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.

     

Oncologic outcomes obtained after neoadjuvant and adjuvant chemotherapy for the treatment of urothelial carcinomas of the upper urinary tract: a review

Introduction

Nephroureterectomy with excision of a bladder cuff is the gold standard in the treatment of upper urinary tract carcinomas (UTUC). But especially for patients suffering from advanced tumor stages, life expectancy has not improved over the years with local recurrence or distant metastases being the main reasons for treatment failure. Chemotherapy in an adjuvant or neoadjuvant setting seems therefore to be a promising approach.

Methods

The literature of the last 20 years was searched using Medline. Articles were chosen by using the given abstracts. Only articles written in English and not older than 20 years were considered.

Results

Most information concerning chemotherapy of urothelial carcinomas is gained from studies comprising patients suffering from lower urinary tract carcinomas. The combination of methotrexate, adriamycin, vinblastine and cisplatin as well as the combination of gemcitabine and cisplatin are the most used chemotherapy regimens in advanced UCC and have shown beneficial results. The summarized data of studies for UTUC contained no level one information. Down staging effects as well as prolongation of survival have been shown for some patients treated with neoadjuvant chemotherapy, but because of the small study groups and the retrospective design, no definite conclusions can be drawn from these results. In addition, there exists an uncertainty for preoperative staging. Results for adjuvant chemotherapy are lacking.

Conclusion

No definite recommendations for peri-operative chemotherapy in UTUC can be derived from the current literature. Current therapy is largely based on extrapolation from the bladder cancer literature. Prospective studies dedicated to UTUC are needed.     

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.

Intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinomas: predictors and impact on subsequent oncological outcomes from a national multicenter study

Objectives

To identify predictive factors and assess the impact on oncological outcomes of intravesical recurrence after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC).

Methods

Using a national multicentric retrospective dataset, we identified all patients with UTUC who underwent a RNU between 1995 and 2010 (n = 482). Intravesical recurrence was tested as a prognostic factor for survival through univariable and multivariable Cox regression analysis.

Results

Overall, intravesical recurrence occurred in 169 patients (35 %) with a median age of 69.2 years (IQR: 60–76) and after a median follow-up of 39.5 months (IQR: 25–60). Actuarial intravesical recurrence-free survival estimates at 2 and 5 years after RNU were 72 and 45 %, respectively. On univariable analyses, previous history of bladder tumor, tumor multifocality, laparoscopic approach, pathological T-stage, presence of concomitant CIS and lymphovascular invasion were all associated with intravesical recurrence. On multivariable analysis, previous history of bladder cancer, tumor multifocality and laparoscopic approach remained independent predictors of intravesical recurrence. Existence of intravesical recurrence was not correlated with worst oncological outcomes in terms of disease recurrence (p = 0.075) and cancer-specific mortality (p = 0.06).

Conclusions

In the current study, intravesical recurrence occurred in 35 % of patients with UTUC after RNU. Previous history of bladder cancer, tumor multifocality, concomitant CIS and laparoscopic approach were independent predictors of intravesical recurrence. These findings are in line with recent published data and should be considered carefully to provide a definitive surveillance protocol regarding management of urothelial carcinomas regardless of the location of urothelial carcinomas in the whole urinary tract.     

Concomitant carcinoma in situ as an independent prognostic parameter for recurrence and survival in upper tract urothelial carcinoma: a multicenter analysis of 772 patients

Purpose

The purpose of this study is to assess the association of concomitant carcinoma in situ (CIS) with disease recurrence and cancer-related death in a multi-institutional series of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).

Methods

We collected retrospectively the data of 772 patients treated with RNU and ipsilateral bladder cuff excision at 9 international institutions in Asia, Europe, and Northern America from 1987 to 2008. Surgical specimens were processed according to standard pathologic procedures at each institution. Univariable and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality.

Results

Concomitant CIS was present in 88 patients (11.4%); it was associated with more advanced pathologic stage, higher tumor grade, and presence of lymphovascular invasion (all P-values?P-values?P?=?0.007) and CSS (HR: 1.7, P?=?0.048). Similar findings were reconfirmed in subgroups analyses limited to T2, organ confined, and N0/Nx UTUC, or patients who did not receive adjuvant chemotherapy.

Conclusions

Presence of concomitant CIS is an independent predictor of both RFS and CSS in patients treated with RNU for UTUC. This information may be useful in risk stratification of UTUC patients for follow-up and additional therapy.     

Salvage topical therapy for upper tract urothelial carcinoma

Purpose

Topical therapy (TT) for upper tract urothelial carcinoma (UTUC) has been explored as a kidney sparing approach to treat carcinoma in situ (CIS) and as adjuvant for endoscopically treated Ta/T1 tumors. In bladder cancer, data support use of salvage TT for repeat induction. We investigate the outcomes of salvage TT for UTUC in patients ineligible for or refusing nephroureterectomy.

Methods

A single-center retrospective review on patients receiving salvage TT via percutaneous nephrostomy tube or cystoscopically placed ureteral catheters was performed. Primary outcome was response to therapy based on International Bladder Cancer Group criteria.

Results

51 patients with 58 renal units (RUs) received TT. Of these, 17 patients with 18 RUs received the second-line TT, with a median follow-up of 36.5 months (IQR 24.5–67 months). 44% (8/18) received salvage TT for refractory disease and 56% (10/18) as reinduction. 5 RUs with CIS were unresponsive to initial TT and went on to receive salvage TT, of which 20% (1/5) responded. 13 RUs recurred or relapsed following initial TT and received salvage TT for papillary tumors, with 62% (8/13) responding.

Conclusion

Our data provide preliminary clinical rationale for the second-line TT for refractory and recurrent, endoscopically managed papillary UTUC in patients ineligible for or refusing nephroureterectomy. However, refractory upper tract CIS appears to have poor response to salvage TT.

     

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.     

Gender differences in radical nephroureterectomy for upper tract urothelial carcinoma

Purpose

Women have been associated with adverse outcomes after radical cystectomy for lower tract urothelial carcinoma. We evaluated the prognostic value of gender in an international cohort of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).

Methods

We retrospectively studied 754 patients treated with RNU for UTUC without neoadjuvant chemotherapy at nine centers located in Asia, Canada, and Europe. Univariable and multivariable Cox regression analyses were used to address recurrence-free (RFS) and cancer-specific survival (CSS) estimates. Median follow-up was 40?months (interquartile range: 18?C75).

Results

The majority of patients was of men (516, 68.4%). Women were older than men at the time of RNU (median: 69.2 vs. 66.5?years; P?=?0.0003). Women were less likely to have high-grade disease, undergo lymph node dissection, and to receive adjuvant chemotherapy. Gender was not associated with pathologic stage, lymph node metastasis, lymphovascular invasion, concomitant CIS, tumor architecture, or tumor necrosis. On univariable Cox regression analyses, there was no association between gender and cancer recurrence (P?=?0.76) or cancer-specific mortality (P?=?0.30). On multivariable Cox regression analyses that adjusted for the effects of clinicopathologic features, gender was not associated with disease recurrence (P?=?0.47) or cancer-specific survival (P?=?0.15).

Conclusions

We found no difference in histopathologic features and outcomes between men and women treated with RNU for UTUC. Nevertheless, epidemiologic and mechanistic molecular studies should be encouraged to design, analyze, and report gender-specific associations to aid in our understanding of gender impact on UTUC incidence, progression, and metastasis.     

Impact of the length of time between diagnosis and surgical removal of urologic neoplasms on survival

Objective

Our aim was to assess the effect of surgical wait time on the survival of patients with urological neoplasms, including prostate, bladder, penile, and testicular cancers and upper tract tumours (UTUC).

Materials and methods

Current, relevant studies were identified from the literature. Keywords used for article retrieval were as follows: delay; surgery; prostate cancer; urothelial carcinoma; renal cell carcinoma; testicular cancer; bladder; renal pelvis; ureter; and survival.

Results

Regarding the length of surgical wait time, it does not matter in cases of incidental T1a renal cell carcinomas. In other cases of renal cell carcinomas, surgery should be considered within <1 month; it is of crucial importance in bladder cancer and should be <1 month for a TURBT in cases of non-muscle-invasive bladder cancer and <1 month for a radical cystectomy in cases of muscle-invasive bladder cancer; it is important in invasive UTUC and should be <1 month for a radical nephroureterectomy; it is not crucial in cases of low-risk prostate cancer. In any other case, radical prostatectomy should be considered within <2 months; it is important in testicular cancer and should be fewer than 10 days for an orchiectomy.

Conclusion

Prolonged surgical wait times have an impact on the overall quality of life and anxiety of the patient. Extending the wait time beyond a given threshold can also have a negative impact on the patient’s clinical outcomes, but this threshold differs between urological neoplasms.     

Disease-free survival as a surrogate for overall survival in upper tract urothelial carcinoma

Objectives

The primary endpoint in trials of perioperative systemic therapy for urothelial carcinoma is 5-year overall survival (OS). A shorter-term endpoint could significantly speed the translation of advances into practice. We hypothesized that disease-free survival (DFS) could be a surrogate endpoint for OS in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU).

Patients and methods

The study included 2,492 patients treated with RNU with curative intent for UTUC.

Results

2/3-year DFS estimates were 78/73 %, and the 5-year OS estimate was 64 %. The overall agreements between 2- and 3-year DFS with 5-year OS were 85 and 87 %, respectively. Agreements were similar when analyzed in subgroups stratified by pathological stages, lymph node status, and adjuvant chemotherapy. The kappa statistic was 0.59 (95 % CI 0.55–0.63) for 2-year DFS/5-year OS and 0.64 (95 % CI 0.61–0.68) for 3-year DFS/5-year OS, indicating moderate reliability. The hazard ratio for DFS as a time-dependent variable for predicting OS was 11.5 (95 % CI 9.1–14.4), indicating a strong relationship between DFS and OS.

Conclusions

In patients treated with RNU for UTUC, DFS and OS are highly correlated, regardless of tumor stage and adjuvant chemotherapy. While significant differences in DFS, assessed at 2 and 3 years, are highly likely to persist in OS at 5 years, marginal DFS advantages may not translate into OS benefit. External validation is necessary before accepting DFS as an appropriate surrogate endpoint for clinical trials investigating advanced UTUC patients.     

Predictive tools for clinical decision-making and counseling of patients with upper tract urothelial carcinoma

Background

Upper tract urothelial carcinoma (UTUC) is a rare disease with a highly heterogeneous biologic behavior. Accurate individualized prediction of the behavior of UTUC could help guide personalized clinical decision-making regarding optimal therapy.

Methods

A MEDLINE literature search was performed on UTUC predictive tools. We recorded input variables, prediction form, number of patients used to develop the prediction tools, outcomes being predicted, prediction tool-specific features, predictive accuracy, and whether internal or external validations were performed. Each prediction tool was classified according to the clinical disease state it addressed and the outcome it predicted.

Results

The literature search generated five published tools for UTUC staging and prognostication. None of these prediction tools have undergone external validation yet. Two tools focused on the clinical decision-making regarding conservative management versus radical nephroureterectomy (RNU), lymphadenectomy versus not, and neoadjuvant systemic therapy versus not. Three tools focused on the prognosis after RNU, thereby helping in the decision-making regarding adjuvant systemic chemotherapy.

Conclusions

Management of UTUC is challenging, and there are no high-level data to guide physicians and patients. Prognostic tools relying on data from large cohorts of patients are currently the best source of information for evidence-based management of UTUC patients.     

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.     

Impact of micropapillary histological variant on survival after radical nephroureterectomy for upper tract urothelial carcinoma

Purpose

To assess the impact of micropapillary histological variant on oncological outcome after radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinomas (UTUCs).

Methods

A French multicenter retrospective study was performed on patients who underwent RNU between 1995 and 2010. Pathological reports were reviewed to identify patients with pure urothelial carcinomas (PUC) and those with micropapillary histological variant (MPC). Uni- and multivariate Cox regression analyses were performed to identify factors predictive of survival.

Results

Overall, 519 patients were included and divided into two groups: 480 PUC and 39 MPC. Median follow-up were 28 and 19 months, respectively (p = 0.63). There was no difference between the two groups for gender, age and tumor location (pelvicalyceal or ureteral). MPC was associated with high-stage and high-grade UTUC (p < 0.001 and 0.04). No difference was observed between the two groups for 5-year cancer-specific survival (76.1 vs. 88.2 %; p = 0.54). The 5-year metastasis-free survival was significantly lower in the MPC group (48.9 vs. 73.8 %; p = 0.037). In multivariate analysis, pT stage, lymphovascular invasion, margin status and adjuvant chemotherapy administration were independent predictors of specific survival (p = 0.002; 0.001; 0.02; 0.01), contrary to histological variant (p = 0.94).

Conclusions

Micropapillary histological variant was associated with advanced UTUC and reduced metastasis-free survival after RNU. It should be considered as an aggressive tumor and thus be stated in any pathological report after radical surgery.     

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.     

Predictive factors of recurrence and survival of upper tract urothelial carcinomas

Objective

UTUCC is a rare tumor, and most reports on prognostic factors come from small single-center series. The objective of this article was to provide an updated overview of current clinical, pathological and biological prognostic factors of UTUC.

Methods

PubMed was searched for records from 2002 to 2010 using the terms ??prognostic factors??, ??recurrence??, ??survival??, and ??upper tract urothelial carcinoma??. Among identified citations, papers were selected based on their clinical relevance.

Results

Classical clinical factors that influence UTUC prognosis include age, presence of symptoms, hydronephrosis, and interval from diagnosis. Many biomarkers have shown promises to better appraise the natural course of UTUC although none is currently used in clinical practice. Stage, grade, lymph node metastases, lymphovascular invasion, tumor necrosis, and tumor architecture are strong pathological parameters. RNU is the standard treatment of localized UTUC. Both laparoscopic and open approaches seem to offer similar cancer control. Lymph node dissection increases staging accuracy and might confer a survival benefit.

Conclusion

RNU is the standard treatment for most patients with UTUC. Recent multicenter studies confirmed the prognostic value of classical prognostic parameters. Better survival prediction might be obtained with prognostic systems including clinical data and new biomarkers.     

A Randomized Prospective Study Comparing Long-Term Intravesical Instillations of Mitomycin C and Bacillus Calmette-Guerin in Patients with Superficial Bladder Carcinoma

Purpose

We compared the efficacy and toxicity of long-term mitomycin C versus bacillus Calmette-Guerin (BCG) instillation in patients at high risk for recurrence and progression of superficial bladder carcinoma.

Materials and Methods

Our randomized comparison study included 261 patients with primary dysplasia, or stage Tis, stage T1, grade 3 and multiple recurrent stage Ta/T1, grade 1 or 2 disease. Mitomycin C (40 mg.) or Pasteur strain BCG (120 mg.) was instilled weekly for 6 weeks, then monthly for up to 1 year and every 3 months during year 2.

Results

After a median followup of 39 months 49 percent of the patients given BCG and 34 percent given mitomycin C were disease-free (p less than 0.03), compared to 48 and 35 percent, respectively, of those with stage Ta or T1 disease, and 54 and 33 percent, respectively, of those with dysplasia or stage Tis tumor. Tumor progressed in 13 percent of patients, with no statistically significant difference observed regarding progression between the mitomycin C and BCG groups. Side effects were more common after BCG instillation, with 5 cases of severe side effects compared to 1 in the mitomycin C group. Treatment was stopped due to toxicity in 10 percent of the patients.

Conclusions

The majority of patients tolerated long-term intravesical therapy well. BCG instillation was hampered by more frequent side effects. BCG was superior regarding recurrence prophylaxis, since patients given BCG had fewer recurrences and a significantly longer time to treatment failure compared to those treated with mitomycin C. No statistically significant difference was observed regarding progression.     

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.

     

Significance of ADC value for detection and characterization of urothelial carcinoma of upper urinary tract using diffusion-weighted MRI

Purpose

To evaluate utility of diffusion-weighted magnetic resonance imaging (DWI) to detect and predict the histological characteristics of upper urinary tract urothelial carcinomas (UTUCs).

Materials and methods

We retrospectively evaluated 20 suspicious lesions from 19 patients. MRI study included conventional sequences and DWI with apparent diffusion coefficient (ADC) maps calculated between b = 0 and b = 1,000. ADC values were measured within two different regions of interest (ROI): a small identical ROI placed in the most restrictive part of the tumour and a larger ROI covering two-thirds of the mass surface. The mean ADC values of the tumours were compared with that of normal renal parenchyma using an unpaired Student’s t test. Association between ADC values and histological features was tested using non-parametric tests.

Results

Overall, 18 tumours were confirmed histologically as UTUCs. DWI failed to detect two cases of UTUCs (one CIS and one small tumour of 5 mm). There was no statistically significant difference in ADC values measured with the small or large ROI (p = 0.134). The mean ADC value of UTUC was significantly lower than that of the normal renal parenchyma (p < 0.001). No statistical association was found between ADC values and pathological features (location, p = 0.35; grade, p = 0.98; muscle-invasive disease, p = 0.76 and locally advanced stage, p = 0.57).

Conclusion

DWI may be interesting tool for detecting UTUCs regarding the difference of ADC values between the tumours and surrounding healthy tissues. In regard to low frequency of UTUCs, the association of ADC values and histological characteristics need further investigations in a large prospective multi-institutional study.     

Upper tract urothelial carcinoma following intravesical bacillus Calmette-Guérin therapy for nonmuscle-invasive bladder cancer: Results from a multi-institutional retrospective study

Objectives

The aim of this study was to clarify the prognostic indicators for upper tract urothelial carcinoma (UTUC) following intravesical bacillus Calmette-Guérin (BCG) therapy for nonmuscle-invasive bladder cancer (NMIBC).

Antegrade perfusion with bacillus Calmette-Guérin in patients with non-muscle-invasive urothelial carcinoma of the upper urinary tract: who may benefit?

Background

There is paucity of data on bacillus Calmette-Guérin (BCG) perfusion in patients with non-muscle-invasive urothelial carcinoma (NMIUC) of the upper urinary tract (UUT).

Objective

To assess the long-term results of BCG perfusion in patients with UUT NMIUC in terms of efficacy and tolerability.

Design, setting, and participants

Retrospective analysis of 55 consecutive patients (64 renal units [RUs]) with UUT NMIUC prospectively followed according to a standardised protocol for a median of 42 mo (range: 2-237 mo). Our series includes negatively selected patients, most of whom were not eligible for radical surgery, with additional invasive urothelial carcinoma of the urinary tract in roughly one-third of the cases.

Intervention

Antegrade BCG perfusion of the UUT was performed either with curative intent for carcinoma in situ (Tis; 42 RUs) or with adjuvant intent after ablation of Ta/T1 tumours (22 RUs).

Measurements

Primary outcome measures were recurrence-free, progression-free, and nephroureterectomy-free survival. The secondary outcome measure was treatment tolerability.

Results and limitations

Recurrence occurred in 30 of 64 RUs (47%), 17 of 42 (40%) with Tis and 13 of 22 (59%) with Ta/T1 tumours. Progression occurred in 11 of 64 RUs (17%), 2 of 42 (5%) with Tis and 9 of 22 (41%) with Ta/T1 tumours. Nephroureterectomy was eventually performed in 7 of 64 RUs (11%), 2 of 42 (5%) with Tis and 5 of 22 (23%) with Ta/T1 tumours. Patients treated with curative intent for Tis tended to have better recurrence-free survival (p = 0.42) and significantly better progression-free survival (p < 0.01) and nephroureterectomy-free survival (p = 0.05) compared with those treated with adjuvant intent after ablation of Ta/T1 tumours. Adverse events, mostly minor, occurred in a total of 11 patients (20%), with one case of fatal Escherichia coli septicaemia.

Conclusions

In our patients with UUT NMIUC, antegrade BCG perfusion resulted in a high kidney-preservation rate. Patients treated with curative intent for Tis apparently benefited in terms of local disease control more than those treated with adjuvant intent after ablation of Ta/T1 tumours. Treatment tolerability was good.