant positive association between mRNA expression of AR1 and KRT5 (rs: 0.3171, P

The role of the androgen receptor (AR) in non-muscle-invasive bladder cancer (NMIBC) remains controversial. We retrospectively analyzed the mRNA expression of AR using RT-qPCR in 95 patients with high-risk NMIBC treated with a bladder-sparing approach and correlated AR with clinical data and recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). The mRNA expression of AR and KRT5, i.e., the basal-like subtype, was strongly correlated (rs = 0.456; p < 0.001). AR (p = 0.053) and KRT5 (p = 0.029) mRNA expression was negatively correlated with tumor grade. Kaplan–Meier analyses indicated significantly prolonged CSS (p = 0.020) and OS (p = 0.015) and a trend towards longer RFS (p = 0.051) in patients with high AR expression. High KRT5 expression was associated with significantly longer RFS (p = 0.033), CSS (p = 0.029) and OS (p = 0.030), while high KRT20 expression was associated with reduced RFS (p = 0.042). In multivariable analysis, none of the molecular markers was an independent prognostic factor. When performing a substratification with regard to molecular markers and clinicopathological parameters, high AR expression showed improved OS in patients with high KRT20 mRNA expression (p = 0.041). Women showed significantly longer OS in cases with high AR expression (p = 0.011). High AR was associated with significantly improved CSS in males (p = 0.044) and patients with instillation therapy (p = 0.040), while OS was improved regardless of instillation therapy. Younger patients with high AR expression had significantly improved RFS (p = 0.021), CSS (p = 0.014) and OS (p = 0.007). RFS was also improved in patients with high AR and low expression of either KRT5 (p = 0.003) or KRT20 (p = 0.014), but not in patients with high expression of KRT5 or KRT20. In conclusion, high AR mRNA expression is correlated with KRT5 mRNA expression and is associated with an improved outcome in high-risk NMIBC.

We present one case of a metachronous, atypical, multifocal renal oncocytoma with a concomitant chromophobe renal cell carcinoma (RCC) of the contralateral side and one case of bilateral and multifocal oncocytomas. Oncocytomas are benign renal tumours that rarely appear bilateral or multifocal or with coexisting RCC. A common pathogenic denominator of oncoytomas and RCC is being discussed. The first case was a 63 years old patient presenting with a history of nephrectomy for a pT1 G1 pN0 R0 papillary RCC 4 years prior to presentation, showed two tumours of a singular kidney. Upon nephron-sparing surgery one typical and one atypical oncocytoma with an invasion of the perinephric fat were found. Comparative genomic hybridisation was performed. Both tumours revealed genetic alterations with loss of genetic material on chromosome 1p. The second case was a 62 years old patient presenting with multifocal and bilateral renal tumours of undeclared dignity upon imaging. During open exploration all tumours could be removed by nephron-sparing surgery and were identified as oncocytomas. Again comparative genomic hybridisation was performed. All 4 tumours revealed genetic alterations with loss of genetic material on chromosome 1p, one of the tumours an additional loss of chromosome 10.

Clear cell renal cell carcinoma (ccRCC) characterized by a tumor thrombus (TT) extending into the inferior vena cava (IVC) generally indicates poor prognosis. Nevertheless, the risk for tumor recurrence after nephrectomy and thrombectomy varies. An applicable and accurate prediction system to select ccRCC patients with TT of the IVC (ccRCC/TT) at high risk after nephrectomy is urgently needed, but has not been established up to now. To our knowledge, a possible role of microRNAs (miRs) for the development of ccRCC/TT or their impact as prognostic markers in ccRCC/TT has not been explored yet. Therefore, we analyzed the expression of the previously described onco-miRs miR-200c, miR-210, miR-126, miR-221, let-7b, miR-21, miR-143 and miR-141 in a study collective of 74 ccRCC patients. Using the expression profiles of these eight miRs we developed classification systems that accurately differentiate ccRCC from non-cancerous renal tissue and ccRCC/TT from tumors without TT. In the subgroup of 37 ccRCC/TT cases we found that miR-21, miR-126, and miR-221 predicted cancer related death (CRD) accurately and independently from other clinico-pathological features. Furthermore, a combined risk score based on the expression of miR-21, miR-126 and miR-221 was developed and showed high sensitivity and specificity to predict cancer specific survival (CSS) in ccRCC/TT. Using the combined risk score we were able to classify ccRCC/TT patients correctly into high and low risk cases. The risk stratification by the combined risk score (CRS) will benefit from further cohort validation and might have potential for clinical application as a molecular prediction system to identify high- risk ccRCC/TT patients.

Objective Photodynamic diagnosis (PDD) of superficial bladder cancer decreases recurrence rates. We present oncological results of a randomized, prospective study, comparing transurethral resection (TUR) performed under conventional white light (WL) with PDD. The follow-up period is the longest reported to date. As costs might be reimbursed by prolonged recurrence-free survival in certain patients cost analysis in regard to risk-groups was performed. Material and methods Using chi-square test and log-rank test we compared recurrence rates of 103 patients after WL-TUR and of 88 patients after PDD-TUR. Cost analysis was performed according to risk-groups of recurrence. Results Mean follow-up was 99 months. Recurrence rate was 57% in WL vs. 28% in PDD (p < 0.001). Costs incurred by subsequent TUR averaged € 2310 per WL patient vs. € 713 per PDD patient. Savings per patient by PDD amounted to € 1597. PDD costs were reimbursed in low, intermediate and high risk patients, respectively. Conclusions PDD-TUR is significantly superior to conventional WL-TUR in terms of recurrence rate. While economic benefit is most prominent in intermediate risk patients, PDD related costs are reimbursed in all risk-groups.