Preliminary report of a multicentric study on environmental risk factors in Ta-T1 transitional cell carcinoma of the bladder. A study from Gruppo Studi Tumori Urologici Foundation

OBJECTIVE: The distribution of potential environmental risk factors among patients affected by superficial transitional cell carcinoma of the bladder (TCCB) has been analyzed. METHODS: Patients affected by superficial TCCB underwent TUR and early intravesical chemotherapy. Detailed data about age, sex, residence, employment, active and passive cigarette smoking, water resource and hair dye use were centralized. Analysis has been conducted on 474 patients affected by Ta-T1 G1-2 TCCB at medium risk for recurrence. Patients with primary single Ta G1-2, Tis or T1G3 tumors were excluded from the present analysis. RESULTS: Over 80% of the patients lived in urban areas, 22% were employed in industries presumed at risk for bladder cancer, 8% used hair dye and 75% were smokers. Bottled water was the only water resource in 42% of the patients. Employment in industry at risk (p = 0.01) and cigarette smoking (p = 0.04) resulted in being statistically related to tumor multiplicity. Moreover, the period of cigarette smoking was significantly longer in patients with recurrent tumors (p = 0.026). The municipal water supply represented the main water source in never-smokers (p = 0.01) rather than in smokers and in patients harboring T1 rather than Ta tumors (p = 0.03). CONCLUSIONS: Employment in industry at risk and cigarette smoking resulted in being related to tumor multiplicity. The length of exposure to cigarette smoking was related to the natural history of the tumor. A drinkable water source emerged as a risk factor in absence of cigarette smoking.     

pT1 bladder cancer.

pT1 bladder tumors invade the lamina propria and are more aggressive biologically than superficial pTa or in situ carcinomas (Tis). Among patients with pT1 tumors treated by transurethral resection (TUR), 30% develop a muscle-invasive neoplasm within 3-5 years, but intravesical chemotherapy or BCG reduce progression rates to 20 and 14%, respectively. Tumor variables favoring progression include multiple, recurrent pT1 tumors, high grade (G3), solid configuration and associated Tis. Many pT1 tumors can be managed conservatively, but patients failing an adequate trial (3-6 months) of TUR and intravesical therapy are best treated by cystectomy.     

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.     

Transurethral resection and sequential chemo-immunoprophylaxis in primary T1G3 bladder cancer

OBJECTIVES: T1G3 superficial bladder cancer is considered to be at high risk for progression, and in some institutions early cystectomy is advocated. Other authors and personal experience suggest that conservative treatment, such as TURBT followed by intravesical prophylaxis, may be adequate in the majority of cases. The purpose of the present phase II study was to assess the tolerability and efficacy of sequential intravesical administration of a chemotherapeutic agent, epirubicin, followed by BCG, after TURBT. MATERIALS AND METHODS: 81 patients with primary T1G3 superficial bladder cancer, without evidence of Tis or upper tract tumor, underwent TURBT and intravesical prophylaxis with weekly epirubicin 50 mg for 8 weeks followed by weekly BCG Connaught 120 mg for 6 weeks. A control cystoscopy with bladder mapping and/or TUR of suspicious areas was performed at 15-17 weeks. Then patients were followed-up with 3-month urinary cytology and cystoscopy. RESULTS: The sequential chemo-immunoprophylaxis was generally well tolerated. After a mean follow-up of 48 months recurrent tumors were found in 19 patients (23.4%) and progressive disease in 6 cases (7.4%). Of 6 progressions, 4 patients died (5%) of the disease. CONCLUSION: Sequential chemo-immunoprophylaxis with epirubicin followed by BCG is well tolerated and seems to be efficacious in primary T1G3 bladder cancer. The recurrence progression and disease-specific mortality rates were acceptable so that this study seems to confirm previous data which show that TURBT and intravesical prophylaxis are appropriate treatment for the majority T1G3 tumors.     

The effect of repeat transurethral resection on recurrence and progression rates in patients with T1 tumors of the bladder who received intravesical mitomycin: a prospective, randomized clinical trial

PURPOSE: We compared the outcomes of repeat transurethral resection plus intravesical mitomycin C with initial transurethral resection of bladder plus intravesical MMC in patients with newly diagnosed pT1 transitional cell carcinoma of the bladder in terms of recurrence, progression and overall survival. MATERIALS AND METHODS: Of 148 newly diagnosed patients with T1 bladder cancer 142 were prospectively randomized in 2 groups between January 2001 and January 2005. A total of 74 patients underwent second TURB and received adjuvant MMC intravesically (group 1) and 68 patients received adjuvant MMC following the initial TURB (group 2). All repeat TURB operations were performed 2 to 6 weeks following initial TURB. Patients with incomplete resection, Cis or muscle invasive disease were excluded from study. The first dose of mitomycin C (40 mg per week for a total of 8 weeks) was instilled intravesically in all patients during the first 24 hours after the last surgery. RESULTS: Mean followup was 31.5 months (range 6 to 48) with no difference between the 2 groups. The rate of recurrence-free survival was 86.35% (SE 0.4%), 77.67% and 68.72% in group 1, and 47.08%, 42.31% and 37.01% in group 2 for the first, second and third year, respectively (overall 74.32% vs 36.76%, log rank 0.0001). Recurrence was observed in 19 of the 74 (25.68%) patients in group 1 and in 43 of the 68 (63.24%) patients in group 2. Ten of the 19 (52.63%) patients in group 1 and 35 of the 43 (81.39%) patients in group 2 had recurrence within 12 months. Recurrence was observed in 17.6%, 25% and 60% of patients with G1, G2 and G3 tumors, respectively, in group 1. The same rates for group 2 were 25%, 64% and 90%. The RFS rate was significantly worse in the high grade group (G2 and G3) (p <0.001). Progression was observed at 4.05% for group 1 compared to 11.76% for group 2 (log rank 0.0974). OS was 91.89% and 89.71% in group 1 and 2, respectively (log rank 0.732). CONCLUSIONS: The high recurrence rate in patients who did not undergo ReTUR is due to a high residual tumor rate following initial TURB. The benefit of ReTUR is especially true for high grade tumors. Since intravesical MMC was present in both groups, this study has shown that intravesical chemotherapy does not compensate for inadequate resection. Progression does not seem to be affected by ReTUR although there was a trend favoring the ReTUR group. We recommend ReTUR for patients with primary high grade T1 disease to achieve better recurrence-free survival.     

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.     

Management and prognosis of transitional cell carcinoma superficial recurrence in muscle-invasive bladder cancer after bladder preservation

PURPOSE: To assess the bladder preservation rate and cancer-specific survival after conservative treatment of superficial relapses in invasive tumors after bladder preservation. MATERIAL AND METHODS: Fifty-one patients with invasive bladder tumor (T2) were treated using transurethral resection (TUR) followed by three cycles of systemic chemotherapy (carboplatin-vinblastine). After three weeks, an endoscopic reappraisal was made including deep TUR of the site of the original tumor and multiple cold cup biopsies. Forty-two patients retained their bladder (33 complete responses and 9 partial responses). RESULTS: With a median follow-up of 63 months, 18 patients recurred as superficial TCC tumor (43%). Fourteen patients with high grade superficial recurrence were treated with TUR and Bacillus Calmette-Guerin (BCG) instillations; two patients (G2-3 T1) with TUR as well as endovesical mytomicine, and two patients with low grade recurrence with only TUR. With a median follow-up of 44 months after TUR of first superficial relapse, there was only one case with progression of the disease without any evidence of bladder tumor. Two cystectomies were made due to carcinoma in situ (Cis) persistence and high grade superficial recurrence. Eighty-three percent of the patients who had superficial recurrence retained their bladders, with 94% cancer-specific survival. CONCLUSIONS: A very strict follow-up is mandatory due to the high rate of superficial relapses (43%). Cis is the most frequent type of superficial recurrence. Superficial recurrences in bladder preservation may be treated with TUR and BCG instillations when they are high grade and and/or associated with Cis. Superficial recurrences do not imply a worse prognosis for bladder preservation or cancer-specific survival.     

Therapy of superficial bladder carcinomas

Treatment of superficial bladder carcinoma was derived by several large randomized trials. This group of cancers is stratified by differentiation grade and stage in three groups of different risk profiles (Ta G1-2 vs. T1 G1-2 vs. Tis/T1 G3). Standard therapy is fractionated transurethral resection (TUR). Adjuvant therapy after transurethral resection is not indicated in primary Ta G1-2 tumors because there is a low recurrence rate and no risk of tumor progression. The recurrence rate can be decreased up to 15% in recurrent Ta or T1 G1-2 tumors by intravesical therapy with mitomycin C (20 mg/instillation) or adriamycin (50 mg/instillation). Therapy should be limited to early (within 24 h post-TUR) and short-term treatment (4 x weekly, 5 x monthly). Alternatively, patients can be treated by intravesical BCG (strain Connaught or strain RIVM). Maintenance therapy is advantageous according to recurrence rate. Tumors with great malignant ability (Tis or T1 G3) will be treated initially with adjuvant BCG. Patients who fail are candidates for radical cystectomy within 3-6 months after initial diagnosis. There is no need - except in clinical trials - for the administration of unverified or not admitted drugs. Copyright Copyright 1999 S. Karger AG, Basel     

组织培养加药物敏感性测定在表浅膀胱癌术后丝裂霉素灌注化疗中的指导作用

目的 探讨组织培养加药物敏感性测定在指导表浅膀胱癌术后丝裂霉素(MMC)膀胱灌注化疗中的应用价值.方法 原发表浅膀胱移行细胞癌患者41例.男30例,女11例.平均年龄55岁.TNM分期:Ta 10例、T1 31例.病理分级:G1 9例、G2 22例、G3 10例.采用经尿道电切或膀胱部分切除术保留膀胱.肿瘤标本依次行三维组织培养和改良噻唑盐(MTT)法药物敏感性测定.生长抑制率>70%为高度敏感,50%～70%为中度敏感,<50%为不敏感.41例患者术后均行MMC标准膀胱灌注化疗.无复发随访时间5年,中途复发者则随访结束.结果 41例患者癌组织经1 g/L浓度MMC作用2 h后不敏感13例,其中Ta 1例、T1 12例(P=0.009),G1 1例、G2 7例、G35例(P=0.101).灌注化疗后随访3～5年,复发16例(39%),其中Ta 1例、T1 15例(P=0.059),G210例、G3 6例(P=0.016).对MMC不敏感组的复发率为77%(10/13),敏感组仅为21%(6/28,P=0.004).单因素Kaplan-Meier生存分析和Log-rank检验结果显示,平均无肿瘤复发时间不敏感组为16.5个月,敏感组为49.2个月(P<0.001).多因素Cox回归分析显示对MMC敏感性是独立预后因子(P=0.008).此法预测MMC膀胱灌注化疗效果的准确率为78%.结论 利用组织培养药物敏感性测定方法指导表浅膀胱癌术后MMC灌注化疗,可提高疗效,降低肿瘤复发率.     

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.     

Preliminary European results of local microwave hyperthermia and chemotherapy treatment in intermediate or high risk superficial transitional cell carcinoma of the bladder

INTRODUCTION: Superficial bladder cancer can be treated by transurethral resection (TUR) and adjuvant intravesical therapy. Intravesical bacillus Calmette-Guérin (BCG) has been proven to be more efficacious with respect to recurrence prevention than intravesical chemotherapy, although at the cost of more severe side effects. There is a need for a new treatment modality with higher efficacy and less toxicity. The subject of this study is the efficacy of local microwave hyperthermia and chemotherapy treatment in intermediate or high risk superficial transitional cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Ninety eligible patients received adjuvant treatment with a combination of mitomycin-C (MMC) and local microwave hyperthermia. All patients had multiple or recurrent Ta or T1 TCC of the bladder and were classified as intermediate or high risk according to EAU criteria. In total, 41 patients were BCG failures. The treatment regimen included 6 to 8 weekly sessions followed by 4 to 6 monthly sessions. Follow-up consisted of video-cystoscopy and urine cytology every 3 months. All patients were observed for 2 years. RESULTS: Kaplan-Meier analyses of the total group (N = 90) indicated that 1 year after treatment only 14.3% (SE 4.5%) of all patients experienced a recurrence. After 2 years of follow-up the risk of recurrence was 24.6% (SE 5.9%). No progression in stage and grade was observed. CONCLUSION: Microwave induced hyperthermia combined with MMC has promising value in intermediate or high risk superficial bladder cancer patients compared to literature data of BCG and/or intravesical chemotherapy, particularly where other treatments, i.e. BCG, have failed.     

Significance of random bladder biopsies in superficial bladder cancer

OBJECTIVES: We investigated to what extent biopsies of normal-appearing urothelium taken from patients with superficial bladder cancer (Ta, T1, Tis) showed malignant disease and whether those findings had impact on therapeutical decisions. PATIENTS AND METHODS: 1033 consecutive patients presenting with Ta, T1 or Tis (carcinoma in situ) superficial bladder tumors at increased risk for recurrence underwent multiple random biopsies from normal-appearing urothelium during transurethral resection (TUR). Patients with small, primary, singular tumors (smaller or equal to 1cm) were excluded from random biopsies. RESULTS: No tumor was found in the random biopsies of 905 patients (87.6%). 128 patients (12.4%) showed urothelial bladder cancer in their random biopsies (Tis: 74, Ta: 41, T1: 12, T2: 1). In 14 patients, where transurethral resection of the primary tumor revealed no signs of malignancy, urothelial bladder cancer was detected in the random biopsy material: Ta 8 patients, Tis 5 patients and T1 one patient. 21 patients with Ta tumors and 29 patients with T1 disease showed concomitant Tis. Upstaging of the primary, resected tumor by histological examination of the random biopsy material occurred in 75 patients (7%). Altogether, due to the random biopsy results therapy was altered in 70 patients (6.8%) of our series: It changed intravesical chemotherapy to BCG in 45, provoked a second TUR in 48 and cystectomy in 15 patients. CONCLUSIONS: While the clinical significance of random biopsies is still controversial, random biopsy results had strong impact on therapeutical decisions in our series. Regarding random bladder biopsies a simple tool for the urologist to identify high risk groups of patients, we recommend them as part of the routine management of superficial bladder cancer.     

A 1‐year maintenance after early adjuvant intravesical chemotherapy has a limited efficacy in preventing recurrence of intermediate risk non‐muscle‐invasive bladder cancer

Study Type – Therapy (RCT)
Level of Evidence 1b

OBJECTIVE

To evaluate the efficacy of 1‐year maintenance after a 6‐week cycle of early intravesical chemotherapy, as the role of maintenance in intravesical chemotherapy is debated.

PATIENTS AND METHODS

Between May 2002 and August 2003, 577 patients with non‐muscle‐invasive bladder cancer (NMI‐BC) underwent transurethral resection (TUR) and early intravesical chemotherapy (epirubicin, 80 mg/50 mL). They were randomized between a 6‐week induction cycle and the induction cycle plus maintenance with 10 monthly instillations. In all, 95 patients with T1G3, Tis or single and primary Ta–T1 G1–G2 tumours were excluded; 482 patients at intermediate risk of recurrence continued the study. All patients had cytology and cystoscopy at 3‐monthly intervals for the first 2‐years and 6‐monthly thereafter.

RESULTS

The tumours’ characteristics were equally distributed between the two arms. Treatment interruption for toxicity was required in 39 patients. One death due to toxicity of early instillation occurred. The median follow‐up was 48 months. Ten patients (2.5%) progressed and 117 patients (29.6%) recurred. No statistically significant difference in the recurrence‐free rate (RFS) was detected between the two arms (P = 0.43). An advantage in favour of the maintenance arm was evident only at 18 months after TUR (P = 0.03). A trend for a higher benefit from maintenance in primary and multiple tumours was detected.

CONCLUSIONS

In patients with intermediate risk NMI‐BC treated by TUR and early adjuvant chemotherapy, adding a maintenance regimen with monthly instillations for 1 year is of limited efficacy in preventing recurrence.     

Retrospective analysis of transurethral resection, second-look resection, and long-term chemo-metaphylaxis for superficial bladder cancer: indications and efficacy of a differentiated approach

BACKGROUND AND PURPOSE: Because of controversy concerning risk factors for progression, recurrence, and persistence of bladder cancer, we reviewed the data of our patients with superficial bladder tumors. Based on a differentiated approach with second-look transurethral resection (TUR) and/or intravesical metaphylaxis, we wanted to answer the following questions: Was this approach efficient? What risk factors demand a second-look TUR? Is surveillance appropriate for patients at low risk? MATERIALS AND METHODS: Retrospectively we analyzed the data of 251 patients with superficial bladder cancer with a mean follow-up time of 69 (range 20 to 107) months. We focused on recurrence rates, tumor-persistence and progression, and types of adjuvant treatment. An early reintervention within 6 to 8 weeks after primary resection was defined as a second-look TUR. To judge the necessity of early reintervention and metaphylaxis, we performed a matched-pair analysis for the low-risk group. RESULTS: Tumor stages included T(a) (170 patients, 68%); T(1) (72 patients, 29%); carcinoma in situ (CIS) (9 patients, 4%). Grades included grade 1 (58 patients, 23%); grade 2 (117 patients, 47%); and grade 3 (76 patients, 30%). Thirty-eight (15%) tumors were already classified as recurrent. A second-look TUR was performed on 222 (88%) patients, indicating a persistence rate of 25%. Persistence rates for low-risk tumors (T(a) grade 1/2) were 9%; rates for T(a) grade 3 tumors were significantly higher. Risk factors for persistence were multilocularity and higher grade and stage. Matched-pair analysis for the low-risk group did not show any significant advantage for second-look TUR. After complete resection of T(1) grade 3 tumors, the risk of progression is similar to that for tumors of lower grade and stage. The overall recurrence rate was 25%, with a higher risk of upstaging in cases of higher stage or grade and multilocular and persisting tumors. CONCLUSION: The overall tumor recurrence rate of 25% reflects the efficacy of our differentiated approach with selective use of second-look TUR and intravesical metaphylaxis (intravesical chemotherapy). Second-look TUR is indicated for multifocal and recurrent tumors or in patients whose tumors put them at high risk. Patients with grade 2/3 tumors, multifocal grade 1 tumors, and all T(1) tumors received metaphylaxis; intravesical bacillus Calmette-Guerin was instilled in patients with CIS. With this regimen, even in T(1) grade 3 stages, organ preservation can be achieved.     

T1G3膀胱尿路上皮癌复发与进展影响因素分析

目的探讨影响T1G3膀胱尿路上皮癌复发与进展的因素,为临床治疗提供循证医学依据。方法回顾性分析1997年至2009年我科治疗的62例行经尿道膀胱肿瘤电切术(TURBT)+膀胱灌注治疗的T1G3膀胱尿路上皮癌患者,对这些患者进行随访并对生存预后进行分析。生存函数运用Kaplan-Meier法,单因素和多因素分析运用Cox回归,并采用Log-rank法行显著性检验。结果中位随访期40个月(6～140个月),41例(66.0%)复发,2、5年无复发生存率分别为43.4%、35.1%。14例(23.0%)出现进展,2、5年无进展生存率分别为86.4%、83.5%。将与复发相关的危险因素纳入Cox回归多因素生存分析后提示肿瘤复发的危险因素为肿瘤数目(RR=2.250)、肿瘤大小(RR=1.039)、既往复发情况(RR=2.162),P均<0.05;与进展相关的危险因素纳入Cox回归多因素生存分析,提示肿瘤进展的危险因素为肿瘤数目(RR=3.695)。结论肿瘤数目是T1G3膀胱尿路上皮癌复发最大的影响因素,其次为既往复发情况和肿瘤大小,肿瘤数目是肿瘤进展的相关因素;T1G3膀胱尿路上皮癌需结合肿瘤数目、肿瘤大小、既往复发情况综合考虑治疗方案。     

Restaging transurethral resection of high risk superficial bladder cancer improves the initial response to bacillus Calmette-Guerin therapy

PURPOSE: This study was an evaluation of whether restaging transurethral resection (TUR) of superficial bladder cancer improves the early response to bacillus Calmette-Guerin (BCG) therapy. MATERIALS AND METHODS: A total of 347 patients with high risk superficial bladder cancer (high grade Ta and T1 tumors associated with carcinoma in situ) underwent a single transurethral resection (TUR, 132 patients) or restaging TUR (215 patients) before receiving 6 weekly intravesical BCG treatments. The patients were evaluated for response (presence or absence of tumor) at first followup cystoscopy, at 6 and 12 months after treatment, and evaluated for disease stage progression within 3 years of followup. RESULTS: Of the 132 patients who underwent a single TUR before BCG therapy, 75 (57%) had residual or recurrent tumor at the first cystoscopy and 45 (34%) later had progression, compared with 62 of 215 patients (29%) who had residual or recurrent tumors and 16 (7%) who had progression after undergoing restaging TUR (p = 0.001). CONCLUSIONS: Restaging TUR of high risk superficial bladder cancer improves the initial response rate to BCG therapy, reduces the frequency of subsequent tumor recurrence and appears to delay early tumor progression.     

影响膀胱肿瘤术后复发的COX回归模型多因素分析

采用ＣＯＸ回归模型对２０１例次保留膀胱手术的患者进行多因素分析，其中ＴＵＲＢｔ（经尿道膀胱肿瘤电切术）１６３例次；膀胱部分切除术３８例次，７２例次复发，总复发率３８５％。结果显示肿瘤的综合分级分期、分级、分期、既往复发史依次为影响术后肿瘤复发的主要危险因素，而术后膀胱灌注药物为主要保护性因素。同时Ｌｏｇｒａｎｋ检验计算及比较两种术式术后的复发率。结果显示Ｔ１或（和）Ｇ１患者ＴＵＲＢｔ术后的复发率低于膀胱部分切除术，Ｔ３，４或（和）Ｇ３患者膀胱部分切除术后的复发率低于ＴＵＲＢｔ，Ｔ２Ｇ２患者两种术式术后复发率无差别。     

Intravesical Bacillus Calmette-Guerin treatment improves patient survival in T1G3 bladder tumours

OBJECTIVE: To study the clinical and pathological factors that affect recurrence, progression and survival in pT1G3 bladder tumours treated conservatively. MATERIAL AND METHODS: From January 1979 to December 1996, 80 patients were conservatively treated for pT1G3 bladder tumours. All patients were studied for potential prognostic factors such as: age, sex, previous tumour recurrence, tumour size, multiple tumours, carcinoma in situ, and intravesical instillations. A longitudinal, retrospective, observational and analytical study was conducted to evaluate four different types of events: recurrence, progression, overall survival, and disease-specific survival. The chi(2) (Fischer exact test) and student t tests were used to assess the prognostic value of the qualitative and quantitative variables. Estimations of the survival distributions were calculated according to the Kaplan-Meier method and compared with the Log rank test. Multivariate analysis of the data was performed with Cox proportional hazard models. RESULTS: Among the 80 patients, 67 (84%) were men and 13 (16%) were women, with median age of 65.5 years. The median tumour size was 20 mm, most had single tumour (58.8%) and carcinoma in situ was found in six patients (7.5%). Thirty patients were treated with transurethral resection (TUR) of the bladder tumour and 50 patients were treated with TUR followed by BCG. The two groups of patients were comparable and followed up during a median time of 61 and 65 months, respectively (p=0.454). Kaplan-Meier estimators and Log rank tests demonstrated that patients with TUR alone recurred (p<0.0001), progressed (p<0.040) and died (overall survival: p<0.009; disease-specific p<0.040) earlier than patients who received intravesical instillations of BCG. The results were confirmed with Cox models and odds-ratios are presented. CONCLUSION: In this study, BCG adjuvant immunotherapy was the only factor affecting recurrence, progression and survival. Conservative treatment using TUR followed by BCG may improve disease-specific survival.     

Initial conservative treatment for grade 3 Ta-1 superficial bladder cancer

We retrospectively investigated the therapeutic outcomes of our series of 7 Ta and 62 T1 bladder cancers with grade 3 (G3) malignancy in 61 men and 8 women having a mean age of 66.2 years. Following transurethral resection of bladder tumor (TURBT), 35 and 6 patients received intravesical instillations of bacillus Calmette-Guerin (BCG) and anthracycline-derivants, respectively, whereas 15 received no adjuvant therapy. Five and 2 patients received systemic and local chemotherapy with irradiation, respectively, and six underwent radical cystectomy for invasive potential. The 5-year nonrecurrence, progression-free, and overall (cancer-specific) survival rates were 66, 82%, and 76 (88%), respectively, after a median follow-up of 52 months. The 5-year non-recurrence rates were 24% in non-adjuvant, 85% in BCG, 0% in anthracycline-derivants, 65% in systemic and local chemoradiation therapy, and 68% in cystectomy. The 5-year progression-free and overall (cancer-specific) survival rates of the patients treated with BCG instillation were 91% and 94 (100)%. There were no significant differences in the 5-year non-recurrence and progression-free rates between 12 patients with carcinoma in situ (CIS) and 23 patients without CIS. Complete TUR of all visible tumors and a reliable histopathological diagnosis of appropriate specimens bearing the muscle layer are mandatory for assessment of recurrence. G3 Ta-1 bladder cancers and CIS showed a high risk of recurrence, and required aggressive treatment. Since BCG therapy following TURBT significantly reduced the risk of recurrence and progression, adjuvant BCG therapy is considered to be the most promising initial conservative treatment for G3 Ta-1 bladder cancers.     

Therapy of superficial bladder carcinoma

Topical therapy is administered after transurethral resection (TUR) for superficial cancer to reduce the frequency of recurrence, to avoid local tumor progression and to increase the survival rate. However, the results of prospective randomized studies on topical chemotherapy show that successful reduction of tumor recurrence is limited to a small group of patients. Topical immunotherapy with BCG seems to be more efficient, but prospective multicenter studies have not confirmed the superiority of BCG treatment. At present neither chemotherapy nor immunotherapy can influence progression or survival rate. It therefore seems advisable to continue to enroll patients with superficial bladder tumors in prospective studies to obtain more information on treatment schedules and their side-effects and therapeutic activity. The following information may be helpful in deciding on individual treatment schedules for patients with superficial bladder cancer: (1) Carcinoma in situ is the only therapeutic indication for topical therapy, and BCG may be more potent than chemotherapy. (2) Patients with pTaG1 tumor should be excluded from topical therapy. (3) Topical therapy may not be indicated at all for pT1G3 tumors. The rate of local progression and distant metastasis is high and cannot be influenced by this form of adjuvant treatment. (4) At present no drug of first choice is known. (5) Early application of intravesical chemotherapy immediately after TUR has no advantage over delayed treatment. (6) Long-term chemoprophylaxis is equivalent to short-term prophylaxis (6-24 months) in effect. (7) Immunotherapy with BCG can be limited to a period of 6 months.