European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2017 Update

Context

The European Association of Urology (EAU) Guidelines Panel on Upper Urinary Tract Urothelial Carcinoma (UTUC) has prepared updated guidelines to aid clinicians in the current evidence-based management of UTUC and to incorporate recommendations into clinical practice.

European Guidelines on Upper Tract Urothelial Carcinomas: 2013 Update

Context

The European Association of Urology (EAU) guideline group for upper tract urothelial carcinoma (UTUC) has prepared updated guidelines to aid clinicians in assessing the current evidence-based management of UTUC and to incorporate present recommendations into daily clinical practice.

Objective

To provide a brief overview of the EAU guidelines on UTUC as an aid to clinicians in their daily clinical practice.

Evidence acquisition

The recommendations provided in the current guidelines are based on a thorough review of available UTUC guidelines and articles identified using a systematic search of Medline. Data on urothelial malignancies and UTUCs in the literature were searched using Medline with the following keywords: urinary tract cancer; urothelial carcinomas; upper urinary tract, carcinoma; renal pelvis; ureter; bladder cancer; chemotherapy; nephroureterectomy; adjuvant treatment; instillation; neoadjuvant treatment; recurrence; risk factors; nomogram; and survival. References were weighted by a panel of experts.

Evidence synthesis

There is a lack of data in the current literature to provide strong recommendations (ie, grade A) due to the rarity of the disease. A number of recent multicentre studies are now available, and there is a growing interest in UTUC in the recent literature. Overall, 135 references have been included here, but most of these studies are still retrospective analyses. The TNM 2009 classification is recommended. Recommendations are given for diagnosis as well as radical and conservative treatment (ie, imperative and elective cases); additionally, prognostic factors are discussed. Recommendations are also provided for patient follow-up after different therapeutic options.

Conclusions

These guidelines contain information for the management of individual patients according to a current standardised approach. Physicians must take into account the specific clinical characteristics of each individual patient when determining the optimal treatment regimen including tumour location, grade, and stage; renal function; molecular marker status; and medical comorbidities.     

European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update. European Association of Urology Guideline Group for urothelial cell carcinoma of the upper urinary tract

ContextThe European Association of Urology (EAU) Guideline Group for urothelial cell carcinoma of the upper urinary tract (UUT-UCC) has prepared new guidelines to aid clinicians in assessing the current evidence-based management of UUT-UCC and to incorporate present recommendations into daily clinical practice.ObjectiveThis paper provides a brief overviewof the EAU guidelines on UUT-UCC as an aid to clinicians in their daily practice.Evidence acquisitionThe recommendations provided in the current guidelines are basedon a thorough reviewof available UUT-UCC guidelines and papers identified using a systematic search of Medline. Data on urothelial malignancies and UUT-UCCs in the literature were searched using Medline with the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract, carcinoma, transitional cell, renal pelvis, ureter, bladder cancer, chemotherapy, nephroureterectomy, adjuvant treatment, neoadjuvant treatment, recurrence, risk factors, and survival. A panel of experts weighted the references.Evidence synthesisThere is a lack of data in the current literature to provide strong recommendations due to the rarity of the disease. A number of recent multicentre studies are now available, whereas earlier publications were based only on limited populations.However, most of these studies have been retrospective analyses. The TNM classification 2009 is recommended. Recommendations are given for diagnosis as well as for radical and conservative treatment; prognostic factors are also discussed. Recommendations are provided for patient follow-up after different therapeutic options.ConclusionsThese guidelines contain information for the diagnosis and treatment of individual patients according to a current standardised approach. When determining the optimal treatment regimen, physicians must take into account each individual patient's specific clinical characteristics with regard to renal function including medical comorbidities; tumour location, grade and stage; and molecular marker status.     

European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update

Context

The European Association of Urology (EAU) Guideline Group for urothelial cell carcinoma of the upper urinary tract (UUT-UCC) has prepared new guidelines to aid clinicians in assessing the current evidence-based management of UUT-UCC and to incorporate present recommendations into daily clinical practice.

Objective

This paper provides a brief overview of the EAU guidelines on UUT-UCC as an aid to clinicians in their daily practice.

Evidence acquisition

The recommendations provided in the current guidelines are based on a thorough review of available UUT-UCC guidelines and papers identified using a systematic search of Medline. Data on urothelial malignancies and UUT-UCCs in the literature were searched using Medline with the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract, carcinoma, transitional cell, renal pelvis, ureter, bladder cancer, chemotherapy, nephroureterectomy, adjuvant treatment, neoadjuvant treatment, recurrence, risk factors, and survival. A panel of experts weighted the references.

Evidence synthesis

There is a lack of data in the current literature to provide strong recommendations due to the rarity of the disease. A number of recent multicentre studies are now available, whereas earlier publications were based only on limited populations. However, most of these studies have been retrospective analyses. The TNM classification 2009 is recommended. Recommendations are given for diagnosis as well as for radical and conservative treatment; prognostic factors are also discussed. Recommendations are provided for patient follow-up after different therapeutic options.

Conclusions

These guidelines contain information for the diagnosis and treatment of individual patients according to a current standardised approach. When determining the optimal treatment regimen, physicians must take into account each individual patient's specific clinical characteristics with regard to renal function including medical comorbidities; tumour location, grade and stage; and molecular marker status.     

Das Urothelkarzinom des oberen Harntraktes

Upper urinary tract urothelial carcinoma (UTUC) is an uncommon but potentially lethal disease. Accurate risk stratification remains a challenge owing to the difficulty of clinical staging. Identification of risk factors may lead to individualized treatment and patient counselling and holds the potential to improve outcome. A non-systematic PubMed/Medline literature research was performed to identify and summarize clinical and pathological risk factors and urine-based markers which are associated with clinical outcome.Although knowledge of potential prognostic factors has improved over the last 5 years the overall evidence on UTUC risk factors remains limited and prospective, randomized trials are still missing. Radical nephroureterectomy is currently standard treatment for high-grade and muscle invasive UTUC. Several clinical and pathological factors (e.g. stage, grade, age, hydronephrosis, lymphovascular invasion, tumor necrosis and architecture, delay between diagnosis and surgery) were identified to be associated with outcome. Urinary cytology and fluorescence in-situ hybridization are the most commonly used urinary markers.Prospective randomized controlled trials are urgently needed to identify new risk factors and assess the efficacy. The incorporation of such prognosticators into multivariable prediction models may help to guide decision-making with regard to type of treatment, performance of lymphadenectomy and consideration of neoadjuvant or adjuvant systemic therapy.     

Distinct patterns and behaviour of urothelial carcinoma with respect to anatomical location: how molecular biomarkers can augment clinico-pathological predictors in upper urinary tract tumours

Purpose

Upper urinary tract urothelial carcinoma (UTUC) shares many similarities with bladder-UC, but there is strong evidence on a clinical, aetiological, epidemiological and genetic level that key differences exist. In this review, we aim to highlight how UTUC differs from bladder-UC and report on the utility of molecular markers in the diagnosis and management of UTUC.

Materials and methods

A systematic literature search was conducted using the Medline and Embase databases and specific keyword combinations: ‘urothelial carcinoma’, ‘bladder cancer’, ‘transitional cell carcinoma’, ‘upper tract’, ‘upper urinary tract’, ‘genetics’, ‘prognosis’ and ‘biomarkers’.

Results

UTUC has specific acquired (e.g. Balkans nephropathy, phenacetin abuse) and genetic hereditary non-polyposis colorectal cancer risk factors compared with bladder-UC. In general, the molecular biology of UC is broadly similar, irrespective of location in the urinary tract. However, there are distinct genetic (microsatellite instability) and epigenetic (hypermethylation) differences between some UTUC and bladder-UC. Clinical-pathological variables (e.g. hydronephrosis, tumour architecture, tumour location, stage and grade) have independent predictive power in UTUC, but tissue and urinary biomarkers can improve the clinical prediction of recurrence, invasion and survival in UTUC, though the evidence level is weak.

Conclusions

UTUC shares many similarities with bladder-UC, but there is strong evidence that they should be considered as distinct urothelial entities. Prospective multi-institutional studies investigating molecular markers are urgently needed to augment clinic-pathological predictors in UTUC.     

Conservative treatment of upper urinary tract tumors

The histological appearance and the clinical behaviour of upper urinary tract urothelial tumours are almost identical to those of the bladder. Superficial papillary tumours rarely progress and turn to invasive disease despite a high frequency of recurrence. Technical developments in the endourology field have allowed full endoscopic access to upper tract tumours. Endoscopic resection or ablation of the tumour can be undertaken safely and effectively through ureteroscopy or percutaneous nephroscopy with low risk of extra-renal tumour seeding. For superficial (Ta, T1), low grade (I, II) tumours, a conservative approach can be selected without compromising survival and prognosis. For muscle invasive > T2 or high grade (III) tumours, nephroureterectomy remains the treatment of choice. Intracavitary BCG used after percutaneous resection reduces the risk of recurrence of upper tract urothelial tumours regardless of the grade. Finally, the world literature and our personal experience have shown that the tumour grade and stage are the two independent factors that affect survival of patients with upper urinary tract tumours.     

机器人辅助技术在双侧上尿路尿路上皮癌治疗中的应用和研究进展

上尿路尿路上皮癌(Upper tract urothelial carcinoma,UTUC)是一种泌尿系相对罕见的疾病,其双侧发病则更为罕见。病因学上,UTUC和膀胱癌有一些共同的致病因素,但两种疾病在临床特征和外科治疗上则不尽相同。随着泌尿外科腹腔镜手术的普及,腹腔镜下根治性肾-输尿管切除术和膀胱袖口状切除术(Laparoscopic nephroureterectomy with bladder cuff excision,LNUBCE)已经成为泌尿外科治疗UTUC的主流方法。机器人外科手术系统因其直观清晰的手术视觉效果和较高的灵敏度,弥补了腹腔镜手术存在的缺陷,使机器人根治性肾-输尿管切除术和膀胱袖口状切除术(Robotic nephroureterectomy with bladder cuff excision,RNUBCE)逐渐被大家所接受。本文对近年机器人手术系统在双侧上尿路尿路上皮癌治疗中的应用和研究进展进行综述。     

International validation of the prognostic value of subclassification for AJCC stage pT3 upper tract urothelial carcinoma of the renal pelvis

Study Type – Prognosis (inception cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Tumour stage is a powerful predictor of clinical outcomes and the most important factor driving clinical decision‐making after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC). It has been suggested that renal pelvic pT3 subclassification into microscopic infiltration of the renal parenchyma (pT3a) versus macroscopic infiltration or invasion of peripelvic adipose tissue (pT3b) has strong prognostic value. This is an external validation study of the prognostic value of pT3 subclassification of renal pelvic UTUC in a large international cohort of patients treated with RNU. pT3b UTUC is associated with features of aggressive tumour biology, disease recurrence and cancer‐specific mortality. However, pT3 subclassification is not an independent predictor of clinical outcomes.

OBJECTIVE

• ? To externally validate the prognostic value of subclassification of pT3 renal pelvic upper tract urothelial carcinoma (UTUC) in a large international cohort of patients treated with radical nephroureterectomy (RNU).

PATIENTS AND METHODS

• ? The RNU specimens with pT3 UTUC of the renal pelvis from 284 patients at 11 centres located in Asia, North America and Europe were retrospectively evaluated. All specimens were reviewed by genitourinary pathologists at each institution. Tumours were categorized as pT3a (microscopic infiltration of the renal parenchyma) or pT3b (macroscopic infiltration of the renal parenchyma and/or infiltration of peripelvic adipose tissue).

RESULTS

• ? Overall, 148 (52%) tumours were classified as pT3a and 136 (48%) as pT3b. Patients with pT3b disease were more likely to have high‐grade tumours and sessile tumour architecture (all P≤ 0.02). Patients with pT3b tumours were at increased risk of disease recurrence (5‐year estimates: 55% versus 42%, P= 0.012) and cancer‐specific mortality (CSM) (5‐year estimates: 48% versus 40%, P= 0.04). Lymph node status, tumour architecture and tumour grade were independently associated with disease recurrence, whereas lymph node status, tumour architecture and lymphovascular invasion were independently associated with CSM. Subclassification of pT3 tumours was not associated with recurrence or CSM in multivariable analyses.

CONCLUSION

• ? Patients with pT3b UTUC were more likely to have tumours with aggressive pathological features and were at higher risk of disease recurrence and CSM after RNU compared with patients with pT3a disease. However, the pT3 subclassification did not remain an independent predictor of disease recurrence or CSM after controlling for tumour grade, lymph node status, tumour architecture and lymphovascular invasion.

     

Guía clínica del carcinoma urotelial de vejiga no músculo-invasivo de la Asociación Europea de Urología. Actualización de 2011

Context and objectiveTo present the 2011 European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC).Evidence acquisitionLiterature published between 2004 and 2010 on the diagnosis and treatment of NMIBC was systematically reviewed. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned.Evidence synthesisTumours staged as Ta, T1, or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection (TUR) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TUR is essential for the patient's prognosis. Where the initial resection is incomplete or where a high-grade or T1 tumour is detected, a second TUR should be performed within 2-6 wk. In papillary tumours, the risks of both recurrence and progression may be estimated for individual patients using the scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups (separately for recurrence and progression) is pivotal to recommending adjuvant treatment. For patients with a low risk of tumour recurrence and progression, one immediate instillation of chemotherapy is recommended. Patients with an intermediate or high risk of recurrence and an intermediate risk of progression should receive one immediate instillation of chemotherapy followed by a minimum of 1 yr of bacillus Calmette-Guérin (BCG) intravesical immunotherapy or further instillations of chemotherapy. Papillary tumours with a high risk of progression and CIS should receive intravesical BCG for 1 yr. Cystectomy may be offered to the highest risk patients, and it is at least recommended in BCG failure patients.ConclusionsThese abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice.     

Long term outcomes of ureteroscopic management of upper tract urothelial carcinoma

ObjectivesUpper tract urothelial carcinoma (UTUC) is relatively rare. While nephroureterectomy is considered the gold standard for treatment, endoscopic nephron- sparing techniques have emerged for select cases with equivalent cancer specific survival (CSS). We present the largest series with longest follow-up to date of retrograde ureteroscopy as the primary treatment of UTUC.MethodsA retrospective review was performed of 258 patients diagnosed with UTUC who were initially evaluated and managed by a single surgeon. Patients were followed from 1994 to 2017. Clinical records were evaluated for patient and tumor characteristics, operative parameters and outcomes. Statistical analysis was performed to identify risk of recurrence, progression, cancer and overall survival.ResultsFollowing exclusion criteria, 168 patients were evaluated. Average tumor size on initial excision was 16.8mm. Mean age of the cohort was 70 years, with mean follow-up of 5.53 years. The 5-year overall survival was 80.9%, but CSS was 92.6%. Recurrence free survival was 30% with average tumor size on recurrence of 6.39mm. Progression free survival was 75% with a renal preservation rate of 71.4%.ConclusionsUreteroscopic management of UTUC is a successful alternative to nephroureterectomy in select cases of UTUC. With strict surveillance protocols to manage frequent local recurrence rates, it is possible to achieve high renal preservation rates with acceptable CSS, even in the long-term.     

Nefroureterectomía radical asistida por robot para el carcinoma urotelial del tracto urinario superior: resultados peri y postoperatorios

IntroductionThe treatment of urothelial tumours of the upper urinary tract at high risk of specific mortality is based on radical nephroureterectomy. Robotic-assisted laparoscopic radical nephroureterectomy (RARNU) is still under investigation to definitively establish the safety of this procedure in the management of urothelial tumours of the upper urinary tract. The primary objective is to evaluate the intra- and postoperative safety of RARNU and, subsequently, to evaluate the medium-term oncological results.MethodsOur study is a retrospective, mono-centric study with a collection of RARNUs conducted between 1st January 2015 and 1st October 2021. The RARNUs were performed with the assistance of the Da Vinci Si® robot, then from 2017 the Da Vinci Xi® robot. Whenever possible, the entire procedure was carried out without re-docking.ResultsBetween 1st January 2015 and 1st October 2021, 29 RARNUs were carried out at our centre. Complete surgery without re-docking was possible in 80% of cases with the Da Vinci Xi® robot. One patient required conversion to open surgery due to difficult dissection. A percentage of 50 of tumours were classified as T3 or T4. The 30-day complication rate was 31%. The median length of hospitalisation was 5 days. The disease-free survival at the mean survival time (27.5 months) was of 75.2%. One patient had a recurrence in the nephrectomy compartment and no patient had a peritoneal or trocar orifice recurrence.ConclusionPerforming RARNU for the management of tumours of the upper urinary tract appears to meet the criteria of surgical safety and those of oncological safety.     

Seguimiento oncológico después de cistectomía radical basado en patrones de recidiva tumoral y sus factores de riesgo

ContextFollowing cystectomy, approximately 50% of patients will present tumour recurrence. A recurrence may be local, systemic or occur in the urethra or upper urinary tract.ObjectiveTo analyse the characteristics, risk factors and outcomes of patients with tumour recurrence following cystectomy so as to subsequently propose a cancer follow-up protocol.Acquisition of evidenceAnalysis of original articles and reviews related to tumour recurrence and follow-up after radical cystectomy for urothelial tumour. Articles were obtained from Pubmed searches.Summary of the evidenceSystemic and local recurrences following cystectomy appear in 20%-35% and 5%-15% of cases, respectively. Some 80%-90% are diagnosed in the first 3 years, with the majority concentrated in the first 24 months. Common factors related to an increased risk of local and systemic recurrence are a pathologic stage ≥ pT3, the presence of positive margins and the extension of the lymphadenectomy. The incidence of recurrence in the upper urinary tract and urethra is 2%-6% and 4%-6%, respectively. Both types of recurrence may appear late and share risk factors such as signs of multifocal disease, a history of non-muscle-invasive bladder cancer, multiplicity, presence of ISC, urinary tract tumours and prostatic urethral tumours. Tumours in the distal ureteral cystectomy specimen and tumours in the prostatic urethra are also risk factors related to the appearance of tumours in the urinary tract and urethra, respectively.ConclusionUnderstanding the natural history of urothelial bladder carcinoma and the risk factors related to the appearance of tumour recurrence following cystectomy are essential for designing an appropriate follow-up protocol. The follow-up of patients with risk factors for local or systemic recurrence will achieve maximum efficiency during the first 3 years. The follow-up should be extended for patients with risk factors for presenting upper urinary tract or urethral tumours.     

Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ confined urothelial carcinoma following radical nephroureterectomy

ObjectiveCarcinoma in situ (CIS) is associated with increased risk of progression when found with high-grade non-muscle-invasive bladder cancer, yet its impact is less clear in the upper urinary tract. In the current study, we evaluated the impact of concomitant CIS on recurrence-free survival and cancer-specific survival following radical nephroureterectomy for upper tract urothelial carcinoma (UTUC).Materials and methodsA multi-institutional retrospective cohort of 1,387 patients undergoing radical nephroureterectomy was identified. Concomitant CIS was defined as the presence of CIS in association with another pathologic stage; patients with CIS alone were excluded from the analysis. The presence of concomitant CIS served as the exposure variable with disease recurrence and cancer-specific mortality as the outcomes. Organ-confined disease was defined as AJCC/UICC stage II or lower.ResultsConcomitant CIS was identified in 371 of 1,387 (26.7%) patients and was significantly more common in patients with a previous bladder cancer history, high grade, and high stage tumors. In a multivariable analysis, concomitant CIS was a predictor of disease recurrence (HR = 1.25, P = 0.04) and cancer specific mortality (HR = 1.34, P = 0.05) for patients with organ-confined UTUC, but not in the entire cohort. Other prognostic variables, such as grade, stage, lymphovascular invasion, and lymph node status, were associated with poorer overall and recurrence-free survival for all patients.ConclusionThe presence of concomitant CIS in patients with organ-confined UTUC is associated with a higher risk of recurrent disease and cancer-specific mortality. This information may be useful in refining surveillance protocols and in more appropriate selection of patients for adjuvant chemotherapy.     

Secondary bladder cancer after upper tract urothelial carcinoma in the US population

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? It is known that a certain percentage of patients treated for upper tract urothelial carcinoma (UTUC) will go on to develop a secondary bladder cancer; however, the risk factors for developing a secondary bladder tumour have not been studied in a population‐based setting. Given the large changes in how UTUC has been diagnosed and managed in recent years, this study aimed to evaluate the natural history of UTUC in the US population over a 30‐year period, with a particular emphasis on the development of secondary bladder cancer.

OBJECTIVE

• ? To assess the natural history of upper tract urothelial carcinoma (UTUC) and the development of lower tract secondary cancer.

PATIENTS AND METHODS

• ? Patients diagnosed with UTUC between 1975 and 2005 were identified within nine Surveillance, Epidemiology and End Results registries.
• ? Baseline characteristics of patients with and without secondary bladder cancer were compared.
• ? A multivariate logistic regression model was fitted to test if the year of diagnosis predicted the likelihood of developing a secondary bladder cancer.

RESULTS

• ? Of the 5212 patients with UTUC, 242 (4.6%) had a secondary bladder cancer (range: 1.7–8.2%).
• ? There was a mean interval of 26.5 (95% CI: 22.2–30.8) months between cancer diagnoses.
• ? Compared with those without secondary tumours, patients with secondary bladder malignancy were more likely to present with larger tumours (4.2 vs 3.1 cm, P < 0.001) and with tumours located in the ureter (P < 0.001).
• ? Year of diagnosis was not a predictor of the likelihood of having a secondary bladder malignancy in a multivariate analysis controlling for demographic and tumour characteristics (odds ratio: 0.99; 95% CI: 0.95–1.03)

CONCLUSIONS

• ? Patients with larger urothelial tumours located in the ureter were those most likely to develop a secondary lower tract tumour.
• ? No longitudinal changes in the rate of secondary bladder cancer were noted among patients with UTUC over the 30‐year study period.

     

Synchronous and metachronous urothelial carcinoma of the upper urinary tract and the bladder: Are they clonally related? A systematic review

Purpose: Following radical nephroureterectomy for upper urinary tract urothelial carcinoma (UTUC), intravesical recurrence (IVR) is found in 22% to 47% of patients. Patients with a primary urothelial carcinoma of the bladder (UCB) have an increased risk of a future UTUC (1%–5%). Paired UTUC and UCB might represent clonally related tumors due to intraluminal seeding of tumor cells or might be separate entities of urothelial carcinoma caused by field cancerization. We systematically reviewed all the relevant literature to address the possible clonal relation of UTUC and paired UCB. Materials and Methods: MEDLINE, EMBASE, and COCHRANE databases were systematically searched for relevant citations published between January 2000 and July 2019. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Of 5038 citations identified, 86 full papers were screened, and 9 studies met the inclusion criteria. Results: The populations studied and the molecular techniques used to assess clonality of UTUC and paired UCB differed largely over time. Eight studies reported on primary UTUC and meta- or synchronous IVR without a history of UCB. A total of 118 tumors (55 UTUC and 63 IVR) from 49 patients were included, of which 94% seemed to be clonally related. Five studies reported on primary UCB and subsequent UTUC with a total of 61 tumors (30 UCB and 31 UTUC) from 14 patients; a possible clonal origin was identified for 85% of the tumors. Conclusion: Taking into account the limitations of microsatellite technology in comparison to Next Generation Sequencing and currently accepted concepts of tumor heterogeneity and evolution, this systematic review shows that most, if not all, UTUC and paired UCB likely are clonally related.     

FISH analysis of washing urine from the upper urinary tract for the detection of urothelial cancers

Introduction

To evaluate FISH analysis of washing urine from the upper urinary tract (UUT) in comparison with cytology (Cyt) for the detection of urothelial cancers.

Patients and methods

In 82 patients with symptoms or abnormalities of the UUT sampling of washing urine for FISH and Cyt and a stepwise diagnostic work-up (e.g. retrograde ureteropyelography, ureterorenoscopy and endoscopic biopsy) were performed. In case of endoscopically and/or histologically proven malignancy patients either underwent nephroureterectomy, partial ureterectomy or local treatment. Sensitivity and specificity for FISH and Cyt as well as its combination were determined.

Results

Urothelial cancer of the UUT was detected in 20 patients. Eleven patients underwent nephroureterectomy, six partial ureterectomy and three endoscopic tumour treatment. This revealed nine pTa, three pT1 and seven muscle-invasive tumours. Twelve tumours were classified as low and seven as high-grade tumours. In one patient with a macroscopic unequivocal finding of tumour, endoscopic laser ablation without histologic confirmation was performed. FISH was evaluable in 76 patients and detected 16 tumours with a sensitivity and specificity of 84.2 and 91.1 %, respectively. Cyt was performed in 79 and was evaluable in 78 patients. It detected ten tumours with a sensitivity and specificity of 52.6 and 91.4 %, respectively. Cyt and FISH together detected 19 tumours with (sensitivity 100 % and specificity 83.6 %).

Conclusion

FISH was more sensitive than and equally specific to Cyt in the detection of urothelial cancers of the UUT. Both markers in combination revealed the best sensitivity, making it a possible approach in future settings.     

Ureteroscopic and percutaneous management of upper tract urothelial carcinoma (UTUC): systematic review

What's known on the subject? and What does the study add? Endoscopic management of upper tract urothelial carcinoma (UTUC) using either ureteroscopy and laser ablation, or percutaneous resection, is a management option for treating selected low‐grade tumours with favourable characteristics. However, the evidence base for such practice is relatively weak, as the reported experience is mainly limited to small case series (level of evidence 4), or non‐randomised comparative studies that are unmatched for tumour stage (level of evidence 3b), with variability of follow‐up duration and reported outcome measures. The present systematic review comprehensively reviews the outcomes of all studies of endoscopic management of UTUC, including the role of topical adjuvant therapy. It establishes for the first time a structured reference for endoscopic management of UTUC, and is a foundation for further clinical studies.

OBJECTIVE

• ? To systematically review the oncological outcomes of upper tract urothelial carcinoma (UTUC) treated with ureteroscopic and percutaneous management.
• ? The standard treatment of UTUC is radical nephroureterectomy (RNU). However, over the last two decades several institutions have treated UTUC endoscopically, either via ureteroscopic ablation or percutaneous nephroscopic resection of tumour (PNRT), for both imperative and elective indications.

METHODS

• ? For evidence acquisition the Pubmed database was searched for English language publications in December 2011 using the following terms: upper tract (UT) transitional cell carcinoma (TCC), upper tract TCC, UTTCC, upper tract urothelial cell carcinoma, upper tract urothelial carcinoma, UTUC, endoscopic management, ureteroscopic management, laser ablation, percutaneous management, PNRT, conservative management, ureteroscopic biopsy, biopsy, BCG, mitomycin C, topical therapy.

RESULTS

• ? There are no randomised trials comparing endoscopic management with RNU. Most published studies were retrospective case series (and database reviews), or unmatched comparative studies.
• ? There was strong selection bias for favourable tumour characteristics in many endoscopically treated groups.
• ? There was variation in medical comorbidity and indication for treatment across different study groups.
• ? The biopsy verification of underlying UTUC pathology was inconsistent.
• ? The follow‐up in most studies was limited, typically to a mean 3 years.

CONCLUSIONS

• ? There is a high rate of UT recurrence with endoscopically managed UTUC, and a grade‐related risk of tumour progression and disease‐specific mortality.
• ? Overall, renal preservation may be high with ≈20% of patients proceeding eventually to RNU. For highly selected Grade 1 (or low‐grade) disease managed in experienced centres, 5‐year disease‐specific survival (DSS) may be equivalent to RNU, although the small study groups and short follow‐ups preclude comments on less favourable Grade 1 (or low‐grade) tumour characteristics, or DSS, in the longer‐term.
• ? For Grade 3 (or high‐grade) disease, DSS outcomes are poor and endoscopic management should only be considered for compelling imperative indications in the context of the patient's overall life expectancy and competing comorbidity.

     

Upper urinary tract disease: what we know today and unmet needs

Purpose

Upper tract urothelial carcinoma (UTUC) is a rare and poorly investigated disease. Intense collaborative efforts have increased our knowledge and improved the management of the disease. The objective of this review was to discuss recent advances and unmet needs in UTUC.

Methods

A non-systematic Medline/PubMed literature search was performed on UTUC using the terms “upper tract urothelial carcinoma” with different combinations of keywords. Original articles, reviews and editorials in English language were selected based on their clinical relevance.

Results

UTUC is a disease with specific epidemiologic and risk factors different to urothelial carcinoma of the bladder (UCB). Similarly to UCB, smoking increases the risk of UTUC and worsens its prognosis, whereas aristolochic acid (AA) exposure and mismatch repair genes abnormality are UTUC specific risk factors. A growing understanding of biological pathways involved in the tumorigenesis of UTUC has led to the identification of promising prognostic/predictive biomarkers. Risk stratification of UTUC is difficult due to limitations in staging and grading. Modern imaging and endoscopy have improved clinical decision-making, and allowed kidney-sparing management and surveillance in favorable-risk tumors. In high-risk tumors, radical nephroureterectomy (RNU) remains the standard. Complete removal of the intramural ureter is necessary with inferiority of endoscopic management. Post-RNU intravesical instillation has been shown to decrease bladder cancer recurrence rates. While the role of neoadjuvant cisplatin based combination chemotherapy and lymphadenectomy are not clearly established, the body of evidence suggests a survival benefit to these. There is currently no evidence for adjuvant chemotherapy (AC) in UTUC.

Conclusions

Despite growing interest and understanding of UTUC, its management remains challenging, requiring further high quality multicenter collaborations. Accurate risk estimation is necessary to avoid unnecessary RNUs while advances in technology are still required for optimal kidney-sparing approaches.     

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.