Diagnosis Of Upper Tract Urothelial Carcinoma Research Articles

Risk factors and prognosis of intravesical recurrence after surgical management of upper tract urothelial carcinoma: A 30-year single centre experience

ObjectiveTo review the incidence, predictors and prognosis of bladder cancer recurrence after management of upper tract urothelial carcinoma (UTUC). Patients and methodsWe retrospectively reviewed patients who were surgically treated for UTUC from 1983 to 2013. The tumours were categorised according to the 1997 Tumour-Node-Metastasis (TNM) staging and the three-tiered World Health Organization grading systems. The primary endpoint was the occurrence of any intravesical recurrence after treatment. We studied the possible risk factors that may contribute to development of intravesical recurrence, as well as the prognosis of the patients who had recurrence. ResultsIn all, 297 patients were eligible for analysis. Recurrent bladder tumours occurred in 139 patients (46.8%). The mean (range) time to recurrence after surgery was 33 (6–300) months. Neither sex, past history of bladder tumours, concomitant bladder tumour, the side of the tumour, UTUC stage, grade, presence of carcinoma in situ or multicentricity at the time of diagnosis of UTUC, were significant predictors of intravesical tumour recurrence. Ureteric tumour was the only identified risk factor (P=0.02). Post-treatment bladder recurrence was a significant predictor of later urethral recurrence (P=0.002). ConclusionsIn our present series, bladder cancer recurrence of urothelial malignancy occurred in nearly half of the patients after surgical management of UTUC. Ureteric tumour was the only identifiable risk factor, thus patients with ureteric tumours may benefit from prophylactic intravesical chemoimmunotherapy. Bladder recurrence does not appear to affect the cancer-specific survival after surgical management of UTUC.

MP78-11 POSITIVE PREDICTIVE VALUE OF CT UROGRAPHY FOR UPPER TRACT UROTHELIAL CARCINOMA DIAGNOSIS USING DIAGNOSTIC URETEROSCOPY AS THE REFERENCE STANDARD

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma II1 Apr 2017MP78-11 POSITIVE PREDICTIVE VALUE OF CT UROGRAPHY FOR UPPER TRACT UROTHELIAL CARCINOMA DIAGNOSIS USING DIAGNOSTIC URETEROSCOPY AS THE REFERENCE STANDARD Timothy Chan Chang, Ishay Mintz, Yuval Bar-Yosef, Simon Conti, Sophie Barnes, Diego Mercer, Nicola Mabjeesh, Joseph Liao, and Mario Sofer Timothy Chan ChangTimothy Chan Chang More articles by this author , Ishay MintzIshay Mintz More articles by this author , Yuval Bar-YosefYuval Bar-Yosef More articles by this author , Simon ContiSimon Conti More articles by this author , Sophie BarnesSophie Barnes More articles by this author , Diego MercerDiego Mercer More articles by this author , Nicola MabjeeshNicola Mabjeesh More articles by this author , Joseph LiaoJoseph Liao More articles by this author , and Mario SoferMario Sofer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2099AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES CT Urography (CTU) is the initial imaging modality of choice for assessing upper urinary tract pathology, including upper tract urothelial carcinoma (UTUC). However, despite abnormal findings on CTU suggestive of UTUC, follow-up diagnostic ureteroscopy (DURS) is frequently negative. We aim to assess the positive predictive value (PPV) of CTU for UTUC using DURS as the reference standard. METHODS The study group comprised 79 consecutive patients from 2 academic institutions. They had CTU findings of upper tract wall thickening, hydronephrosis, a filling defect and/or contrast enhancement diagnosed in consensus by 2 radiologists as suspicious for UTUC. DURS, with either wash cytology when endoscopically negative or biopsies when endoscopically positive, was used as the reference standard. The results of DURS were classified as UTUC, benign lesions (BL) and no pathological findings (NPF). Statistical analysis was conducted. RESULTS Solitary CTU suspected findings were reported in 45 (57%) patients, including thickness in 8 (10%), hydronephrosis in 5 (6%), filling defect in 30 (38%) and enhancement in 2 (3%). Combinations of suspected findings were reported in 34 (43%) patients. DURS revealed 41 (52%) UTUC, 14 (18%) BL and 24 (30%) NPF. Table shows the calculated PPV. The combination of CTU findings had higher PPV in comparison to solitary findings for detection of UTUC (65% vs 42%, respectively; p<0.05, OR 2.5, 95% CI 1.007-6.28) as well as for overall endoscopic pathological findings (82% vs 60%, respectively; p<0.05, OR 3.1, 95% CI 1.07-9.02). Arbitrary stratification of solitary CTU findings as minor UTUC predictors (PPV<50%: thickening, hydronephrosis and enhancement) and major UTUC predictors (PPV≥50%: filling defect) resulted in a statistically significant better prediction for the major group (p<0.05; OR 7.2, 95% CI 1.39-38.15). CONCLUSIONS The best PPV of CTU diagnosis of UTUC is achieved based on a combination of findings, with filling defect appearing to be the most significant among them. In the absence of filling defect, other CTU findings, such as thickening, hydronephrosis and enhancement, are not predictive for UTUC. We suggest that the need for DURS in these cases should be re-considered in correlation with other data (e.g., cytology, biomarkers, history of heavy smoking, recurrent hematuria, etc.). DURS remains the diagnostic standard for deciding whether or not to proceed to nephroureterectomy. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1035 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Timothy Chan Chang More articles by this author Ishay Mintz More articles by this author Yuval Bar-Yosef More articles by this author Simon Conti More articles by this author Sophie Barnes More articles by this author Diego Mercer More articles by this author Nicola Mabjeesh More articles by this author Joseph Liao More articles by this author Mario Sofer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

1039 - Positive predictive value of CT urography for upper tract urothelial carcinoma diagnosis using diagnostic ureteroscopy as the reference standard

1039 - Positive predictive value of CT urography for upper tract urothelial carcinoma diagnosis using diagnostic ureteroscopy as the reference standard

Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC).

Upper-tract urothelial carcinoma (UTUC) is a relatively uncommon disease with limited available evidence on specific topics. The purpose of this article was to review the previous literature to summarize the current knowledge about UTUC epidemiology, diagnosis, preoperative evaluation and prognostic assessment. Using MEDLINE, a non-systematic review was performed including articles between January 2000 and February 2016. English language original articles, reviews and editorials were selected based on their clinical relevance. UTUC accounts for 5-10% of all urothelial cancers, with an increasing incidence. UTUC and bladder cancer share some common risk factors, even if they are two different entities regarding practical, biological and clinical characteristics. Aristolochic acid plays an important role in UTUC pathogenesis in certain regions. It is further estimated that approximately 10% of UTUC are part of the hereditary non-polyposis colorectal cancer spectrum disease. UTUC diagnosis remains mainly based on imaging and endoscopy, but development of new technologies is rapidly changing the diagnosis algorithm. To help the decision-making process regarding surgical treatment, extent of lymphadenectomy and selection of neoadjuvant systemic therapies, predictive tools based on preoperative patient and tumor characteristics have been developed. Awareness regarding epidemiology, diagnosis, preoperative evaluation and prognostic assessment changes is essential to correctly diagnose and manage UTUC patients, thereby potentially improving their outcomes.

A Pilot Study of In Vivo Confocal Laser Endomicroscopy of Upper Tract Urothelial Carcinoma.

Tissue diagnosis of upper tract urothelial carcinoma (UTUC) is limited by variance in tumor sampling by standard ureteroscopic biopsy. Optical imaging technologies can potentially improve UTUC diagnosis, surveillance, and endoscopic treatment. We previously demonstrated in vivo optical biopsy of urothelial carcinoma of the bladder using confocal laser endomicroscopy (CLE). In this study, we evaluated a new 0.85-mm imaging probe in the upper urinary tract and demonstrated feasibility and compatibility with standard ureteroscopes to achieve in vivo optical biopsy of UTUC. Fourteen patients scheduled for ureteroscopy of suspected upper tract lesions or surveillance of UTUC were recruited. After intravenous (IV) administration of fluorescein, CLE was performed using a 0.85-mm-diameter imaging probe inserted through the working channel of standard ureteroscopes. Acquired confocal video sequences were reviewed and analyzed. A mosaicing algorithm was used to compile a series of images into a single larger composite image. Processed CLE images were compared with standard histopathologic analysis. Optical biopsy of the UTUC using CLE was effectively achieved during standard ureteroscopy. There were no adverse events related to IV fluorescein administration or image acquisition. Confocal imaging of UTUC showed characteristic features similar to urothelial carcinoma of the bladder, including papillary structure, fibrovascular stalks, and pleomorphism. Lamina propria in normal areas of the renal pelvis and ureter was also identified. We report an initial feasibility of CLE of UTUC. Pending further clinical investigation, CLE may become a useful adjunct to ureteroscopic biopsy, endoscopic ablation, and surveillance of UTUC.

Identification of circulating microRNA signatures for upper tract urothelial carcinoma detection.

The involvement of circulating microRNAs (miRNAs) in cancer and their potential as diagnostic and prognostic biomarkers are becoming increasingly known. However, the significance of circulating miRNAs in upper tract urothelial carcinoma (UTUC) has remained to be investigated. The present study performed a genome wide serum miRNA analysis using a deep sequencing platform for initial screening. Subsequently, serum samples of 46 UTUC patients and 30 cancer free individuals with hematuria were subjected to a quantitative reverse transcription polymerase chain reaction analysis. The expression of thirteen miRNAs (miR-664a-3p, miR-423-5p, miR-431-5p, miR-191-5p, miR-92a-3p, miR-22-3p, miR-26a-5p, miR-33b-3p, miR-16-5p, let-7a 5p, let-7b-5p, let-7f-5p and let-7c) was significantly different in serum from UTUC patients compared with that in control samples. Receiver operator characteristic analysis showed that 10 miRNAs (miR-664a-3p, miR-431-5p, miR-423-5p, miR-191-5p, miR-33b-3p, miR-26a-5p, miR-22-3p, miR-16-5p, let-7b-5p and let-7c) had the potential to distinguish individuals with UTUC from the controls (areas under the curve >0.8). The present study provided the first evidence for the potential use of circulating miRNAs as biomarkers for UTUC diagnosis, which remains to be verified by further studies.

Safety and diagnostic accuracy of percutaneous biopsy in upper tract urothelial carcinoma.

To assess the diagnostic accuracy and safety of percutaneous biopsy for upper tract urothelial carcinoma (UTUC). From 2002 to 2013, 26 upper tract lesions in 24 patients (20 men; median [range] age 67.8 [51.7-85.9] years) were percutaneously biopsied. Analysis was separated based on lesion appearance: (i) mass infiltrating renal parenchyma, (ii) filling defect in the collecting system, (iii) urothelial wall thickening. We tracked immediate complications and tract seeding on follow-up imaging. Of the 26 upper tract lesions, 15 (58%) were masses infiltrating the renal parenchyma (mean [range] size 5.4 [1.1-14.0] cm), six (23%) were urothelial wall thickenings (mean [range] size 0.8 [0.4-1.1] cm), and five (19%) were filling defects within the renal pelvis or calyx (mean [range] size 2.7 [1.0-4.6] cm). Definitive diagnosis of UTUC was made by biopsy in 22 of 26 lesions (85%). Biopsy characterised 14 of 15 infiltrative masses and five of five filling defects; biopsy characterised three of six cases of urothelial wall thickening. CT follow-up was available for 19 patients (73%) at a median (range) of 13.6 (1.0-98.9) months. Three patients (11%) developed recurrence in the nephrectomy bed at 5.6, 9.7, and 29.0 months after biopsy; none were attributed to tract seeding after independent review, because recurrence was remote from the biopsy site. Percutaneous biopsy is effective for diagnosis of UTUC, providing tissue diagnosis in 85% of cases. While case reports cite a risk of tract seeding, no cases of recurrence were definitely attributable to percutaneous biopsy. Thus, for upper tract urothelial lesions, which are not amenable to endoscopic biopsy, percutaneous biopsy is a safe and effective technique.

Imagerie des tumeurs des voies excrétrices supérieures : état de l’art pour le rapport scientifique annuel de l’Association française d’urologie

To propose a state of the art regarding imaging techniques for the diagnosis and work-up of upper tract urothelial carcinoma (UTUC). A systematic review of the scientific literature was performed in the Medline database (PubMed) until 2014 using different associations of the following keywords: urothelial carcinomas; upper urinary tract; ureter; renal pelvis; CT scan; MRI; ultrasound; urography. Imaging has a prominent role in the diagnosis, extension and follow-up assessment of upper tract urothelial cancers (UTUC). The couple ultrasound/intravenous urography made way for the multidetector computed tomography urography (MDCTU) and for the magnetic resonance imaging urography (MRU), which can also be combined in some cases. This review of the literature presents available techniques for the exploration of the upper urinary tract, the main protocols (in particular the interest of furosemide addition), details the interpretation techniques for searching UTUC on serial imaging, as well as the main differential diagnoses, and their accuracy. Finally, the role of imaging, according to patient's context is discussed. The combination or fusion of different modalities (CT, MR…) for the same objective is highlighted and presented as the likely evolution of UTUC imaging. MDCTU is nowadays the gold standard imaging modality for the diagnosis of UTUC.

Diagnosis of upper tract urothelial carcinoma—a comparative study of urinary cytology and surgical biopsy

Upper tract urothelial carcinoma (UTUC) is defined as urothelial carcinoma (UC) arising in the renal pelvis and ureter. Upper tract (UT) cytology and biopsy evaluation can be technically challenging. The aim of the study is to evaluate the diagnostic modality and sensitivity of urine cytology and ureteroscopic biopsy for the diagnosis of UTUC. All patients with UTUC who underwent radical nephroureterectomy or ureterectomy with preoperative cytology and/or biopsy from January 1, 2000 to September 30, 2011 at our institution were included in this study. The sensitivity of each diagnostic modality was calculated with respect to tumor grade, stage, and size. A total of 143 cytology specimens and 54 biopsies from 65 patients were evaluated. For low-grade UTUC, the sensitivities for biopsy, lower tract cytology, and UT cytology were 68.4%, 27.3%, and 37.5%, respectively. These numbers were 82.9%, 40.7%, and 80.6% for high-grade UTUC. By combining the UT cytology and biopsy, the diagnostic sensitivities were increased to 87.5% for low-grade UTUC and 100% for high-grade UTUC. The consistency of tumor grade between biopsy and surgical specimen were 63.2% for low-grade UTUC and 68.6% for high-grade UTUC. Both UT cytology and biopsy showed higher sensitivity in detecting high-grade UTUC versus low-grade UTUC. The sensitivities of UT cytology and ureteroscopic biopsy in detecting high-grade UTUC were comparable. The sensitivity was greatly improved when these diagnostic modalities were combined. As expected, the selective UT cytology evaluation had superior sensitivity in detecting UTUC than did the lower tract cytology sampling.

Prognostic value of prior history of urothelial carcinoma of the bladder in patients with upper urinary tract urothelial carcinoma: results from a retrospective multicenter study.

Patients with urothelial carcinoma (UC) often develop multifocal metachronous tumors throughout the genitourinary tract. In the present study, we evaluated the prognostic value of prior history of UC of the bladder (UCB) in patients with upper tract urothelial carcinoma (UTUC) in an international multi-institutional cohort. Data from 785 patients who underwent radical nephroureterectomy (RNU) with ipsilateral bladder cuff resection at nine academic institutions in Europe and the USA between 1987 and 2008 were reviewed. Log-rank tests and Cox proportional hazards regression models were used for univariable and multivariable analyses. The median follow-up of the whole cohort was 34 months (interquartile range 15-66 months). Five hundred and fifty-eight (72 %) patients had no UCB before the diagnosis of UTUC; a prior history of non-muscle-invasive and muscle-invasive UCB before the UTUC was found in 179 (23 %) and 36 (5 %), respectively. History of UCB before RNU was an independent predictor of both recurrence-free survival (p = 0.012; no UCB vs. non-muscle-invasive UCB: hazard ratio (HR) 1.4, p = 0.082; no UCB vs. muscle-invasive UCB: HR 2.1, p = 0.007) and cancer-specific survival (p = 0.008; no UCB vs. non-muscle-invasive UCB: HR 1.2, p = 0.279; no UCB vs. muscle-invasive UCB: HR 2.3, p = 0.008) on multivariable Cox regression analyses that included age, gender, surgical type, stage, grade, presence of concomitant carcinoma in situ, presence of lymphovascular invasion, and lymph node status. Prior history of muscle-invasive UCB was significantly associated with an increased risk of disease recurrence and cancer-specific death in patients with UTUC.

Chronic Kidney Disease and Upper Tract Urothelial Carcinomas

Upper tract urothelial carcinomas (UTUC) have high prevalence rates in patients with chronic kidney disease (CKD), including dialysis patients and kidney transplant recipients. Analgesic nephropathy, Balkan endemic nephropathy, and aristolochic acid (AA) nephropathy share the common association with the development of CKD and UTUC. Genome studies allow identification of patients with genetic predisposition to Balkan endemic nephropathy and AA nephropathy. Furthermore, the identification of aristolactam deoxyribonucleic acid (DNA) adducts now provides robust evidence for AA exposure in UTUC patients, even in the absence of recallable exposure history. Diagnosis and treatment of UTUC in CKD patients are challenging. Clinical diagnosis of UTUCs in CKD patients with the available urological and imaging methods is much more difficult than in patients with normal renal function due to atrophic kidneys and poor excretory functions in these patients. High prevalence rates of contralateral upper tract and urinary bladder involvements of UC in CKD, either at presentation or recurrence, raise concerns of the necessity and techniques as well as perioperative risk of complete urinary tract exenteration. The standard treatment of radical nephroureterectomy with bladder cuff excision for UTUC patients may result in deterioration of renal function, rendering adjuvant chemotherapy unsuitable. This special issue collectively addresses these important topics regarding UTUC in CKD patients. The authors in one paper nominate three mutant genes (CELA1, HSPG2, and KCNK5) in Balkan endemic nephropathy patients, which are associated with angiogenesis. This finding suggests that angiogenesis might play an important role in the development of Balkan endemic nephropathy. Another paper shows an elevated risk of urothelial carcinomas (UC) in ESRD patients with the analysis of a national wide cohort in Taiwan. Female patients have 9–18 folds of increased risk of UC as compared to 4–14 folds in male ESRD patients, which may reflect female predominance in AA consumption. One paper discusses the challenges of UTUC diagnosis in CKD patients. It reviews the detection rate of UTUCs in dialysis patients and kidney transplant recipients with the use of a variety of imaging and urological methods in the literature. Combination use of urological and imaging methods has been suggested for diagnosing UTUCs in symptomatic dialysis patients and kidney transplant recipients. Another paper develops a predictive model for postoperative renal insufficiency in UTUC patients undergoing radical nephroureterectomy, which help in selecting eligible patients for cisplatin based adjuvant chemotherapy. Older age, lower estimated glomerular filtration rate before surgery, smaller tumor size, renal pelvis tumor, and absence of hydronephrosis or multifocal tumors are predictors for ineligibility for adjuvant chemotherapy. One paper describes modified incision complete urinary tract exenteration for UC in dialysis patients, providing short operative time, early oral feeding, and no major perioperative complications of this modified surgical procedure. Another paper reviews epidemiological evidence of AA exposure associated with occurrence of nephropathy and UC, including AA exposure scenarios in Belgium, Taiwan, and the Danube River as well as occupational exposure in Chinese herbalists. The identification of aristolactam DNA adducts in these patients further corroborates biological plausibility of AA exposure contributing to the occurrence of UTUC. Li-Jen Wang Joelle L. Nortier Bin Tean Teh Cheng-Keng Chuang Shen-Yang Lee

Ureteroscopic Biopsy of Upper Tract Urothelial Carcinoma: Comparison of Basket and Forceps

To compare two different biopsy devices for upper tract urothelial carcinoma (UTUC) and evaluate the pathologic result obtained by these devices. From January 2008 to December 2010, 414 ureteroscopies were performed and 504 biopsies were taken for evaluation of UTUC. Two biopsy devices were compared: 2.4F stainless steel flat wire basket and 3F cup biopsy forceps. The effect of the biopsy device on obtaining an adequate pathologic specimen was evaluated using univariate and multivariate binary logistic regression analysis. We also investigated whether tumor grade determination was affected by the biopsy device among patients with a diagnostic biopsy. Diagnosis was successful in 63% and 94% in the forceps and basket groups, respectively (P < 0.0001). Among biopsies with a definite diagnosis of UTUC, specific grade was determined in 80% and 93% in the forceps and basket groups, respectively (P = 0.033). In subgroup analysis of tumors larger than 10 mm in diameter, diagnosis was obtained in 80% and 94% in the forceps and basket groups, respectively (P = 0.037). Cytologic evaluation was found to increase diagnostic rates. The stainless steel flat wire basket was shown to be superior to the 3F cup biopsy forceps in terms of obtaining tissue diagnosis and providing specific grade.

Prognostic significance of non-muscle-invasive bladder tumor history in patients with upper urinary tract urothelial carcinoma

ObjectiveTo evaluate the prognostic factors for survival and disease recurrence in patients treated surgically for upper tract urothelial carcinoma (UTUC), focusing especially on the impact of history of non-muscle-invasive bladder cancer. Patients and methodsA single-center series of 221 consecutive patients who were treated surgically for UTUC between January 1999 and December 2010 was evaluated. Patients who had a history of bladder tumor at a higher stage than the upper tract disease, preoperative chemotherapy, or previous contralateral UTUC were excluded. None of the patients included in this study had distant metastasis at diagnosis of UTUC. In total, 183 patients (mean age 66 years, range 36–88) were then available for evaluation. Tumor multifocality was defined as the synchronous presence of 2 or more pathologically confirmed tumors in any upper urinary tract location (renal pelvis or ureter). All patients were treated with either open radical nephroureterectomy (RNU) or open conservative surgery. Recurrence-free probabilities and cancer-specific survival were estimated using the Kaplan-Meier method and Cox regression analyses. ResultsFifty-one patients (28%) had previous carcinoma not invading bladder muscle. Previous history of non-muscle-invasive bladder cancer was significantly associated with tumor multifocality (P < 0.001), concomitant bladder cancer (P < 0.001), higher tumor stage (P = 0.020), and lymphovascular invasion (P = 0.026). Using univariate analyses, history of non-muscle-invasive bladder cancer was significantly associated with an increased risk of both any recurrence (HR = 2.17; P = 0.003) and bladder-only recurrence (HR = 3.17; P = 0.001). Previous carcinoma not invading bladder muscle (HR = 2.58; P = 0.042) was an independent predictor of bladder-only recurrence. Overall 5-year disease recurrence-free (any recurrence and bladder-only recurrence) survival rates were 66.7% and 77%, respectively. Previous history of non-muscle-invasive bladder cancer was not associated with cancer-specific survival. Our results are subject to the inherent biases associated with high-volume tertiary care centers. ConclusionsPatients with previous history of non-muscle-invasive bladder cancer had a higher risk of having multifocal and UTUC with higher tumor stages (pT3 or greater). History of bladder tumor was an independent predictor of bladder cancer recurrence but had no effect on non-bladder recurrence, and cancer-specific survival in patients who underwent surgical treatment of UTUC.

A delay in radical nephroureterectomy can lead to upstaging

Prognosis (case series). 4. To examine the association between the delay from diagnosis of upper-tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU), and the pathological features and outcomes, as the decision to proceed to RNU for an individual patient is complex. The records of 187 patients who had RNU were reviewed; the interval from diagnosis to RNU was analysed as both a continuous (months) and categorical variable (<3 vs > or =3 months). Logistic regression and survival analyses were used to evaluate the association between time from diagnosis to RNU with pathological characteristics and clinical outcomes. The median time from diagnosis to RNU was 45 days (interquartile range 68). A delay from diagnosis to RNU analysed as a continuous variable was associated with advanced stage, higher grade, previous endoscopic procedure, tumour necrosis, infiltrative tumour architecture, and lymphovascular invasion (P = 0.034), but not disease recurrence or cancer-specific mortality. In the subgroup of patients (90, 48.1%) who had muscle-invasive disease (> or =pT2) a longer delay from diagnosis to RNU as a continuous variable was associated with advanced stage (P = 0.030), higher grade (P = 0.014), infiltrative tumour architecture (P = 0.044), lymphovascular invasion (P = 0.034), disease recurrence (P = 0.02), and cancer-specific mortality (P = 0.03). Our data suggest that a delay in the interval from diagnosis to RNU is associated with more advanced disease stage. These findings might have important implications for trial design in the ongoing evaluation of neoadjuvant regimens. Timely consideration of definitive treatment for patients with high-risk UTUC is of high importance. Further studies are necessary to validate these hypothesis-generating findings.