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.     

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.     

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.     

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.     

Efficacy of intravesical bacillus Calmette-Guerin for carcinoma in situ of bladder

Three months after an initial 6-week course ofintravesical bacillus Calmette-Guerin (BCG) given between January 1990 and March 2005, 94 (90%) out of 104 patients with carcinoma in situ (CIS) of the bladder achieved a complete response (CR). The 5- and 10-year recurrence-free rates were 67 and 60%, respectively (median follow-up 42 months). Three months after a second course ofintravesical BCG given to 23 patients who failed the initial induction course for CIS was evaluated. Of these, 96% achieved a CR, and the 5- and 10-year recurrence-free rates were 56 and 28%,respectively (median follow-up 23 months). Only one patient who received a second course of BCG therapy showed disease progression. Two of the 4 patients with BCG-refractory CIS of the bladder achieved CR after intravesical gemcitabine therapy and maintained a tumor-free status beyond 6 months. Five of the 16 patients showing disease progression had upper urinary tract cancer, 4 had recurrent or muscle invasive bladder cancer, 6 had prostatic involvement of CIS, and one patient had urethral recurrence. Three of the 16 patients died. Bladder preservation was achieved in 97 of the 104 patients, although 7 patients ultimately underwent radical cystectomy and urinary diversion for aggressive disease. In conclusion, some patients may be managed safely by repeated endoscopic resection and intravesical therapy with cystectomy postponed until objective evidence of progression exists.     

Clinical outcomes of bacillus Calmette-Guérin instillation therapy for carcinoma in situ of urinary bladder

Objectives:   We analyzed the clinical outcomes of instillation therapy with Bacillus Calmette-Guerin (BCG) to treat carcinoma in situ (CIS) and searched for prognostic factors that could predict disease progression.
Methods:   Between January 1995 and January 2001, 185 patients (male, 155; female, 30) diagnosed with bladder CIS underwent weekly BCG instillations (80 mg of Tokyo 172 strain) for eight weeks. Primary, concomitant, and secondary CIS was found in 62 (33.5%), 60 (32.4%) and 63 (34.1%), patients, respectively. Seventy-five (40.5%) and 64 (34.6%) patients had limited and extensive CIS, respectively. The median follow up period was 37.5 months (range 4–95 months).
Results:   The overall complete response rate was 86.5%. The five-year progression-free survival rate was 78.5%. Several factors, such as age (<60 or ≥60 years), gender, previous transurethral resection, type of CIS, and CIS extension (three or more positive sites out of four to six biopsy sites was defined as extensive), were examined by multivariate analysis to predict progression. The extension of CIS was the only independent prognostic factor. The five-year recurrence-free rate of complete responders ( n  = 160) was 66.0%. Radical cystectomy was performed in 10 patients (6.3%) during follow up incomplete responders, of whom seven had invasive bladder cancer. Extravesical involvement was identified in 30 patients (16.2%) among whom, 21 (11.3%) had upper urinary tract recurrence and nine (4.9%) had prostatic involvement.
Conclusion:   Therapy with BCG is effective against CIS, the extent of which might be a prognostic factor. Disease progression including extravesical involvement should be carefully monitored over the long-term after BCG therapy.     

Arthritis following intravesical instillation of BCG for urothelial cancers

BACKGROUND: Intravesical instillation of bacillus Calmette-Guerin (BCG) is efficient for prophylaxis of superficial bladder cancer and treatment for carcinoma in situ (CIS) of the upper urethelial cancer. However, the incidence of adverse effects is relatively high, and those include reactive arthritis. We retrospectively evaluated the incidence and the outcome of reactive arthritis following intravesical BCG therapy for urothelial cancers. PATIENTS AND METHODS: Intravesical instillations of BCC were performed in 192 cases (218 courses) between January 1998 and January 2002. BCG was instilled for prophylaxis of superficial bladder cancer recurrence in 170 (195 courses), treatment for CIS in 7 (8 course), and treatment for CIS in 7 (8 courses), and treatment for CIS in upper urinary tract in 15 (15 courses). RESULTS: Arthritis was recognized in 8 cases (3.7%, 8/218 courses), and 7 of them were identical to reactive arthritis following BCG therapy. Remaining 1 patient was diagnosed as rheumatoid arthritis (RA), and the relation between arthritis and intravesical BCG instillation was unclear. Mean number of BCG instillation was 5.6 (3-8 times). All reactive arthritis were occurred within 4 weeks after the last BCG instillation, i.e., BCG induced urinary tract infection, and 6 of them were polyarthritis. Concurrence of conjunctivitis was seen in one patient. HLA-B27 was negative in 4 examined patients. A nonsteroidal anti-inflammatory drug (NSAID) was used in all 8 patients, anti-tuberculous agents were used in 3, and prednisolone was added in 3, Arthritis was improved within 2 months in patients received prednisolone, however, it persisted longer than 3 months in patients without prednisolone. CONCLUSION: Arthritis was recognized in higher incidence than previous reports following intravesical instillation of BCG. All cases except one, diagnosed as RA, were diagnosed as reactive arthritis (Reiter's syndrome). However, correlation between HLA-B27 and arthritis was not clear in this study. Administration of steroidal drug was thought to improve arthritis in shorter duration.     

Oncological outcome of retroperitoneoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma

OBJECTIVE: To report the oncological outcome of retroperitoneoscopic nephroureterectomy (RNU) with bladder cuff excision for upper urinary tract transitional cell carcinoma (TCC), and to compare the outcome with that of the traditional open nephroureterectomy (ONU). PATIENTS AND METHODS: From January 2001, 48 patients with upper urinary tract TCC were enrolled in the study; 25 had RNU and 23 had ONU. Oncological parameters (disease-free survival and disease-specific survival) were calculated from the time of surgery to the date of last follow up and were analysed by the Kaplan-Meier method. RESULTS: Mean follow up was 24.3 months in the RNU group, significantly shorter than in the ONU group. Bladder recurrence was identified in two patients with grade 3 pathological stage pT3, one patient with grade 3 stage pT2 disease and two patients with grade 2 stage pT2 disease. Multiple organ metastases in the lung, liver and lymph nodes were associated with bladder recurrence in two cases (grade 2 stage pT3, and grade 3 stage pT3). The recurrence rate was 20% (5 of 25 cases) and mean time to recurrence was 9.5 months. In the ONU group, bladder recurrence and metastases developed in four and three patients, respectively. The recurrence rate was 17% (4 of 23 cases) and mean time to recurrence was 23.4 months. No significant difference was detected in the disease-free survival rate and cancer-specific survival rate between the two groups (P=0.759 and P=0.866, respectively). CONCLUSION: The oncological outcome of RNU appears to be equivalent to that of ONU. Moreover, long-term follow up is necessary to evaluate the oncological outcome in comparison to ONU.     

Role of Chemotherapy and Immunotherapy for Urinary Upper Tract Cancer

Background and objectiveThe gold standard for open radical nephroureterectomy is currently being challenged by minimally invasive procedures for upper tract tumour management. A nephron-sparing approach may be proposed in patients with an anatomic or functionally solitary kidney, bilateral disease, significant chronic renal insufficiency, or medical comorbidities in whom major surgical procedure would be poorly tolerated.Material, methods and resultsLocal recurrence has been observed in 65% of patients with endoscopically treated upper tract tumours, with an average time to recurrence of <10 mo. Adjuvant topical immunotherapy or chemotherapy agents have been reported in the literature for treatment and prophylaxis of transitional cell carcinoma. Two major techniques are usually recommended for the administration of mitomycin C (MMC) and bacillus Calmette-Guérin (BCG): perfusion through a percutaneous nephrostomy tube or by retrograde reflux from the bladder with an indwelling double-J stent in the Trendelenburg position. BCG therapy has been reported to provide cure in approximately 50% of renal units with carcinoma in situ; however, papillary and solid tumour recurrences of the urinary upper tract cannot be prevented with BCG therapy. Adjuvant therapy is considered safe, with no systemic side-effects resulting from perfusion with MMC as topical therapy following endoscopic resection of upper urinary tract carcinoma. In contrast, up to 25% of patients may have granulomatous involvement of the urinary tract after BCG administration.ConclusionThe efficacy and safety of this conservative approach warrants further evaluation, as long-term follow-up is necessary to confirm previously reported oncologic data. Moreover, adjuvant therapy may be proposed with the patient's consent, as it requires a strict ureteroscopic surveillance protocol.     

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.     

Retroperitoneal nephroureterectomy with excision of cuff of the bladder for upper urinary tract transitional cell carcinoma: comparison of laparoscopic and open surgery with long-term follow-up

OBJECTIVES: To compare outcome and long term follow up of laparoscopic retroperitoneal nephroureterectomy with excision of cuff of bladder (LRPNUT-BCE) and standard open nephroureterectomy with excision of cuff of bladder (ONUT-BCE) in patients of upper urinary tract transitional cell carcinoma (UTTCC). MATERIAL AND METHODS: From January 1998 to October 2006, we have performed over 55 cases of nephroureterectomy with excision of cuff of bladder for UTTCC. Out of these, 48 patients undergoing LRPNUT-BCE and ONUT-BCE were categorized retrospectively into group A (21), and group B (27), respectively. The clinical data including intraoperative, postoperative, and follow-up data was recorded for two groups and analyzed statistically. RESULTS: The mean operating time was significantly higher in-group A (P < 0.001). The different techniques of bladder cuff excision were used in group A. The mean analgesic use, hospital stay and weeks to normal activity were significantly lesser in-group A (P < 0.001). The intraoperative, postoperative complications and mean follow up were comparable in two groups. There was no local recurrence in either group. The bladder recurrence and distant metastases were comparable in two groups (group A-9.52%, group B-11.1% and group A-9.52%, group B-11.1%, respectively). The 5-year recurrence free, cancer specific and overall survivals were comparable in two groups. CONCLUSIONS: On long-term follow-up of oncological efficacy, LRPNUT-BCE satisfactorily compares with traditional open surgery (ONUT-BCE) with longer operating time, while decreasing postoperative morbidity and extending benefits of minimally invasive surgery to the patients.     

腹腔镜与开放手术治疗上尿路移行上皮肿瘤的远期疗效比较

目的：比较后腹腔镜下与开放性肾、输尿管及膀胱袖状切除术治疗上尿路移行上皮肿瘤的远期临床疗效。方法：回顾性分析48例行后腹腔镜下肾、输尿管及膀胱袖状切除术及55例行开放性肾、输尿管及膀胱袖状切除术患者的临床资料,比较两种术式术中、术后各种参数的差异。结果：后腹腔镜组与开放手术组患者在性别、年龄、肿瘤位置、及肿瘤分期上的差异无统计学意义。后腹腔镜组在术中估计出血量、术后住院时间等方面明显优于开放组（P〈0．05）。术后平均随访26．4个月,后腹腔镜组与开放组总生存率分别为79．17％、85．19％,疾病特异生存率分别为91．67％、94．44％,组间差异均无统计学意义（P〉0．05）。两组无瘤复发生存率分别为79．17％、72．22％,两组膀胱无复发生存率分别为79．17％、79．63％,组间差异均无统计学意义（P〉0．05）。结论：与传统开放手术相比,后腹腔镜下手术具有出血少、创伤小、患者痛苦少、恢复快、住院时间短等特点,并且二种手术方式具有相同的远期疗效。     

Retroperitoneal lymph node dissection (RPLD) in conjunction with nephroureterectomy in the treatment of infiltrative transitional cell carcinoma (TCC) of the upper urinary tract: impact on survival

OBJECTIVES: To evaluate the prognostic impact of retroperitoneal lymph node dissection (RPLD) performed during nephroureterectomy on time to recurrence and survival in patients with infiltrative transitional cell carcinoma (TCC) of the upper urinary tract. METHODS: The charts of 82 patients with T2-T4 TCC of the upper tract were retrospectively reviewed. The median patient age was 67.7 yr. Seventy-nine patients underwent nephroureterectomy and three had partial nephrectomy. Forty patients (48.8%) had RPLD with removal of more than five nodes after nephroureterectomy (group 1), whereas 42 (51.2%) had nephroureterectomy only (group 2). Median follow-up was 64.7 mo. The prognostic role of RPLD, T (2 vs. 3-4), G (2 vs. 3), N (0 vs. 1-2 vs. x), age (<65 vs. >65 yr) and sex on time to recurrence and survival were evaluated. RESULTS: Median time to recurrence and overall survival were 51.2 and 52.5 mo, respectively, in group 1 and 18.5 and 21.2 mo in group 2. Univariate analysis demonstrated that RPLD and T and N status were significantly related both to time to recurrence (p=0.009, 0.008, and 0.009, respectively) and survival (p=0.000006, 0.003, and 0.003). When analyzed using the Cox proportional hazard model, RPLD and T category were the only two factors demonstrating independent significance on overall survival (p=0.004 and 0.008). CONCLUSIONS: The results indicate a possible curative role of RPLD in the treatment of patients with infiltrative TCC of the upper urinary tract. Further randomized trials are needed to confirm these results.     

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.     

Impact of diagnostic ureteroscopy on long-term survival in patients with upper tract transitional cell carcinoma

PURPOSE: We determine whether diagnostic retrograde ureteroscopy for evaluation of upper tract transitional cell carcinoma adversely affects survival outcomes in terms of urothelial and metastatic tumor recurrence, and tumor-free and overall survival. MATERIALS AND METHODS: A total of 96 patients underwent total nephroureterectomy or resection of the distal ureter with a bladder cuff for upper tract transitional cell carcinoma. Of the patients 48 (study group) had undergone preoperative diagnostic ureteroscopy while 48 (control group) had not. Grade and stage of disease were compared, and time to recurrence, and disease-free and overall survival were analyzed. RESULTS: Grade and stage of disease were equivalent in both groups. There were no significant differences in recurrence rates, time to recurrence or mortality between the groups. Metastases developed in 9 patients (18.8%) in the control group and 6 (12.5%) in the study group (p = 0.58), while 5 (10.4%) in each group died of metastases of upper tract carcinoma (p = 1.00). Kaplan-Meier estimates were 0.67 and 0.71 for metastasis-free survival at 5 years (p = 0.25, not significant) and 0.87 and 0.76 for overall 5-year survival (p = 0.75, not significant) for the study and control groups, respectively. CONCLUSIONS: Diagnostic ureteroscopy has no clinically apparent adverse effect on long-term or disease specific survival of patients with upper tract transitional cell carcinoma who subsequently undergo standard definitive surgical management.     

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.     

Nephroureterectomy for treating upper urinary tract transitional cell carcinoma: time to change the treatment paradigm?

OBJECTIVE: To evaluate factors associated with disease recurrence and survival in patients undergoing nephroureterectomy for upper urinary tract transitional cell carcinoma (UUT-TCC) in one centre over an 18-year period. PATIENTS AND METHODS: The records of patients who had a nephroureterectomy for UUT-TCC at our institution from 1986 to 2004 were reviewed for clinical, pathological and treatment period data. Cox's proportional hazards regression model was used to test the statistical significance of several potential prognostic factors for recurrence and survival. RESULTS The median overall duration of follow-up was 2.5 years for 184 patients. Significant prognosticators for disease-specific survival (DSS) by univariate analysis were tumour stage (P < 0.01), tumour grade (P < 0.01), node-positive disease (P < 0.01), multifocality (P = 0.03), previous cystectomy (P < 0.01) and synchronous bilateral UUT-TCC (P = 0.02). On multivariate analysis, only tumour stage (P = 0.03) and grade (P = 0.01) correlated with DSS. The median recurrence-free survival duration was 2.4 years. In 44 patients, the disease recurred outside the bladder; 15 (8.2%) had local recurrence, 20 (10.9%) distant metastasis, and nine (4.9%) both local and distant recurrence. Bladder tumours occurred in 40 (26.1%) patients with no previous cystectomy. The evaluation of treatment outcome during three periods of the study showed no significant effect on DSS. CONCLUSION: Tumour stage and grade correlated with DSS in this cohort, with no improvement in outcome over the 18-year period assessed. Patients with high-stage and high-grade disease continue to fare poorly, suggesting a need for changing the treatment protocol. Judiciously applying a multimodal approach to the management of high-risk patients by incorporating neoadjuvant chemotherapy and surgical resection might provide, for the first time, the opportunity to improve patient outcome.     

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.     

Alternating mitomycin C and BCG instillations versus BCG alone in treatment of carcinoma in situ of the urinary bladder: a nordic study

OBJECTIVES: To evaluate whether, in patients with carcinoma in situ (CIS) of the urinary bladder, alternating instillation therapy with mitomycin C (MMC) and bacillus Calmette-Guerin (BCG) was more effective and less toxic than conventional BCG monotherapy. METHODS: Patients were stratified prospectively for primary, secondary, and concomitant CIS and randomized to one of two regimens. Patients in the alternating group received six weekly intravesical instillations of MMC 40 mg, followed by alternating monthly instillations of BCG 120 mg and MMC for one year. In the monotherapy group, only BCG was instilled on the same schedule. RESULTS: Of 323 enrolled patients, 304 were eligible for analysis. After an overall median follow-up of 56 months, the Kaplan-Meier disease-free estimate for BCG monotherapy was significantly better than that for alternating therapy (p=0.03; log rank test). Risk for progression appeared lower in the BCG monotherapy group (p=0.07), but no differences existed in survival. Besides the regimen, CIS category also predicted outcome to some extent. BCG monotherapy caused significantly more local side-effects and premature cessation of instillation treatment than did the alternating therapy. However, no differences were observed in the number of serious side-effects. CONCLUSION: One-year BCG monotherapy was more effective than the alternating therapy for reducing recurrence and compared well with the best regimens reported from substantially smaller series. The alternating therapy was better tolerated.     

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.