Clinical outcome of conservative therapy for stage T1, grade 3 transitional cell carcinoma of the bladder

BACKGROUND: The objective of this study was to retrospectively investigate the effectiveness of transurethral resection of bladder tumor (TURBT) and intravesical instillation therapy for stage T1, grade 3 (T1G3) transitional cell carcinoma (TCC) of the urinary bladder. METHODS: Between January 1995 and December 1997, 97 patients with T1G3 TCC of the urinary bladder were treated by TURBT and adjuvant intravesical instillation with bacillus Calmette-Guérin (BCG) or other anticancer agents. The recurrence-free survival rates were evaluated according to several clinicopathological factors. The cases that progressed to muscle invasive disease were also analysed. RESULTS: In this series, the median follow-up period was 25 months (range, 5- 41) after the initial TURBT. Intravesical recurrence was noted in 44 patients (45%), and the 1, 2, and 3 year recurrence-free survival rates were 72%, 58%, and 42%, respectively. Multivariate analyses revealed that the risk of intravesical recurrence was significantly higher for patients who did not receive BCG therapy, irrespective of age, gender, tumor size, multiplicity, pathological stage, concomitant carcinoma in situ, and lymphovascular involvement. Moreover, after a median of 10 months, disease progression occurred in seven patients (7%), of which only one patient was treated by BCG therapy after initial TURBT. CONCLUSION: These findings suggest that intravesical instillation with BCG combined with TURBT is an effective conservative treatment for T1G3 TCC of the bladder. Patients with negative prognostic factors should be treated by BCG rather than other anticancer agents after TURBT.     

A clinical study of renal pelvic and ureteral cancer: prognosis and frequency of subsequent bladder cancer following surgical treatment

PURPOSE: A retrospective investigation of patients presenting with renal pelvic and ureteral cancer was performed. This study focused on the prognostic factors and frequency of subsequent bladder cancer following surgical treatment. MATERIALS AND METHODS: Forty-five patients presenting with transitional cell carcinoma, who had undergone nephroureterectomy at the Department of Urology, Okayama Central Hospital, from March 1990 to November 2000, were reviewed. Various factors were evaluated according to survival and non-bladder cancer occurrence rates. The Kaplan-Meier method was used in the analyses. RESULTS: Patients consisted of 33 males and 12 females (mean age was 71.7). Seventeen patients exhibited renal pelvic cancer, 25 cases displayed ureteral cancer and three subjects presented with multiple cancers. Eleven patients had received treatment for precedent or coexistent superficial bladder cancer by transurethral resection. The overall 5-year survival rate was 71.9%. Ten patients died as a result of the disease; in all cases, lymph node or distant metastasis had progressed. Pathological T factor, tumor grade and pN factor demonstrated a significant effect on survival; however, sex, age, tumor localization and incidence of subsequent bladder cancer had no influence on survival. The 5-year non-bladder cancer occurrence rate was 38.8%; additionally, all subsequent bladder cancer was disclosed within three years. Tumor multiplicity exclusively in the upper urinary tract significantly affected occurrence of bladder cancer. T factor and tumor grade revealed no correlation to occurrence. CONCLUSIONS: Adjuvant chemotherapy for prevention of clinical metastasis should be considered in cases involving pT3 or higher stage, grade 3, or in instances of pathologically confirmed lymph node metastasis. The significant occurrence of subsequent bladder cancer in the case of tumor multiplicity suggested that prophylactic therapy such as intravesical BCG instillation or chemotherapy might be beneficial.     

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.     

Long-term efficacy of hyperthermic intravesical chemotherapy for BCG-unresponsive non-muscle invasive bladder cancer

BackgroundThe recommended treatment for patients with Bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) is radical cystectomy (RC). However, many patients refuse, or are unfit for RC. Therefore, alternative bladder-sparing treatment modalities are needed for BCG-unresponsive NMIBC. In this study we sought to assess the long-term efficacy of hyperthermic intravesical chemotherapy (HIVEC) as alternative to radical cystectomy in BCG-unresponsive non-muscle invasive bladder cancer patients.Methods and materialsRetrospectively collected data from 56 patients with BCG-unresponsive NMIBC who received ≥5 HIVEC instillations between October 2014 and March 2020 was analyzed. All patients met the BCG-unresponsive criteria according to the current EAU guideline on NMIBC 2020. Patients were followed-up with cystoscopy and/or bladder biopsies, urine cytology and annually CT-urography. The Primary outcome was the high grade (HG) recurrence-free survival (RFS), defined as the time from the first HIVEC instillation until histologically confirmed intravesical recurrence or last follow-up. The Kaplan Meier method was used to estimate survival outcomes. Secondary outcomes were: complete response rate (CR), adverse events (AE), assessed by the Common Terminology Criteria for Adverse Events v5.0 (CTCAE) and tumor progression to muscle invasive disease or distant metastases.ResultsThe median follow-up was 32.2 months (IQR 13.7–44.8). The 1- and 2-year HG-RFS was 53% (SE:6.8) and 35% (SE:6.9), respectively. The CR for patients with CIS was 70% (21/30) at 6 months. Overall, 80% of the population developed an AE, only 1 was classified as CTCAE ≥3. Limitation of this study was the small sample size.ConclusionHIVEC resulted in a 2-year HG-RFS of 35% for BCG-unresponsive NMIBC patients without severe side-effects and therefore HIVEC seems to be an alternative treatment option for patients who refuse or are unfit for RC.     

初发T1G3膀胱尿路上皮癌行膀胱全切还是保留膀胱手术?

目的 比较根治性膀胱全切与保留膀胱手术治疗初发T1G3膀胱尿路上皮癌的临床效果.方法 初发T1G3膀胱尿路上皮癌患者113例.男91例,女22例.年龄27～88岁,平均64岁.初次治疗保留膀胱患者81例,行根治性膀胱全切患者32例.采用Kaplan-Meier生存分析及log-rank检验比较2组患者5年总生存率及肿瘤特异性生存率.结果 初次治疗保留膀胱患者81例中行经尿道肿瘤电切术74例、膀胱部分切除7例,术后随访6～140个月,平均64个月,术后5年总生存率为64.2%(52/81),肿瘤特异性生存率为77.8%(63/81).根治性膀胱全切治疗32例,术后随访4～141个月,平均62个月.术后5年总生存率为59.4%(19/32),肿瘤特异性生存率为75.0%(24/32).2组术后5年总生存率及肿瘤特异性生存率比较差异均无统计学意义(P>0.05).结论 保留膀胱手术或根治性膀胱全切治疗初发T1G3膀胱癌,5年总生存率和肿瘤特异性生存率差异无统计学意义.膀胱全切治疗初发T1G3膀胱肿瘤至少有50%的病例有过度治疗的可能.     

Predictive clinico-pathological factors to identify BCG,unresponsive patients,after re-resection for T1 high grade non-muscle invasive bladder cancer

IntroductionSeventy-five percent of bladder cancers are non-muscle invasive. The treatment strategy includes the transurethral resection of bladder tumor (TURB) followed by intravesical immunotherapy with the bacillus of Calmette-Guerin (BCG) or chemotherapy, depending on the grade of bladder tumor. Despite a proper BCG intravesical instillations schedule, up to 40% of patients present a failure within 2 years. The aim of this retrospective study was to investigate the predictive factors in the response to BCG in patients with a high-grade non-muscle invasive bladder cancer diagnosis.Materials and methodsPatients with non-muscle invasive bladder cancer from 13 hospitals and academic institutions were identified and treated, from January 1, 2002, until December 31, 2012, with TURB and a subsequent re-TURB for restaging before receiving BCG. Follow-up was performed with urine cytology and cystoscopy every 3 months for 1 year and, successively every 6 months. Univariate and multivariate Cox regression models addressed the response to BCG therapy. Kaplan-Meier overall survival (OS) and cancer-specific survival (CSS) estimates were determined for BCG responsive vs. BCG unresponsive patients.ResultsA total of 1,228 patients with non-muscle invasive bladder cancer were enrolled. Of 257 (20.9%) patients were BCG unresponsive. Independent predictive factors for response to BCG were: multifocality (HR: 1.4; 95% CI 1.05–1.86; P = 0.019), lymphovascular invasion (HR: 1.75; 95% CI 1.22–2.49; P = 0.002) and high-grade on re-TURB (HR: 1.39; 95% CI 1.02–1.91; P = 0.037). Overall survival was significantly reduced in BCG-unresponsive patients compared to BCG-responsive patients at 5 years (82.9% vs. 92.4%, P < 0.0001) and at 10 years (44.2% vs. 74.4%, P < 0.0001). Similarly, cancer-specific survival was reduced in BCG-unresponsive patients at 5 years (90.6% vs. 97.3%, P < 0.0001) and at 10 years (72.3% vs. 87.2%, P < 0.0001).ConclusionMultifocality, lymphovascular invasion, and high-grade on re-TURB were independent predictors for response to BCG treatment. BCG-unresponsive patients reported worse oncological outcomes.     

膀胱癌经尿道电切除术后吡柔比星膀胱灌注预防复发临床观察

目的:探讨吡柔比星膀胱内灌注预防膀胱癌术后复发的疗效、安全性。方法:45例膀胱癌经尿道电气化术后患者分2组,分别用吡柔比星和卡介苗定期行膀胱内灌注,随访10～33个月,了解灌注后肿瘤复发情况及并发症。结果:卡介苗组复发率为13.6%(3/22),副反应率为81.8%(18/22);吡柔比星复发率为13.0%(3/23),副反应率为91.3%(21/23),两组肿瘤复发率、并发症无显著差异,但卡介苗严重副反应高于吡柔比星(P<0.05)。结论:吡柔比星膀胱灌注预防膀胱癌复发的有效率与卡介苗相同,但严重副反应明显减少,是一种有效的药物。     

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.     

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。     

Results of Transurethral Resection Plus Adjuvant Intravesical Chemotherapy for Superficial Bladder Cancer

Background : We analyzed the results of conservative therapy for superficial bladder cancer to determine the risk factors for recurrence and progression.
Methods : Between May 1984 and February 1997, 111 patients with primary superficial bladder cancer were treated by a transurethral resection with or without intravesical instillation of chemotherapy, or for patients with concomitant carcinoma in situ (CIS), bacillus Calmette-Guerin. We examined the relationship between tumor stage, grade, incidence of concomitant CIS and recurrence-free survival according to pathologic findings and the drugs instilled.
Results : The incidence of concomitant CIS in pTI, grade 3 tumors was significantly higher than that in pTa, grade 1 tumors (42% vs. 3%, P= 0.006). The 5-year recurrence-free survival rate of all patients was 73%. There was no significant difference in recurrence-free survival and pathologic stage, tumor grade, presence of concomitant CIS, or drugs used for instillation. However, the recurrence-free survival in patients with 5 tumors was significantly lower than in patients with less than 5 tumors. Of the 111 patients, only 3 patients demonstrated disease progression and underwent a radical cystectomy, while 1 patient with a pTI b, grade 3 tumor developed a tumor in the ureter. No patient died of bladder cancer.
Conclusion : Our results indicate that the prognosis of superficial bladder cancer patients with a high-stage, high-grade (pTI, grade 3) tumor is favorable when treated by a transurethral resection and intravesical instillation. Bacillus Calmette-Guerin therapy is useful to prevent the recurrence of tumors with concomitant CIS.     

二次电切在降低非肌层浸润性膀胱癌初次电切术后复发率中的临床价值

目的探讨经尿道膀胱肿瘤二次电切术（Re-TURBT）在降低T_a和T₁期非肌层浸润性膀胱癌（NMIBC）电切术后肿瘤复发率的临床价值。 方法回顾性分析2015年2月至2018年11月我院86例诊断为T_a和T₁期的NMIBC患者。患者接受单次经尿道膀胱肿瘤电切术为对照组（40例）,接受二次经尿道膀胱肿瘤切除术为观察组（46例）,两组患者首次电切术中均联合了吉西他滨即刻膀胱灌注化疗。统计观察组二次电切的阳性率及肿瘤分期分级变化情况,同时比较两组患者术后2年内的肿瘤复发及进展情况。 结果两组患者年龄、性别、吸烟史、肿瘤最大径、肿瘤个数、首次电切病理分期比较差异无统计学意义（P>0.05）。观察组二次电切术后的病理结果显示,11例（23.91%）检出残余癌,5例出现临床分期升级,4例病理分级升级。观察组术后2年总复发率低于对照组（P<0.05）。两组术后2年总进展率差异无统计学意义（P>0.05）。 结论Re-TURBT可明显降低T_a和T₁期NMIBC电切术后肿瘤复发率,同时可获得更准确的肿瘤分期,具有一定的临床价值。     

Intravesical bacillus Calmette-Guerin therapy for stage T1 grade 3 transitional cell carcinoma of the bladder: recurrence,progression and survival in a study of 57 patients

PURPOSE: Stage T1 grade 3 transitional cell carcinoma of the bladder is associated with a high risk of tumor recurrence and progression. We report our experience with stage T1 grade 3 bladder tumors treated with bacillus Calmette-Guerin (BCG) therapy in the last 10 years. MATERIALS AND METHODS: We analyzed the outcome in 57 consecutive patients treated with intravesical BCG for stage T1 grade 3 bladder cancer between 1991 and 2001. After initial transurethral resection all patients received a 6-week course of BCG therapy consisting of 1 instillation weekly. All patients underwent systematic biopsies at the end of the first BCG course. 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. Patients with residual tumor received a second course of 6 weekly instillations. Time to tumor recurrence and progression, and the rate of patient survival were retrospectively analyzed. RESULTS: Median followup was 53 months (range 9 to 110). Minimum followup was 2 years in 36 cases (63.2%) and 5 years in 28 (49.1%). After the first BCG course 50 patients (87.7%) had no residual disease, while 7 (12.3%) had residual tumor. The recurrence and progression rates were 42.1% and 22.8%, respectively. The rate of delayed cystectomy was 14%. The rate of disease specific survival was 87.7%. CONCLUSIONS: Our study confirms that BCG therapy is effective conservative treatment for patients with stage T1 grade 3 bladder tumors.     

The management of T1G3 bladder cancer

INTRODUCTION: The treatment of T1G3 bladder cancer is still a controversial issue. Nowadays, intravesical bacillus Calmette-Guérin (BCG) instillation is considered to be the treatment of choice for patients with high-grade superficial bladder tumour after transurethral resection of all visible tumour. The aim of this retrospective study was to determine the effects and results of this approach, recurrence and progression rates in patients with T1G3 superficial bladder tumours. MATERIALS AND METHODS: 43 patients (28 male, 15 female; mean age 65.5 years, range 21-82) with T1G3 TCC (transitional cell carcinoma) bladder tumour underwent transurethral resection and subsequent intravesical BCG according to Morales protocol, in the period 1993-1998 at our institution. The mean follow-up period was 52.5 (range 30-96) months. RESULTS: After one or more initial courses of therapy, 33 patients were disease-free. Twelve patients (27.90%) had recurrent tumour after a median of 7 (range 3-46) months. After a second course of BCG treatment, 6 patients had no evidence of disease, 3 patients had progression and 3 had recurrence. Progression occurred in 7 (16.27%) patients after a median of 19 (range 3-43) months. Five patients underwent radical cystectomy and the remaining 2 underwent bladder-preserving therapies. Two patients died of TCC and 3 due to disease-unrelated conditions. CONCLUSION: Intravesical BCG instillation can be recommended as treatment modality for responders with T1G3 TCC bladder tumour. The benefit of the second course of intravesical BCG therapy has to be confirmed in further investigations.     

Clinical study of bladder cancer: Proteinuria as a predictor of recurrence and efficacy of intravesical bacille Calmette–Guerin therapy

AIM: We studied the clinical characteristics of bladder cancer, with special attention to the clinical and pathological variables that affect tumor stage, relapse and efficacy of intravesical therapy. METHODS: We reviewed the medical records of 152 patients of the Saiseikai Central Hospital who had been diagnosed as having bladder cancer between 1981 and 2001. RESULTS: The age of the patients ranged from 24 to 88 years, with a median of 63.5 years. The median follow up was 52.4 months (range, 0.5-259.5 months). There was no difference in the incidence of gross hematuria as a presenting symptom among the patients with invasive cancer, superficial cancer and carcinoma in situ (CIS). However, the incidence of urinary frequency and painful urination did differ significantly between patients. Although patients with invasive cancer had a longer time to hospital visit than those with superficial cancer, this time difference was not statistically significant. Presence of proteinuria, multifocality and intravesical bacille Calmette-Guerin (BCG) therapy were the significant predictors of relapse after transurethral resection (TUR). Presence of proteinuria was shown to adversely affect the efficacy of intravesical BCG therapy. In the BCG-treated group, 3-year relapse-free survival was 78.4% for patients without proteinuria and 40.0% for those with proteinuria; this difference was statistically significant (P = 0.0277). CONCLUSIONS: Time to hospital visit did not influence the pathological stage of cancer in patients included in the present study. Presence of proteinuria, multifocality and BCG therapy were the significant predictors of relapse after TUR. Presence of proteinuria was shown to adversely affect the efficacy of intravesical BCG therapy. Proteinuria might be helpful in predicting tumor relapse and efficacy of intravesical BCG therapy in clinical settings, along with other markers.     

新辅助动脉化疗在肌层浸润性大体积膀胱癌保留膀胱治疗中的价值

目的评估术前新辅助动脉化疗联合经尿道手术在直径超过3cm的肌层浸润性膀胱癌保留膀胱治疗的临床价值。方法对于较大体积(直径3cm)的28例肌层浸润性膀胱肿瘤(T2N0M0~T4aN0M0)采用新辅助动脉化疗联合手术治疗,观察动脉化疗效果,分析肿瘤降期率、保留膀胱率、肿瘤复发率,Kaplan-Meier法计算总体生存率、无肿瘤复发生存率,并绘制生存曲线。结果 26例(92.9%)患者动脉化疗有效,肿瘤可见明显缩小,经3~5次动脉介入治疗后行经尿道切除术+膀胱灌注完成保留膀胱治疗;动脉化疗无效2例,立即行根治性全膀胱切除术。26例完成保留膀胱治疗的患者,术后肿瘤病理分期降低19例(73.1%),无变化为7例。肿瘤复发8例(复发率为30.8%),其中,浅表性复发5例,局部浸润性复发2例,远处转移1例。28例患者总体生存率:3年69%,5年62.1%。无肿瘤复发生存率:5年44.07%。最终25例患者得到保留膀胱(保留膀胱率89.3%)。结论直径3cm的较大体积浸润性膀胱肿瘤采用术前新辅助动脉化疗治疗,可使肿瘤降期降级及体积缩小,有利于经尿道完全切除,可有效提高患者生存率,同时保留了膀胱,大大提高患者生存质量,对不愿或不宜行膀胱全切的患者是一个理想的选择。     

Clinical study of prognostic factors of superficial bladder cancer treated with intravesical bacillus Calmette-Guerin

Intravesical instillation of Tokyo 172 strain Bacillus Calmette-Guérin (BCG) was performed in 96 patients with initial superficial bladder cancer (Ta and T1) after transurethral resection (TUR) of tumour as a prophylaxis against tumour recurrence. The recurrence rate of tumours was estimated by the person-years method, comparing it with that of historical controls. There were statistically significant decreases in recurrent tumours following BCG therapy. To clarify the efficacy of intravesical BCG therapy, the prognostic significance of several factors was evaluated in patients with bladder cancer treated with TUR and instillation of BCG. The prophylactic effects were statistically better for those with multiple tumours, grade 3 lesions or Ta lesions than for control patients. No correlation between purified protein derivative (PPD) responsiveness and favourable results could be observed. Our results suggest that intravesical BCG instillation can alter the biological behaviour that affects the recurrence of superficial bladder cancer, especially for multiple, high grade or Ta tumours.     

三种灌注药物预防膀胱癌术后复发的疗效观察

探讨几种常用灌注药物预防膀胱癌术后复发的疗效。方法：将９３例患者分为３组，第一组用丝裂霉素Ｃ２０ｍｇ，第二组用卡介苗６０ｍｇ，第三组用ＢＣＧ６０ｍｇ加白细胞介素－２（ＩＬ－２）１００００ｕ行膀胱灌注。结论丝裂霉素Ｃ、ＢＣＧ及ＢＣＧ加ＩＬ－２膀胱灌注预防膀胱癌术后复发，疗效十分肯定，其中ＢＣＧ加ＩＬ－２灌注效果更好。     

吡柔比星加卡介苗膀胱灌注预防肿瘤复发的效果及尿中IL-8变化的临床意义

目的 比较吡柔比星（THP）加卡介苗或单用卡介苗膀胱灌注预防膀胱肿瘤复发的疗效，并测定灌注后IL-8的变化，探讨其与疗效的关系。方法对62例膀胱部分切除术后患者分别给予THP加卡介苗或单用卡介苗膀胱灌注预防复发，用酶联免疫学方法测定灌注前后尿中IL-8的浓度。赔果联合用药组复发率明显低于单用BCG组，两组灌注后尿中IL-8的浓度均有明显的变化，但两组之间无显著性差别。结论THP加BCG膀胱灌注可有效降低膀胱肿瘤复发率，而这一效果是作用机制不同药物的叠加作用，而不是化疗药物对免疫药物疗效的放大作用。     

Recurrence of Primary Superficial Bladder Cancer Treated with Prophylactic Intravesical Tokyo 172 Bacillus Calmette-Guerin: A Long-Term Follow-up

Background Long-term results after transurethral resection (TUR) and prophylactic intravesical Tokyo 172 bacillus Calmette-Guerin (BCG) therapy for primary superficial bladder cancer were analyzed by multivariate analysis, and factors affecting the recurrence of bladder tumors after this therapy were examined.
Methods One-hundred and forty-one consecutive patients with primary superficial bladder cancer who consulted the Department of Urology at Wakayama Medical College and affiliated hospitals between May 1985 and May 1990 were studied. Tokyo strain BCG was given intravesically (80 mg in 40mL saline) weekly for 6 weeks.
Results The 5-year cumulative recurrence-free rate by the Kaplan-Meier method was 0.702 in 141 patients with primary superficial bladder cancer. The 5-year recurrence-free function using the proportional hazard model was 0.743. Using the Cox proportional hazard model, variables that significantly contributed to recurrence after intravesical BCG included female sex, tumor size less than 1 cm in diameter, and T1 tumor stage. Patient age, tumor type, multiplicity, tumor grade, and concomitant carcinoma in situ did not contribute to recurrence.
Conclusion Long-term results showed that prophylactic intravesical Tokyo strain BCG after TUR for primary superficial bladder cancer is also effective in preventing the recurrence of bladder cancer, and the biologic behavior of superficial bladder cancer other than stage T1 tumor may be altered after intravesical BCG.     

Ablative and prophylactic effects of BCG Tokyo 172 strain for intravesical treatment in patients with superficial bladder cancer and carcinoma in situ of the bladder. Bladder cancer BCG Study Group]

We investigated the effects of intravesical instillation of BCG Tokyo 172 strain on patients with superficial bladder cancer and CIS of the bladder for tumor ablation and prophylaxis. This is the first controlled multicenter study for governmental approval of BCG Tokyo 172 strain for the treatment of superficial bladder cancer and CIS of the bladder. One hundred-fifty-seven patients (125 with Ta or T1, and 32 with CIS) were treated by 80 mg of BCG diluted in 40 ml of saline, once a week for 8 weeks. The dose and interval adopted in this multicenter study was determined by the previous Phase II study conducted by the same Study Group. Out of 125 superficial tumor Ta, T1, 83 (66.4%) showed complete disappearance of the tumor (CR) and 26 (20.8%) partial disappearance (PR), and out of 32 CIS, 27 (84.4%) showed CR and 2 (6.3%) PR. Among those patients showing CR, and PR who were treated with additional TUR-Bt, 98 patients were randomised for a controlled study of prophylactic BCG instillation. Prophylactic treatment consisted of 40 mg of BCG diluted in 40 ml of saline, monthly for 12 months. Forty-two patients were assigned to the treatment group, whereas the remaining 56 to the control group without any prophylactic instillation. Three cases showed tumor recurrence during the prophylactic phase. Twenty-five cases could not be treated for the whole course of prophylactic instillation mainly due to bladder irritable symptoms. Recurrent free curves were compared till 1050 days after the initiation of the study. However, there was no significant difference between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)