Evaluation of Patterns of Presentation, Practice, and Outcomes of Upper Tract Urothelial Cancer: Protocol for an Observational, International, Multicenter, Cohort Study by the Clinical Research Office of the Endourology Society

Background: Available guidelines on the management of upper tract urothelial carcinoma (UTUC) are restricted due to the lack of strong evidence-based recommendations. Adequate, well-powered randomized trials are missing due to the rarity of the disease. To overcome this problem, we need alternative study designs to provide generalizable data. Objective: The primary aim of this registry is to provide a real-world overview on patterns of presentation and management of UTUC. Secondary objectives include comparison of outcomes of different treatments and tumor stages and evaluation of compliance with the current European Association of Urology recommendations for UTUC. Methods: For this observational, international, multicenter, cohort study, clinical data of consecutive patients suspected of having UTUC, irrespective of type of management, will be prospectively collected up to 5 years after inclusion. Data on the patterns of presentation, diagnostics, and treatment as well as short-, mid-, and long-term oncological and functional outcomes will be analyzed. Possible associations between variables, basal characteristics, and outcomes will be tested by multivariable analyses. The methodology will address potential sources of bias and confounders. Results: The registry was initiated in November 2014 after obtaining institutional review board approval. Data collection started in December 2014. At the time of submission of this manuscript, 2451 patients from 125 centers from 37 countries were included. Inclusion of patients will be closed 5 years after initiation of the registry. Quality checks will be performed centrally with continuous communication and feedback with the centers to ensure accuracy. The first results are expected in the first trimester of 2020. Conclusions: This large observational prospective cohort will generate landmark "real-world" data and hypotheses for further studies. We expect these data to optimize the management of UTUC, provide insights on harms and benefits of treatment, and serve as quality control

Impact of adjuvant gemcitabine containing chemotherapy following radical nephroureterectomy for patients with upper tract urothelial carcinoma: Results from a propensity-score matched cohort study

BACKGROUND: The evidence regarding perioperative adjuvant chemotherapy and personalized surveillance strategies for upper tract urothelial carcinoma is limited. OBJECTIVE: To evaluate whether adjuvant gemcitabine containing chemotherapy affects the oncological outcomes of advanced upper tract urothelial carcinoma (UTUC). METHODS: The CROES-UTUC registry is an observational, international, multi-center study on patients diagnosed with UTUC. Patient and disease characteristics from 2380 patients with UTUC were collected, and finally 738 patients were included in this analysis. The primary outcome of this study was recurrence-free survival. Propensity score matching was performed. Kaplan-Meier and multivariate Cox regression analyses were performed by stratifying patients according to the treatment of adjuvant chemotherapy. RESULTS: A total of 738 patients were included in this analysis, and 59 patients received adjuvant chemotherapy (AC), including 50 patients who received gemcitabine. A propensity score matching was performed, including 50 patients who received gemcitabine containing treatment and 50 patients without adjuvant chemotherapy. Disease recurrence occurred in 34.0% of patients. The recurrence rate in the AC group was 22.0%, which was significantly lower than the non-AC group (46.0%). Kaplan-Meier analyses also showed that AC was associated with a lower likelihood of tumor recurrence (p = 0.047). However, AC was not significantly associated with a higher overall survival (OS) (p = 0.908) and cancer-specific survival (CSS) (p = 0.979). Upon multivariate Cox regression analysis, AC was associated with a lower risk of tumor recurrence (HR = 0.297, p = 0.028). CONCLUSION: The present study confirms that adjuvant gemcitabine containing chemotherapy could decrease the risk of tumor recurrence in patients with locally advanced UTUC following nephroureterectomy. However, more studies are need to draw a clearer image of the value of this treatment method.STORZ to the Clinical Research Office of the Endourology Society (CROES

Fluoroscopy-use during ureterorenoscopy: are urologists concerned about radiation exposure? A nationwide survey in Belgium and The Netherlands

Introduction: To evaluate the use and awareness of radiation during URS among Belgian and Dutch urologists. Material and methods: An online questionnaire was send to all members of the Belgian and Dutch Association of Urology. Results: 170 urologists finished the complete questionnaire. 10% of the respondents are not familiar with the ALARA-principle. 29% starts with a KUB and 48% makes an XRPG at the beginning of the procedure. 85% uses fluoroscopy to place a wire or ureteral access sheet, 18% during stone treatment, 59% to screen for missed stones or calyces, 90% to place a JJ-stent or ureter-catheter and 23% to check for extravasation. 82% do not document radiation data. 51% does not wear a dosimeter during fluoroscopy. Almost all wear a lead apron during fluoroscopy, 47% uses additional thyroid shields and only 4% uses lead glasses. 88% intentionally reduces fluoroscopy time, 75% reduces the exposed area with a diaphragm, 72% brings the radiation source close to the patient and 44% uses pulsed fluoroscopy. Conclusion: There is a wide variety in the use and awareness of radiation during URS. To further reduce radiation and its negative effect for patients and medical staff, awareness about radiation safety should increase among urologists

Could the region you live in prevent or precipitate kidney stone formation due to mineral intake through tap water? An analysis of nine distribution regions in Flanders

Objectives: To analyse the mineral content of tap water in Flanders and assess if the region one lives in could prevent or precipitate stone formation due to a difference in mineral content. Methods: Data from six water companies providing tap water to nine regions in Flanders regarding calcium, magnesium, potassium, sodium and sulphate content in tap water was retrieved. Minimum and maximum values were collected and compared between the different geographical regions. Results: The highest calcium level was found in region 9 with a value of 157.0 mg/L, which is almost 10 times the value found in region 8 (16.1 mg/L). Region 6 had the highest magnesium (31.8 mg/L), potassium (30.5 mg/L), sodium (126.6 mg/L) and sulphate (218.5 mg/L) levels. The lowest level of magnesium (2.7 mg/L) was found in region 1, which was almost 12 times lower as in Region 6. Region 9 had the lowest level of potassium (1.5 mg/L), which is a factor 20 lower than Region 6. The lowest sodium and sulphate levels were found in region 8 (6.8 mg/L and 3.0 mg/L), respectively. The difference between the highest and lowest level of sulphate was a factor 70. Conclusion: There is a broad range in the minerals found in tap water between the different production sites in the nine distribution regions in Flanders. However, due to the high standards tap water has to meet in Flanders, the region one lives in will not lead to a higher or lower risk of kidney stone formation if the advised 2 to 3 L per day are consumed

How well tolerated is supine percutaneous nephrolithotomy?

Supine percutaneous nephrolithotomy (PCNL) has been described in 1988 and several modifications followed since. Despite claimed benefits, supine PCNL is still neglected by the majority of urologists. Lack of experience and the fear of complications are possible explanations for the resistance to supine positioning. This review evaluates recent literature on the use of supine PCNL, focussing on benefits and safety. The Clinical Research Office of the Endourological Society Global Study and several (retrospective) reports comment on efficacy and safety of PCNL, differences in techniques, or identify conditions and patient factors for best practice. Anesthesiologic benefits (especially in the high risk, cardiopulmonary compromised, patient) and anatomical advantages are described in supine position theoretically favoring safety of supine PCNL. However, there are no prospective randomized studies conducted to support this assumption. Overall, benefits in efficacy or safety, of one position over the other, are not yet proven. Supine PCNL has advantages in selected patients. Ultimately, the decision on position should be made on patient's characteristics and surgeon's preference and experienc

Lessons learned from the CROES percutaneous nephrolithotomy global study

The purpose of the study was to give an overview of the data derived from the CROES PCNL Global Study published previously in 25 articles. A comprehensive overview of the outcome of the CROES PCNL Global Study was made, analysed and compared with the current literature and guidelines. Percutaneous nephrolithotomy (PCNL) was predominately performed in prone position. Although the supine position claims to be favourable over the prone approach, the present study showed a longer operation time and lower stone-free rate (SFR). This might be explained by differences in definition in operation time and methods in the evaluation of residual stones. Ultrasound (US)-guided access proves beneficial in lowering puncture time and radiation exposure. Renal anomalies can safely be treated by PCNL and have similar outcomes to a normal situation. In patients with a solitary kidney, however, there is a lower SFR and more bleeding. Also, severe chronic kidney disease (CKD) patients have less favourable outcome. Morbidity and complications following PCNL are dominated by fever (10.5%) and bleeding (7.8%). A matched control analysis confirmed that antibiotic prophylaxis gives a threefold lower post-operative fever rate. In a multivariate analysis, it was elegantly demonstrated that bleeding was directly related to the size of the dilatation: the larger the bore, the higher the chance for bleeding. Elderly patients are at higher risk of complications and longer hospital stay. Overall, obese patients have similar outcome as the general population; however, super-obese (BMI > 40) patients have a higher chance of more severe complications. For the first time, this database illustrated a significant relationship between results and complications of PCNL, and caseload volume. The optimal case volume per centre appears to be 120 PCNL's/year. Finally, a nomogram has been developed that enables better patient counselling and decision-making. The CROES PCNL Global Study is the largest real-life study providing new insights into general and special conditions. Because of the vast number of patients included, rare conditions including renal anomalies, solitary kidneys and patient characteristics like severe CKD, super obesity and old age could be analysed. Besides this information, a nomogram was developed. And for the first time, the influence of caseload volume was establishe

Confocal laser endomicroscopy for upper tract urothelial carcinoma: Validation of the proposed criteria and proposal of a scoring system for real-time tumor grading

Purpose: Confocal laser endomicroscopy (CLE) is a fluorescence-based fiber-optic imaging technique with the potential for intraoperative grading of upper tract urothelial carcinoma (UTUC). This study aims to (1) investigate the prevalence of the previously proposed CLE criteria for bladder cancer in papillary UTUC, (2) estimate the diagnostic value of CLE for UTUC grading and (3) propose a scoring system for a more quantifiable approach of CLE-based grading of UTUC. Materials and methods: Ureteroscopic CLE was performed in patients with UTUC. Following CLE imaging, co-localized biopsies were taken for histopathologic comparison. Postoperatively, two blinded raters assessed the CLE images. Results: Fifty-three papillary UTUCs (34 low grade and 19 high grade) were imaged with CLE in 36 patients. All the previously described CLE criteria were identifiable in varying proportions. After excluding 10 non-diagnostic recordings (5 low grade and 5 high grade) due to insufficient image quality, the histopathologic grade was correctly identified with CLE in 26 low-grade UTUCs (90%) and in 12 high-grade UTUCs (86%). The most prevalent CLE criteria with the highest diagnostic potential were cellular organization, morphology and cohesiveness of cells. A scoring system was proposed with these criteria, which yielded similar diagnostic accuracies. Conclusions: Based on the previously proposed criteria, CLE enables accurate grading of papillary UTUC at a non-diagnostic rate of 19%. The most prevalent CLE criteria with the highest diagnostic potential for grading of papillary UTUC are cellular organization, morphology and cohesiveness of cells. The proposed scoring system may simplify the assessment of CLE images for UTUC grading but external validation is required

New technologies for upper tract urothelial carcinoma management

Purpose of review Image enhancement techniques and optical diagnostic tools have emerged in the quest to improve diagnostics and treatment in patients with upper urinary tract carcinoma (UTUC). The aim of the present report is to describe their mechanisms of action and to assess the current evidence on applicability and utility in UTUC. Recent findings Image enhancement techniques including narrow band imaging, Image1 S, and photodynamic diagnosis aim at better visualization of malignant urothelium and especially flat tumours or carcinoma in situ which are often difficult to see with white light endoscopy. Conducted studies in the upper tract are scarce but first results show that tumour detection seems to be better for narrow band imaging and photodynamic diagnosis-guided inspection. Optical diagnostic tools as confocal laser endomicroscopy and optical coherence tomography aim at providing real time optical biopsies giving pathologic information. A pilot study of optical coherence tomography proved its feasibility to visualize, grade and stage low and high-grade UTUC. Summary Better visualization of suspect lesions and optical diagnostic techniques providing real time optical biopsies aim to facilitate in higher diagnostic precision and optimal individualized treatment of our patients with UTUC. As the disease is rare, studies are scarce but indispensable for future implication of these technique

Diagnostic dilemmas in patients with upper tract urothelial carcinoma

Upper tract urothelial carcinoma (UTUC) is a rare condition and recommendations based on a high level of evidence for diagnosis, treatment and follow-up monitoring are lacking. Current decision-making is often based on evidence from trials investigating urothelial carcinoma of the lower tract. Radical nephroureterectomy has been the standard of care for UTUC but kidney-sparing treatment using endoscopic approaches has been established for a select patient group with low-grade and low-stage disease. Optimal treatment choice requires correct tumour characterization. According to available recommendations, diagnostic work-up of UTUC includes evaluation by CT urography or MRI urography, cystoscopy and urine cytology. Ureterorenoscopy and lesion biopsy are grade C recommendations in patients with suspected UTUC. When kidney-sparing treatment is planned, ureterorenoscopy and biopsy should be considered and are the procedures of choice in most cases. These diagnostics have limitations and their accuracy varies in defining tumour characteristics and predicting grade and stage. Urinary tests have higher sensitivity than cytology for detection of lower tract urothelial carcinoma but evidence of their benefit in UTUCs is lacking. New optical and image enhancement techniques are being developed to facilitate real-time diagnostics with increased accuracy. A new diagnostic algorithm for patients with suspected UTUC that integrates the diagnosis, treatment and clinical risk stratification is require

Surgical teaching in urology: patient safety and educational value of ‘LIVE’ and ‘SEMI-LIVE’ surgical demonstrations

Purpose: To evaluate the opinion of urologists and their audience regarding patient safety and educational value of live surgical demonstrations (LSD) and semi-live surgical demonstrations (semi-LSD). Methods: Following the ‘2017 Challenges in Endourology’ meeting, a survey addressing patient safety and the educational value of LSD and semi-LSD was disseminated online to all participants. Survey outcomes of LSD and semi-LSD were compared. Results: All 279 respondents attended both LSD and semi-LSD. Overall, 53% of said respondents stated that patient safety was always the highest priority for LSD, while 74% noted the same for semi-LSD. The complication risk in LSD was perceived equal by 57% of the respondents when compared to cases of similar difficulty in routine practice, while 38% perceived it as a greater risk. For semi-LSD, the complication risk was perceived equal by 84%, while 5% perceived it to be a greater risk in comparison to general practice. On a scale from 0 (no value) to 10 (highly valuable), the average educational value of LSD and semi-LSD was rated 8.4 and 8.3, respectively. A substantial percentage of the surgeons who perform LSD express concerns that live surgery is not the optimal setting to ensure patient safety. Conclusions: LSD remains a popular tool for surgical education among urologists and their audience. However, patient safety remains a concern and is perceived less of a concern for semi-LSD. The educational value of LSD and semi-LSD was scored equally high. Therefore, we should consider to advocate the use of semi-LSD more often