The management of stage T1 grade 3 transitional cell carcinoma of the bladder

The number of Mini‐Reviews per issue is being increased to three for the foreseeable future. As mentioned before, I believe they add to the reader‐friendliness of the journal, and are enjoyable and informative. This month, the controversial topics of T1 G3 bladder cancer, surgery for penile fractures and managing patients on warfarin are dealt with. I hope that readers will feel free to write to me if they have strong feelings about these or any other subjects in the Journal.     

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.     

Recurrence and progression of stage T1, grade 3 transitional cell carcinoma of the bladder following intravesical immunotherapy with bacillus Calmette-Guerin

PURPOSE: We prospectively examined the incidence of recurrence and progression in patients with stage pT1, grade 3 carcinoma of the bladder following complete transurethral resection of the bladder tumor and adjuvant immunotherapy with bacillus Calmette-Guerin (BCG). MATERIALS AND METHODS: Between July 1987 and March 1999, 123 patients presenting to our clinic with superficial urothelial carcinoma (stage pT1, grades 1 to 3) received adjuvant intravesical immunotherapy with BCG after histologically confirmed complete transurethral tumor resection. Disease was stage pT1, grade 3 in 44 patients (36%). Median followup was 28 months (mean 43, range 5 to 141). RESULTS: Of the patients 36 (82%) with bladder preservation remained tumor-free during followup after 1 or 2 cycles of BCG. Superficial tumor recurred in 5 patients (11%) and muscle invasive progression was noted in 7 (16%). Radical cystectomy was performed in 4 cases (9%). Of the patients 5 (11%) died of cancer. Tumor-free survival for all patients was 89% (39 of 44). CONCLUSIONS: Adjuvant immunotherapy with BCG after complete transurethral resection of bladder tumor represents a highly effective primary treatment of stage pT1, grade 3 carcinoma of the bladder. Immediate radical cystectomy does not appear necessary.     

Contemporary management of stage T1 transitional cell carcinoma of the bladder

PURPOSE: Transitional cell carcinoma involving the lamina propria (stage T1) is associated with a high recurrence and progression rate with implications for patient survival and quality of life. A better understanding of the natural history of and treatment alternatives for this tumor may improve the outcome in patients with this stage of bladder cancer. MATERIALS AND METHODS: Literature of the last decade was comprehensively reviewed in regard to clinical and pathological diagnosis, adjuvant treatments, prognosis, and the role and timing of cystectomy. The information was gathered from MEDLINE, current urology journals, abstracts from recent urological meetings and personal experience. RESULTS: High grade and the depth of lamina propria invasion are important prognostic factors. Early diagnosis and accurate pathological assessment are essential for determining the most adequate treatment pathway. Initial treatment consists of complete transurethral resection and adjuvant treatment with intravesical instillation of bacillus Calmette-Guerin (BCG). Immediate postoperative instillation of mitomycin C decreases the risk of recurrence possibly related to tumor implantation. Intravesical treatment does not substantially decrease the chance of progression. Lack of a complete response to BCG at 3 to 6 months, high grade, the depth of lamina propria invasion, the association of carcinoma in situ and prostate mucosa or duct involvement represent significant predictors for progression. Cystectomy should be suggested for recurrent stage T1 tumor after BCG, new onset or persistent carcinoma in situ, tumor located at a difficult site for resection, prostatic duct or stromal involvement and muscle invasion. CONCLUSIONS: High grade stage T1 transitional cell carcinoma is a highly malignant tumor. Complete resection followed by immediate mitomycin C instillation and 6 weekly BCG instillations results in an acceptably low recurrence and progression rate. Rigorous long-term surveillance and continuous reconsideration of radical cystectomy in concordance with the evolution of the disease are essential.     

Clinical outcome of chemoradiotherapy for T1G3 bladder cancer

Abstract:   The aim of this study was to determine the clinical outcome of a bladder-sparing approach using chemoradiotherapy (CRT) for T1G3 bladder cancer.   Between May 2000 and August 2007, 11 patients with T1G3 bladder cancer and who were negative for macroscopic residual tumor were treated by CRT after transurethral resection of bladder tumor (TUR-Bt). Pelvic irradiation was given at a dose of 40 Gy in 4 weeks. Intra-arterial administration of cisplatin and systemic administration of methotrexate were carried out in the first and third weeks of radiotherapy. One month after CRT, response was evaluated by restaging TUR-Bt. For persistent tumor after CRT or tumor recurrence, patients received additional treatment. Median follow-up was 21.2 months. Complete response was achieved in 10 of 11 patients (90.9%). Local recurrence for the entire group of 11 patients was 22.1% at both 2 and 5 years. Tumor progression was 0% at 5 years. Disease-specific survival rates were 100% at 5 years. All of survivors retained functioning bladders. Bladder preservation by CRT is a curative treatment option for T1G3 bladder cancer and a reasonable alternative to intravesical treatment or early cystectomy.     

Analysis of factors predicting intravesical recurrence of superficial transitional cell carcinoma of the bladder without concomitant carcinoma in situ

BACKGROUND: The objective of this study was to investigate risk factors for intravesical recurrence in patients with superficial bladder cancer without concomitant carcinoma in situ (CIS). METHODS: In this series, we analyzed data from patients with newly diagnosed superficial Ta or T1 transitional cell carcinoma (TCC) of the bladder without concomitant CIS who underwent complete transurethral resection (TUR) without any adjuvant intravesical instillation therapies. Multivariate analysis was used to determine significant risk factors affecting intravesical recurrence after TUR. Differences in clinicopathological features between primary and recurrent tumors were also characterized. RESULTS: Among 341 patients undergoing TUR of Ta or T1 bladder cancer, 187 diagnosed as having concomitant CIS and/or treated with adjuvant intravesical therapy were excluded, and the remaining 154 were evaluated. Intravesical recurrence was detected in 64 of the 154 patients, showing a 5-year recurrence-free survival rate of 58.3%. Among several factors examined, only tumor size was significantly associated with intravesical recurrence. Multivariate analysis identified tumor size as an independent predictor for intravesical recurrence irrespective of other parameters including age, gender, multiplicity, growth pattern, grade and stage. Recurrent tumors were significantly smaller and of a lower grade and lower stage than primary tumors, despite the absence of differences in growth pattern and the multiplicity between them. CONCLUSIONS: These findings suggest that primary tumor size could be used as a potential risk factor for predicting intravesical recurrence following TUR of superficial TCC of the bladder without concomitant CIS, and that the pathological characteristics of recurrent tumors are more favorable than those of primary tumors.     

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.     

Analysis of prognostic factors related to primary superficial bladder cancer tumor recurrence in prophylactic intravesical epirubicin therapy

PURPOSE: The aims of the present study were to examine the effects of intravesical instillation of epirubicin on tumor recurrence and to identify tumors that are at a high risk of recurrence. METHODS: Forty-five patients with primary superficial bladder cancer were treated with prophylactic intravesical epirubicin following transurethral resection of the bladder tumor (TUR-BT). Epirubicin (20 mg) was administered intravesically every second week for 4 months and then once a month or every 2 weeks for next 8 months. Patients were analyzed with respect to prognostic factors related to tumor recurrence. RESULTS: The overall recurrence-free rate, calculated using the Kaplan-Meier method, was 76.1 and 52.3% at 2 and 5 years after operation, respectively. These results were better than those reported for patients treated with TUR-BT alone. A univariate analysis demonstrated that high-grade, T1, sessile, large (> or = 2 cm) and multiple tumors were a significantly high risk for recurrence. A multivariate analysis performed by using the Cox proportional hazard model with stepwise selection showed that morphologic features (pedunculated or sessile) were the most prognostic factors for recurrence. This was followed by age and tumor size. The remaining four factors were not found to contribute significantly to recurrence. CONCLUSIONS: Epirubicin appears to be effective in preventing the recurrence of superficial bladder cancer. Morphologic features, patient age and size of the tumor were considered independent risk factors. The risk of recurrence for each tumor should be taken into consideration when the intravesical adjuvant therapy protocol is being selected.     

Presentation, location and overall survival of pelvic recurrence after radical cystectomy for transitional cell carcinoma of the bladder

OBJECTIVES

To evaluate the presentation, location and overall survival of pelvic recurrence after radical cystectomy (RC) for transitional cell carcinoma (TCC) of the bladder.

PATIENTS AND METHODS

We reviewed a consecutive series of 130 patients who had a limited bilateral pelvic lymph node dissection (PLND) and RC between 1987 and 2000, and who later developed pelvic recurrence. All patients were staged N0M0 before RC and no patient received neoadjuvant radio/chemotherapy. The boundaries of the limited PLND were the pelvic side‐wall between the genitofemoral and obturator nerves, and the bifurcation of iliac vessels to the circumflex iliac vein. Pelvic recurrence was defined as a radiographic soft‐tissue density of ≥2 cm below the bifurcation of the aorta. Kaplan‐Meier and Cox proportional hazards analyses were used to determine if imaging or symptomatic presentation, age, pT stage, and pN status were predictive of overall survival.

RESULTS

The median (range) time from RC to pelvic recurrence was 7.3 (1.2–55.4) months. No patients had concomitant distant metastasis. Of the patients, 61.5% were diagnosed with pelvic recurrence because of symptoms, and 38.5% by surveillance computed tomography (CT). Of the 130 patients, 128 died, with a median survival from the time of pelvic recurrence of 4.9 (0.1–129.3) months. The median overall survival time for pelvic recurrence diagnosed with CT was 21.6 months, vs 10.6 months for symptomatic presentations (P < 0.001). In the uni‐ and multivariate models, type of presentation (CT vs symptomatic) and pT stage were predictors of overall survival, while age and pN status were not.

CONCLUSION

The prognosis of patients with pelvic recurrence after RC for TCC is poor even with subsequent therapy, emphasizing the need for optimum local control at the time of initial treatment.     

Prognostic factors for survival and bladder recurrence in transitional cell carcinoma of the upper urinary tract

BACKGROUND: Prognostic factors for survival in transitional cell carcinoma of the upper urinary tract have been extensively evaluated, but detailed analyses of patterns of bladder recurrence after surgery have been rare. METHODS: The outcome and tumor recurrence of 93 patients with transitional cell carcinoma of the upper urinary tract surgically treated between 1975 and 1999 were reviewed, retrospectively. Disease-specific survival by pathologic stage and grade were analyzed by the Kaplan-Meier METHOD: Prognostic factors for survival and bladder recurrence were examined by univariate and multivariate analysis. RESULTS: The 5-year disease-specific survival rates of the patients with pTa, T1 and T2 were 92.9%, 100% and 88.9%, respectively. However, that of the pT3 patients was 61.9% and the median survival of the pT4 cases was only 7 months. Bladder recurrence was seen in 40 cases and recurrences occurred within 1 year in 32 of these patients. The stage and grade of metachronous bladder tumors usually resembled those of primary tumors, but invasive recurrences were seen in 19% of recurrent cases with primary pTa, pT1 tumors. The significant prognostic factor for survival was pathologic stage (pT3, pT4), but no significant variables were detected for bladder recurrence by multivariate analysis. CONCLUSIONS: The prognosis of pT3, pT4 patients is poor and effective systemic adjuvant therapy is necessary. Invasive bladder recurrence occurred in 19% of patients with superficial primary tumors. As no significant prognostic variables for bladder recurrence were identified, careful follow up for bladder recurrence is important even if the primary tumors are non-invasive.     

Clinical study of transitional cell carcinoma of the prostate associated with bladder transitional cell carcinoma

BACKGROUND: Transitional cell carcinoma of the prostate in patients with bladder cancer appears to influence the prognosis and affects the decision about therapeutic modality. Therefore, it is important to characterize transitional cell carcinoma associated with bladder cancer. METHODS: From April 1980 to December 1998, 81 male patients underwent total cystoprostatectomies for transitional cell carcinoma of the bladder. The 81 cystoprostatectomy specimens were examined to clarify the characteristics of prostatic involvement by transitional cell carcinoma. The extent, origin, mode of spread and risk factor of prostatic involvement as well as the prognosis were investigated. In 13 of 15 patients with prostatic involvement the prostate was examined by sequential step sections. RESULTS: Prostatic involvement was observed in 15 of 81 patients (18.5%). Prostatic urethral involvement, invasion to prostatic duct/acinus, prostatic stromal invasion and extraprostatic extension and/or seminal vesicle involvement were recognized in 12 (80%), 14 (93.3%), six (40%), and five (33.3%) of the 15 patients, respectively. Twelve of the 15 patients (80%) with prostatic involvement had papillary or non-papillary tumors (i.e. carcinoma in situ) both in the prostatic urethra and prostatic duct. In 10 of these 12 patients (88.3%), there was contiguity between prostatic urethral and ductal tumors. Seven of the 23 patients (30.4%) with carcinoma in situ of the bladder showed prostatic involvement, which increased to 50% in the presence of carcinoma in situ of the trigone or bladder neck. CONCLUSIONS: Eighty per cent of the patients with prostatic involvement showed papillary or non-papillary tumors both in the prostatic urethra and prostatic duct. There was a high level of contiguity between both tumors. Patients with carcinoma in situ of the trigone or bladder neck revealed significantly higher incidence of prostatic involvement.     

经尿道膀胱肿瘤电切术加肿瘤基底扩大电灼治疗T_1期膀胱尿路上皮癌的疗效观察

目的:探讨经尿道膀胱肿瘤电切术(TURBT)加肿瘤基底部扩大电灼(EC)对减少非肌层浸润性膀胱尿路上皮癌早期复发的意义。方法:临床及病理诊断为非肌层浸润性膀胱尿路上皮癌400例,按收治顺序间隔分为TURBT+EC组和TURBT组各200例,前者在TURBT后加做EC,而后者则行标准TURBT。术后常规膀胱化疗和随访。所有患者均于术后1、3、6、12、18、24个月行膀胱镜检查。通过膀胱镜随访,统计两组2年内首次复发率。用χ2进行两组间率的比较。结果:TURBT+EC组和TURBT组得到随访的分别为191例和193例。TURBT+EC组第1、3、6、12、18、24个月复发率分别为3.7%(7例)、7.9%(15例)、7.9%(15例)、4.7%(9例)、2.1%(4例)、2.1%(4例);TURBT组复发率分别为11.4%(22例)、14.0%(27例)、11.9%(23例)、4.1%(8例)、3.1%(6例)、2.1%(4例)。TURBT+EC组的复发率明显低于TURBT组,两组数据经统计学处理,其中第1个月复发率比较,差异有统计学意义(P0.01);第3个月复发率比较,差异有统计学意义(P0.05);2年总的首次复发率分别为28.3%(54例)和46.6%(90例),差异有统计学意义(P0.01)。并且可以看出,对差异率的贡献主要是术后前3个月。结论:TURBT+EC可减低非肌层浸润性膀胱尿路上皮癌的术后复发率,对减少早期复发尤其有意义。可能得益于EC使基底部肿瘤残留几率的减低。并且几乎不增加手术创伤,技术简便。     

Bladder sparing approach for initial T1G3 bladder cancer: Do multifocality,size of tumor or concomitant carcinoma in situ matter? A long‐term analysis of 132 patients

OBJECTIVES: In T1 bladder cancer (BC) multifocality, size of tumor (> or =3 cm) and concomitant carcinoma in situ (CIS) are used to stratify patients' risk. We compared the long-term results in patients with initial T1G3 bc treated with transurethral resection of the bladder (TURB), bacille Calmette-Guérin (BCG) instillations and repeat resection with special regard to these clinical risk factors. The aim was to determine if they influence the outcome in the bladder sparing approach for initial T1G3 bc. METHODS: One hundred and thirty-two consecutive patients with initial T1G3 and no prior history of BC were identified. All patients completed six weekly adjuvant BCG instillations followed by control TURB. Follow-up consisted of cystoscopy with bladder wash cytology every 3 months for 2 years and every 6 months thereafter. RESULTS: Forty-two percent of patients had residual disease, 65% developed recurrence of any stage and 41% had progression to muscle-invasive disease. Cancer-specific survival was 89% and 78% at 5 and 10 years, respectively. Only CIS was significantly correlated with all end points on multivariate analysis. While the presence of one or two risk factors was not related to recurrence, progression or cancer-related death, the presence of all three risk factors predicted the latter. CONCLUSIONS: While no guideline has been established for the decision between cystectomy and bladder sparing, concomitant CIS and the presence of all three risk factors together seem to predict an adverse oncological outcome in the bladder sparing approach.     

Intravesical recurrence after bladder sparing treatment of small cell carcinoma of the bladder: Characteristics,treatment, and outcome

Introduction

Small cell carcinoma of the bladder (SCCB) is a rare and lethal disease. Previously, we and others have reported a bladder sparing strategy with platinum-etoposide-based chemotherapy followed by radiotherapy of the bladder. Little is known on frequency and treatment of intravesical recurrence following this approach. The objective of this study is to describe the incidence of intravesical recurrences and their management.

Stage T1, grade 3 transitional cell carcinoma of the bladder: an unfavorable tumor?

Transurethral resection only was performed in 172 patients with initial stage Ta, T1 transitional cell carcinoma of the bladder. Additional treatment during the course of disease was given to 9 patients with carcinoma in situ and to 8 patients with tumor progression. The mean followup was 106 months. The 10-year survival rates were 95 per cent for patients with stage Ta, grade 1 disease, 89 per cent for stage Ta, grade 2, 84 per cent for stage Ta, grade 3, 78 per cent for stage T1, grade 2 and 50 per cent for stage T1, grade 3. The percentage of first tumor recurrence at the same site increased with tumor grade (stage T1, grade 3 was 74 per cent). The recurrence rate in stage T1, grade 3 tumors (4.08) differed significantly from the other groups of superficial tumors. The tumor progression rate for stage T1, grade 3 tumors (32.5 per cent) was significantly higher as well. The characteristics of stage T1, grade 3 tumors with and without progression were different in regard to multiplicity, recurrence rate, mean interval to recurrence and type of tumor invasion. Of the 13 patients who died of progressive neoplastic disease 11 presented initially with stage T1, grade 3 tumors. When these results are considered it is obvious that a patient with a stage T1, grade 3 tumor deserves additional therapy, such as chemotherapy, immunotherapy or phototherapy.     

错配修复基因hMLH1在膀胱移行细胞癌中的表达及其意义

目的 观察错配修复基因hMLH1在膀胱移行细胞癌中的表达,探讨hMLH1与膀胱移行细胞癌的关系.方法 通过免疫组织化学方法 测定hMLH1在80例膀胱移行细胞癌中及20例正常膀胱组织中的表达.结果 hMLH1在膀胱移行细胞癌中的低表达率(32.5%)明显高于在正常膀胱组织中的低表达率(0%),差异有统计学意义(P＜0.05),且hMLH1在膀胱移行细胞癌中的低表达与肿瘤的分期分级有关(P＜0.05).结论 hMLH1的低表达与膀胱移行细胞癌的发生有关,与肿瘤的高分期和高分级有关,hMLH1的低表达在浸润性及分化差的膀胱移行细胞癌多见.