Bladder and upper tract urothelial cancer

PURPOSE: While there are data available indicating the incidence and prevalence of bladder and upper tract urothelial cancer, population level data on resource use, costs and patterns of care for these cancers are limited. We quantified the economic impact of caring for patients with bladder and upper tract urothelial cancer, and determined the primary drivers for such costs in the population in the United States. MATERIALS AND METHODS: The analytical methods used to generate these results have been described previously. RESULTS: An increasing proportion of patients with bladder and upper tract urothelial cancer were being treated in the outpatient setting. Most care was provided by urologists and visit frequency was directly related to disease stage. Only a small proportion of patients potentially eligible for chemotherapy, ie those with advanced disease, sought specialized care from oncologists. Office based diagnostic tests such as cytology were not commonly done, although a substantial number of patients with bladder cancer underwent cystoscopy. The use of excretory urography in these patients was decreasing, while the use of computerized tomography was increasing. Ileal conduits were the most frequently performed type of urinary diversion following cystectomy. The cystectomy rate remained unchanged for a decade. Intravesical therapy was done infrequently in patients with bladder cancer. Annual costs for treating bladder and upper urinary tract cancers were $1 billion and $64 million, respectively, in 2000. These costs represented a $164 million increase over 1994 levels, which outpaced inflation. CONCLUSIONS: The costs of treating bladder cancer increased steadily during a 6-year period despite a decrease in inpatient care. Coupled with a lack of substantial change in transurethral resection and cystectomy rates, this suggests that the primary cost drivers are increased outpatient testing, eg computerized tomography and cystoscopy, and an increase in the number of diagnosed cases. Greater focus on selective use of testing modalities, preventive care such as smoking cessation and earlier identification of patients at risk may help curtail further expenditure with regard to managing bladder and upper urinary tract cancers.     

A clinical study on 34 cases of urothelial cancer of upper urinary tract

Thirty-four cases of tumor of the renal pelvis or ureter or both have been treated in our department during the past decade. The primary tumor was in the renal pelvis in 11 cases, in the ureter in 21 cases and in the ureter and renal pelvis in 2 cases, a co-existent tumor in the bladder was found in 4 cases. Seventeen patients had a tumor on the right side and 17 on the left side. The most frequent symptom was gross hematuria (70.6%) and flank pain was the presenting symptom in 7 cases (20.6%). On the intravenous pyelography, a filling defect in the renal pelvis or ureter (41.2%) and nonvisualization (53.0%) were frequent findings. Twenty-nine cases had undergone total nephroureterectomy with resection of a bladder cuff, 3 had simple nephrectomy and 2 had open biopsy alone. Postoperative radiation therapy was done in 1 case, chemotherapy in 10 cases, and 6 cases of them were treated by CAP therapy (cis-dichlorodiamine platinum, doxorubicin and cyclophosphamide). Actual and relative 5-year survival rates were 53.8% and 63.5%, and no significant difference was found in survival rate between the patients with renal pelvic tumors and those with ureteral tumors.     

Local excision of urothelial cancer of the upper urinary tract

In 9 of 93 patients (9.7%) with urothelial cancer of the upper tract (7 renal pelvis tumors, 3 ureteral tumors), conservative surgery was employed using a free peritoneal autotransplant for replacement of the renal pelvis in 5 kidneys. Absolute indications for conservative surgery were solitary kidneys/nonfunctioning contralateral kidneys in 4 patients and bilateral tumors in 1 patient. Local recurrences developed 1-3 years after operation in 4 of 6 kidneys (3 patients), 3 of which had grade-2 and grade-3 primary lesions. All patients were treated successfully by repeated local excision. In the presence of a normal contralateral kidney, local tumor excision was done electively in 4 patients (3 low-grade/low-stage lesions, 1 high-risk patient), none of these patients developed recurrences. Two patients died without evidence of tumor recurrence, 7 patients are free of tumor at an average follow-up of 23 months (range 5-65 months). Local excision of urothelial cancer should be considered not only for solitary kidneys, bilateral tumors and cases with renal failure, but also for low-stage/low-grade localized tumors, leaving the patient better prepared for later treatment of a possible recurrence due to the well recognized chance of a multiplicity of tumors in time and space.     

Clinical significance of lymphovascular invasion in upper urinary tract urothelial cancer

OBJECTIVES

To clarify the significance of lymphovascular invasion (LVI) in patients with pT3N0M0 upper urinary tract (UUT) urothelial carcinoma (UC) relative to prognosis in terms of disease‐specific survival, as LVI, which implies both blood vessel and lymph vessel involvement, is reportedly a poor prognostic factor in patients with UUT‐UC.

PATIENTS AND METHODS

The clinical records of 90 patients who had surgery for UUT‐UC were reviewed retrospectively. The median patient age was 71 years and the median follow‐up was 42 months. The prognostic significances of LVI (with vs without), T stage (<1 vs 2–4), grade (1–2 vs 3), N stage (0 vs 1–2), age (≤70 vs >70 years), gender and tumour location (renal pelvis vs ureter) for survival time were evaluated.

RESULTS

LVI of UUT‐UC was found in 34 patients (37.8%). There were significantly higher frequencies of LVI with advancing stage and lymph node metastasis. Kaplan‐Meier analysis showed that LVI was strongly associated with disease‐specific survival in all patients (P < 0.001) and in patients with pT3N0M0 disease (P < 0.001). Univariate analyses showed that LVI, T stage, N stage and tumour grade were significantly related to disease‐specific survival in all patients (P < 0.001, <0.001, 0.003 and 0.007, respectively). Multivariate analysis using Cox proportional hazards model showed that LVI was the only prognostic factor with independent significance for disease‐specific survival (P < 0.001).

CONCLUSIONS

LVI appears to be an important and independent prognostic factor for UUT‐UC in patients treated by nephroureterectomy. Our data suggest that the LVI status might be a predictive marker for disease‐specific survival in patients with T3N0M0 UTT‐UC.     

Lymphadenectomy at the time of nephroureterectomy for upper tract urothelial cancer

Context

The role of lymph node dissection (LND) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial cancer (UTUC) is still controversial.

Objective

To analyze the impact of lymph node invasion on the outcome of patients, the staging, and the possible therapeutic role of LND in UTUC.

Evidence acquisition

A Medline search was conducted to identify original articles, review articles, and editorials addressing the role of LND in UTUC. Keywords included upper tract urothelial neoplasms, lymphadenectomy, lymph node excision, lymphatic metastases, nephroureterectomy, imaging, and survival.

Evidence synthesis

Regional nodes are frequently involved in UTUC and represent the most common metastatic site. Regional nodal status is a significant predictor of patient outcomes, especially in invasive disease. Therefore, select patients treated with RNU at high risk for regional nodal metastases should undergo LND to improve disease staging, which would identify those who could benefit from adjuvant systemic therapy. Several retrospective studies suggested the potential therapeutic role of LND in UTUC. An accurate LND could remove some nodal micrometastases not identified on routine pathologic examination, thus improving local control and cancer-specific survival. Radical surgery and LND might be curative in a subpopulation with limited nodal disease, as described in bladder cancer. A clear knowledge of the limits of LND and a template of LND for UTUC are still needed.

Conclusions

An extended LND can provide better disease staging and may be curative in patients with limited nodal disease. However, current evidence is based on retrospective studies, which limits the ability to standardize either the indication or the extent of LND. Prospective trials are required to determine the impact of LND on survival in patients with UTUC and identify patients for a risk-adapted approach such as close follow-up or adjuvant chemotherapy.     

The emerging role of lymphadenectomy in upper tract urothelial carcinoma

Within the last decade, there has been an increased focus on lymphadenectomy or lymph node dissection (LND) in patients with upper tract urothelial carcinoma (UTUC). Although the data with regards to LND in UTUC are sparse, investigators are beginning to evaluate the role and define the anatomy to understand how LND may affect outcomes in patients with UTUC. This article reviews the history of LND for UTUC, outlines the relative anatomy, and evaluates the arguments and evidence for, and against, LND in patients with UTUC.     

Risk factors for the development of bladder cancer after upper tract urothelial cancer

OBJECTIVES: To determine the clinical and pathologic risk factors for initial intravesical recurrence in patients with primary renal pelvic and/or ureteral cancer and to examine the progression in the bladder in patients having high risk factors for intravesical recurrence. METHODS: This study included 69 patients with renal pelvic and/or ureteral cancer. We excluded patients with distant metastases, those with a short period of follow-up, and those having a previous history or concomitance of bladder cancer. The exclusion criteria were chosen to avoid contamination by patients with a poor prognosis who might die of the primary cancer before bladder cancer development. Multivariate analysis by Cox's proportional hazards model was used to determine what clinical and pathologic variables significantly affected the initial intravesical recurrence of cancer. We also studied the stage progression of cancer that recurred in the bladder. RESULTS: Initial intravesical recurrence of the cancer was found in 22 patients during a median follow-up period of 53 months (range 12 to 225). The intravesical disease-free rate after upper tract urothelial cancer was 65% (rate of disease recurrence in bladder 35%) at 5 years by the Kaplan-Meier method. The extent (multifocality) of the upper urinary cancer (P = 0.0038) and pathologic stage (P = 0.0409) independently influenced intravesical recurrence. Age, sex, adjuvant chemotherapy, configuration of the primary tumor, primary cancer size, and pathologic grade did not affect recurrence. The rate of stage progression also was not influenced by the extent of the disease in the upper urinary tract. CONCLUSIONS: The extent and pathologic stage of cancer in the upper urinary tract were significant and independent factors for initial intravesical recurrence of cancer. However, no difference was found in clinical outcome in terms of stage progression between patients having high risk factors for intravesical recurrence and those without them.     

The percutaneous treatment of upper urinary tract urothelial tumours

Summary This paper reports the management of eight upper urinary tract (UUT) transitional cell tumours (TCC) treated by percutaneous endoscopic resection (n=7) or laser coagulation. Two patients with small, solitary-low-grade TCC and negative urine cytology are free of recurrence after 2 years. Of the remainder, two died of TCC, two proceeded to nephroureterectomy for highgrade or recurrent invasive tumors, one underwent a second percutaneous resection of a recurrent superficial TCC and one was lost to follow-up. The patient who died from high-grade invasive TCC had tumour protruding from the nephrostomy track. We feel that percutaneous surgery has a very limited place in the management of UUT TCC and should be reserved for palliation of proven solitary, low-grade superficial tumours with negative cytology in patients requiring conservative treatment.     

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.

     

Impact of endourology on diagnosis and management of upper urinary tract urothelial cancer

The technique of transurethral ureteropyeloscopy was used in 43 patients with upper urinary tract urothelial tumors. Diagnosis was confirmed in 19 of 22 renal pelvic tumors (86 per cent) and 19 of 21 ureteral tumors (90 per cent). The major complication rate in this series is low (7 per cent) and did not appear to influence unfavorably subsequent management or outcome. A total of 21 patients underwent conservative endourological management of the upper tract tumor. The local recurrence rate was 20 per cent (1 of 8) for renal pelvic tumors and 15 per cent for distal ureteral tumors (2 of 13). The technique of ureteropyeloscopy should be added to the standard diagnostic regimen for the investigation of upper tract filling defects and conservative endourological techniques can be used safely for management of selected cases of upper tract urothelial tumor.     

Optimizing management of upper tract urothelial carcinoma

Upper tract urothelial cancer (UTUC) is a rare cancer of the urothelium, comprising only a fraction of cases as compared to urothelial tumors of the bladder. As a result, systemic treatment approaches in bladder cancer are often applied to patients with UTUC. Given the anatomical location of these tumors, the age, the comorbid conditions of these patients with UTUC, and the need for radical nephroureterectomy for treatment, most patients have substantial impairment of renal reserve. There is growing evidence for the benefit of perioperative chemotherapy in this disease. Patients with UTUC have high rates of microsatellite instability and fibroblast growth factor receptor 3 mutations as compared to their bladder counterparts presenting unique, important subsets in UTUC. Immune checkpoint inhibitors targeting the programmed death receptor 1 and ligand have provided a new second-line treatment option for patients with UTUC and appear particularly well suited for patients with microsatellite instability. More work in understanding the molecular gene signatures and its relationship to response to chemotherapy, immunotherapy, and targeted therapy is needed to continually optimize care for patients with all stages of disease. Advances in UTUC are possible, when one accounts for the unique clinical and biological features of this disease.     

Molecular aspects of upper tract urothelial carcinoma

ObjectivesPrimary upper tract urothelial carcinoma (UTUC) is a relatively rare tumor with up to 60% of cases being muscle invasive at presentation. In this article we review the molecular biology of UTUC, an understanding of which may help to address some of the dilemmas surrounding the diagnosis and treatment of this disease and ultimately lead to the introduction of personalized treatment plans.MethodsThe literature search on the molecular aspects of UTUC was performed using the National Library of Medicine database.ResultsUTUC and urothelial carcinomas of the bladder share many common biological pathways. UTUC are more commonly associated with conditions such as Balkan Endemic Nephropathy and Hereditary Non Polyposis Colon Cancer (HNPCC), the molecular basis of which is now being understood. A large number of potential biomarkers have been studied to help identify robust prognostic markers in UTUC.ConclusionAdvances in our understanding of the biology of UTUC is may in the future help to identify novel druggable targets, clinically applicable biomarkers and guide treatment of the rare but lethal condition.     

Upper tract urothelial cancer

Upper tract transitional cell carcinoma is a lethal disease with half the patients dead within 5 years of diagnosis. Unlike urothelial tumours arising in the bladder, the disease is more likely to be invasive at the time of diagnosis and in part reflects the poorer prognosis. It is a biologically aggressive disease with a high chance of recurrence even after local control. Diagnosis is made by a combination of upper tract imaging, urine cytology and ureteroscopic biopsy. Organ-confined disease is amenable to radical surgery, whereas superficial low-grade disease may be managed endoscopically. A number of prognostic factors have been incorporated into nomograms to predict non-organ-confined disease. Even those with apparently organ-confined disease are prone to recurrence. As a result regular surveillance protocols are in place to identify both local and metastatic spread as well as metachronous bladder lesions.     

Upper tract urothelial cancer

Upper tract transitional cell carcinoma is a lethal disease with half the patients dead within 5 years of diagnosis. Unlike urothelial tumours arising in the bladder, the disease is more likely to be invasive at the time of diagnosis and in part reflects the poorer prognosis. It is a biologically aggressive disease with a high chance of recurrence even after local control. Diagnosis is made by a combination of upper tract imaging, urine cytology and ureteroscopic biopsy. Organ-confined disease is amenable to radical surgery, whilst superficial low-grade disease may be managed endoscopically. A number of prognostic factors have been incorporated into nomograms to predict non-organ confined disease. Even those with apparently organ-confined disease are prone to recurrence. As a result regular surveillance protocols are in place to identify both local and metastatic spread as well as metachronous bladder lesions.