Cost-effectiveness analysis of different treatment modalities in BCG-unresponsive NMIBC.

OBJECTIVE: Radical cystectomy (RC) is the standard of care (SOC) in BCG-unresponsive NMIBC and is associated with a significant health-related quality-of-life burden. Recently, promising results have been published on Gemcitabine/Docetaxel, Pembrolizumab, and Hyperthermic Intravesical Chemotherapy (HIVEC) as salvage therapy options trying to increase the rate of bladder preservation. Here, we performed a Cost-Effectiveness-Analysis of those treatment modalities. PATIENTS AND METHODS: We developed a Markov model from a payer's perspective drawing on clinical data of single-arm trials testing intravesical gemcitabine/docetaxel and pembrolizumab in BCG-unresponsive NMIBC, as well as clinical data from patients receiving hyperthermic intravesical chemotherapy HIVEC (n = 29) as intravesical salvage chemotherapy at our uro-oncological centre in Cologne. Costs were simulated utilising a non-commercial diagnosis-related groups grouper, utilities were derived from comparable cost-effectiveness studies. We used a Monte Carlo simulation to identify the optimal treatment, comparing the incremental cost effectiveness ratios (ICERs) at a willingness-to-pay threshold of €50 000 (euro)/quality-adjusted life year (QALY). RESULTS: Over a horizon of 10 years, gemcitabine/docetaxel, HIVEC, and pembrolizumab were associated with costs of €48 353, €64 438, and €204 580, as well as a gain of QALYs of 6.16, 6.48, and 6.00, resulting in an ICER of €26 482, €42 567, and €184 533 respectively, in comparison to RC with total costs of €21 871 and a gain of QALYs of 5.01. Monte Carlo simulation identified HIVEC as the treatment of choice under assumption of a WTP of <€50 000. CONCLUSION: Considering a WTP of <€50 000/QALY, gemcitabine/docetaxel and HIVEC are highly cost-effective therapeutic options in BCG-refractory NMIBC, while RC remains the cheapest option. At its current price, pembrolizumab would only be cost-effective assuming a price reduction of at least 70%.

Deep-Learning-Based Image Denoising in Imaging of Urolithiasis: Assessment of Image Quality and Comparison to State-of-the-Art Iterative Reconstructions.

This study aimed to compare the image quality and diagnostic accuracy of deep-learning-based image denoising reconstructions (DLIDs) to established iterative reconstructed algorithms in low-dose computed tomography (LDCT) of patients with suspected urolithiasis. LDCTs (CTDIvol, 2 mGy) of 76 patients (age: 40.3 ± 5.2 years, M/W: 51/25) with suspected urolithiasis were retrospectively included. Filtered-back projection (FBP), hybrid iterative and model-based iterative reconstruction (HIR/MBIR, respectively) were reconstructed. FBP images were processed using a Food and Drug Administration (FDA)-approved DLID. ROIs were placed in renal parenchyma, fat, muscle and urinary bladder. Signal- and contrast-to-noise ratios (SNR/CNR, respectively) were calculated. Two radiologists evaluated image quality on five-point Likert scales and urinary stones. The results showed a progressive decrease in image noise from FBP, HIR and DLID to MBIR with significant differences between each method (p < 0.05). SNR and CNR were comparable between MBIR and DLID, while it was significantly lower in HIR followed by FBP (e.g., SNR: 1.5 ± 0.3; 1.4 ± 0.4; 1.0 ± 0.3; 0.7 ± 0.2, p < 0.05). Subjective analysis confirmed best image quality in MBIR, followed by DLID and HIR, both being superior to FBP (p < 0.05). Diagnostic accuracy for urinary stone detection was best using MBIR (0.94), lowest using FBP (0.84) and comparable between DLID (0.90) and HIR (0.90). Stone size measurements were consistent between all reconstructions and showed excellent correlation (r2 = 0.958-0.975). In conclusion, MBIR yielded the highest image quality and diagnostic accuracy, with DLID producing better results than HIR and FBP in image quality and matching HIR in diagnostic precision.

German specialists treating testicular cancer follow different guidelines with resulting inconsistency in assessment of retroperitoneal lymph-node metastasis: clinical implications and possible corrective measures.

BACKGROUND: Testicular germ cell tumors (GCTs) are aggressive but highly curable tumors. To avoid over/undertreatment, reliable clinical staging of retroperitoneal lymph-node metastasis is necessary. Current clinical guidelines, in their different versions, lack specific recommendations on how to measure lymph-node metastasis. OBJECTIVE: We aimed to assess the practice patterns of German institutions frequently treating testicular cancer for measuring retroperitoneal lymph-node size. METHODS: An 8-item survey was distributed among German university hospitals and members of the German Testicular Cancer Study Group. RESULTS: In the group of urologists, 54.7% assessed retroperitoneal lymph nodes depending on their short-axis diameter (SAD) (33.3% in any plane, 21.4% in the axial plane), while 45.3% used long-axis diameter (LAD) for the assessment (42.9% in any plane, 2.4% in the axial plane). Moreover, the oncologists mainly assessed lymph-node size based on the SAD (71.4%). Specifically, 42.9% of oncologists assessed the SAD in any plane, while 28.5% measured this dimension in the axial plane. Only 28.6% of oncologists considered the LAD (14.3% in any plane, 14.3% in the axial plane). None of the oncologists and 11.9% of the urologists (n = 5) always performed an MRI for the initial assessment, while for follow-up imaging, the use increased to 36.5% of oncologists and 31% of urologists. Furthermore, only 17% of the urologists, and no oncologists, calculated lymph-node volume in their assessment (p = 0.224). CONCLUSION: Clear and consistent measurement instructions are urgently needed to be present in all guidelines across different specialistic fields involved in testicular cancer management.

Prediction of Response to Cisplatin-Based Neoadjuvant Chemotherapy of Muscle-Invasive Bladder Cancer Patients by Molecular Subtyping including KRT and FGFR Target Gene Assessment.

Patients with muscle-invasive urothelial carcinoma achieving pathological complete response (pCR) upon neoadjuvant chemotherapy (NAC) have improved prognosis. Molecular subtypes of bladder cancer differ markedly regarding sensitivity to cisplatin-based chemotherapy and harbor FGFR treatment targets to various content. The objective of the present study was to evaluate whether preoperative assessment of molecular subtype as well as FGFR target gene expression is predictive for therapeutic outcome­rate of ypT0 status­to justify subsequent prospective validation within the "BladderBRIDGister". Formalin-fixed paraffin-embedded (FFPE) tissue specimens from transurethral bladder tumor resections (TUR) prior to neoadjuvant chemotherapy and corresponding radical cystectomy samples after chemotherapy of 36 patients were retrospectively collected. RNA from FFPE tissues were extracted by commercial kits, Relative gene expression of subtyping markers (e.g., KRT5, KRT20) and target genes (FGFR1, FGFR3) was analyzed by standardized RT-qPCR systems (STRATIFYER Molecular Pathology GmbH, Cologne). Spearman correlation, Kruskal−Wallis, Mann−Whitney and sensitivity/specificity tests were performed by JMP 9.0.0 (SAS software). The neoadjuvant cohort consisted of 36 patients (median age: 69, male 83% vs. female 17%) with 92% of patients being node-negative during radical cystectomy after 1 to 4 cycles of NAC. When comparing pretreatment with post-treatment samples, the median expression of KRT20 dropped most significantly from DCT 37.38 to 30.65, which compares with a 128-fold decrease. The reduction in gene expression was modest for other luminal marker genes (GATA3 6.8-fold, ERBB2 6.3-fold). In contrast, FGFR1 mRNA expression increased from 33.28 to 35.88 (~6.8-fold increase). Spearman correlation revealed positive association of pretreatment KRT20 mRNA levels with achieving pCR (r = 0.3072: p = 0.0684), whereas pretreatment FGFR1 mRNA was associated with resistance to chemotherapy (r = −0.6418: p < 0.0001). Hierarchical clustering identified luminal tumors of high KRT20 mRNA expression being associated with high pCR rate (10/16; 63%), while the double-negative subgroup with high FGFR1 expression did not respond with pCR (0/9; 0%). Molecular subtyping distinguishes patients with high probability of response from tumors as resistant to neoadjuvant chemotherapy. Targeting FGFR1 in less-differentiated bladder cancer subgroups may sensitize tumors for adopted treatments or subsequent chemotherapy.

Management of Germ Cell Tumours of the Testis in Adult Patients. German Clinical Practice Guideline Part I: Epidemiology, Classification, Diagnosis, Prognosis, Fertility Preservation, and Treatment Recommendations for Localized Stages.

INTRODUCTION: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic's background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages. METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements. RESULTS: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma. CONCLUSION: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes.

Lymph Node Assessment in Prostate Cancer: Evaluation of Iodine Quantification With Spectral Detector CT in Correlation to PSMA PET/CT.

PURPOSE: The aims of this study were to evaluate spectral detector CT (SDCT)-derived iodine concentration (IC) of lymph nodes diagnosed as metastatic and benign in prostate-specific membrane antigen (PSMA) PET/CT and to assess its potential use for lymph node assessment in prostate cancer. PATIENTS AND METHODS: Thirty-four prostate cancer patients were retrospectively included: 16 patients with and 18 without lymph node metastases as determined by PSMA PET/CT. Patients underwent PSMA PET/CT as well as portal venous phase abdominal SDCT for clinical cancer follow-up. Only scan pairs with a stable nodal status indicated by constant size as well as comparable prostate-specific antigen (PSA) levels were included. One hundred benign and 96 suspected metastatic lymph nodes were annotated and correlated between SDCT and PSMA PET/CT. Iodine concentration in SDCT-derived iodine maps and SUVmax in ultra-high definition reconstructions from PSMA PET/CT were acquired based on the region of interest. RESULTS: Metastatic lymph nodes as per PSMA PET/CT showed higher IC than nonmetastatic nodes (1.9 ± 0.6 mg/mL vs 1.5 ± 0.5 mg/mL, P < 0.05) resulting in an AUC of 0.72 and sensitivity/specificity of 81.3%/58.5%. The mean short axis diameter of metastatic lymph nodes was larger than that of nonmetastatic nodes (6.9 ± 3.6 mm vs 5.3 ± 1.3 mm; P < 0.05); a size threshold of 1 cm short axis diameter resulted in a sensitivity/specificity of 12.8%/99.0%. There was a significant yet weak positive correlation between SUVmax and IC (rs = 0.25; P < 0.001). CONCLUSIONS: Spectral detector CT-derived IC was increased in lymph nodes diagnosed as metastatic in PSMA PET/CT yet showed considerable data overlap. The correlation between IC and SUVmax was weak, highlighting the role of PSMA PET/CT as important reference imaging modality for detection of lymph node metastases in prostate cancer patients.

Impact of the COVID-19 Pandemic on Urologists in Germany.

BACKGROUND: In order to contain the coronavirus disease 2019 (COVID-19) pandemic, Germany has implemented drastic restrictions on public or social life, while health institutions are invoked to postpone elective procedures. Although urologists are less involved in the direct treatment of COVID-19 patients, the current situation strongly affects the urological work routine. OBJECTIVE: To analyze the impact of the COVID-19 pandemic on various aspects of work and personal life among urologists in Germany. DESIGN, SETTING, AND PARTICIPANTS: A total of 589 urologists in Germany participated in an online survey between March 27 and April 11, 2020. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Participants were stratified into subgroups according to professional characteristics. RESULTS AND LIMITATIONS: Most urologists rated Germany as "well prepared" and the increasing restrictions of social life as "very positive." Routine operation was more restricted in hospitals than in the outpatient sector (p = 0.046). Moreover, urologists from the outpatient sector felt significantly less prepared for the COVID-19 pandemic (p = 0.001), reported a higher shortage of protective medical equipment (p < 0.001), and described a tendency toward a higher level of threat (p = 0.054). Although restrictions regarding telemedicine approaches were reported by 60% of participants, the outpatient sector used telehealth more frequently than hospitals (25.5% vs 17.0%, p < 0.001). Limitations include the national design and the restricted survey period. CONCLUSIONS: This survey systematically evaluates the impact of the COVID-19 pandemic on personal and professional aspects of German urologists. We identified several issues, such as a higher shortage of medical protective equipment in the outpatient sector that could trigger specific measures to further improve the quality of urological care in Germany. PATIENT SUMMARY: We evaluated a potential impact of the coronavirus disease 2019 (COVID-19) pandemic on professional and personal aspects of the urologists in Germany. Our results suggest that the outpatient sector should receive specific attention as, for example, shortage of protective equipment was more common.

Online Discussion on #KidneyStones: A Longitudinal Assessment of Activity, Users and Content.

INTRODUCTION: Twitter is a popular microblogging platform for the rapid dissemination of information and reciprocal exchange in the urological field. We aimed to assess the activity, users and content of the online discussion, #KidneyStones, on Twitter. METHODS: We investigated the Symplur Signals analytics tool for Twitter data distributed via the #KidneyStones hashtag over a one year period. Activity analysis reflected overall activity and tweet enhancements. We assessed users' geolocations and performed an influencer analysis. Content analysis included the most frequently used words, tweet sentiment and shares for top tweets. RESULTS: 3,426 users generated over 10,333 tweets, which were frequently accompanied by links (49%), mentions (30%) and photos (13%). Users came from 106 countries across the globe and were most frequently from North America (63%) and Europe (16%). Individual and organisational healthcare professionals made up 56% of the influencers of the Twitter discussion on #KidneyStones. Besides the words 'kidney' (used 4,045 times) and 'stones' (3,335), 'pain' (1,233), 'urine' (1,158), and 'risk' (1,023) were the most frequently used words. 56% of tweets had a positive sentiment. The median (range) number of shares was 85 (62-587) for the top 10 links, 45.5 (17-94) for the top 10 photos, and 44 (22-95) for the top 10 retweets. CONCLUSION: The rapidly growing Twitter discussion on #KidneyStones engaged multiple stakeholders in the healthcare sector on a global scale and reached both professionals and laypeople. When used effectively and responsibly, the Twitter platform could improve prevention and medical care of kidney stone patients.

Analysis of drug-related problems in three departments of a German University hospital.

BACKGROUND: During the last decades, pharmaceutical care services have been developed and implemented to optimize drug therapies and ensure medication safety. To investigate the need for pharmaceutical care services, drug-related problems can be measured. OBJECTIVE: Thus, the aim of this study was to analyse number, type and occurrence of drug-related problems in different clinical departments. SETTING: A pharmaceutical care service was established on general wards in Urology, Neurology and Gastroenterology at the University Hospital RWTH Aachen, Germany. METHOD: For each of a total of 306 patients, a pharmacist conducted an extended medication history, performed medication reconciliation, conducted medication safety checks and if drug-related problems were discovered, gave valid recommendations to the attending healthcare team. Drug-related problems were classified using the APS-Doc system. For statistical analyses, SAS(®) 9.1.3, SAS Institute, Cary NC, USA was applied. The project was approved by the local ethics committee. MAIN OUTCOME MEASURE: Type, occurrence and frequency of DRP in different medical departments. RESULTS: On average, 2.3 drug-related problems per patient were documented for all three departments. Drug-related problems were found in each category of the APS-Doc system. The most pronounced drug-related problems found were drug-drug interactions (34.6 %). 37 % of the identified drug-related problems occurred before hospital admission, 27 % during transitional care, and 36 % on the ward. Subgroup analysis revealed specific drug-related problem patterns for each clinical department. The number of drug-related problems was found to be associated with the number of drugs and age. CONCLUSION: Drug-related problems frequently occur in all investigated clinical departments. A holistic pharmaceutical care service could be an option to address this issue. In case of limited resources, individual drug-related problem patterns can be used as a basis for a tailored pharmaceutical care service. As number of drugs and age have been shown to be significant risk factors, it is crucial that the healthcare team including the pharmacist pays special attention to elderly patients and those with polymedication.