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.     

Total cystectomy after intravesical bacillus Calmette-Guérin (Tokyo strain) therapy for superficial bladder cancer: Experience in Japan

To clarify which patients might most require total cystectomy after intravesical bacillus Calmette-Guérin (BCG) therapy, we reviewed data for 111 individuals with superficial bladder cancer. Of the 111 patients, 73 received the BCG treatment for prophylaxis of intravesical recurrence after transurethral resection (group 1), 24 therapeutically for Ta or T1 tumours (group 2), and 14 for eradicating carcinomas in situ (CIS, group 3). Although the BCG therapy significantly reduced frequencies of recurrence in group 1, 27 patients (37%) did develop tumours again. Tumours disappeared in 18 of 24 patients (75%) in group 2, and in 11 of 14 (79%) in group 3. The rate of disease progression was 6% for all 111 patients: 3% (2/73) for group 1, 17% (4/24) for group 2, and 7% (1/14) for group 3. A total of 16 of the 111 patients (14%) underwent total cystectomy, the respective figures being 7% in group 1, 29% in group 2, and 29% in group 3. Indications for total cystectomy were progression in 7, recurrent multiple tumours in 5, persistent CIS in 2, a contracted bladder in 1, and occurrence of bilateral renal pelvic cancer in 1. Thus, 4 of 6 patients (67%) who had tumours unresponsive to BCG therapy in group 2 demonstrated progression and necessitated total cystectomy. Because tumours persisting after BCG therapy are frequently of the muscle-invasive type, such cases should be regarded as candidates for immediate total cystectomy.     

Management of clinical T1 bladder transitional cell carcinoma by radical cystectomy

High-grade bladder cancer involving the lamina propria is considered superficial disease. This spectrum is generally treated with TUR plus intravesical therapy. However, significant understaging jeopardizes long-term survival and improvements and radical surgery represents a provocative alternative. We evaluated disease-free and cancer-specific survival (CSS) in our cohort of patients with high-grade T1 tumors. A total of 318 patients with bladder cancer underwent radical cystectomy between 1990 and 2000 at our institution. Of these, 66 had cT1 tumors with or without Carcinoma in-situ (CIS). Our multidisciplinary bladder cancer database was queried to perform a multivariate analysis on clinical parameters such as: age, race, sex, cystectomy year, intravesical therapy, angiolymphatic-invasion and tumor upstage in relation to recurrence and survival. The clinical stage was accurate in 44 of the cases (66%). However, 27% were upstaged by cystectomy and 12% of the cT1 + CIS patients had nodal disease. Patients with cT1 tumors plus CIS had a significantly worse CSS. Those with persistent disease after an initial course of BCG therapy appeared to have worse CSS also. At a median follow up of 4 years, overall cancer-specific mortality was 22%, however, pathologic T1 +/- CIS had 92% CSS at 10 years. Our data suggests that some cT1 bladder cancer tumors have assiduous clinical courses evidenced in staging discrepancies. For high-grade tumors, early cystectomy and orthotopic diversion increases life expectancy significantly and should be carry out early rather than late.     

Clinical outcome of high-grade non-muscle-invasive bladder cancer: A long-term single center experience

Objectives:   To report on the long-term clinical outcome of high-grade (G3) non-muscle-invasive bladder cancer (NMIBC) patients treated at a single institution.
Methods:   A retrospective analysis of 93 patients with NMIBC treated between January 1991 and September 2005 was performed. Patients were divided into three groups on the basis of treatment they received after transurethral resection (TUR) of the bladder. Forty-seven patients received adjuvant intravesical epirubicine after TUR of the bladder (Group 1). Twenty-four patients received intravesical bacillus Calmette–Guérin (BCG) (Group 2). A radical cystectomy (RC) was performed on twenty-two patients (Group 3).
Results:   Median follow up was 68.7 months. Overall, thirty patients (33%) experienced tumor recurrence. The survival rates of Group 3 were significantly higher than the 71 patients undergoing conservative therapy (Group 1 and 2). There was no statistically significant difference between Group 1 and 2, but treatment failure in patients treated with epirubicine was significantly higher than in those with BCG. Cases without concomitant carcinoma in situ (CIS) showed statistically significantly higher survival rates than those with concomitant CIS.
Conclusions:   RC provides excellent survival rates in patients with high-grade NMIBC. Adjuvant therapy with BCG after a complete TUR of the bladder may be an effective treatment for high-grade NMIBC. If a conservative treatment is preferred to RC, co-existence of a concomitant CIS should be considered with caution.     

Possible factors affecting response to intravesical bacillus Calmette-Guérin (Tokyo 172 Strain) therapy for carcinoma in situ of the bladder: A multivariate analysis

To evaluate clinicopathological factors affecting response to intravesical instillation therapy with the bacillus Calmette-Guérin (BCG) Tokyo 172 strain for carcinoma in situ (CIS) of the bladder, we reviewed data for 84 patients treated between 1985 and 1996. Median follow-up was 56 months. The patients comprised three groups: primary (only the in situ lesion, 31 patients), subsequent (found after treatment of a gross neoplasm, 20), and concomitant (found together with a gross neoplasm, 33). A complete response was found in 62 (74%) of the 84 patients. Intravesical BCG therapy eradicated tumour cells in 74% of the primary group, 70% of the subsequent group, and 76% of the concomitant group. Multivariate logistic regression analysis revealed that the presence of gross haematuria and patient age were significantly associated with a complete response to the intravesical BCG therapy (p<0.05). On the other hand, gender, irritative bladder symptoms, type of extent of CIS, histological grade of CIS, BCG dose, and number of times BCG was given did not exert any significant influence. The 5-year recurrence rate was 33% for the 62 patients for whom a complete response was once achieved. Patients aged 60 or older had a higher probability of recurrence than those less than 60 years of age (p<0.05). Disease progression was found in 13% of the 84 patients and total cystectomy was performed in 19%. The present finding that patient age is related to the response to intravesical BCG therapy may point to a role for the reduced host immunocompetence in elderly individuals.     

Treatment of Bacillus Calmette-Guerin refractory superficial bladder cancer: further intravesical therapy

We here report our clinical experience with salvage therapy for patients with bacillus Calmette-Guerin (BCG)-refractory superficial bladder cancer and discuss current approaches to the disease, especially focusing on bladder preservation. First, we evaluated the efficacy of an initial 6-week course of intravesical BCG in 93 patients with carcinoma in situ (CIS) of the bladder. Of these, 91% achieved a complete response (CR) at the evaluation at 3 months. The 2- and 5-year recurrence-free rates were 71 and 67%, respectively (mean follow-up 39 months). These results support the intravesical BCG as a first-line therapy for CIS. Next, we assessed the efficacy of a second course of intravesical BCG for 16 patients who failed the initial induction course for CIS. Of these, 94% achieved CR at the evaluation at 3-month, and the 2- and 5-year recurrence-free rates were 62 and 46%, respectively (mean follow-up 28 months). None of the patients who received a second course had disease progression. Thus, a second course of BCG therapy seems to be a reasonable option for CIS patients failing the initial course. We also report our initial experience with intravesical gemcitabine therapy for 3 patients with BCG-refractory CIS of the bladder and 1 patient with recurrent multiple tumors. Gemcitabine (1500 mg in 100 ml saline) was given in the bladder for 1 hour twice weekly for a total of 12 treatments. The treatment was associated with minimal bladder irritation and systemic absorption, and was well tolerated except in a 90-year-old man who discontinued therapy because of grade 2 toxicity. Two patients achieved CR and maintained a tumor-free status beyond 14 months, suggesting that the intravesical gemcitabine is a promising salvage therapy for BCG-refractory superficial bladder cancer.     

T2a transitional cell carcinoma of the bladder: long-term experience with intravesical immunoprophylaxis with bacillus Calmette-Guerin

PURPOSE: In this prospective study we evaluate the effect of combined transurethral resection of early muscle invasive bladder cancer and immunotherapy with bacillus Calmette-Guerin (BCG) in patients unfit for radical cystectomy or refusing more aggressive therapies. MATERIALS AND METHODS: A total of 22 patients with a mean age 73.6 years were included in the study. Inclusion criteria were histologically proven muscle invasive transitional cell carcinoma of the bladder with a tumor-free second resection and negative staging examinations in patients unfit for radical cystectomy or refusing more aggressive therapies. All patients received 6 weekly instillations of 120 mg. BCG starting 14 to 21 days after the last transurethral resection of the tumor. Followup at 3 months included cystoscopy, urinary cytology, ultrasound of the abdomen and chest x-ray. Every 6 months computerized tomography of the abdomen and bone scans were performed. RESULTS: The overall 5-year survival rate was 69.1%, while the disease specific 5-year survival rate was 94%. One muscle invasive recurrence was noted at 69 months, which was again treated with the same regimen but ultimately led to radical cystectomy 21 months later. One patient died of progressive recurrence in the upper urinary tract. The 5-year recurrence-free survival rate was 46.5%. The only severe complication was BCG pneumonitis. CONCLUSIONS: The data show encouraging results for transurethral resection of bladder tumor with intravesical BCG therapy in select patients with T2a bladder cancer who are not candidates for radical cystectomy.     

Recurrence and progression in stage T1G3 bladder tumour with intravesical bacille Calmette-Guérin (Danish 1331 strain)

OBJECTIVE: To report recurrence and progression rates in patients with T1G3 superficial bladder carcinoma treated with intravesical bacille Calmette-Guérin (BCG, Danish 1331 strain) after complete transurethral resection. PATIENTS AND METHODS: Data from the records of 111 patients with T1G3 bladder carcinoma treated between January 1991 and December 1999 were analysed for recurrence, progression, salvage therapy and survival. RESULTS: Of the 111 patients with T1G3 bladder tumours, 69 had intravesical BCG therapy, 20 radical cystectomy and 22 only transurethral resection (TUR). Of the 69 patients receiving BCG therapy 37 (54%) had no recurrence, and 24 (35%) had a recurrence that was not muscle-invasive (Ta/T1) and were treated with TUR only. The remaining eight (12%) progressed to muscle invasion and had salvage cystectomy. During the follow-up six patients died, four from disease and three from other causes, while the remaining 63 are alive and well. Of the other 42 patients, 15 are alive after radical cystectomy and 18 after TUR. CONCLUSION: This series further confirms the benefits of intravesical BCG (Danish 1331) in an adjuvant setting; furthermore, this treatment facilitates bladder preservation by reducing recurrences and delaying the progression in many patients.     

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.     

Long-term results of intravesical bacillus Calmette-Guérin therapy for stage T1 superficial bladder cancer

OBJECTIVES: To examine in a prospective study the incidence of recurrence and progression in patients with Stage T1 bladder carcinoma after complete transurethral resection of the bladder tumor and adjuvant immunotherapy with bacillus Calmette-Guérin (BCG). METHODS: Between July 1987 and April 1999, 126 patients presenting to our clinic with a superficial urothelial carcinoma of the bladder (Stage pT1, grade 1-3) received adjuvant intravesical immunotherapy with BCG after complete transurethral resection of the bladder tumor. In the case of recurrence of superficial tumor (pTa, pT1, or carcinoma in situ), patients received a second cycle of BCG. For muscle-invasive tumor progression (pT2, pT3, or pT4), radical cystectomy was recommended. Six of the patients (5%) presented with Stage pT1,G1 tumor, 74 (59%) with Stage pT1,G2 tumor, and 46 patients (36%) with Stage pT1,G3 tumor. Median follow-up was 53 months (range 3 to 144). RESULTS: One hundred eight patients (86%) remained tumor-free with a retained bladder during the follow-up after one or two 6-week cycles of BCG. Twenty-four patients (19%) had a recurrence of superficial tumor, 13 (10%) had muscle-invasive progression after the first BCG cycle, and an additional 4 (3%) had progression after the second BCG cycle. Six patients (5%) underwent radical cystectomy, and 9 patients (7%) died as a result of tumor progression. The tumor-free survival rate of all patients was 89% (112 of 126). CONCLUSIONS: Adjuvant immunotherapy with BCG after complete transurethral resection of the bladder tumor represents a highly effective primary treatment for Stage T1 carcinoma of the bladder. Even in Stage pT1,G3 tumor, immediate radical cystectomy does not appear necessary.     

T1G3 transitional cell carcinoma of the bladder: recurrence, progression and survival

OBJECTIVES: To report our experience with T1G3 bladder tumours over the last 10 years. PATIENTS AND METHODS: We analysed the outcome of 74 consecutive patients treated for a T1G3 bladder cancer between 1991 and 2001. Fifty-seven patients (77%) were treated with transurethral resection (TUR) plus six weekly instillations of bacillus Calmette-Guérin (BCG) therapy. Ten patients (13.5%) with contraindications to BCG or with a small T1a tumour were treated with TUR plus mitomycin-C, and seven (9.5%) were treated with TUR alone because of their age. Patients treated with BCG had systematic biopsies taken at the end of the first course. Patients with residual tumour received a second course of six weekly instillations. Patients with negative biopsies received maintenance BCG therapy consisting of intravesical instillations each week for 3 weeks given 3, 6, 12, 18, 24, 30 and 36 months after the first course. RESULTS: The median follow-up was 53 months. The overall recurrence rate was 46% and the overall progression rate 19%. The rate of delayed cystectomy was 8% and that of disease-specific survival 91%. In patients who received BCG therapy, the recurrence and progression rates were 42% and 23%, respectively. In this group the rate of disease-specific survival was 88%. CONCLUSION: This study confirms that maintenance BCG therapy is an effective treatment for T1G3 bladder tumours, with an acceptable rate of bladder preservation.     

Multivariate evaluation of factors affecting recurrence,progression, and survival in patients with superficial bladder cancer treated with intravesical bacillus Calmette-Guérin (Tokyo 172 strain) therapy: Significance of concomitant carcinoma in situ

To evaluate the relative importance of clinicopathological factors affecting recurrence, progression, and survival in patients with superficial bladder cancer (pTa and pT1) undergoing bacillus Calmette-Guérin (BCG) therapy (Tokyo 172 strain), we reviewed data for 146 patients treated between 1985 and 1998. The median follow-up period was 64.7 months. Tumour recurrence, progression, and death were evaluated as endpoints using Cox's proportional hazards model. The 5-year recurrence-free rate was 56% for all 146 patients. Those with a past history of bladder cancer (n = 73) had significantly earlier recurrence than those without (n = 73, p = 0.017) and this tended to be the case for concomitant CIS (n = 34) although this did not reach statistical significance. The 5-year progression rate was 15% for all 146 patients and univariate analysis revealed that the presence of concomitant CIS was significantly associated with disease progression (p = 0.002). Multivariate analysis using the proportional hazards model confirmed the finding that only one factor, concomitant CIS, was significantly associated with progression. The 5-year survival rate was 84% for all 146 patients. Furthermore, univariate and multivariate analyses revealed that patient age, history of bladder cancer, and concomitant CIS were variables significantly related to patient survival. The present findings suggest that careful follow-up is mandatory after BCG instillation therapy for patients with superficial bladder cancer and concomitant CIS because of their relatively poor prognosis.     

Recurrence and progression of T1G3 transitional cell carcinoma of the bladder treated with intravesical bacillus Calmette-Guérin

OBJECTIVE: To examine the incidence of recurrence and progression in patients with stage T1, grade-3 carcinoma of the bladder treated with endovesical bacillus Calmette-Guérin (BCG) after complete transurethral resection. MATERIAL AND METHODS: From May 1995 to June 2002, 937 patients with superficial bladder cancer underwent transurethral resection. 46 patients (4.9%) had T1G3 tumors. All patients received endovesical BCG therapy 2-3 weeks after transurethral resection, given in 6 sessions as weekly instillations of 120 ml Pasteur strain BCG in 50 ml saline. Success was defined by normal cytology and cystoscopy, and normal bladder biopsies. Recurrent tumors were resected and a second or third cycle of therapy was given according to pathological status. Progressive tumors were managed by radical cystectomy, radiotherapy and/or chemotherapy depending on the nature of the tumor or clinical status of the patient. RESULTS: During follow-up 60.7% of the patients (28 of 46) remained tumor free after only 1 BCG cycle and 73.9% (34 of 46) after the third BCG cycle, and the bladder was preserved in all. Muscle-invasive progression was noted in 10 (21.7%) patients at the end of the BCG cycles. Radical cystectomy was done in 10 patients. The tumor-free survival rate of all patients including those who underwent cystectomy is 84.8% (39 of 46) with a median follow-up of 61 (range 39-118) months. CONCLUSION: Adjuvant immunotherapy with BCG after complete transurethral resection of the bladder tumor represents a highly effective treatment for bladder preservation in stage pT1, grade-3 carcinoma of the bladder. pT1G3 tumors with early high-grade recurrence after failed immunotherapy should be regarded as candidates for early radical cystectomy.     

The natural history of bladder carcinoma in situ after initial response to bacillus Calmette-Gúerin immunotherapy

ObjectivesTo explore patterns of recurrence, muscle invasion, and disease specific mortality in patients with bladder carcinoma in situ (CIS) who responded to an induction course with intravesical bacillus Calmette-Gúerin (BCG) immunotherapy.MethodsBetween June 1985 and December 2003, 104 patients (mean age 67 years) were diagnosed with either pure (38 patients) or concomitant (66 patients) CIS. Patients who responded to one (92 patients) or two (12 patients) induction courses of intravesical BCG instillation were included in the study. Response was determined and monitored by routine periodic bladder biopsies. Outcome of patients and the effect of various prognostic parameters were assessed after a median follow-up of 75 months.ResultsThe 5- and 10-year recurrence-free survival rates were 63% and 54%, respectively. The 5- and 10-year muscle-invasive-free survival rates were 79% and 77%, and the 5- and 10-year disease-specific survival rates were 90.5 and 85.8%, respectively. Median time to recurrence, muscle invasion, and disease-specific mortality was 18, 19, and 40 months, respectively. Pure and concomitant CIS were associated with a similar outcome. The recurrence of nonmuscle-invasive tumor did not increase the risk for muscle invasion or mortality.ConclusionsPure and concomitant bladder CIS share similar biologic behavior. Muscle-invasive disease is expected in about 25% of the BCG responders followed for long time periods and disease-specific mortality in 15%. Tumor recurrence, whether nonmuscle-invasive or muscle-invasive, follows a similar time table suggesting that these are not sequential but parallel and independent processes.     

Use of Nd:YAG laser in treatment of bladder cancer

A total of 53 patients were treated with neodymium:yttrium-aluminum garnet (Nd:YAG) laser and followed up for two years. Three patients had carcinoma in situ (CIS); 4 had Ta lesions; and 28 had TINxMo, 8 had T2NxMo, and 10 had T3NxMo lesions. The patients with CIS received a combination of Nd:YAG laser and intravesical bacillus Calmette Guérin (BCG) instillation. The remainder of the patients received no supplementary chemotherapy. No tumor recurrence was noted in those with Ta lesions. Tumor recurred in 18 per cent of patients with T1 lesions, and 33 per cent of those with T2 lesions; 80 per cent of patients with T3 lesions had resistant or residual tumors. In patients with CIS, there was no tumor recurrence. Nd:YAG laser is effective in Ta, T1, and T2 bladder cancers, with low recurrence rate and minimal complications. In very select, high-risk patients with small lesions, and in those who refuse cystectomy, there may be a place for laser therapy for either palliation or definitive treatment of T3 invasive tumors of the bladder.     

T1G3 bladder cancer--indications for early cystectomy

OBJECTIVES: To review our experience with early radical cystectomy in patients with T1G3 Transitional Cell Carcinoma of bladder (TCC). PATIENTS AND METHODS: Thirty patients, who underwent early radical cystectomy over a 10-year period for clinical stage T1G3 TCC bladder, were studied. Of these 21 (70%) had radical cystectomy without treatment with intravesical chemo/immunotherapy. The number of tumours, presence or absence of Carcinoma In-Situ (CIS) and the pathological stage of the cystectomy specimen were recorded in each patient. Disease specific survival was determined in the subgroups using Kaplan-Meier estimates. RESULTS: Seventeen patients underwent radical surgery for a single tumour without concomitant CIS (Group A). The other 13 had multiple tumours with or without concomitant CIS or a single tumour with CIS (Group B). The disease was upstaged after cystectomy in 1 (6%) patient in Group A compared to 7 (55%) in Group B, (p = 0.009). Nine (53%) had pT0 disease in Group A compared to 0% in Group B, (p = 0.0017). The 5-year cancer specific survival rates were 92% in Group A and 82% in Group B. CONCLUSIONS: In patients with multiple T1G3 tumours with or without associated CIS, or in those with single T1G3 tumour with associated CIS the incidence of the disease being already muscle invasive at the time of clinical diagnosis is 55%. Early radical cystectomy should be advocated in this group. Conversely, for a single T1G3 tumour without associated CIS, conservative bladder preserving strategy with immuno-chemotherapy and close surveillance is justified.     

Superficial pT1G3 bladder tumor: 24 case reports

The authors report 24 patients presenting a transitional tumor of bladder pT1G3 collected between January 1996 and December 2000. They represent 19% of the superficial tumors of bladder. Two patients had of straightaway a cystectomy after resection for an unverifiable tumor by endoscopy and another after a second resection discovering a real pT2. Only 5 patients received a BCG therapy is 24% of the cases. A recurrence without progression has been noted in 38% of the cases and a progression in 19% of the patients. These last patients had a cystectomy and with a follow-up to 28 months, no recurrence has been noted.     

Is second course intravesical Bacillus Calmette-Guerin therapy for recurrent carcinoma in situ of the bladder useful?

We evaluated the usefulness of second course intravesical bacillus Calmette-Guerin (BCG) therapy for carcinoma in situ (CIS) of the bladder that failed to respond to the initial BCG therapy. Between January 1995 and December 2000, 185 patients with CIS of the bladder underwent an initial 6- or 8-week course of intravesical BCG instillation with an average follow-up period of 40.9 months (range: 3.8 to 94.8 months). Of the 185 patients, 160 (86.5%) completely responded to an initial course of BCG therapy. During follow up, 49 (30.6%) of the complete responders had recurrent transitional cell carcinoma. Overall, 9 (36.0%) of the 25 patients who did not respond completely to the initial 6- or 8-week course of BCG therapy and 22 (44.9%) of the 49 who had recurrent tumor after initial complete response, a total of 31 patients received the second course intravesical BCG therapy. Of the 9 incomplete responders, 8 (88.9%) achieved a complete response after the second course BCG therapy. With an average follow-up period of 39.6 months (range: 2.8 to 62.2 months), 2 (22.2%) of the 8 had recurrence. On the other hand, 17 (77.3%) of the 22 with recurrent tumor after the initial complete response developed recurrence with an average follow-up period of 14.1 months (range: 2.8 to 55.2 months). Seven (31.8%) of the 17 patients had disease progression to muscle invasion. Subsequently, cystectomy was done in 10 (58.8%) and radiation in 1 (5.9%). Our results suggest that a selected group of incomplete responders with initial BCG therapy may benefit from continued second course BCG. However, in patients who had recurrence after initial BCG success, the benefits of second course BCG therapy are limited. Careful surveillance and aggressive therapy on optimal timing are mandatory.     

Long-term follow-up of sequential intravesical gemcitabine and docetaxel salvage therapy for non-muscle invasive bladder cancer

IntroductionIntravesical gemcitabine and docetaxel (Gem/Doce) has been established as a safe and efficacious salvage treatment for recurrent NMIBC since 2015. Despite widespread adoption of this regimen, long-term outcomes have not been described. We report our experience with intravesical Gem/Doce following BCG failure in a large cohort of patients with extended follow-up.MethodsWe retrospectively identified 97 patients at our institution treated with Gem/Doce for high-risk NMIBC after BCG failure between 2009 and 2017. Patients received six weekly intravesical Gem/Doce instillations. Monthly maintenance for 2 years was initiated if disease free at first follow-up. Outcomes included recurrence-free survival (RFS), high-grade recurrence-free survival (HG-RFS), progression-free survival (PFS), cystectomy-free survival (CFS), cancer-specific survival (CSS), and overall survival (OS). Survival probabilities were estimated using the Kaplan-Meier method.ResultsMedian follow-up was 49 months. Median age was 73 years, and 71% of the cohort had CIS containing disease. Thirty five percent of the cohort had BCG-unresponsive disease. Complete response at 3-month surveillance was 74% and median duration of response was 25 months. At 1, 2, and 5 years, HG-RFS was 60%, 50%, and 30%, respectively. HG-RFS was similar among BCG-unresponsive patients and the overall cohort. During follow-up, 20 patients underwent cystectomy and 15 patients experienced disease progression. Five-year PFS, CFS, CSS, and OS were 82%, 75%, 91%, and 64%, respectively.ConclusionsIn this long-term analysis, intravesical Gem/Doce for high-risk NMIBC after BCG failure yielded a 75% 5-year bladder preservation rate and a 91% 5-year cancer-specific survival rate. Further prospective trials are warranted.     

Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ-confined TCC at radical cystectomy

OBJECTIVES: Carcinoma in situ (CIS) is a nonpapillary, high-grade, potentially aggressive, and unpredictable manifestation of transitional cell carcinoma (TCC) of the bladder. The aim of this study was to assess whether presence of concomitant CIS has a detrimental effect on cancer control after radical cystectomy. METHODS: The records of 812 consecutive patients who underwent radical cystectomy and pelvic lymphadenectomy for bladder TCC at three US academic centres were reviewed. Ninety-nine of 812 (12%) patients had CIS only at radical cystectomy and were excluded from the analyses. RESULTS: Three hundred thirty of the 713 (46.3%) patients had concomitant CIS at radical cystectomy. Patients with TCC involvement of the urethra were more likely to have concomitant CIS than not (61% vs. 40%, p=0.018). Concomitant CIS was significantly more common in patients with lower cystectomy stages and higher tumour grades. In univariate, but not multivariate, analysis, patients with concomitant CIS versus those without were at increased risk of disease recurrence (p=0.0371). In patients with organ-confined disease, concomitant CIS was an independent predictor of disease recurrence (p=0.048 and p=0.012, respectively) but not bladder cancer-specific mortality (p=0.160 and p=0.408, respectively) after adjusting for the effects of standard postoperative features. CONCLUSIONS: Concomitant CIS in the cystectomy specimen is common, and patients with concomitant CIS are at increased risk of urethral TCC involvement. The presence of concomitant CIS appears to confer a worse prognosis in patients with non-muscle-invasive TCC treated with radical cystectomy.