Intravesical instillation of mitomycin-C in 242 patients with superficial bladder cancer at high risk of recurrence: long-term results.

OBJECTIVE: The present study evaluated the long-term results of intravesical mitomycin C (MMC) instillation after transurethral resection (TUR) in 242 consecutive patients with superficial bladder cancer at high risk of recurrence (stage Ta, grade 1-3, or stage T1, grade 1 and 2, primary multiple or recurrent tumor). MATERIALS AND METHODS: 242 patients were treated with weekly instillations of 40 mg MMC for 8 weeks after TUR. Tumor-free patients then followed a maintenance course with monthly instillations for 3 months. RESULTS: Median follow-up of disease-free patients is 43.5 (range 23-112) months. The incidence of first recurrence is 59.5% (144/242 patients) with a median time to first recurrence of 29 months. 95 patients (39.3%) remained disease-free. Three had disease progression as the first event. The risk of recurrence was significantly higher for multifocal tumors (p = 0.0023, hazard ratio 1.79, 95% CI 1.23-2.59). Overall, patients have been followed for a median time of 57 (range 10-114) months. During this period the recurrence rate was 4.9. Eleven more patients had disease progression. The progression rate is 5.8% (14/242), with a mean time to progression of 34 months. At present 209 patients are alive, 6 have died of bladder cancer, 16 of causes unrelated to the disease and 11 (4.5%) have been lost to follow-up. Thus the crude survival rate is 86.4%, disease-specific mortality 2.5%, and non-disease-specific mortality 6.6%. CONCLUSIONS: Patients with multiple tumors seem to benefit the least from MMC instillation. Probably recurrent disease could be better prevented with intravesical bacillus Calmette-Guérin.     

The value of perioperative mitomycin C instillation in improving subsequent bacillus calmette-guerin instillation efficacy in intermediate and high-risk patients with non-muscle invasive bladder cancer: a prospective randomized study

Purpose: We evaluated the efficacy of perioperative mitomycin C (MMC) instillation to improve subsequent bacillus Calmette-Guérin (BCG) instillation efficacy in intermediate and high risk patients with non-muscle invasive bladder cancer (NMIBC). Materials and Methods: From November 2004 to May 2006, 51 patients with intermediate or high risk NMIBC were enrolled in this prospective randomized trial. In group A, patients were treated with perioperative MMC (40 mg MMC in 40 mL saline was administered within 6 hours of surgery) followed by delayed (at least 15 days from surgery) BCG instillations (once a week for 6 weeks, 5 x 108 colony-forming units in 50 mL saline). Patients in group B were treated with delayed BCG instillations alone. The primary end points were recurrence-free interval and recurrence rate. Results: There were 25 and 26 patients in groups A and B, respectively. Median follow-up was 41.3 months (range 8 to 64) in group A and 40.9 months (range 6 to 68) in group B. Recurrence rate was 36 % (9 of 25) and 19.3 % (5 of 26) in group A and B, respectively (p = 0.052). Median time to the first recurrence was 8 months in group A and 7 months in group B (p = 0.12). Conclusions: The present study showed no statistically significant difference in terms of recurrence rate and median time to first recurrence between intermediate or high-risk patients with NMIBC who were treated with early single dose instillation of MMC plus delayed BCG and those who were treated with only BCG.     

Vergleich der Effektivität der Langzeitinstillation mit Mitomycin C gegen Kurzzeitprophylaxen mit MMC oder Bacillus Calmette-Guerin

BACKGROUND: Adjuvant instillation therapy with chemo- or immunotherapeutic agents is an integral component in the treatment of non-muscle-invasive bladder cancer. There is, however, no general consensus on the choice of medication and the optimal duration of therapy. This multicenter trial compared a long-term treatment regimen with mitomycin C (MMC) with two short-term treatment approaches with MMC or bacille Calmette-Guérin (BCG) for intermediate-/high-risk bladder tumor after transurethral resection. In patients with low-risk bladder tumors, the effectiveness of six weekly MMC instillations was determined and compared with the results of patients not receiving adjuvant treatment. MATERIAL AND METHODS: A total of 495 patients with intermediate-/high-risk bladder tumor (recurrent and/or multifocal pTaG1, pTaG2-3, or pT1G1-3) were randomly administered either BCG-RIVM 2x108 CFU in six weekly instillations, MMC 20 mg in six weekly instillations, or MMC 20 mg in six weekly instillations with subsequent monthly instillations for 3 years. A total of 132 low-risk patients (first diagnosis of a unifocal pTaG1 bladder tumor) were randomly allocated to two treatment arms. In the first arm, 20 mg MMC were instilled weekly six times. In the control arm, the patients received no adjuvant therapy. RESULTS: The 3-year recurrence-free rate in the patients of the intermediate-/high-risk group was 65.5% (95% CI: 55.9-73.5%) in the BCG arm and 68.6% (95% CI: 59.9-75.7%) in the MMC short-term arm. In the MMC long-term arm, the 3-year recurrence-free rate was significantly higher at 86.1% (95% CI: 77.9-91.4%, log-rank test: p=0.001). There was no increased toxicity observed with long-term administration of MMC. In the low-risk group, the 3-year recurrence-free rate after adjuvant therapy was 74% (95% CI: 60.0-83.8%) and in the patients receiving no adjuvant treatment 63% (95% CI: 46.6-75.5%, corresponding to a hazard ratio of 0.58 (95% CI: 0.28-1.18%). The difference between the treatment arms was not significant. CONCLUSION: Long-term prophylaxis with MMC results in a significantly reduced recurrence rate in intermediate-/high-risk bladder cancer with a comparable toxicity profile in comparison to short-term MMC or short-term BCG. Our study showed no significant decrease of the recurrence rate in low-risk tumors with six adjuvant MMC instillations. This treatment approach thus does not represent an alternative to early instillation.     

Early and large-dose intravesical instillation of epirubicin to prevent superficial bladder carcinoma recurrence after transurethral resection

OBJECTIVE: To prospectively compare the prevention of tumour recurrence by four intravesical adjuvant administration protocols, and thus elucidate the efficacy of early and high total dose instillations of epirubicin to prevent superficial bladder tumour recurrence after transurethral resection of bladder tumour (TURBT). PATIENTS AND METHODS: In all, 69 patients with Ta/T1 bladder cancer were randomly assigned to four intravesical administration protocols: A, delayed instillation (first instillation 7 days after TURBT) and low-dose (30 mg once every 2 weeks, six times): B, early instillation (three instillations before 7 days after TURBT) and low-dose; C, delayed and high-dose (30 mg once weekly 12 times) instillation; D, early and high-dose. The influence of the instillation protocols and tumour characteristics on the probability of recurrence-free survival was examined using Kaplan-Meier analysis and a Cox regression hazard model. RESULTS: The early-instillation and high-dose groups had relatively lower recurrence rates after 6 months (A, 30%; B, 25%; C, one of 12; and D, none) and 1 year (50%, 35%, four of nine and one of eight, respectively). Patients who received 360 mg epirubicin (C and D) had a significantly better recurrence-free survival than those receiving 180 mg (A and B; P = 0.012). Preoperative urine cytology and tumour multiplicity were significantly associated with recurrence. However, multivariate analysis of the risk of recurrence using a Cox proportional hazard model showed that urine cytology (hazard ratio 3.11, 95% confidence interval 1.08-8.94, P = 0.04) and total dose (0.32, 0.11-0.92, P = 0.03) were independent prognostic factors for recurrence. CONCLUSION: Patients who received a high-dose epirubicin instillation had a significantly lower recurrence rate but the benefit of early instillation was not confirmed, as the study group was too small.     

Comparative study on prophylactic intravesical instillation of bacillus Calmette-Guerin (BCG) and adriamycin for superficial bladder cancers

In this study we evaluated 77 patients with superficial bladder cancer who were treated with either intravesical bacillus Calmette-Guerin (BCG) (44 patients) or doxorubicin hydrochloride (Adriamycin, ADR) (33 patients) for prophylaxis of tumor recurrence after transurethral resection. The estimated actuarial probability of non-recurrence rate at three years for the BCG group was 73.0%, and the actuarial non-recurrence rate for the ADR group was 27.3%; a statistically significant difference (p = 0.0013). A comparison between the two groups was also made according to the patient's background, including whether the tumor was initial or recurrent, solitary or multiple, and the tumor grade. In all areas of the study, except for grade-1 tumors, the BCG group was significantly superior to the ADR group. The efficacy of BCG therapy as a result of different BCG treatment protocol was evaluated for six weekly instillations 1) without further maintenance instillation, 2) followed by 12 months of maintenance, and 3) followed by more than 18 months of maintenance. Long-term maintenance BCG instillation group (more than 18 months) showed the most favorable results, however, the differences were not statistically significant. These results indicate that intravesical BCG instillation was significantly superior to ADR in the prevention of bladder cancer recurrence and that six weekly intravesical BCG instillations may provide adequate prophylactic effects against recurrence of superficial bladder cancers.     

ＭＭＣ和ＢＣＧ交替灌注防治膀胱癌术后复发

目的：观察丝裂霉素Ｃ（ＭＭＣ）和卡介苗（ＢＣＧ）化学免疫预防膀胱癌术后复发的疗效。方法：对８６例浅表性膀胱癌患者术后应用ＭＭＣ２０mg和ＢＣＧ６０mg,每周１次进行交替膀胱藻注,共灌注１２次,以后每间隔３个月灌注１次,持续２年,结果：随记２．４－８年,平均４．８４年,肿瘤复发率为８．１％,结论：ＭＭＣ和ＢＣＧ交替膀胱灌注可减少膀胱癌术后复发率。     

Weekly mitomycin C followed by monthly bacillus Calmette-Guerin or alternating monthly interferon-alpha2B and bacillus Calmette-Guerin for prophylaxis of recurrent papillary superficial bladder carcinoma

PURPOSE: We evaluated alternatives to bacillus Calmette-Guerin (BCG) monotherapy using a new combination of chemotherapy and immunotherapy for recurrent superficial bladder carcinoma. MATERIALS AND METHODS: A total of 236 patients with frequently recurrent stage Ta or T1 bladder tumors were enrolled in our prospective, randomized, multicenter Finnbladder IV study. The initial mitomycin C instillation was instilled in all patients perioperatively after transurethral resection, followed by 4 weekly instillations of mitomycin C. Thereafter patients were randomized to receive monthly for up to 1 year BCG only or interferon-alpha2b and BCG alternating monthly. Primary end points were time to initial recurrence, recurrence rate (number of recurrences per patient-year) and recurrence index (number of recurrent tumors per patient-year). RESULTS: Of the 236 randomized patients 205 were eligible for study with a median overall followup of 30.7 months. Monthly BCG was superior to alternating monthly interferon-alpha and/or BCG with respect to time to initial recurrence (log rank test p <0.00001) as well as recurrence rate (0.4 versus 0.9, p <0.00001) and index (0.9 versus 3.0, p <0.00001). Side effects were limited. CONCLUSIONS: Monthly BCG given for up to 1 year preceded by perioperative and an additional 4 weekly mitomycin C instillations is a well tolerated mode of instillation therapy, providing excellent tumor control comparable to that of the best reported instillation regimens. No benefit was obtained by alternating interferon-alpha2b with BCG.     

Intravesical bacillus Calmette-Guerin instillation therapy for carcinoma in situ of the urinary bladder and prediction of effects by urinary cytologic examination

PURPOSE: We investigated the effects of intravesical BCG instillations for carcinoma in situ (CIS) of the urinary bladder. And we have retrospectively analyzed the prediction of effects by fresh urinary cytologic examinations before instillation. MATERIAL AND METHODS: 33 patients were treated for bladder CIS (1991-1997) with a median follow-up of 30 months (range from 9 to 90 months). The patients (27 males and 6 females) ranged in age from 46 to 91 (average 71 years) and received 6 to 12 weekly BCG Tokyo 172 strain 80 mg instillations. They were divided into 3 groups based on tumor history: primary (9), secondary (15), concurrent (9). The prediction of effects were analyzed by scoring fresh urinary cytologic examinations before instillation. RESULTS: 22 cases (67%) were responded and they have remained free of disease for follow-up period. The statistic evaluation proved to show the significance between the effects of treatment and the sum of scoring (cellular appearance and existence of large nuclear cells). CONCLUSION: We confirmed the effects of this treatment. The prediction of effect of this treatment seemed to be indicative by fresh urinary cytologic examinations before instillation, especially cellular appearance and existence of large nuclear cells.     

Prevention of recurrent urinary tract infections by intravesical administration of hyaluronic acid and chondroitin sulphate: a placebo-controlled randomised trial

Background

Urinary tract infection (UTI) is a prevalent condition in women during their lifetime with a high rate of recurrence within 3–6 mo.

Objectives

Our aim was to investigate the efficacy and tolerability of the intravesical administration of combined hyaluronic acid (HA) and chondroitin sulphate (CS) in female patients with a history of recurrent UTI.

Design, setting, and participants

We conducted a prospective, randomised, double-blind, placebo-controlled study comparing the intravesical instillation of HA-CS with placebo in women with recurrent UTI.

Intervention

Participants were randomised to receive 50 ml of sterile sodium HA 1.6% and CS 2.0% solution (IALURIL^®) weekly for 4 wk and then monthly for 5 mo.

Measurements

The primary end point of the study was defined as the mean number of UTI per patient per year. Participants were evaluated addressing UTI status/urinary symptoms and with a general health-related quality-of-life (QoL) questionnaire at baseline and after 3, 6, 9, and 12 mo.

Results and limitations

In the intention-to-treat analysis, 57 women were randomly allocated to HA-CS (n = 28) or placebo (n = 29). The UTI rate per patient per year at the end of the study (12 mo) (mean ± SD: −86.6% ± 47.6 vs −9.6% ± 24.6; mean difference: 77%; 95% confidence interval, 72.3–80.8; p = 0.0002) and the mean time to UTI recurrence (52.7 ± 33.4 vs 185.2 ± 78.7 d; p < 0.001) were significantly reduced after treatment with HA-CS compared with placebo. Overall urinary symptoms and QoL measured by questionnaires significantly improved compared with placebo (Pelvic Pain and Urgency/Frequency questionnaire symptom score: 14.53 ± 4.32 vs 9.88 ± 6.77; p = 0.004; SF-36 QoL score: 78.6 ± 6.44 vs 53.1 ± 4.72; p < 0.001). No serious adverse event was reported.

Conclusions

Compared with placebo, HA-CS intravesical instillations significantly reduced UTI rate without severe side effects while improving symptoms and QoL over a 12-mo period in patients with recurrent UTI.

Trial registration

ISRCTN 76354426.     

A randomized controlled trial of short-term versus long-term prophylactic intravesical instillation chemotherapy for recurrence after transurethral resection of Ta/T1 transitional cell carcinoma of the bladder

PURPOSE: In a prospective randomized controlled study, we investigated the optimal schedule for intravesical instillation of epirubicin for maximizing its effect on prophylaxis and disease progression after transurethral resection of newly diagnosed Ta/T1 bladder cancer. MATERIALS AND METHODS: The patients were instilled with epirubicin (30 mg/30 ml in normal saline) within 24 hours after transurethral resection and then randomized into 2 groups after a definite histopathological diagnosis of Ta/T1 bladder cancer. One group of 77 patients received 19 intravesical instillations of epirubicin in the year after transurethral resection (group 1). The second group of 73 patients received 9 intravesical instillations of epirubicin during the 3 months after transurethral resection (group 2). Nonrecurrence rates and toxicity were compared. RESULTS: In the followup period, 10 group 1 patients (13.0%) and 23 group 2 patients (31.5%) had recurrent disease. The 3-year nonrecurrence rate was 85.2% in group 1, whereas it was 63.9% in group 2. The nonrecurrence rate of group 1 was significantly higher than that of group 2 throughout the observation period (p = 0.005). The incidence and severity of toxicity were not significantly different between the 2 groups. CONCLUSIONS: Our study indicates that long-term instillation of epirubicin is more effective than short-term instillation in preventing recurrence after transurethral resection of Ta/T1 bladder cancer.     

早期吡柔比星膀胱内灌注预防膀胱癌术后复发

目的:探讨膀胱肿瘤电切术(TURBt)后早期应用吡柔比星灌注化疗预防肿瘤复发的疗效。方法:对112例病理证实的膀胱移行细胞癌患者,59例行早期灌注(Ⅰ组),53例行常规灌注(Ⅱ组)。Ⅰ组于术后6小时内将30mg吡柔比星溶于40ml蒸馏水膀胱内灌注,保留2小时后排出,术后7天开始规律膀胱灌注;Ⅱ组于术后7天开始吡柔比星规律膀胱灌注,比较两组患者膀胱肿瘤复发率。结果:随访7~54个月,平均35个月,Ⅰ组6例膀胱肿瘤复发,Ⅱ组13例复发,差异有统计学意义;不良反应包括尿路刺激征、肉眼血尿等,两组比较差异无统计学意义。结论:TURBt后早期开始吡柔比星膀胱灌注化疗,可以显著降低膀胱肿瘤复发率。     

吡柔比星术后即刻膀胱灌注联合常规灌注预防表浅性膀胱癌术后复发的对照研究

目的：比较吡柔比星两种膀胱内灌注方法预防表浅性膀胱癌术后复发的有效性及安全性。方法：将52例经尿道膀胱癌电切术后表浅性膀胱癌患者随机分为两组。每次吡柔比星灌注剂量30mg,治疗组术后24h内膀胱灌注1次,此后每周灌注1次,连续8周,再改为每月灌注1次,至术后1年。对照组术后2周开始灌注,此后每周灌注1次,连续8周,再改为每月灌注1次,至术后1年。结果：全部病例均获随访,时间为12～24个月,平均随访16．3个月。其中治疗组随访期内2例复发,复发率8％;对照组随访期内4例复发,复发率14％,两组复发率比较差异有统计学意义（P〈0．05）,不良反应主要为尿路刺激症状。结论：本研究显示,吡柔比星膀胱灌注预防表浅性膀胱癌术后复发的疗效满意,用药方便,患者耐受性好;术后即刻膀胱灌注联合常规灌注较常规灌注可以降低肿瘤复发率,值得推荐。     

Bacillus Calmette-Guérin therapy in stage Ta/T1 bladder cancer: prognostic factors for time to recurrence and progression

OBJECTIVE: To report prognostic factors for time to recurrence and progression after bacillus Calmette-Guérin (BCG) prophylaxis in patients with stage Ta/T1 papillary bladder cancer. PATIENTS AND METHODS: The clinical records were assessed retrospectively for 236 patients with papillary stage Ta/T1 bladder cancer treated with BCG between 1986 and 2000. Patients with known carcinoma in situ were excluded. The median (range) follow-up was 44 (4-155) months. The effect of 13 variables on the time to recurrence and progression was evaluated using multivariate Cox proportional hazard regression and Kaplan-Meier analyses. RESULTS: The recurrence rate was markedly reduced for all grades and stages. Patients with a negative first cystoscopy and maintenance BCG had a significantly longer time to recurrence than those treated with an induction course alone (P < 0.001). Thirty-seven patients (16%) progressed in stage. The result of the first cystoscopy (P < 0.001), tumour grade (P = 0.003) and six or fewer initial instillations (P = 0.002) had prognostic importance for the time to progression. Twenty-eight patients (12%) had a history of an upper tract tumour, which was 3-10 times the expected rate. Age, number of tumours, number of positive cystoscopies, length of tumour history before BCG, BCG strain and treatment year had no influence on time to recurrence and progression. CONCLUSIONS: Maintenance treatment does not seem to be necessary among patients with TaG1-G2 disease after a negative first cystoscopy, as the progression rate was very low. One new finding was that BCG seemed to be equally effective among patients with or with no history of an upper tract tumour. Another new and surprising finding was that patients treated with fewer than six induction instillations, because of very bothersome side-effects, had an increased risk of tumour progression and of local failure.     

Comparison of three schedules of intravesical epirubicin in patients with non-muscle-invasive bladder cancer

OBJECTIVES: To study the additive effect of either an early instillation or maintenance instillations of adjuvant intravesical epirubicin, as compared to the epirubicin "standard" treatment schedule only, in patients with non-muscle-invasive bladder cancer. METHODS: Patients with intermediate- and high-risk urothelial cell carcinoma of the bladder, except carcinoma in situ, were randomised for adjuvant intravesical instillations with 50mg epirubicin/50 ml NaCl for 1h. Group 1 received 4 weekly and 5 monthly instillations (standard schedule), group 2 received the same schedule as group 1, but with an additional instillation <48 h after transurethral resection of bladder tumour (TURBT), and group 3 received the same scheme as group 1, but with additional instillations at 9 and 12 mo (maintenance schedule). Standard follow-up was 5 yr and consisted of cystoscopy, cytology, and registration of adverse events. RESULTS: A total of 731 patients were eligible for quasi intention-to-treat analysis. Side-effects were minimal for all treatment groups. After 5-yr follow-up, respectively, 44.4%, 42.7%, and 45.0% (log-rank test, p=0.712) of the patients in groups 1, 2, and 3 were recurrence free, and 90.0%, 87.7%, and 88.2% (log-rank test, p=0.593) of the patients, respectively, were progression free. CONCLUSIONS: In the quasi intention-to-treat analysis there is no difference in the 5-yr recurrence-free period between the treatment groups, despite one instillation within 48 h of TURBT or two maintenance instillations up to 1 yr, in addition to the "standard" schedule.     

Clinicopathological Evaluation of Repeated Courses of Intravesical Bacillus Calmette-Guerin Instillation for Preventing Recurrence of Initially Resistant Superficial Bladder Cancer

Purpose

The efficacy of repeated courses of intravesical bacillus Calmette-Guerin (BCG) for superficial bladder cancer was assessed with particular attention to initially resistant cases.

Materials and Methods

A total of 75 patients with stages Ta to T1b superficial transitional cell bladder carcinoma received 6 weekly instillations of 80 mg. Tokyo strain BCG in 40 ml. saline followed by 6 instillations at monthly intervals. If tumors recurred, another course of treatment was given with surgery.

Results

Of 17 patients (22.7 percent) with recurrent tumor at followup periods of up to 84 months 12 received an additional course of BCG instillations according to the same protocol after transurethral resection of bladder tumors, and 10 (83.3 percent) showed no further recurrence with or without additional surgery and BCG therapy after a median followup of 42.9 months. Thus, the overall success rate with this approach was 90.7 percent (68 of 75 patients). Comparison of patients with and without recurrence revealed a significant difference in number of tumors before therapy (p less than 0.05), and a pronounced tendency (p = 0.00507) for recurrence after prior systemic chemotherapy or intravesical instillation.

Conclusions

The results suggest that up to 3 courses of repeated intravesical instillation of BCG are effective even for cases that initially did not respond, and that best results may be achieved if no other prior chemotherapy has been attempted.     

Therapeutic effects and predictive factors for successful intravesical hyaluronic acid instillation in patients with interstitial cystitis/bladder pain syndrome

ObjectiveHyaluronic acid (HA) is currently used in Taiwan as intravesical instillation for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). This study investigated the therapeutic effects of HA on IC/BPS in the Taiwanese population.Materials and methodsMen and women aged ≥18 years with documented IC/BPS were initially treated with four weekly intravesical HA instillations (treatment time, 1 month) and then with five monthly instillations (total treatment time, 6 months). Clinical assessments included the evaluation of the Visual Analog Scale (VAS) score of bladder pain, O'Leary–Sant Symptom (OSS) score, IC Symptom Index (ICSI), IC Problem Index (ICPI), functional bladder capacity (FBC), uroflowmetry parameters, and global response assessment (GRA). Therapeutic effects were compared between responders (GRA increased ≥ 2 scales) and nonresponders (GRA increased < 2). Multivariate linear analysis was used to determine predictive factor for successful treatment.ResultsA total of 64 patients (3 men and 61 women) with mean age of 49.4 years (range, 20–79) completed the study. Compared with the baseline data, VAS, ICSI, ICPI, OSS score, daytime frequency, nocturia, and FBC all improved at 1 month or 6 months after starting HA treatment. Significantly more improvements in ICSI, ICPI, OSS score, VAS, and FBC were noted in the responders than in the nonresponders at 6 months of treatment. A low-grade glomerulation was the only predictor for successful treatment response to intravesical HA treatment.ConclusionIntravesical HA administrations improved IC symptoms, decreased bladder pain, and decreased frequency after four instillations, and decreased nocturia and increased bladder capacity after completion of all nine instillations. Low-grade glomerulation predicts successful outcome.     

Intravesical combined chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin is not indicated for superficial bladder cancer.

PURPOSE: The short-term effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin (BCG) administered repeatedly for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 24 patients aged a median of 70 years between March 1996 and February 1999, and were compared with those of BCG monotherapy in 50 patients from March 1990 to February 1999. PATIENTS AND METHODS: The patients underwent intravesical instillation of the Tokyo strain BCG with or without epirubicin after transurethral resection (TUR) of bladder cancer. For the combined treatment, at 1-2 weeks after TUR, epirubicin (40 mg) and BCG (80 mg) were istilled into the bladder by turns once a week for 12 weeks. For the group receiving only BCG, 80-mg instillations were done with the same schedule. Thereafter, the patients were followed by cystoscopy and urinary cytology every 3 months for up to 3 years after intravesical therapy. RESULTS AND CONCLUSIONS: At 2 years after treatment, the simple recurrence rate was 26.1% (6/23) in patients with chemoimmunotherapy and 32.0% (16/50) in BCG-treated patients. Adverse reactions, including increased frequency of urination, urgency and miction pain, were observed in 18 patients (85.7%) undergoing chemoimmunotherapy and 58.0% undergoing BCG monotherapy. One patient receiving chemoimmunotherapy was withdrawn from treatment because of symptoms of severe bladder irritation due to the instillation. Intravesical chemoimmunotherapy using epirubicin and BCG was finally found to be inferior in comparison with BCG monotherapy for the prophylaxis of recurrence of superficial bladder cancer.     

A combined intravesical therapy with hyaluronic acid and chondroitin for refractory painful bladder syndrome/interstitial cystitis

The aims of this study were to evaluate the efficacy and tolerability of intravesical instillations of high-molecular-weight hyaluronic acid (HA) 1.6% and chondroitin sulfate (CS) 2.0% in patients with refractory painful bladder syndrome/interstitial cystitis (PBS/IC) and to observe their impact on Quality of Life. Twenty-three women were enrolled. They received bladder instillations with HA and CS weekly for 20 weeks and then monthly for 3 months. Mean follow-up after completion of therapy was 5 months. We observed a significant improvement in urinary symptoms on voiding diaries and Visual Analogue Scale for frequency (p = 0.045), urgency (p = 0.005), and pain (p = 0.001). The O'Leary-Sant Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index resulted in a significant improvement in both scores (p = 0.004 and 0.01, respectively). The Pelvic Pain and Urgency/Frequency Symptom Scale only showed significant improvement in the symptom score (p = 0.001). This promising experience seems to offer an additional therapeutic option in patients with refractory PBS/IC.     

The schedule and duration of intravesical chemotherapy in patients with non-muscle-invasive bladder cancer: a systematic review of the published results of randomized clinical trials

OBJECTIVES: Intravesical chemotherapy has been studied in randomized clinical trials for >30 yr; however, the optimal schedule and duration of treatment are unknown. The objective is to determine the effect of schedule and duration of intravesical chemotherapy on recurrence in patients with stage Ta T1 bladder cancer. METHODS: A systematic review was conducted of the published results of randomized clinical trials that compared intravesical instillations with respect to their number, frequency, timing, duration, dose, or dose intensity. RESULTS: One immediate instillation after transurethral resection (TUR) is recommended in all patients. In low-risk patients, no further treatment is recommended before recurrence. In patients with multiple tumors, one immediate instillation is insufficient treatment. Additional instillations may further reduce the recurrence rate; however, no recommendations can be made concerning their optimal duration. A short intensive schedule of instillations within the first 3-4 mo after an immediate instillation may be as effective as longer-term treatment schedules (grade C). Instillations during > or =1 yr in intermediate-risk patients seem advisable only when an immediate instillation has not been given (grade C). Higher drug concentrations and optimization of the drug's concentration in the bladder may provide better results (grade C). CONCLUSIONS: The optimal schedule and duration of intravesical chemotherapy after an immediate instillation remain unknown. Future studies should focus on the eradication of residual disease after TUR and the prevention of late recurrences.     

沙培林膀胱灌注对浅表性膀胱癌患者术后疗效观察

目的 研究沙堵林(OK-423)膀胱灌注预防浅表性膀胱癌术后的疗效及安全性.方法 将78例浅表型膀胱癌患者随机分成两组.沙培林组(40例)术后1周开始常规灌注沙培林5KE,膀胱内灌注保留2h,每周1次连续6周,之后每月1次连续8个月.对照组(38例)灌注吡柔比星30mg,灌注方法 同沙墙林组.结果随访6～36个月.原发...