Alpha-interferon in superficial bladder cancer: a Northern California Oncology Group Study

Thirty-five patients with superficial transitional carcinoma of the bladder were treated intravesically with escalating doses of recombinant alpha-2-interferon administered weekly for 8 weeks. Of the 19 patients with high-grade intraepithelial neoplasia (17 carcinoma in situ [CIS], two severe dysplasia, all cytology positive), six (32%) had complete resolution of all histologic and cytologic evidence of disease (complete response). An additional three patients (16%) had complete resolution of CIS, but the interval appearance of a low-grade transitional cell neoplasm. Five (26%) had a partial response (complete resolution of all evidence of CIS on multiple bladder biopsies but persistently positive cytologic preparations). Sixteen patients with recurrent papillary tumors and extensive prior therapy were also treated. Four (25%) had a complete response. Twenty-three of the 35 patients had prior intravesical therapy. Seven of the 23 (30%) patients with prior intravesical chemotherapy or immunotherapy had a complete or partial response to interferon, while eight of the 12 patients (67%) without prior intravesical treatment responded. These responses were achieved with minimal local and systemic toxicity. Of the ten complete responders, five remain in continuous unmaintained remission for 18+ to 37+ months. Intracavitary alpha-2-interferon is an effective new treatment for some patients with bladder cancer.     

Prognostic significance of urine cytology on initial follow-up after intravesical mitomycin C for superficial bladder cancer

Seventy patients were given courses of intravesical mitomycin C for residual transitional cell carcinoma of the bladder following partial resection or biopsy. The patients were reassessed 3 months after the initiation of treatment by cystoscopy and cytology from cystoscopic urines and bladder washings. Twelve had no visible cancer at cystoscopic study but had positive urine cytologic findings. The incidence of tumor recurrence, cystectomy, radiotherapy, and deaths due to bladder cancer for this group of cytologically positive partial responders was analyzed. Thirty-three percent (4/12) required cystectomy, none underwent radiation therapy and none died of bladder cancer. These outcomes were compared with that of complete responders (negative cystoscopic and cytologic results) and partial responders with visible tumor (reduction by greater than 50%). We conclude that in high-grade carcinomas, particularly carcinoma in situ, positive urine cytologic findings at the initial 3-month follow-up visit following treatment with intravesical mitomycin C is as ominous a prognostic indicator as endoscopic or biopsy evidence of cancer.     

BCG (Bacillus of Calmette Guerin) therapy of high-risk superficial bladder cancer

BCG (Bacillus of Calmette Guerin) has been used for more than 20 years and is currently the most active agent for superficial bladder cancer therapy. Intravesical BCG therapy is effective in prophylaxis after transurethral resection of papillary tumours and in the treatment of carcinoma in situ (cis). In most series BCG is more effective than intravesical chemotherapy, although it is more toxic. There is some evidence that BCG therapy improves survival and progression rates of patients with high-risk superficial bladder cancer decreasing the proportion who require radical cystectomy. A review of the current information on BCG therapy of high-risk superficial bladder cancer is reported.     

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.     

Urethral involvement in female patients with bladder cancer. A study of 22 cystectomy specimens

The cystectomy specimens of 22 female patients with various types of bladder cancer were studied for evidence of urethral involvement. The bladder showed high-grade invasive transitional cell carcinoma in 18 patients, in 14 cases in association with flat carcinoma in situ (multifocal in 11 cases and unifocal in three). Three patients had multifocal carcinoma in situ of the bladder without evidence of invasion, and one patient had multifocal high-grade noninvasive papillary carcinoma. Urethral carcinoma in situ was observed in four of 14 patients (29%) with multifocal carcinoma in situ of the bladder, in three cases extending into the periurethral glands. This frequent concurrence of carcinoma in situ of the bladder with urethral and periurethral gland involvement, analogous to the carcinomatous involvement of the prostatic urethra and ducts in male patients, warrants caution in the intravesical therapy of female patients with superficial bladder cancer. The urethra showed invasive carcinoma in three of 18 patients (17%) with invasive bladder cancer (stromal invasion in two cases and vascular invasion in one). This finding reconfirms the use of routine urethrectomy in conjunction with cystectomy in female patients with invasive bladder cancer. An incidental finding was the presence of condylomatous changes in the urethra in five cases (23%).     

Intravesical therapy for superficial bladder cancer

Approximately 54,400 new cases of transitional cell carcinoma of the bladder were reported in the United States in 1999, with an estimated 12,500 deaths attributable to this cancer. Close to 75% of all bladder tumors are confined to the urothelium (stage Ta, or carcinoma in situ), and nearly 30% of papillary tumors invade the lamina propria (stage T1). The majority of superficial tumors are low grade with low rates of progression. Transurethral resection is the standard initial treatment for transitional cell carcinoma. Intravesical therapy is an important adjunct to transurethral resection in patients with superficial bladder cancer, many of whom are at risk for disease recurrence and progression. Cytotoxic and immunomodulating agents and, more recently, photosensitizers have demonstrated utility against superficial transitional cell carcinoma. Many studies have assessed and continue to examine the efficacy of various agents at different doses and in different combinations and schedules. Recently, valrubicin (Valstar) won Food and Drug Administration (FDA) approval only for the treatment of refractory carcinoma in situ. However, bacillus Calmette-Guérin (BCG) and mitomycin (Mutamycin) remain the most commonly used, most effective agents available for prophylaxis against recurrence and subsequent progression of superficial bladder cancer. This article reviews traditional and alternative intravesical agents useful in the therapy and prophylaxis of superficial transitional cell carcinoma of the bladder.     

A prospective randomized trial of maintenance versus nonmaintenance intravesical bacillus Calmette-Guérin therapy of superficial bladder cancer

Between August 1981 and July 1984, 93 patients with polychronotopic superficial papillary carcinoma (Ta and/or T1), flat carcinoma in situ (Tis), or concomitant superficial papillary and in situ bladder carcinoma were entered into a prospective randomized trial of maintenance v nonmaintenance intravesical bacillus Calmette-Guérin (BCG) therapy. Forty-six patients who received BCG weekly for 6 weeks were compared with 47 patients receiving the six-weekly doses of BCG plus monthly BCG for 2 years. Both groups were evaluated every 3 months by cytology, cystoscopy, and biopsy. A significant reduction in the number of recurrent tumors per patient-month was demonstrated for both groups (P less than .0001); however, the difference in reduction of tumors between the two groups was not significant. Additionally, patients receiving maintenance and nonmaintenance therapy had similar tumor recurrence and progression rates. These results indicate that monthly maintenance BCG does not prevent, delay, or reduce tumor recurrence or progression observed with the 6-week regimen. Maintenance BCG was associated with increased local toxicity, primarily dysuria, frequency, and urgency. Dosage reduction was required in 22 of 47 patients (46.8%). When the data were subjected to multivariate analysis, the presence or absence of tumor following induction BCG and PPD skin test results were found to be significant variables. Controlling for either the presence or absence of tumor following induction BCG, tumor recurrence and progression rates were not significantly different for the two treatment groups. However, the absence of tumor after induction BCG was associated with a longer disease-free duration (P = .00001) and time to progression (P = .095). Patients with a reactive tuberculin skin test before and after induction BCG had significantly less tumor recurrences than patients with different PPD skin tests results (P = .02). Tumor progression was not related to tuberculin skin testing.     

Intravesical adjuvant chemotherapy for superficial transitional cell bladder carcinoma: results of a randomized trial with epirubicin comparing short-term versus long-term maintenance treatment

PURPOSE: Intravesical instillation of epirubicin (EPI) is one of the most effective adjuvant therapies for non-muscle-invasive bladder cancer after transurethral resection. We evaluated the optimal duration of EPI instillation in a multi-institution prospective randomized clinical study. METHODS: Between June 1995 and May 1998, a total of 125 patients with superficial bladder cancer (transitional cell carcinoma grade 1 or 2) were enrolled in this study, and 102 patients were fully evaluated for recurrence. Two protocols for intravesical therapy (arm A - 30 mg EPI/30 ml saline 19 times over 1 year; arm B - 30 mg EPI/30 ml 12 times over 5 months) were established. Instillations were given every week for 4 weeks and then every 2 weeks for 4 months in arm B. After 5 months of treatment, maintenance was performed with seven further instillations (one every month for 7 months) in arm A. The analyzed background factors were the therapeutic method, gender, history (primary or recurrent tumor), stage (T classification), grade, number of tumors, and tumor size. RESULTS: There were no significant differences in the analyzed background factors between the two arms, and there were no serious side effects in the study. In an intent-to-treat analysis, the overall 3-year recurrence-free survival rates were 48.5% in arm A and 55.1% in arm B. The difference between the two groups was not significant. CONCLUSIONS: This analysis indicated that extended prophylactic maintenance instillation of EPI was not significantly effective in reducing bladder cancer recurrence.     

HR+/HER-2+晚期乳腺癌一线维持治疗的疗效分析

目的探讨激素受体阳性(HR+)/人表皮生长因子受体2阳性(HER-2+)的晚期乳腺癌患者经一线治疗达到疾病控制后,维持治疗与否对总生存期(OS)的影响。方法收集1999年1月1日至2018年3月1日HR+/HER-2+晚期乳腺癌患者的临床病理资料。根据一线治疗结束后是否维持治疗分为无维持治疗组与维持治疗组。生存分析采用Kaplan-Meier法,多因素分析用Cox比例风险模型。结果共纳入HR+/HER-2+乳腺癌患者84例,维持治疗组65例(77.4%),无维持治疗组19例(22.6%),两组中位OS分别为53.8个月和28.6个月,差异有统计学意义(P=0.015)。Cox多因素分析显示,一线维持治疗是影响HR+/HER-2+晚期乳腺癌患者OS的独立因素(HR=0.456,95%CI:0.238~0.873,P=0.018)。维持治疗组中,接受单纯靶向治疗、单纯内分泌治疗、单纯化疗、靶向联合化疗与靶向联合内分泌治疗的患者分别为15例、10例、6例、13例和21例,中位OS分别为37.0个月、未达到、45.9个月、53.8个月和90.3个月。5个维持治疗亚组中位OS的差异有统计学意义(P=0.026)。与无维持治疗组比较,靶向联合内分泌治疗和单纯内分泌治疗可显著延长HR+/HER-2+晚期乳腺癌患者的中位OS(P=0.005,P=0.023)。结论HR+/HER-2+晚期乳腺癌患者经一线治疗达到疾病控制后,接受维持治疗可延长生存。     

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.     

Idarubicin in the intravesical treatment of superficial transitional-cell carcinoma of the bladder (ta-t1) - a phase I-ii study

Local recurrences of superficial transitional cell carcinoma of the bladder (TCCB) can be significantly reduced by intravesical treatment following transurethral resection (TUR) but they are not fully abolished. There is a need to gain experience with new agents. Anthracyclines, such as doxorubicin and epirubicin, have been clearly demonstrated to be active against superficial TCCB by intravesical route. Idarubicin is an anthracycline, much more lipophilic than doxorubicin, inhibiting tumour cell growth at lower concentrations. The aim of this study was to evaluate the tolerability and the ablative efficacy on a marker lesion of weekly intravesical instillations of idarubicin given at different doses and concentrations. Seventeen patients, affected by superficial TCCB, Ta-T1 G1-G2, after TUR of all tumours except one, that was used as a 'marker lesion', were treated intravesically with idarubicin weekly for two months. The drug, in the first 4 patients, was administered at the dose of 15 mg diluted in 30 mi of normal saline solution and maintained in the bladder for one hour. Because of severe chemical cystitis, the dose was reduced to 10 mg in 40 mi in the following 13 patients. The study was closed because of the severe local toxicity. In eight (47%) patients the treatment was interrupted for local toxicity between the first and sixth week and in 5 more patients pharmacological therapy was required because of severe chemical cystitis. No systemic toxicity was evident. Three patients achieved a complete response. Our experience shows that idarubicin is not indicated in the intravesical therapy of superficial TCCB because of severe chemical cystitis limiting the administration of doses able to explicate a relevant antitumoral action.     

Maintenance therapy for superficial bladder cancer

Transurethral resection remains the standard for first-line treatment of transitional cell carcinoma of the bladder. This technique clearly defines the pathologic grade and is essential in determining the clinical stage of the bladder tumor. Intravesical therapy is an important adjunct to transurethral resection in the management of patients with superficial bladder cancer, many of whom are at risk for disease recurrence and progression. Pharmacotherapy consisting of cytotoxic and immunomodulating agents has demonstrated utility against superficial transitional cell carcinoma. Bacillus Calmette-Guérin and mitomycin (Mutamycin) remain the more commonly used and most effective agents in the prophylaxis against recurrence and progression of superficial bladder transitional cell carcinoma. Many studies have examined their efficacy at different schedules. This article reviews the traditional intravesical agents that are useful in the therapy and prophylaxis of superficial transitional cell carcinoma of the bladder. It also addresses their long-term efficacy when used as maintenance therapy in higher-risk patients.     

Carcinoma in situ of the urinary bladder. Effect of associated neoplastic lesions on clinical course and treatment

Clinical courses of 67 patients with carcinoma in situ (CIS) of the urinary bladder during 14 years from 1971 to 1984 were investigated according to the clinical type of CIS and treatment methods. CIS was classified into four types: the primary group included 18 patients who had neither prior nor simultaneous tumors of the urinary tract; the secondary group included 10 patients who had CIS diagnosed subsequent to the treatment of superficial papillary bladder tumor; the concurrent group included 14 patients who had CIS concomitantly with superficial papillary bladder tumor; and the nonpapillary T1 group included 25 patients who presented with CIS with concomitant nonpapillary T1 tumor. As a rule, the initial treatment was conservative (transurethral resection [TUR] or intravesical chemotherapy) for the primary, secondary, and concurrent CIS groups, whereas treatment was radical (total cystectomy or irradiation) for the nonpapillary T1 group. Five-year survival rates of the primary, secondary, concurrent, and nonpapillary T1 groups were 41%, 100%, 49%, and 68%, respectively. Secondary CIS revealed a rather good prognosis, probably due to the early detection of CIS and early application of intravesical chemotherapy when compared to other groups. Except for patients with nonpapillary T1 tumors, the 5-year rate of malignant progression (invasion or metastasis) and multiple recurrences leading to delayed cystectomy was 81% in 16 patients treated by TUR, whereas it was 39% in 21 patients treated by instillation therapy. It appears likely that intravesical chemotherapy was preferable to other conservative therapies as an initial treatment of CIS. Radical therapy, however, may be the choice for CIS with nonpapillary T1 tumors, ab initio.     

Localized bladder cancer

Opinion statement Transitional cell carcinoma (TCC) of the bladder makes up 90% of bladder cancers. The approach to the management of localized TCC includes accurate clinical and histologic diagnosis and staging with pathologic material obtained through endoscopy. Once the diagnosis of superficial TCC has been established, histologically based prognostic factors guide which therapy or combination of therapies is indicated in the management of individual patients. Surgery alone (transurethral resection) is appropriate initial therapy for noninvasive papillary TCC. For lamina propria invasive tumors and carcinoma in situ, intravesical immunotherapy with bacille Calmette-Guérin (BCG) is often the first line of treatment to decrease tumor recurrence and to possibly decrease progression and improve survival. Intravesical chemotherapy and interferon are alternative therapies that can also decrease recurrence rates. For BCG-refractory TCC, durable response rates with alternative intravesical therapies are low. For superficial TCC that is refractory to endoscopic procedures and intravesical agents or for disease progression, radical cystectomy with neobladder formation or other forms of urinary diversion is the treatment of choice.     

Intravesical chemotherapy of superficial bladder tumors in a controlled trial with cis-platinum versus cis-platinum plus hyaluronidase

Twenty-three patients with superficial transitional cell carcinoma of the urinary bladder were randomized for intravesical chemotherapy with either cis-platinum or cis-platinum plus hyaluronidase, an enzyme promoting diffusion factor. Treatment was administered at 3-week intervals and checked for efficacy by repeated cystoscopies after every three instillations. Hematologic and biochemical tests were repeated prior to each treatment and, these, in additional to the cystoscopic findings, served for final evaluation of results and toxicity. The complete response rate was found to be superior with cis-platinum than with cis-platinum plus hyaluronidase. The complete plus partial response rates were equal in both groups. We conclude that the addition of hyaluronidase to cis-platinum revealed no superiority to cis-platinum alone, and both modes of treatment showed similar clinical efficacy as other drugs previously used for intravesical chemotherapy.     

Controversial issues and optimal management of stage T1G3 bladder cancer

The management of T1G3 bladder cancer is controversial. Diagnostic methods, such as bladder mapping or second-look transurethral resection are recommended to assess risk. Bacillus Calmette-Guérin intravesical therapy with a maintenance regimen is recommended for solitary T1G3 tumors. The timing of radical cystectomy for these patients is controversial, but early recurrence during intravesical therapy is an indication for radical cystectomy. Multifocal disease, concomitant carcinoma in situ and disease in the prostatic urethra and bladder neck also suggest aggressive disease and cystectomy should be considered in these patients.     

The 4th study of prophylactic intravesical chemotherapy with Adriamycin in the treatment of superficial bladder cancer: the experience of the Japanese urological cancer research group of Adriamycin

A multicentric randomised trial was conducted for the purpose of investigating the efficacy of intravesical chemoprophylaxis of superficial bladder cancer. A total of 443 patients (number of evaluable patients, 284) were registered from July 1987 to December 1989 and randomised into 3 groups. Group A received 21 intravesical instillations of Adriamycin (ADM) at 20 mg/40 ml physiological saline for 2 years after undergoing transurethral resection (TUR); group B was given the same dose as group A but received 6 intravesical instillations for 2 weeks before undergoing TUR; and group C served as a control and underwent TUR only. Better prophylactic effects were obtained in group A. The overall non-recurrence rates calculated for groups A and B differed significantly (P<0.05) on=" day=" 240,=" and=" those=" determined=" for=" groups=" a=" and=" c=" were=" also=" significantly=" different=">P<0.01) on=" day=" 480.=" no=" benefit=" was=" obtained=" using=" intravesical=" instillation=" prior=" to=" tur=" (group=" b).=" the=" major=" side=" effects=" encountered=" were=" pollakisuria=" and=" miction=" pain,=" which=" occurred=" in=" 32%=" of=" the=" patients=" in=" group=" a=" and=" in=" 52%=" of=" those=" in=" group=">Presented at the 4th International Conference on Treatment of Urinary Tract Tumors with Ariamycin/Farmorubicin, 16–17 November 1990, osaka, Japan     

Comparison of the prophylactic usefulness of epirubicin and doxorubicin in the treatment of superficial bladder cancer by intravesical instillation: a multicenter randomized trial

A multicentric randomized trial was conducted for the purpose of investigating the prophylactic efficacy of intravesical epirubicin instillation following transurethral resection of superficial bladder cancer in comparison with the efficacy of doxorubicin. The patients were centrally randomized into 2 groups and received 19 intravesical instillations of epirubicin or doxorubicin at 30 mg/30 ml physiological saline twice a week for 4 weeks and then once monthly for 11 months. A total of 150 patients with Ta and T1 superficial bladder cancer were entered in the trial, and 114 were evaluable. The nonrecurrence rates determined for each group at 1 and 2 years by the Kaplan-Meier method were 92.8% and 88.6%, respectively, for the epirubicin group and 86.4% and 81.7%, respectively, for the doxorbicin group. The differences between the two groups were not statistically significant. The main side effects encountered in this study were symptoms of bladder irritation such as micturitional pain, pollakisuria, and hematuria. The respective frequencies of those symptoms were 10%, 15.0%, and 5.0% in the epirubicin group and 14,8%, 14.8%, and O in the doxorubicin group. These results suggest that epirubicin is a useful drug, comparable with doxorubicin, for intravesical instillation chemotherapy in the prophylactic treatment 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     

Prognostic value of p53 overexpression in bladder tumors treated with Bacillus Calmette-Guerin

Bacillus Calmette-Guerin intravesical therapy is the standard treatment of superficial bladder tumors at high risk of recurrence and progression to muscle-invasion disease. To date, there is no well established predictive factor of response to Bacillus Calmette-Guerin intravesical therapy. The prognostic value of p53 overexpression in bladder tumors is controversial. Most investigators have found no correlation between p53 status assessed before Bacillus Calmette-Guerin intravesical therapy and patient outcome. On the other hand, it is acknowledged that the persistence of p53 overexpression after Bacillus Calmette-Guerin intravesical therapy is predictive of progression in patients treated for carcinoma in situ. Since conflicting data have been reported, further evaluation of the impact of p53 overexpression in patients treated with Bacillus Calmette-Guerin intravesical therapy for bladder carcinoma is required.