Prophylaxis of recurrence in superficial bladder carcinoma by intravesical chemotherapy--comparative study between instillation of combined double anticancer agents and single anticancer agent

We performed a study to compare the usefulness of double or single anticancer agents in the prophylactic treatment after the transurethral resection (TUR) of superficial bladder cancer. We experienced 127 superficial bladder cancer cases. Of these cases, 42 were treated with intravesical adriamycin (ADR) and peplomycin (PEP), 56 with ADR, PEP, epirubicin (epi-ADR) or pirarubicin (THP) only, and the remaining 29 with TUR only. Nonrecurrence rates were significantly higher in the intravesical treated cases than in the cases with TUR only, and also significantly higher in the cases treated with ADR and PEP than the other treated cases. We concluded that intravesical chemotherapy with combined agents was more effective than with a single agent.     

The expression of thymidine phosphorylase is a prognostic predictor for the intravesical recurrence of superficial bladder cancer

Background Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor, has been implicated in the angiogenesis of bladder cancer. The aim of this study is to investigate the association between TP expression and the clinicopathologic findings, and the prognostic value. Methods TP immunohistochemical staining was performed in specimens from 71 patients (50 men and 21 women) with superficial bladder cancer (pTa or pT1). Thirty-nine patients had received intravesical instillation of tetrahydropyranyladriamycin (THP) after transurethral resection (TUR) and the other 32 had not. For immunohistochemistry, paraffin-embedded specimens were stained with mouse monoclonal antibody against TP. When more than 10% of tumor cells were positively stained, staining was defined as positive. The correlations between TP immunostaining and clinicopathological features were analyzed. Multivariate analysis, using the Cox proportional hazard model, was performed to determine the risk factors for intravesical recurrence. Results Specimens from 29 of the 71 patients (19 men and 10 women) were positive for TP. The expression of TP was not correlated with age, sex, histological grade, multiplicity, or morphology. Also, TP expression was not associated with whether the cases were primary or recurrent. Multivariate analysis demonstrated that the decreased expression of TP and the use of THP instillation could be independent predictors of a higher rate of intravesical recurrence-free bladder cancer. Conclusion The present study suggests that immunohistochemical TP staining is useful for predicting the intravesical recurrence of superficial bladder cancer after Transurethral resection of bladder tumor (TUR-Bt).     

FGF2-mediated reciprocal tumor cell-endothelial cell interplay contributes to the growth of chemoresistant cells: a potential mechanism for superficial bladder cancer recurrence

Patients with superficial bladder cancer can be definitively cured by one single transurethral resection (TUR) with additional intravesical chemotherapy; however, up to 75 % of cases display frequent and multiple recurrences. One of the major causes of recurrence is that chemotherapeutic drugs used in intravesical regimens may induce chemoresistance. However, the mechanisms by which these chemoresistant cells develop into recurrent tumors remain unclear. Recent clinical evidence revealed that the expression of pro-angiogenic factor FGF2 was associated with early local relapse in patients with superficial bladder cancer. In this study, we conducted a preliminary investigation of the mechanisms of chemoresistant cells mediated bladder cancer recurrence, focusing on FGF2-initiated tumor cell-endothelial cell interaction on chemoresistant cancer cell growth. We found that the expression of FGF2 was increased in chemoresistant bladder cell lines and in bladder tissues after intravesical chemotherapy. Although chemoresistant bladder cells grow slower than parental cells, chemoresistant bladder cancer cells had stronger ability than parental cells to stimulate endothelial cell migration, growth, and tube formation by producing FGF2. Inversely, endothelial cells significantly promoted chemoresistant bladder cancer growth in vitro and in vivo. Thus, targeting chemotherapy-induced FGF2 upregulation may provide a promising approach to manage the recurrence of superficial bladder cancer.     

The clinical epidemiology of superficial bladder cancer. Dutch South-East Cooperative Urological Group.

Even though the majority of patients with bladder malignancies initially present with low stage disease, the clinical epidemiology of these so-called superficial bladder tumours is not well known. In this paper, disease characteristics at initial presentation and during follow-up are described in 1,745 primary cases documented prospectively in the Netherlands. The risk of recurrent disease after primary treatment is very high: in 60% of cases, at least one recurrence is diagnosed within 5 years (95% CI: 58-62%). In patients with a small solitary pTa grade 1 tumour, the 3-year recurrence risk is 37%. In patients with multiple large high grade pT1 tumours, this risk is as high as 77%, despite a significant beneficial effect of adjuvant intravesical chemotherapy. The actuarial risk of disease progression is 10.2% after 3 years (95% CI: 8.6-11.8%). This risk of progression depends on the patient''s age at diagnosis, tumour stage, grade, multiplicity and the presence of dysplasia or CIS in random urothelium biopsies. The use of intravesical instillations with chemotherapy or BCG vaccine after TUR does not prevent progressive disease, although this finding is difficult to interpret from a non-randomised study. The 5-year relative survival in patients with superficial TCC of the bladder is 86% (95% CI: 84-88%).     

The biology and treatment of superficial bladder cancer

Management of the superficial bladder cancer patient consists of two complementary but separate therapeutic goals: treatment of the existing tumor(s) and prevention of tumor recurrence. At present, the stage, grade, and multicentricity are the major determinants in the natural and therapeutic history of the disease. Although intravesical instillation of chemotherapeutic agents has been used for greater than 20 years, neither its exact role nor the optimal dose or schedule of administration have been established. To date, no dramatic differences in efficacy between the agents commonly used for intravesical chemotherapy, either as definitive therapy or prophylaxis, have been appreciated. These agents do appear to lower the recurrence rate as well as extend the disease-free interval. Since the most thorough experience is with thiotepa, it is the drug against which other agents should be compared in terms of both efficacy and toxicologic evaluation. Different administration schedules and methodologies need further study, such as the utility of continuous bladder irrigation, the use of sequential chemotherapeutic agents to gain cell synchronization, and the use of multiple drug regimens. Because there are multiple factors that influence the occurrence and recurrence of bladder cancer, combined modality therapy deserves testing. Modes of therapy that could be used together because they act through different mechanisms are intravesical chemotherapy, radioactive needle implants, carcinogen modifiers such as pyridoxine, chemoprotective agents such as retinoic acid, and immune stimulants such as BCG. These studies should be performed in a randomized prospective controlled fashion, which may require cooperative multi-institutional involvement to accrue adequate numbers of patients. At this time there are a number of important questions that remain to be answered concerning the treatment of superficial bladder cancer: (1) does this mode of therapy affect overall survival, (2) does prophylactic intravesical chemotherapy alter the incidence of subsequent muscle invasive disease, (3) does intravesical chemotherapy alter the sites, incidence, or responsiveness to systemic chemotherapy of subsequent metastatic disease, and (4) and what is the optimal timing and duration of prophylactic therapy from a cost-effectiveness standpoint?     

Clinical study of G3 superficial bladder cancer without concomitant CIS treated with conservative therapy

OBJECTIVE: The treatment for superficial G3 transitional cell carcinoma (TCC) of the urinary bladder remains controversial. It is important to reveal the clinical features of superficial G3 bladder cancer that can be treated conservatively. PATIENTS AND METHODS: A total of 39 patients with primary superficial bladder cancer (Ta, T1) with G3 components but without concomitant carcinoma in situ (CIS), who had been treated initially with transurethral resection (TUR), were retrospectively analyzed for factors related to tumor recurrence, progression and survival. The patients were 34 males and five females whose age ranged from 49 to 85 years (average, 68 years). Initial tumor stages were Ta in one patient and T1 in 38. Initial treatments were TUR alone in 18 patients and TUR with adjuvant therapy (intravesical chemotherapy or BCG therapy) in 21. Factors examined included age, gender, morphology, size and number of tumors and adjuvant therapies. RESULTS: Follow-up periods were 3-138 months (median, 37 months). Tumor recurrence, progression and cancer death were observed in 23, seven and four cases, respectively. The 5-year progression-free rate (75%) and survival rate (83%) in 39 patients with G3 did not show a statistically significant difference from those of the 109 patients with G1 or the 187 patients with G2 superficial bladder cancer who were treated with TUR initially. Only the rate of recurrence of patients with G3 was significantly higher than that of patients with G2 or G1. Adjuvant therapies reduced the recurrence rate of the patients with G3. Only tumor morphology, papillary or non-papillary, affected both the progression-free rate and the survival rate of patients with G3. There were no statistically significant differences associated with other factors. CONCLUSION: The results suggest that superficial G3 bladder cancer could be treated with TUR initially, especially for papillary tumors.     

Intravesical chemotherapy for maximum prophylaxis of new early phase superficial bladder carcinoma treated by transurethral resection: a combined analysis of trials by the Japanese Urological Cancer Research Group using smoothed hazard function.

BACKGROUND: The effect of intravesical instillation of doxorubicin or epirubicin after transurethral resection (TUR) was estimated from the data of five randomized clinical trials in Japan. The authors provided the estimated hazard function plots with a smoothing technique, to evaluate the prophylactic effect of an intravesical therapy over time and to estimate the natural history of superficial bladder carcinoma. METHODS: Data on a total of 1732 patients from 5 studies of the Japanese Urological Cancer Research Group who were eligible to receive doxorubicin and epirubicin were analyzed. The patients were divided into four subgroups based on their background characteristics. Their tumors were categorized as "primary and solitary," "primary and multiple," "recurrent and solitary," or "recurrent and multiple." RESULTS: Multivariate analysis revealed that intravesical instillation reduced the risk of recurrence to about one-half to two-thirds compared with the controls. The shapes of the graphs that estimated the hazard function for patients with no prophylaxis indicated that multiple tumors showed an earlier peak of recurrence than solitary tumors and recurrent tumors had a higher hazard of recurrence than primary tumors. Graphic presentation of the hazard function in each subgroup suggested that the effect of prophylaxis continued for 500 days after TUR but not for longer. CONCLUSIONS: This analysis indicated that there are two patterns of tumor recurrence of superficial bladder carcinoma after TUR, namely, early phase and late phase. Intravesical chemotherapy may be effective mainly in reducing the hazard for recurrence in the early phase.     

Superficial bladder cancer: part 1. Update on etiology, classification and natural history

Superficial 'nonmuscle-invasive' bladder tumors represent a heterogeneous group of cancers, which include those that are papillary in nature and limited to the mucosa (Ta), high grade, flat and confined to the epithelium (Tis) and those that invade the submucosa or lamina propria (T1). The natural history of these bladder cancers is that of disease recurrence and progression to higher grade and stage. Furthermore, recurrence and progression rates of superficial bladder cancer vary according to several tumor characteristics. The goal in the treatment of superficial bladder cancer is twofold: reducing tumor recurrence and the subsequent need for additional therapies, such as cystoscopy, transurethral resections, intravesical therapy and the morbidity associated with these treatments; and preventing tumor progression and the subsequent need for more aggressive therapy, such as radical cystectomy. The administration of intravesical chemotherapy and immunotherapy has become an important component in accomplishing these goals. This update is the first part of two articles reviewing important contemporary concepts in the etiology, classification and natural history of superficial bladder cancer, while part II of the series will review and highlight important aspects in management of superficial bladder cancer.     

Superficial bladder cancer: part 1. Update on etiology,classification and natural history

Superficial ‘nonmuscle-invasive’ bladder tumors represent a heterogeneous group of cancers, which include those that are papillary in nature and limited to the mucosa (Ta), high grade, flat and confined to the epithelium (Tis) and those that invade the submucosa or lamina propria (T1). The natural history of these bladder cancers is that of disease recurrence and progression to higher grade and stage. Furthermore, recurrence and progression rates of superficial bladder cancer vary according to several tumor characteristics. The goal in the treatment of superficial bladder cancer is twofold: reducing tumor recurrence and the subsequent need for additional therapies, such as cystoscopy, transurethral resections, intravesical therapy and the morbidity associated with these treatments; and preventing tumor progression and the subsequent need for more aggressive therapy, such as radical cystectomy. The administration of intravesical chemotherapy and immunotherapy has become an important component in accomplishing these goals. This update is the first part of two articles reviewing important contemporary concepts in the etiology, classification and natural history of superficial bladder cancer, while part II of the series will review and highlight important aspects in management of superficial bladder cancer.     

Intravesical chemotherapy of superficial bladder tumors

It has been reported that the intravesical instillation therapy had response rates ranging from 60 to 70% for bladder cancer and we could expect its significant efficacy, in terms of clinical benefits with quick response and lower medical cost, in patients of superficial and papillary peduncular tumors with multiple diseases and in diameter of maximum 1 cm. The intravesical instillation should be performed 2-3 times/week and within 2-3 weeks for the purpose to reach the clinical objectives. In order to enhance the efficacy of the intravesical instillation therapy, combined use of multiple anticancer agents or multidisciplinary treatments have been tried, in combination with systemic administration, radiotherapy, hyperthermia and hydro pressure therapy, which obtained remarkable clinical results. However, a comparative study has never been carried out among these treatments. It's a practical treatment that the intravesical instillation is given as an adjuvant therapy after TUR. In case of prophylactic purpose, the frequency and the period are still under discussion on the administration of the drugs. These is no clear idea yet which is optimal, a short period of administration for 1-2 weeks or a longer period for 2-5 years. Adriamycin and mitomycin-C have been commonly used for the intravesical instillation therapy of bladder cancer. BCG has recently had a good clinical response not only for therapeutic purpose of carcinoma in site but also for the prophylactic purpose with its intravesical instillation. Many studies indicated that the intravesical instillation therapy alone could not inhibit recurrence of bladder cancer under the current situation when the incidence of tumor and mechanism of recurrence are not yet clarified completely in epidemiological points of view. For improvement of treatment of bladder cancer, further fundamental studies must be developed and also a randomized trial is clinically needed, taking in consideration backgrounds of the patients, for evaluation of efficacy of bladder cancer treatment.     

Diagnosis and management of superficial bladder cancer

Bladder cancer is the fourth leading cause of cancer in American men, accounting for more than 12,000 deaths annually. It was one of the first malignancies in which carcinogens were recognized as an important factor in its cause. Currently, cigarette smoking is by far the most common cause of bladder cancer, although occupational exposure to arylamines has been implicated in the past. Gross or microscopic hematuria is the most common sign at presentation. Initial radiologic evaluation usually includes the excretory urography (intravenous pyelography), although further evaluation of the renal parenchyma with ultrasound or computed tomography scanning has been advocated by some. These radiologic studies are unable to provide adequate bladder imaging, and thus cystoscopy is required for the diagnosis of bladder cancer. Most bladder cancers present as "superficial" disease, confined to the bladder mucosa or submucosal layer, without muscle invasion. Superficial tumors consist of papillary tumors that are mucosally confined (Ta), papillary or sessile tumors extending into the lamina propria (T1), and carcinoma in situ, which occurs as "flat" mucosal dysplasia, which can be focal, diffuse, or associated with a papillary or sessile tumor. The natural history of these pathologic subtypes differ significantly. Most superficial tumors (60% to 70%) have a propensity for recurrence after transurethral resection. Some (15% to 25%) are at high risk for progression to muscle invasion. Most superficial tumors can be stratified into high- or low-risk groups depending on tumor stage, grade, size, number, and recurrence pattern. It is important to identify those tumors at risk for recurrence or progression so that adjuvant intravesical therapies can be instituted. Many intravesical chemotherapeutic agents have been shown to reduce tumor recurrence when used in conjunction with transurethral tumor resection. Unfortunately, however, none of these agents have proved to be of benefit in preventing disease progression. Most are given intravesically on a weekly basis, although many studies suggest that a single instillation immediately after transurethral resection may be as good as a longer course of therapy. Although all of these drugs have toxicity, they usually are well tolerated. Intravesical bacille Calmette-Guérin (BCG) is an immunotherapeutic agent that when given intravesically is very effective in the treatment of superficial transitional cell carcinoma. Compared with controls, BCG has a 43% advantage in preventing tumor recurrence, a significantly better rate than the 16% to 21% advantage of intravesical chemotherapy. In addition, BCG is particularly effective in the treatment of carcinoma in situ, eradicating it in more than 80% of cases. In contrast to intravesical chemotherapy, BCG has also been shown to decrease the risk of tumor progression. The optimal course of BCG appears to be a 6-week course of weekly instillations, followed by a 3-week course at 3 months in those tumors that do not respond. In high-risk cancers, maintenance BCG administered for 3 weeks every 6 months may be optimal in limiting recurrence and preventing progression. Unfortunately, adverse effects associated with this prolonged therapy may limit its widespread applicability. In those patients at high risk in whom BCG therapy fails, intravesical interferon-alpha with or without BCG may be beneficial in some. Photodynamic therapy has also been used but is limited by its toxicity. In patients who progress or do not respond to intravesical therapies, cystectomy should be considered. With the development of orthotopic lower urinary tract reconstruction to the native urethra, the quality of life impact of radical cystectomy has been lessened.     

The practical use of tumor marker determination in bladder washing specimens. Assessing the urothelium of patients with superficial bladder cancer

Bladder washing specimens from 81 patients with recurrent multifocal superficial bladder cancer were evaluated for DNA profile by flow cytometry and cell-surface blood group (ABH) antigen reactivity by a modified specific erythrocyte adherence test. The study was conducted in a prospective, blind, nonrandomized fashion. Fifteen patients were treated with transurethral resection (TUR) alone and 66 with TUR and intravesical administration of bacillus Calmette-Guerin weekly for 6 weeks (TUR + BCG). Among the patients treated with TUR only, there was a notably greater rate of tumor recurrence and progression in patients with unfavorable tumor markers (aneuploidy and ABH-negative reactivity) than in those with favorable markers (diploidy and ABH-positive reactivity). The difference was less striking in patients treated with BCG, which reduced the frequency of recurrence or progression at 30 months from 87% to 44% and from 60% to 23%, respectively. This favorable effect of BCG was virtually confined to patients with initially favorable markers and to those whose initially unfavorable markers became favorable during BCG administration. Aneuploidy and negative ABH are phenotypic expressions of undifferentiation that can forecast the potential of the urothelium to form new tumors and predict invasion. To an extent, these markers are independent of the grade and stage of the disease. BCG can induce prognostically favorable conversion of the markers expression. Lack of such conversion indicates lack of response to BCG and should be regarded as evidence of persistent disease even if conventional methods do not reveal it. Therefore, sequential determination of markers is useful in monitoring patients with superficial bladder cancer treated with intravesical BCG.     

不同溶剂配制吡柔比星在经尿道膀胱肿瘤电切术后膀胱灌注的疗效观察

目的评价生理盐水和注射用水配制吡柔比星在经尿道膀胱肿瘤电切(TUR-Bt)术后膀胱灌注的疗效和副反应.方法将TUR-Bt术后30例膀胱癌患者随机分为两组,分别用生理盐水和注射用水配制吡柔比星进行膀胱灌注,观察疗效并随访.结果两组随访12～18个月,均无肿瘤复发,术后3,6个月查肝肾功能和血常规均正常.生理盐水组有明显膀胱刺激症12例,术后3个月膀胱镜检查有溃疡形成6例,被迫停止灌药4例.注射用水组有明显膀胱刺激症5例,术后3个月膀胱镜检查有溃疡形成2例,被迫停止灌药1例.结论生理盐水和注射用水配制吡柔比星在TUR-Bt术后膀胱灌注均有较好的预防膀胱癌复发的疗效,但生理盐水组有明显膀胱刺激症,并可引起膀胱溃疡.     

丝裂霉素膀胱灌注预防浅表性膀胱肿瘤复发的远期疗效观察

目的 观察丝裂霉素预防浅表性膀胱肿瘤复发的远期疗效。方法 将１９８０年１月￣１９９１年１２月的８６例浅生膀胱肿瘤患者分为丝裂霉素组（手术＋丝裂霉素灌注）和对照组（单纯手术）,对两组的肿瘤术后复发率、病理分期和细胞分级进行对比观察。结果 丝霉素组７１例,对照组１５例,术后肿瘤复发率分别为４０．８％和６６．７％。丝裂霉素组在术后６月、１２月、２４月、３６月和６０月以上的无瘤率分别为８５．９％,７６．１     

Bladder cancer

The therapeutic principles of bladder cancer are reviewed in the fields of surgery, radiation and chemotherapy. The operative indications for bladder cancer mainly depend on tumor stage, grade, shape, size, the number of tumor, age and social activity of the patient. TUR is applied to the superficial lesion, where 80-100% of five-year survival and 30-85% recurrence rate in a year were obtained. 20-50% for stage B2--C and 6-36% for stage D of five-year survival were observed in patients receiving total cystectomy. By preoperative irradiation therapy, the excellent results were shown in the decrease of a recurrence rate and the prolongation of five-year survival. Thiotepa is one of the most effective drugs when instillated intravesically for superficial lesion and cis-platinum (in systemic use) shows remarkable effects for advanced bladder cancer.     

147例表浅性膀胱癌预后因素分析

目的 :探讨表浅性膀胱癌各种因素与患者预后的关系。方法 :对 147例表浅性膀胱癌进行回顾性分析。结果 :147例中 ,72例术后复发 ( 4 9% ) ,术后 5年复发率为 35.4 %。初诊时为多发者、直径大于 3cm、分级与分期高的肿瘤术后复发率分别高于单发者、直径小于 3cm者、分级、分期低的肿瘤。术后 6个月内肿瘤复发者经治疗后肿瘤再次复发的机会高 ,术后膀胱内灌药可以预防肿瘤复发。结论 :肿瘤分级与分期高、多发肿瘤、直径大于 3cm者及术后膀胱内未灌药者复发率高     

The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin for prophylaxis of recurrence of superficial bladder cancer: a preliminary report

The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin (BCG) for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 29 patients aged a median of 70 years between January of 1991 and May of 1993. The patients received intravesical instillation of 40 mg epirubicin immediately after transurethral resection (TUR) of the bladder cancer. At 1 week after TUR, 80 mg Tokyo-strain BCG was instilled into the bladder once a week for 6 weeks. Thereafter, the patients were followed by cystoscopy and urinary cytology at 3-month intervals until recurrence was detected. Of the 29 patients, 28 had no evidence of disease over a mean follow-up period of 20 months. The 1 case of recurrence occurred at 3 months after TUR and that patient died of cancer progression. The simple recurrence rate was 3.5% after therapy. According to the person-years method, the number of recurrent tumors per 100 patient-months was 0.17. The cumulative nonrecurrence rate determined for all cases was 96.5% at 30 months. Adverse reactions, including urinary frequency, urgency, and miction pain, among others, were observed in 27 patients (93%). Only 1 patient was withdrawn from the treatment because of severe bladder-irritation symptoms due to the BCG instillation. The intravesical chemoimmunotherapy with epirubicin and BCG seemed to be effective for prophylaxis of recurrence of superficial bladder cancer.Paper presented at the 5th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 24–25 September 1993, Hakone, Japan     

Prophylactic intravesical instillation chemotherapy against recurrence after a transurethral resection of superficial bladder cancer: a randomized controlled trial of doxorubicin plus verapamil versus doxorubicin alone

Purpose: We investigated whether verapamil (VR), a known chemosensitizing agent of P-glycoprotein-mediated multidrug resistance, could enhance the preventative effect of doxorubicin (Adriamycin, ADM) on both intravesical recurrence and disease progression after transurethral resection (TUR) of superficial bladder cancer. Methods: The patients were randomized into two groups: one group received an intravesical instillation of ADM (30 mg) plus VR (15 mg) after TUR of superficial bladder cancer (19 times over 1 year), and the other group received ADM alone on the same treatment schedule. The nonrecurrence rate, the incidence of disease progression at the first recurrence and the side effects were compared over a median follow-up of 38.5 months. Results: Of the 226 patients registered, 157 were evaluable. No significant differences were observed in the patients' characteristics between the two groups. Although the incidence of disease progression at the first recurrence was not significantly different between the two groups, the ADM plus VR instillation group did show a significantly higher nonrecurrence rate than the ADM-only instillation group, and such significance persisted even when any possible bias was allowed for in a multivariate analysis. In terms of side effects, the incidence and severity of bladder irritation symptoms were not significantly different between the two groups. Conclusions: Intravesical instillation chemotherapy with ADM plus VR was found to have a significantly greater beneficial effect than with ADM alone for preventing recurrence after TUR of superficial bladder cancer. Received: 11 November 1997 / Accepted: 20 January 1998     

Bacillus Calmette-Guerin (BCG) in the treatment of superficial bladder cancer

Intravesical therapy is currently being used in the management of superficial transitional cell carcinoma of the urinary bladder. Its main objectives constitute treatment of existing or residual tumor, prevention of recurrence of tumor, prevention of disease progression, and prolongation of survival. The initial clinical stage and grade of bladder cancer remains the main determinant factors in survival, irrespective of the treatment. Intravesical chemotherapy has shown a decrease in short-term tumor recurrence rates, but has had no positive impact on disease progression or prolongation of survival. Bacillus Calmette-Guerin (BCG) immunotherapy remains the most effective treatment and prophylaxis modality for superficial bladder cancer and results in a positive outcome on tumor recurrence, disease progression, and prolongation of survival. Although therapy by intravesical BCG instillation is widely accepted as the therapy of choice, the development of BCG-resistant bladder cancer remains a major setback. Thus, there is an urgent need for a major effective therapy for bladder cancer patients who are unresponsive to BCG therapy. This review summarizes briefly the recent highlights and advances in the therapy of superficial bladder cancer. This review also describes our preliminary findings achieved in in vitro model systems and our proposed new approaches to overcome the resistance of bladder cancer cells and render bladder cancer cells responsive to these new therapies.     

上尿路移行细胞癌术后预防性膀胱灌注的临床研究

目的:探讨上尿路移行细胞癌术后预防性膀胱灌注的有效性。方法:61例上尿路移行细胞癌患者行根治性切除术,其中34例患者术后预防性使用吡柔比星膀胱灌注,27例患者单纯随访,比较两组患者2年内膀胱肿瘤的发生率以及发生时间,并观察药物灌注毒副反应发生的情况。结果:吡柔比星灌注组膀胱癌发生率为14.7%,观察随访组膀胱癌的发生率为37.0%,差异有统计学意义(P<0.05),再发时间分别为20个月和14个月,二者比较差异有统计学意义(P<0.05)。患者灌注过程中均耐受,未出现中止灌注的情况。结论:本研究初步显示,吡柔比星预防性膀胱灌注可有效减少膀胱肿瘤的发生,毒副反应少,值得临床推广。