Bacillus Calmette-Guérin instillation treatment for carcinoma in situ of the upper urinary tract

OBJECTIVE: To analyse the efficacy and safety of bacillus Calmette-Guérin (BCG) perfusion treatment forcarcinoma in situ (CIS) of the upper urinary tract. PATIENTS AND METHODS: Six patients with cytologically diagnosed CIS of the upper urinary tract were treated by BCG instillation via retrograde catheterization using a 6 F ureteric catheter or an 8 F indwelling JJ ureteric stent between the ureter and bladder. BCG (Tokyo 172 strain, 80 mg in 100 mL normal saline) was instilled weekly for 4 or 8 weeks. The efficacy and safety of the treatment was assessed. RESULTS: The mean (range) follow-up was 22 (9-38) months; none of the patients died, and all were negative for cytology in urine collected from the upper urinary tracts. However, one patient had recurrent CIS in the prostatic urethra; the patient was treated by intravesical BCG instillation. In all patients, positive cytology became negative after one or two instillations of BCG. The ureter became stenotic in two patients. Although irritative symptoms occurred in all patients, such side-effects disappeared in a few months and were not clinically significant. CONCLUSION: In these six patients retrograde BCG instillation for CIS of the upper urinary tract was effective and safe. Based on the cytology results after only two BCG treatments, the dose or number of BCG instillations could possibly be reduced, but further study is needed.     

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.     

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.     

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.     

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.     

Intravesical bacille Calmette-Guérin in the treatment of carcinoma in situ or high-grade superficial bladder carcinoma after radiotherapy for bladder carcinoma

OBJECTIVE: To evaluate the effectiveness and tolerance of endovesical bacille Calmette-Guérin (BCG) after pelvic radiation therapy for bladder cancer in patients with recurrence as carcinoma in situ (CIS) and/or high-grade superficial bladder cancer. PATIENTS AND METHODS: In a prospective study, 13 patients were treated with weekly instillations of 81 mg BCG Connaught for 6 weeks. for CIS and/or high-grade superficial bladder carcinoma. All had been treated previously with radical radiation therapy for bladder carcinoma. RESULTS: Five patients had no recurrences and six patients retained their bladders, within a median follow-up of 74.5 months. Five patients progressed; two underwent radical surgery and are alive after 75 months of follow-up, and three died from the disease (two were high-risk surgical patients and one had metastatic disease). Another two patients died from intercurrent disease without bladder cancer. Eight patients were alive at a mean (SD range) follow-up of 85 (12, 65-97) months. CONCLUSION: Intravesical BCG is useful for controlling CIS and/or high-grade superficial bladder carcinoma in irradiated bladders and has an acceptable local tolerance: more than a third of patients were free of disease and preserved their bladders. This proportion is acceptable in patients currently scheduled for cystectomy.     

Pharmacokinetic study of intravesical gemcitabine in carcinoma in situ of the bladder refractory to bacillus Calmette-Guérin therapy

INTRODUCTION: Gemcitabine, a chemotherapeutic agent, has been shown to be active against transitional cell cancer of the bladder. The aim of the study was to determine the pharmacokinetic profile of gemcitabine, administered intravesically in patients with carcinoma in situ(CIS). MATERIAL AND METHODS: Nine patients with CIS refractory to intravesical bacillus Calmette-Guérin (BCG) therapy were enrolled. Gemcitabine was given in 50 ml 0.9% NaCl by catheterization and held in the bladder for 1 h, once weekly for 6 consecutive weeks. The pharmacokinetics for gemcitabine metabolites were performed in plasma and serum. Dose levels were: 1,000, 1,250, and 1,500 mg. Clinical evaluation was repeated 4 weeks after therapy and thereafter every 6 months. RESULTS: Grade-1 neutropenia was observed only in 1 patient. Grade-1 urinary frequency and hematuria were observed in 1 and 3 patients, respectively. No grade 2-4 toxicity or clinically relevant myelosuppression were observed. Gemcitabine was detectable in serum, but with an irrelevant pharmacological effect, in only 1 patient treated with 1,500 mg of gemcitabine. With regard to activity, after 6 instillations of this drug, 4 complete responses were observed. CONCLUSION: Intravesical gemcitabine is well tolerated and safe. No systemic absorption with a clinical or pharmacological effect was detected and only slightly irritative bladder symptoms were observed. These results warrant further investigation in phase-II trials.     

Intravesical bacille Calmette-Guérin-induced multiorgan failure after treatment for transitional cell carcinoma

Intravesical bacille Calmette-Guérin (BCG) has been safely used to treat stage Ta and T1 bladder carcinoma since 1976. This report presents the case of a 56-year-old man who presented with multiorgan failure after bacille Calmette-Guérin (BCG) treatment for stage T1 transitional cell carcinoma of the bladder. On admission the patient was jaundiced, had inflammatory infiltrates on chest radiography and required dialysis for renal failure. He had a persisting fever of unknown origin and elevated cholestatic liver function tests, which prompted a liver biopsy.This demonstrated hypersensitivity hepatic granuloma but no organism was identified. He responded well to steroid and antimycobacterial treatment. A small percentage of BCG-treated patients suffer hypersensitivity side-effects (pneumonitis, hepatitis or interstitial nephritis). This complication most commonly follows a traumatic installation. Mycobacteriumbovis is rarely cultured or identified using polymerase chain reaction techniques, and the diagnosis is based on histological findings of granuloma.     

Laparoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma: is it better than open surgery?

OBJECTIVE: In 1991, laparoscopic nephroureterectomy has been introduced as a treatment option for upper tract transitional cell carcinoma. Based on the review of the current literature and personal experience we want to analyze the actual results of this technique in comparison to open surgery. MATERIALS AND METHODS: We performed a MEDLINE/PubMed search and reviewed the literature on laparoscopic and open nephroureterectomy between 1991 and 2004 (n = 1365 patients) including the results of 45 patients who underwent either laparoscopic (n = 23) or open nephroureterectomy (n = 21) during the same period of time at the Klinikum Heilbronn. Demographic, perioperative and follow-up data were compared. RESULTS: The analysis revealed a slightly longer OR-time (276.6 vs. 220.1 min), and significantly lower blood loss (240.9 vs. 462.9 ml) in the laparoscopic series. No differences of minor (12.9 vs. 14.1%) or major complication rate (5.6 vs. 8.3%) were observed. All nine comparative studies revealed a significant dose reduction of the morphine-equivalents after laparoscopy. In all ten comparative series the hospital stay was shorter after laparoscopy, but only in 6 series the difference was statistically significant. The frequency of bladder recurrence (24.0 vs. 24.7%), local recurrence (4.4 vs. 6.3%), and distant metastases (15.5% vs. 15.2) did not differ significantly in both groups. The actual disease-free two-year survival rates (75.2 vs. 76.2%) were similar. The five-year survival rates averaged 81.2% in the three laparoscopic (n = 113 pat.) and 61% in the ten open series (n = 681 pat.) Six port site metastases were reported in 377 (1.6%) analyzed patients occurring 3 to 12 months following laparoscopy. CONCLUSION: Open radical nephroureterectomy still represents the golden standard for the management of upper tract transitional cell carcinoma, however, laparoscopic radical nephroureterectomy offers the advantages of minimally invasive surgery without deteriorating the oncological outcome. In case of advanced tumors (pT3,N+) open surgery is still recommended.     

Co-administration of intravesical bacillus Calmette-Guérin and interferon α-2B as first line in treating superficial transitional cell carcinoma of the urinary bladder

Study Type – Therapy (individual cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? BCG is the standard treatment for superficial bladder cancer. The combination of BCG and interferon‐alfa may be more effective and less toxic than BCG alone. With long term follow up the efficacy and toxicity of combined intravesical BCG and interferon‐α and BCG alone seems to be equal in treatment of superficial bladder cancer.

OBJECTIVE

? To evaluate the efficacy and toxicity of the combination of bacillus Calmette‐Guérin (BCG) and interferon α‐2B (IFNα‐2B) in treating superficial bladder cancer (SBC). The mentioned combination has shown synergism in pre‐clinical studies.

PATIENTS AND METHODS

? The present study is a single‐arm, open‐label, single‐institution prospective trial. Patients with Ta, T1 or in situ carcinoma and no previous intravesical therapy were included between July 2002 and June 2009. ? Patients were treated with weekly intravesical instillation of 27 mg of BCG mixed with 10 million units (MU) of IFNα‐2B for six consecutive weeks followed by 3‐weekly booster instillations at 3 months if there was no recurrence. ? The primary endpoint was disease recurrence. Secondary endpoints were disease progression and toxicity. ? Patients were followed‐up with cystoscopy and urine cytology every 3 months.

RESULTS

? In all, 50 patients were included. ? At a median follow‐up of 55.8 months, 31 (62%) patients were recurrence‐free. ? Progression to muscle invasion occurred in two (4%) and metastasis occurred in two (4%) patients. ? Treatment was well tolerated, with grade III dysuria and frequency occurring in 18 and 14% of patients, respectively, and with 74% of patients being able to complete the maintenance dosage.

CONCLUSION

? The combination of BCG and IFNα‐2B in the patient population with SBC has similar efficacy and toxicity to BCG monotherapy.     

Vesicoureteral reflux after intravesical instillation of bacillus Calmette-Guérin against carcinoma in situ of the bladder

We report a case of vesicoureteral reflux (VUR) 3 years after intravesical instillation of bacillus Calmette-Guérin (BCG, Tokyo 172 strain) against carcinoma in situ of the bladder. The present case suggests that a long-term careful follow-up is needed to detect not only tumor recurrences but also VUR as a late complication after intravesical BCG instillation.     

Tuberculous epididymitis following intravesical Bacillus Calmette-Guérin therapy

Bacillus Calmette-Guérin (BCG) immunotherapy is increasingly being accepted for management of some bladder transitional cell neoplastic lesions. Mild adverse reactions occur frequently. However, an unusual complication of tuberculous epididymitis is reported. A 64-year old man presented with bilateral epididymal mass. Four months earlier he had seven treatments with intravesical BCG instillation (Tokyo 172 strain) for a grade 2 transitional cell carcinoma in situ. Bilateral epididymectomy was performed. Microscopic examination of the epididymis revealed chronic inflammation and necrosis with granulomas and Langhans' giant cells. After the operation, there were no further complications.     

Intravesical instillations with bacillus calmette-guérin for the treatment of carcinoma in situ involving prostatic ducts

OBJECTIVES: Bacillus Calmette-Guérin (BCG) has proven its efficacy in the treatment of carcinoma in situ (CIS) of the prostatic urethra. We performed a retrospective study to evaluate the use of intravesical instillations of BCG in patients with carcinoma in situ involving prostatic ducts after complete transurethral resection (TUR). MATERIAL AND METHODS: Eligibility for the study was CIS of the prostatic urethra involving prostatic ducts. Previous instillation with BCG was an exclusion criterion. Patients were treated with intravesical BCG Connaught (81 mg) administered once a week, over a 6-wk period. TUR loop biopsies of the prostate were performed only when a macroscopic tumor was present. RESULTS: In this retrospective study of 11 patients, 8 (73%) presented with macroscopic tumor in the prostatic urethra. Ten patients (91%) had a simultaneous superficial bladder carcinoma. Eight patients (73%) had tumoral involvement of the bladder neck region. After a median follow-up of 27 mo (n=10 patients), the response in the prostatic urethra was 82%, and the response in the bladder due to superficial tumor recurrence was 64%. Two patients with residual ductal disease in the prostatic urethra were subsequently treated with cystoprostatectomy and are currently free of disease. In one of those patients, the cystoprostatectomy specimen did show prostatic stromal invasion. Another patient developed distant metastatic disease and died a few months after diagnosis. Thus, progression was encountered in two patients (18%). Currently, 90% of patients are alive without evidence of disease and 72.7% have benefitted from this bladder preservation strategy. CONCLUSION: Intravesical BCG is a feasible treatment option for patients with CIS involving prostatic ducts. In this retrospective study, bladder preservation was successful in 8 of 11 patients (70%) and there was only one oncologic death. Obviously, these patients need a careful follow-up with cystoscopy and cytology to detect either recurrence or progression and in those with persistent disease after the initial BCG induction therapy, prompt cystectomy is indicated.     

Bacillus Calmette-Guérin without maintenance therapy for high-risk non-muscle-invasive bladder cancer

Background

Bacillus Calmette-Guérin (BCG) is the standard intravesical treatment of high-risk noninvasive (Ta, T1, Tis) bladder cancer. Maintenance BCG is recommended for maximum efficacy.

Objective

We compared our results in a large cohort of high-risk bladder cancer patients who received BCG without maintenance with published results from randomized maintenance BCG trials.

Design, setting, and participants

A cohort of 1021 patients underwent restaging transurethral resection for high-risk (Ta, T1, Tis) bladder cancer.

Intervention

Patients received a 6-wk induction course of BCG therapy. Responding patients did not receive maintenance BCG. Relapsing patients were eligible for retreatment with BCG. All patients were followed for a minimum of 5 yr.

Measurements

End points were 5-yr tumor- and progression-free survival rates.

Results and limitations

Of 816 complete responders to induction BCG, 2- and 5-yr recurrence-free survival rates were 73% and 46%, respectively. The progression-free survival rate was 89%. Progression-free survival time was 56 mo (95% confidence interval, 55-58 mo). Thirty-two percent of the patients required another course of BCG therapy. We cannot exclude that maintenance BCG may benefit patients beyond 5 yr over induction BCG alone and selective BCG retreatments.

Conclusions

Our results with BCG treatment without maintenance of patients with high-risk non-muscle-invasive bladder cancer compare favorably with trials in which comparable patients received maintenance BCG.