Upper urinary tract instillations in the treatment of urothelial carcinomas: a review of technical constraints and outcomes

Objectives

The role of topical upper urinary tract instillation as adjuvant treatment after conservative management of urothelial carcinomas remains unclear. The aim of this article was to review available techniques and protocols proposed to treat urothelial carcinomas of the upper tract (UTUC).

Methods

Evidence acquisition on UTUC topical instillations was performed by a Medline search using combinations of the following key words: urothelial carcinomas; upper urinary tract; renal pelvis; ureter; adjuvant therapy; recurrence; bacillus Calmette-Guérin (BCG); mitomycin C. A total of 36 publications were included in analysis.

Results

Different approaches have been reported for instillation of the upper tract (UT): percutaneous nephrostomy, retrograde catheterisation and vesico-ureteral reflux. Currently, BCG and mitomycin C are the most commonly agents used for topical treatment of UTUC. A role for BCG in the management of UT carcinoma in situ (CIS) has been demonstrated in retrospective studies, although a definitive efficacy of adjuvant topical therapy after endoscopic resection of Ta/T1 tumours has not yet been proven. No individual study has shown a statistical improvement in survival and recurrence rates.

Conclusion

Currently BCG instillation should be considered as first-line treatment for UT CIS managed conservatively in carefully selected patients. The place for adjuvant topical instillation after ablation of Ta/T1 tumours is less evident and should be evaluated on an individual basis.     

Intrarenal bacillus Calmette-Guérin therapy for carcinoma in situ of the upper urinary tract: long-term follow-up and natural course in cases of failure

OBJECTIVE: To assess the long-term efficacy of intrarenal bacillus Calmette-Guérin (BCG) therapy for the treatment of cytologically diagnosed upper tract carcinoma in situ (CIS) and report the time course in cases of failure. PATIENTS AND METHODS: Fourteen renal units in 11 patients cytologically diagnosed as having upper urinary tract (UUT) CIS were treated with intrarenal BCG instillation. The BCG solution was administered by retrograde ureteric catheterization weekly for 6 weeks. RESULTS: Seven units were radiologically and cytologically free of disease at a median follow-up of 60 months. Two units which showed an initial response had recurrence with ipsilateral UUT CIS. The remaining five units did not respond to BCG. Of seven units with an initial negative response or recurrent UUT CIS, nephroureterectomy was undertaken in one because of coincidental renal cell carcinoma. In four of the remaining six units, invasive pelvic tumour developed at a mean follow-up of 20.5 months after the final instillation. Computed tomography showed wall thickening of the renal pelvis in two and mass-forming tumour in the renal parenchyma mimicking renal cell carcinoma in two. In three of these four cases, retrograde pyelography did not show typical findings of renal pelvic tumour, e.g. filling defect, infundibular obstruction or stenosis. CONCLUSIONS: Intrarenal BCG is effective in the treatment of UUT CIS in a long-term follow-up. In cases with a poor response or ipsilateral recurrence of CIS, there is a high risk of developing invasive tumour. Close follow-up using computed tomography is recommended because of the atypical radiographic findings of such tumours.     

Bacillus Calmette-Guérin Failure in Patients with Non–Muscle-invasive Urothelial Carcinoma of the Bladder May Be Due to the Urologist's Failure to Detect Urothelial Carcinoma of the Upper Urinary Tract and Urethra

BackgroundVarious reasons exist for so-called bacillus Calmette-Guérin (BCG) failure in patients with non–muscle-invasive urothelial bladder carcinoma (NMIBC).ObjectiveTo explore whether urothelial carcinoma of the upper urinary tract (UUT) and/or prostatic urethra may be a cause for BCG failure.Design, setting, and participantsRetrospective analysis of 110 patients with high-risk NMIBC repeatedly treated with intravesical BCG, diagnosed with disease recurrence, and followed for a median time of 9.1 yr.InterventionTwo or more intravesical BCG induction courses without maintenance.Outcome measurements and statistical analysisPrimary outcome was pattern of disease recurrence (BCG failure) within the urinary tract categorised into UUT and/or urethral carcinoma (with or without intravesical recurrence), and intravesical recurrence alone. Secondary outcome was survival. Predictors of UUT and/or urethral carcinoma and the effect of pattern of disease recurrence on cancer-specific survival were assessed with multivariable Cox regression analysis adjusting for multiple clinical and tumour characteristics.Results and limitationsOf the 110 patients, 57 (52%) had UUT and/or urethral carcinoma (with or without intravesical recurrence), and 53 (48%) had intravesical recurrence alone. In patients with UUT and/or urethral carcinoma, bladder carcinoma in situ (Tis) before the first and second BCG course was present in 42 of 57 (74%) and 47 of 57 (82%) patients, respectively. On multivariable analysis, bladder Tis before the first and/or second BCG course was the only independent predictor of UUT and/or urethral carcinoma. Of the 110 patients, 69 (63%) were alive at last follow-up visit, 18 (16%) had died due to metastatic urothelial carcinoma, and 23 (21%) had died of other causes. Pattern of disease recurrence within the urinary tract was not an independent predictor of cancer-specific survival. Main study limitations were retrospective design and limited power for survival analysis.ConclusionsIn our patients with high-risk NMIBC failing after two or more courses of intravesical BCG, UUT and/or urethral carcinoma was detected in >50% of the cases during follow-up. The vast majority of these patients had bladder Tis before the first and/or second BCG course. In patients experiencing the so-called BCG failure, a diagnostic work-up of UUT and prostatic urethra should always be performed to exclude urothelial carcinoma before additional intravesical therapy or even a radical cystectomy is considered.     

Long-term outcome of upper urinary tract carcinoma in situ: Effectiveness of nephroureterectomy versus bacillus Calmette-Guérin therapy

BACKGROUND: We examined the long-term outcome and compared the usefulness of nephroureterectomy with that of bacillus Calmette-Guérin (BCG) therapy for the management of upper urinary tract carcinoma in situ (CIS). METHODS: We retrospectively reviewed the post-treatment course of 17 patients with CIS of the upper urinary tract who had undergone either a nephroureterectomy (group A, n = 6) or BCG therapy (group B, n = 11) at our institute. RESULTS: Median follow up was 58.3 months (range 1-120 months). Four of the six patients in group A (67%) had no recurrence and remained cystoscopically, cytologically and radiographically free of disease. The cytology became negative after an 8-week course in nine of the eleven patients in group B (82%; eight of ten units, 77%). Two of the nine patients showed recurrence after BCG therapy. One patient died of respiratory failure caused by a side-effect of BCG, which was interstitial pneumonia. There was no significant difference in either the 5-year recurrence-free survival or the 5-year cancer-specific survival between groups A and B. CONCLUSIONS: BCG therapy for CIS of the upper urinary tract is as effective as nephroureterectomy in long-term outcome, although it has some dangerous aspects. Further experience with treatment of CIS of the upper urinary tract is required.     

Percutaneous Bacillus Calmette-Guerin perfusion of the upper urinary tract for carcinoma in situ]

We performed percutaneous perfusion of the upper urinary tract with Bacillus Calmette-Guerin (BCG) in 3 patients. Two of them had undergone unilateral nephrectoureterectomy for ureter carcinoma in situ and one had undergone radical cystectomy with bilateral ureterocutaneostomy for invasive bladder carcinoma. However, they suffered recurrent upper urinary tract carcinoma in situ within 2 years after their operation. Under ultrasound control a percutaneous nephrostomy tube was placed in the patient. Before BCG perfusion unobstructed flow from the renal pelvis to the bladder was confirmed and pyelovenous or pyelolymphatic back flow was excluded under fluoroscopy. A dose of 240 mg BCG was dissolved in 150 ml 0.9% saline. The flask was placed 20 cm above the kidney of the resting patient. A continuous flow of approximately 1 ml per minute was maintained. The perfusion was stopped after 2 hours and the nephrostomy tube was closed. Therapy was repeated at weekly intervals for a total of 6 perfusions (1 treatment course). In each of them urine cytology results became negative after 1 treatment course. No severe side effects were observed. Further investigation is also needed to determine whether BCG perfusion of the upper urinary tract could become a conservative treatment for carcinoma in situ of the upper urinary tract.     

Diagnostic and Prognostic Factors in Non-Muscle-Invasive Bladder Cancer and Their Influence on Treatment and Outcomes

ObjectivesThis paper explores the diagnostic and staging procedures available for bladder cancer, the prognostic factors for recurrence and progression of non-muscle-invasive tumours, and the indications for intravesical therapy and cystectomy in patients with non-muscle-invasive, recurrent disease.MethodsThe authors reviewed the literature on diagnosis of bladder cancer, prognostic factors for recurrence and progression of non-muscle-invasive disease, and the indications for intravesical therapy and cystectomy.ResultsThe presence of malignant cells at urinary cytology suggests a high-grade tumour in the urinary tract, but negative urinary cytology does not exclude a low-grade cancer. Transurethral resection of the bladder (TURB) is undertaken in non-muscle-invasive bladder tumours to aid diagnosis and to remove visible lesions and is more effective when guided by blue-light fluorescence than by white light. Repeated TURB may be required because of the risk of residual tumour after initial TURB. A tool from the European Organisation for Research and Treatment of Cancer (EORTC) can be used to assess an individual patient's risk of bladder cancer recurrence and progression. Further treatment options are intravesical chemotherapy, intravesical bacille Calmette-Guérin (BCG) immunotherapy, and cystectomy. Immediate cystectomy is advocated by many specialists for patients with non-muscle-invasive tumour who are at high risk of progression or who do not respond to BCG therapy.ConclusionsUrinary cytology and TURB (preferably under the guidance of fluorescence cystoscopy if carcinoma in situ is suspected) are the mainstays of bladder cancer diagnosis and staging. The likelihood of recurrence or progression can be assessed using a tool developed by the EORTC that is based on common prognostic factors. Patients with disease progression can be offered cystectomy.     

Results of conservative treatment of upper urinary tract transitional cell carcinoma

BACKGROUND: The treatment preserving the kidney for upper urinary tract tumor is still controversial. The indications and results of conservative treatment remain to be elucidated. Experiences of this type of treatment are reported. METHODS: Between April 1981 and March 1998, 14 patients with upper urinary tract transitional cell carcinoma were treated with renal preserving methods. Five were elective and nine were imperative cases. Treatments performed were partial nephrectomy, partial ureterctomy with or without adjuvant chemotherapy, endoscopic tumor resection and topical bacillus Calmette-Guerin instillation in one, 10, two and one patient, respectively. RESULTS: Crude and cause-specific 5 year-survival rates were 91.7 and 100%, respectively. Of 14 patients, five had bladder recurrences, but ipsilateral local recurrence developed in only one patient. Two patients died from metastasis of transitional cell carcinoma 61 and 89 months after initial treatment. The lesions of carcinoma in situ were well controlled with topical bacillus Calmette-Guerin therapy. CONCLUSION: The results of conservative treatment for upper urinary tract tumor were satisfactory and local excision can be indicated for low grade, solitary tumors located in the distal ureter.     

Neo/Adjuvant Therapy in Upper Tract Urothelial Carcinoma

ObjectivesUrothelial carcinoma of the renal pelvis and ureter is a relatively uncommon malignancy. The majority of patients present at a stage in which disease has not penetrated through the muscularis (Tis–T2). These patients are generally treated with radical nephroureterectomy or with renal-sparing procedures in select patients, and overall the prognosis is favorable in this group. However, in patients in whom disease has spread beyond the muscularis and involved adjacent tissues, organs, or lymph nodes, the prognosis is significantly worse, making it important to consider adjuvant or neoadjuvant therapy.MethodsLiterature search using PubMed was conducted to identify the related articles that formed the basis of this review.ResultsThe role of adjuvant external beam radiotherapy in improving local control and survival is unclear both because of the limited number of patients and because of the contradictory results of different studies. Neoadjuvant chemotherapy and concurrent cisplatin administration during radiotherapy appears as an important factor in terms of survival at 5 yr. Similarly, available data in the literature indicate that neo/adjuvant systemic chemotherapy after nephroureterectomy may provide therapeutic benefit in patients with invasive transitional cell carcinoma of the upper urinary tract.ConclusionsAdjuvant radiation therapy after radical upper urinary tract surgery has no impact upon clinical outcome, whereas systemic adjuvant or neoadjuvant chemotherapy does provide significantly better oncologic results.     

Clinical outcome of bacillus Calmette-Guérin perfusion therapy for carcinoma in situ of the upper urinary tract.

BACKGROUND: The objective of this study was to evaluate the efficacy of intrarenal bacillus Calmette-Guérin (BCG) instillation for the treatment of carcinoma in situ (CIS) of the upper urinary tract. METHODS: Sixteen patients who were diagnosed as having CIS of the upper urinary tract were treated with intrarenal BCG instillation. BCG (80 mg) in normal saline was administered once weekly, 6 times in total as one course through a percutaneous nephrostomy tube in 5 patients, and a retrograde ureteric catheterization using a Single-J or Double-J stent in 2 and 9 patients, respectively. RESULTS: During the median follow-up period of 30 months (range: 9-90 months), no patients died, and 13 patients remained cytologically negative in urine collected from the upper urinary tract after BCG treatment was completed. However, one of these 13 patients had CIS in the bladder and prostatic urethra 34 months after the BCG therapy and had to undergo radical cystectomy. The remaining 3 patients experienced recurrence in the upper urinary tract 4, 8, and 11 months after treatment, despite a favorable response to the initial BCG instillation. Of these 3 patients, one patient received an additional course of BCG therapy, while the remaining 2 underwent nephroureterectomy. Bladder irritability or a fever higher than 38 degrees C was observed in 12 or 9 patients, respectively; however, such side-effects were not clinically significant, and no patient received antitubercular treatment. CONCLUSION: Intrarenal instillation of BCG appears to be effective and safe for treatment of CIS of the upper urinary tract; however, further experience and longer follow-up studies of this treatment are required.     

Prognostic factors in patients with carcinoma in situ treated with intravesical bacille Calmette-Guérin

OBJECTIVE: To report prognostic factors and follow-up data for an unselected group of patients with carcinoma in situ (CIS) of the urinary bladder treated with bacille Calmette-Guérin (BCG). MATERIAL AND METHODS: The clinical records of patients with CIS treated with BCG were reviewed. All 173 patients treated between 1986 and 1997 in four hospitals in two Swedish cities were included. The median follow-up period was 72 months (range 6-154 months). The impact of 18 variables on the times to recurrence and progression was studied using multivariate Cox proportional hazard regression and Kaplan-Meier analyses. RESULTS: No pre-treatment variables, including type of CIS and T1G3 tumour, had prognostic value in terms of time to progression. The result of the first cystoscopy had a very strong prognostic importance: 44% of patients with a positive first cystoscopy progressed in stage, 59% were BCG failures and 35% died from urothelial cancer. The corresponding values for patients with a negative first cystoscopy were 11%, 18% and 8%. Fourteen patients (8%) were diagnosed with an upper urinary tract tumour but no variable had prognostic significance. The diagnoses of the upper urinary tract tumours were evenly distributed during follow-up. CONCLUSIONS: We were not able to predict which patients would respond favourably to BCG. Cystectomy should be strongly considered even after a positive first cystoscopy. The accumulated incidence of patients with bladder CIS and a subsequent upper urinary tract tumour is rather high but it is questionable whether the prognosis will improve if routine follow-up urographies are performed.     

Sequential intravesical gemcitabine and mitomycin C chemotherapy regimen in patients with non-muscle invasive bladder cancer

ObjectivesCurrently, there are few options other than cystectomy for the management of BCG refractory non-muscle invasive bladder cancer. We report our experience with intravesical combination chemotherapy using gemcitabine and MMC in such patients.Materials and methodsWe identified all patients with non-muscle invasive bladder cancer who were BCG refractory or intolerant and had been treated with intravesical gemcitabine and MMC at our institution. Patients were treated with a combination of intravesical gemcitabine (1000 mg in 50 ml sterile water) followed sequentially by intravesical MMC (40 mg in 20 ml sterile water) every week for 6 weeks (induction). Induction therapy was followed by a maintenance regimen using the same dose of gemcitabine and MMC once a month for 12 months. Data regarding patient demographics and disease information such as previous intravesical therapy, previous cystoscopy, cytology results, time to recurrence, and side effect profile were collected.ResultsA total of 10 patients (6 male and 4 female) aged 48 to 85 years (median 67 years) underwent treatment with a median follow-up of 26.5 months (4–34 months). Six patients were recurrence free and have maintained their response at a median of 14 months (4–34 months). Four patients had biopsy proven recurrence. Median time to recurrence was 6 months (range 4–13 months). The therapy was well tolerated in all patients. There were no major complications. Two patients experienced irritative lower urinary tract symptoms, which did not require cessation of therapy and one experienced a maculopapillary rash that improved with benadryl.ConclusionsIn patients with recurrent BCG refractory bladder cancer, intravesical combination chemotherapy with gemcitabine and MMC appears to be well tolerated and yields a response in a good proportion number of patients.     

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.     

Ureteroscopic management of upper tract transitional cell carcinoma

The expanding experience with endoscopic techniques for treating upper tract urothelial malignancy demonstrates its safety and efficacy in carefully selected patients. Diagnostic accuracy can be enhanced, and pathologic confirmation of tumor grade and stage is possible. In carefully selected patients who have low-grade and low-stage disease, the results of endourologic management have been encouraging. Patients with an anatomic or functionally solitary kidney, bilateral disease, or significant renal insufficiency can often be considered candidates for endoscopic treatment as the first line of therapy. In the setting of low-grade, low-stage disease in a patient with a normal contralateral kidney, the role of endourologic management remains controversial. Adjuvant topical therapy with mitomycin C or BCG seems to be safe and well tolerated after endoscopic management of upper tract TCC.     

Long-term outcome of initial treatment with Bacillus Calmette-Guérin for carcinoma in situ of the upper urinary tract

To assess appropriate treatment strategies for transitional cell carcinoma in situ (CIS) of the upper urinary tract (UUT), we evaluated the long-term outcome of Bacillus Calmette-Guérin (BCG) perfusion therapy for CIS of UUT. We retrospectively reviewed the medical records of 24 patients who underwent BCG perfusion therapy for CIS of UUT between August 1993 and August 2009. Patients received at least one course of BCG (once weekly for 6 weeks). The median follow-up period was 48.5 months (range 16-201 months). In 23 patients (96%), cytology became negative after one course of BCG perfusion and 12 patients (50%) remained disease-free for a median follow-up of 38. 5 months. In 11 patients positive cytology recurred, and in five of them nephroureterectomy was performed after radiologic studies showed the presence of a tumor in the UUT. Histopathology showed invasive tumor (pT3) in all cases, and three of them experienced distant metastases after surgery. In conclusion, BCG perfusion therapy is effective for the treatment of CIS of UUT with long-term follow-up. However, in cases with a poor response or recurrence of CIS, there is a high risk of developing invasive tumor. Surgical intervention should be immediately considered in such cases after the first course of BCG perfusion therapy.     

Bacillus Calmette-Guérin perfusion therapy for the treatment of transitional cell carcinoma in situ of the upper urinary tract

OBJECTIVES: The aim of this study is to evaluate the efficacy and safety of intrarenal bacillus Calmette-Guérin (BCG) instillation as a treatment for transitional cell carcinoma in situ (CIS) of the upper urinary tract. METHODS: Diagnostic criteria of upper urinary tract CIS were (1) positive urinary cytology, (2) negative multiple random biopsy of the bladder and prostatic urethra, (3) negative radiographic findings in the upper urinary tract and (4) two serial positive cytologies in selective ipsilateral urine sampling from the pyeloureteral system. Eleven patients diagnosed as having upper urinary tract CIS were enrolled in this study. Thus, 11 renal units were treated with BCG instillation. After placing a 6-french Double-J stent, BCG (80 mg) in 40 ml saline was instilled into the bladder weekly, 6 times in total as one course. RESULTS: At the end of one course, 9 cases showed negative urinary cytology. Among these 9 cases, 2 showed recurrence in the upper urinary tract after 4 months and 8 months of disease-free interval, respectively. These 2 cases have received an additional course of BCG instillation, but the urinary cytology did not normalize. Mean recurrence-free time was 19.6 months. Of the other 7 cases who responded to the first course of instillation, 6 cases were alive with no evidence of the disease. The remaining patient died of rectal cancer with no evidence of transitional cell carcinoma (TCC). Of the 2 cases who showed positive urinary cytology even after the first course, 1 underwent nephroureterectomy. The other case was diagnosed as having malignant lymphoma 3 months after the end of this instillation therapy, and he died of malignant lymphoma. As side effects, 8 cases (72.7%) showed bladder irritability, and 4 presented fever higher than 38 degrees C. However, no patient needed antitubercular treatment. CONCLUSION: As for the short-term response, BCG instillation for the treatment of upper urinary tract CIS is considered to be effective and safe. Longer follow-up and further experience with this treatment are required.     

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.     

Percutaneous nephroscopic management of upper urinary tract transitional cell carcinoma: recurrence and long-term followup

PURPOSE: We present long-term results of the percutaneous approach and resection of upper urinary tract transitional cell carcinoma, and we evaluate the prognostic factors related to recurrence. MATERIALS AND METHODS: A total of 34 patients underwent primary percutaneous resection of an upper urothelial tumor. We treated the patients with a superficial tumor that was completely resected macroscopically. Adjuvant topical chemotherapy or immunotherapy was administered. Patients were followed with excretory urography. Ureteroscopy and computerized tomography were obtained when clinically indicated. RESULTS: With a mean followup of 51 months ipsilateral recurrence developed in 41.2%. Median time to recurrence was 24 months. The rate of kidney preservation was 73.5%. Two patients died of the disease. There was a trend of recurrence in patients with multifocal tumors (OR 2.66, 95% CI 0.07-1.92), history of bladder carcinoma in situ (OR 2.4, 95% CI 1.61-3.74), tumor in renal pelvis (OR 6.45, 95% CI 0.01-1.46) and multiple tumor locations (OR 6.53, 95% CI 0.01-1.54). CONCLUSIONS: The percutaneous approach to renal urothelial tumor should be considered a valid option with a good long-term outcome. Recurrence is not uncommon and, as transitional cell carcinoma superficial bladder cancer it may be treated with endourological maneuvers or radical surgery, but with the obligation to a long lasting, strict surveillance.     

Manejo del carcinoma in situ de tramo urinario superior diagnosticado por biopsia ureteroscópica: ¿es el bacilo de Calmette-Guérin una alternativa a la nefroureterectomía?

IntroductionRadical nephroureterectomy (RNU) still represents the gold standard treatment for upper tract urothelial carcinoma (UTUC); however, since the 1980s attempts have been made to treat upper urinary tract CIS (UT-CIS) conservatively. The aim of this study was to compare the outcome of patients with primary UT-CIS treated in our center by means of RNU vs. bacillus Calmette-Guérin (BCG) instillations.MethodsThis retrospective study included patients with diagnosis of primary UT-CIS between 1990 and 2018. All patients had histological confirmation of UT-CIS in the absence of other concomitant UTUC. Histological confirmation was obtained by ureteroscopy with multiple biopsies. Patients were treated with RNU, distal ureterectomy, or BCG instillations. Clinicopathological features and outcomes were compared between the RNU and BCG groups.ResultsA total of 28 patients and 29 renal units (RUs) were included. Sixteen (57.1%) patients (17 RUs) received BCG. BCG was administered via a nephrostomy tube in 4 patients, a single-J ureteral stent in 5, and a Double-J stent in 7. Complete response and persistence or recurrence were detected in ten (58.8%) and seven (41.2%) RUs treated with BCG, respectively. Eight (27.6%) RUs underwent RNU, with contralateral recurrence detected in four (50%), and 4 (13.8%) RUs underwent distal ureterectomy. No differences were found in recurrence-free survival (p = 0.841) and cancer-specific survival (p = 0.77) between the RNU and BCG groups.ConclusionsAlthough RNU remains the gold standard treatment for UT-CIS, our results confirm that BCG instillations are also effective. Histological confirmation of UT-CIS is mandatory before any treatment.     

The outcome of patients on dialysis with upper urinary tract transitional cell carcinoma

PURPOSE: Transitional cell carcinoma is the most common upper urinary tract cancer in Taiwanese patients on dialysis. It is a unique finding compared with Western countries. Unfortunately, the long-term outcomes of patients with upper urinary tract transitional cell carcinoma on dialysis are largely unknown. This study presents clinical outcome of patients on dialysis with upper urinary tract transitional cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all patients with upper urinary tract transitional cell carcinoma who had end stage renal disease and underwent dialysis. Traditional prognostic factors including age, sex, tumor grade, stage and tumor location were analyzed with respect to disease recurrence and survival. RESULTS: A total of 73 patients were included in this study. The major complaints were painless gross hematuria and urethral bloody discharge. Disease relapsed in 40 (54.8%) patients at average time of 15 months (2 to 92). Univariate analysis failed to identify significant prognostic factors for recurrence. The average duration between primary and contralateral metachronous upper urinary tract transitional cell carcinoma recurrence was 36 months (range 5 to 96). Patients on dialysis with upper urinary tract transitional cell carcinoma who had previous or concurrent bladder tumor, or who had a history of recurrent bladder tumor, had high contralateral upper urinary tract transitional cell carcinoma recurrence. (p = 0.038) The statistically significant prognostic factor for disease-free survival was pT stage (p = 0.041). CONCLUSIONS: Patients on dialysis with painless gross hematuria or bloody urethral discharge must undergo detail urinary system evaluation. Since patients with upper urinary tract transitional cell carcinoma on dialysis have a high recurrence rate and metachronous or even multiple, early synchronous tumor characteristics that may be missed by imaging, total urinary tract exenteration is a recommended therapeutic option.     

Long-term intravesical adjuvant chemotherapy further reduces recurrence rate compared with short-term intravesical chemotherapy and short-term therapy with Bacillus Calmette-Guérin (BCG) in patients with non-muscle-invasive bladder carcinoma

OBJECTIVE: We present a randomised, parallel group, multicentre phase 4 trial comparing short- and long-term chemoprophylaxis with Mitomycin C (MMC) with short-term immunoprophylaxis with Bacillus Calmette-Guérin (BCG) after transurethral resection of the bladder for non-muscle-invasive bladder carcinoma. METHODS: Four hundred ninety-five patients with intermediate- to high-risk non-muscle-invasive bladder cancer (recurrent and/or multifocal pTaG1, TaG2-3, and T1G1-3) were randomised to BCG RIVM 2 x 10(8) CFU weekly for 6 wk, MMC 20 mg weekly for 6 wk, or MMC 20 mg weekly for 6 wk followed by monthly instillations for 3 yr. RESULTS: The 3-yr recurrence-free rates were 65.5% (95%CI, 55.9-73.5%) for short-term BCG, and 68.6% (59.9-75.7%) for short-term MMC, whereas recurrence-free rates were significantly increased to 86.1% (77.9-91.4%) in patients with MMC long-term therapy (log-rank test, p=0.001). CONCLUSIONS: Long-term MMC significantly reduced the risk of tumour recurrence without enhanced toxicity compared with both short-term BCG and MMC in patients with intermediate- and high-risk non-muscle-invasive bladder carcinoma. Our data provide a rationale for maintenance intravesical chemotherapy in this population.