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.     

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.     

Initial tumor stage and grade as a predictive factor for recurrence in patients with stage T1 grade 3 bladder cancer

PURPOSE: We evaluated whether the risk of progression and the recurrence rate were different in patients with primary and nonprimary stage T1 grade 3 transitional cell carcinoma of the bladder. MATERIALS AND METHODS: Between 1983 and 1997, 75 patients were treated for stage T1 grade 3 transitional cell carcinoma of the bladder. Of these patients 68 (primary and nonprimary tumor in 58 and 14, respectively) without carcinoma in situ who had not undergone complete cystectomy immediately after diagnosis were included in the study. No maintenance regimen was used. Median followup was 100 months (range 9 to 217). RESULTS: The incidence of multiple tumors in patients with nonprimary tumors was significantly higher than in patients with primary disease (p = 0.035). However, the recurrence-free survival rate in patients with primary T1 GIII bladder tumor was significantly lower than that of patients with nonprimary T1 GIII bladder tumor (p = 0.0016). Multivariate analysis using Cox's proportional hazard regression model revealed that only initial tumor status had statistically significant effects on tumor recurrence (p = 0.007) and no other factors had a significant influence on recurrence-free survival. Progression-free and cancer specific survival rates were also significantly different between the 2 groups (p = 0.036 and 0.0307, respectively). CONCLUSIONS: Our study indicates that patients with primary stage T1 grade 3 bladder cancers have higher recurrence and progression potential than those with nonprimary disease despite the higher incidence of multiple tumors in patients with nonprimary tumors.     

Prognostic value of molecular markers, sub-stage and European Organisation for the Research and Treatment of Cancer risk scores in primary T1 bladder cancer

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The stakes are high when making treatment decisions in T1 bladder cancer (BC). Conservative management may lead to progression and possibly death from BC. Conversely, radical cystectomy could be over‐treatment of non‐progressive disease. The problem for clinicians is that reliable prognostic indices are lacking. We performed a head‐to‐head comparison of two substaging systems, European Organisation for the Research and Treatment of Cancer (EORTC) risk scores and four molecular markers in T1 carcinomas of the bladder treated conservatively with BCG. T1 sub‐stage according to a new system (micro‐invasive [T1m] and extensive‐invasive [T1e]) was the most important clinical variable for predicting progression to carcinoma invading bladder muscle. The performance of the EORTC risk scores was disappointing for this T1 sub‐group. Molecular markers were not significant in multivariable analysis for predicting progression. Future studies may lead to the incorporation of sub‐stage (T1m/T1e) in the TNM classification system for urinary BC to guide clinical decision‐making in T1 BC.

OBJECTIVE

• ? To evaluate the prognostic significance of four molecular markers, sub‐stage and European Organisation for the Research and Treatment of Cancer (EORTC) risk scores in primary T1 bladder cancer (BC) treated with adjuvant bacille Calmette–Guérin.

PATIENTS AND METHODS

• ? The slides of 129 carcinomas of the bladder from two university hospitals were reviewed and the T1 diagnosis was confirmed.
• ? T1 sub‐staging was done in two separate rounds, using a new system that identifies micro‐invasive (T1m) and extensive‐invasive (T1e) T1BC, and then according to invasion of the muscularis mucosae (T1a/T1b/T1c).
• ? The EORTC risk scores for recurrence and progression were calculated.
• ? Uni‐ and multivariable analyses for recurrence and progression were performed using clinicopathological variables, T1 sub‐stage, EORTC risk scores and molecular markers (fibroblast growth factor receptor 3 gene mutation and Ki‐67, P53, P27 expression).

RESULTS

• ? The median follow‐up was 6.5 years. Forty‐two patients remained recurrence‐free (33%). Progression to T2 or metastasis was observed in 38 (30%) patients.
• ? In multivariable analysis for recurrence, multiplicity was significant. In multivariable analysis for progression, female gender, sub‐stage (T1m/T1e) and carcinoma in situ (CIS) were significant.
• ? Molecular markers were significant in univariable and in multivariable analyses for recurrence.
• ? EORTC risk scores were not significant.

CONCLUSIONS

• ? CIS, female gender and sub‐stage (T1m/T1e) were the most important variables for progression.
• ? The additional value of molecular markers was modest.
• ? Sub‐stage (T1m/T1e) could potentially be incorporated in future tumour‐node‐metastasis classifications.

     

An Updated Critical Analysis of the Treatment Strategy for Newly Diagnosed High-grade T1 (Previously T1G3) Bladder Cancer

Context

High-grade T1 (formerly T1G3) bladder cancer (BCa) has a high propensity to recur and progress. As a result, decisions pertaining to its treatment are difficult. Treatment with bacillus Calmette-Guérin (BCG) risks progression and metastases but may preserve the bladder. Cystectomy may offer the best opportunity for cure but is associated with morbidity and a risk of mortality, and it may constitute potential overtreatment for many cases of T1G3 tumours. For purposes of this review, we continue to refer to high-grade T1 lesions as “T1G3.”

Objective

To review the current literature on the management of T1G3 BCa and to provide recommendations for its treatment.

Evidence acquisition

A National Center for Biotechnology Information (NCBI) PubMed search for relevant articles published between 1996 and 9 January 2009 was performed using the Medical Subject Headings “T1G3” or “T1” and “Bladder cancer.” Articles relevant to the treatment of T1G3 BCa were retained.

Evidence synthesis

The diagnosis of T1G3 disease is difficult because pathologic staging is often unreliable and because of the risk of significant understaging at initial transurethral resection (TUR) of bladder tumour. A secondary restaging TUR is recommended for all cases of T1G3. A single dose of immediate post-TUR chemotherapy is recommended. For a bladder-sparing approach, intravesical BCG should be given as induction with maintenance dosing. Immediate or early radical cystectomy (RC) should be offered to all patients with recurrent or multifocal T1G3 disease, those who are at high risk of progression, and those failing BCG treatment.

Conclusions

Both bladder preservation and RC are appropriate options for T1G3 BCa. Risk stratification of patients based on pathologic features at initial TUR or at recurrence can select those most appropriate for bladder preservation compared to those for whom cystectomy should be strongly considered.     

T1G3膀胱癌187例临床分析及预后研究

目的 分析T1G3膀胱癌的临床特点及复发、进展、死亡的风险因素,提高对T1G3膀胱癌的认识和治疗效果. 方法 收集1998年1月至2006年10月天津市泌尿外科研究所诊断为T1G3膀胱癌且资料完整的患者187例.男162例,女25例.年龄35～92岁,平均66岁.进行临床流行病学调查并随访预后情况.寿命表法估计1、2、3、5年复发率、进展率及死亡率.将年龄、性别、出现症状至就诊时间、有无肾积水、手术方式、术后是否即刻灌药、膀胱灌注药物种类、肿瘤直径、肿瘤数量、肿瘤形态、有无原位癌、复发次数、初次复发时间≤6个月作为变量,分别进行肿瘤复发、疾病进展、死亡的Kaplan-meier单因素及Cox多因素生存分析. 结果 本组患者随访12～111个月,平均46个月.肿瘤复发100例(53.5％),进展61例(32.6％),死亡37例(19.8％).1、2、3、5年肿瘤复发率分别为35.0％、60.0％、63.0％、65.0％,疾病进展率分别为12.0％、27.0％、34.0％、38.0％,死亡率分别为0、11.0％、17.0％、26.0％.肿瘤直径、肿瘤数量、即刻灌注、初次复发时间≤6个月是T1G3膀胱癌复发的危险因素;肿瘤形态、原位癌、初次复发时间≤6个月、复发次数是T1G3膀胱癌进展的危险因素.肿瘤进展是患者死亡的危险因素. 结论 肿瘤直径≥3 cm、多发、初次复发时间≤6个月的T1G3膀胱癌患者更容易复发,应加强随访,即刻膀胱灌注可以降低T1G3膀胱肿瘤复发的风险.对肿瘤形态呈结节状、合并原位癌、初次复发时间≤6个月、多次复发等进展高危风险因素的T1G3膀胱肿瘤患者,应早期行膀胱切除.     

TUR and adjuvant intravesical chemotherapy in T1G3 bladder tumors: recurrence, progression and survival in 137 selected patients followed up to 20 years

OBJECTIVES: To evaluate a highly selected population of patients affected by T1G3 bladder transitional cell carcinoma (TCCB) treated by transurethral resection (TUR) and adjuvant intravesical chemotherapy. MATERIALS AND METHODS: Between January 1976 and April 1999, 137 patients with T1G3 TCCB were treated by TUR plus intravesical chemotherapy. Particularly, a sequential combination of mitomycin C (MMC) and epirubicin (EPI) was adopted in 91 patients (66.4%). The main exclusion criteria were concomitant or previous Tis, previous T1G3 TCCB, tumor size greater than 3 centimeters and number of tumors more than 3. TUR was repeated if a superficial tumor recurred. Patients went off study if Tis, recurrent T1G3 or invasive tumor were detected during treatment or thereafter. Adjuvant therapy, recurrence and progression were considered in multivariate analysis regarding recurrence, progression and survival respectively. RESULTS: Observation period was up to 240 months with a minimum of 2 years in 112 patients (82%). Seventy patients (51%) recurred. The recurring tumor was again a T1G3 in 22 (16%) patients. Thirteen patients (9.5%) progressed. The 5-year progression-free survival rate was 90%. Median progression-free survival was 149 months. Twenty-two patients (16%) died, 9 (6.6%) of whom due to bladder cancer. Median overall survival was 155 months. The 3- and 5-year disease-free overall survival rates were 89% and 80% respectively. Ten cystectomies (7.3%) were performed. In conclusion, 123 patients (90%) maintained their intact bladder with a mean disease-free overall survival of 104 months. The sequential combination of MMC and EPI adjuvant therapy resulted more effective to be than single drug chemotherapy on recurrence rate (p=0.0021) but had no impact upon progression (p=0.127) and specific survival (p=0.163). Progression (p<0.001) after conservative treatment was the main prognostic factor for survival. CONCLUSION: A conservative approach is an appropriate therapeutic option for the initial management of selected T1G3 bladder tumors.     

Prognostic significance of mucosal aneuploidy in stage Ta/T1 grade 3 carcinoma of the bladder.

In a prospective series of 71 patients with newly detected grade 3, stages Ta and T1 bladder carcinoma tumor characteristics, including the results of deoxyribonucleic acid (DNA) analysis as well as morphological and DNA characteristics of the grossly normal urothelium, were investigated and related to progression-free survival. The mean duration of followup was 57 months, with a minimum of 24 months. Of the 71 patients 24 underwent primary cystectomy, and 47 were conservatively treated with transurethral resection alone, or followed by instillation therapy or irradiation therapy. Of the cystectomy and conservatively treated patients 2 (8%) and 16 (34%), respectively, died of bladder carcinoma. Among the 47 conservatively treated patients tumor progression could not be predicted by the initial characteristics of tumor stage, papillary or nonpapillary growth, tumor multiplicity, tumor size, existence of 1 or multiple aneuploid cell populations, S phase value, carcinoma in situ and atypia or aneuploidy in the mucosal biopsies. Neither was progression predicted by the recurrence rate during year 1 of observation. However, a change to or persistent mucosal aneuploidy and a change to or persistent morphological abnormality of the mucosa during year 1 of observation were predictive for tumor progression (p = 0.001 and 0.045, respectively). When compared in stepwise regression analysis (Cox's proportional hazard model), DNA aneuploidy in the mucosa at 12 months after diagnosis was a highly significant predictor, whereas morphology added no further prognostic information. Therefore, progression is related to gross chromosomal abnormalities of the mucosa. High risk patients can be identified by evaluation of the grossly normal mucosa, which should be done as part of the initial diagnosis and during followup in conservatively treated patients with stages Ta and T1, grade 3 bladder carcinoma.     

膀胱癌组织Cripto-1和Sox2表达及血清CA125水平及其与临床分期分级的相关性

目的 研究膀胱癌组织Cripto-1、Sox2的表达及血清CA125水平与膀胱癌临床分期和分级的相关性.方法 收集84例膀胱癌患者血液及癌组织标本,分别用免疫组织化学法和化学发光法检测膀胱癌组织Cripto-1、Sox2表达和血清CA125水平,分析与膀胱癌临床分期的相关性.结果 Cripto-1和Sox2在膀胱癌组织的高表达率分别为54.8％和58.3％,两者均与膀胱癌临床分期存在显著的相关性(P＜0.05);膀胱癌患者血清CA125水平与临床分期和分级无显著相关性(P＞0.05).进一步分层分析发现,与血清CA125低水平组相比,血清CA125高水平患者的膀胱癌组织Cripto-1表达与临床分期和分级显著相关(P＜0.05).结论 膀胱癌组织Cripto-1表达与膀胱癌临床分期和分级相关,在膀胱癌恶性潜能及预后判断中可能具有潜在的临床应用价值.     

Prognostic significance of platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in stage pT1 G3 bladder cancer

BACKGROUND: The management of patients with pT1 G3 bladder cancer remains controversial because of the high incidence of recurrence with muscle invasion. Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and has angiogenic activity. The aim of this study was to determine whether the expression of PD-ECGF/dThdPase in bladder cancer tissue was associated with tumor progression and recurrence in patients with pT1 G3 bladder cancer. METHODS: Fifteen patients who were pathologically diagnosed as having pT1 G3 transitional cell carcinoma of the bladder were treated with transurethral resection. Sections of paraffin-embedded bladder tissue were immunohistochemically stained with either mAb654-1, a monoclonal antibody against human PD-ECGF or anti-CD34 monoclonal antibody, respectively. When more than 10% of tumor cells were positively stained with mAb654-1, this section was defined as positive in this study. RESULTS: Eight of 15 sections from patients with pT1 G3 bladder cancer (53%) were positive with PD-ECGF/dThdPase. During follow up, patients in the negative group had no disease progression and only two patients had local recurrence. In contrast, seven of eight positives had recurrence (P < 0.05) and progression was also observed in four recurrent patients. However, there was no statistical relationship between PD-ECGF and CD34 expression in any of the patients. CONCLUSION: The expression of PD-ECGF/dThdPase appears to be an important prognostic factor of pT1 G3 bladder cancer and did not show any significant relationship between PD-ECGF/dThdPase expression and vascular density.     

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.     

Quantification of the survival benefit of early versus deferred cystectomy in high-risk non-muscle invasive bladder cancer (T1 G3)

Objectives  To review understaging and survival of patients who underwent early versus deferred radical cystectomy (RCX) for high-risk non-muscle invasive bladder cancer (NMIBC; T1 G3). Methods  The results of 1,521 RCXs including 1,420 for bladder cancer were reviewed: (1) A total of 114 patients with high-risk NMIBC underwent a single TUR-BT followed by immediate RCX to estimate the understaging rate. (2) As much as 260 patients with NMIBC had long-term follow-up before RCX to determine the upgrading and upstaging over time. (3) We compared survival in patients with initial T1 G3 bladder cancer (BC) treated with early RCX (n = 175) versus deferred RCX (n = 99) for recurrent T1 G3. Results  (1) Our understaging rate was 20.2%. (2) Allowing NMIBC to upgrade portents a 19% survival disadvantage. (3) The 10 years cancer-specific survival rate was 78.7% in early and 64.5% in deferred RCX. Conclusions  Early, as compared to deferred RCX, has a distinct survival advantage for high-risk NMIBC. Patients should be counselled accordingly.     

MC3T3E1细胞分化过程中Cbfα1及相关基因的表达

目的 研究在小鼠前成骨细胞MC3T3E1诱导成骨过程中，总Cbfα1、Cbfα1两种亚型Cbfα1／P56、Cbfα1／P57及碱性磷酸酶、Ⅰ型胶原、骨钙素、骨涎蛋白和骨桥素在前成骨细胞成熟过程中的变化。明确Cbfα1、Cbfα1亚型及相关基因表达与成骨细胞分化的关系，探求与成骨细胞成熟更密切相关的Cbfα1亚型，为进一步的Cbfα1亚型研究提供基础。方法 MC3T3E1细胞在含β-甘油磷酸钠，抗坏血酸的培养基中培养22d，在细胞培养的不同时间（0，4，10，14，18，22d），用α-磷酸奈酚法测定碱性磷酸酶（ALP）活性；VanGieSon苦味酸酸性复红染色法染色细胞Ⅰ型胶原；茜素红染色观察矿化结节形成；半定量RT-PCR检测总Cbfα1mRNA及Cbfα1／P56、Cbfα1／P57mRNA和Ⅰ型胶原、骨钙素、骨涎蛋白、骨桥索mRNA的表达；用Western-blot检测Cbfα1蛋白的表达。结果 MC3T3E1细胞在β-甘油磷酸钠存在的情况下，培养第18d开始出现矿化，第22dⅠ型胶原染色及茜素红染色均观察到明显矿化结节形成。随MC3T3E1细胞的分化，Cbfα1mRNA的表达量逐渐增高，Cbfα1／P57mRNA在第18和22d的表达量明显增高，Cbfα1／P56mRNA无变化。Cbfα1蛋白随MC3T3E1细胞的分化，表达量逐渐增高。同样，随MC3T3E1细胞分化，Ⅰ型胶原、骨钙素、骨桥素和骨涎蛋白mRNA的表达量逐渐增高。ALP活性0～10d逐渐增高，10d后逐渐下降。结论 在MC3T3E1细胞的分化过程中Ⅰ型胶原、骨钙素、骨涎蛋白、骨桥素mRNA随MC3T3E1细胞的分化表达逐渐增高。Cbfα1 mRNA及Cbfα1蛋白的表达随细胞的分化逐渐增高，与其他成骨特异性基因的变化趋势一致，并以Cbfα1／P57mRNA亚型为主。Cbfα1／P57亚型的表达与成骨分化的关系更密切，在进一步的与成骨细胞分化有关的Cbfα1亚型研究应以Cbfα1／P57亚型为主。     

5-aminolaevulinic acid-induced fluorescence cystoscopy during transurethral resection reduces the risk of recurrence in stage Ta/T1 bladder cancer

OBJECTIVE: To assess the influence of 5-aminolaevulinic acid-induced fluorescence cystoscopy (FC) during transurethral resection (TUR) on the recurrence rate and the length of tumour-free interval in stage Ta/T1 transitional cell carcinoma (TCC) of the urinary bladder. PATIENTS AND METHODS: In all, 122 patients with primary or recurrent stage Ta/T1 bladder TCC treated with TUR were enrolled in a prospective randomized study. In group A the TUR was performed with standard white-light endoscopy, and in group B with FC. The patients were followed using standard cystoscopy and urinary cytology. The recurrence-free interval was evaluated in whole groups, for single and multiple, and for primary and recurrent tumours separately. RESULTS: At the time of the first cystoscopy (10-15 weeks after TUR) tumour recurrence was detected in 23 of 62 patients (37%) in group A, but only in five of 60 patients (8%) in group B. The recurrence-free survival rates in group A were 39% and 28% after 12 and 24 months, compared to 66% and 40% respectively in group B (P = 0.008, log-rank test). In separate analyses, the recurrence-free survival rates were significantly higher using FC in multiple (P = 0.001) and in recurrent (P = 0.02) tumours. In solitary and primary tumours the median time to recurrence was also longer in group B, but the difference was not statistically significant. CONCLUSION: 5-aminolaevulinic acid-induced FC during TUR reduces the recurrence rate in stage Ta/T1 bladder TCC. The most significant benefit is in patients with multiple and recurrent tumours.     

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.     

Clinical Outcome in a Contemporary Series of Restaged Patients with Clinical T1 Bladder Cancer

Objectives

To evaluate the indications for early and deferred cystectomy and to report the impact of this tailored approach on survival.

Design, setting, and participants

We retrospectively studied 523 patients seen at our institution who were initially diagnosed with T1 disease between 1990 and 2007.

Measurements

Variables analyzed included age, gender, multifocality, multifocal T1 disease, carcinoma in situ, grade, recurrence rate, and restaging status. End points were overall and disease-specific survival.

Results and limitations

A restaging transurethral resection (TUR) was performed in 523 patients. Of the patients who underwent restaging, 106 (20%) were upstaged to muscle-invasive disease and 417 patients were considered true clinical T1 (cT1); 84 of the latter group underwent immediate cystectomy. The median follow-up for survivors was 4.3 yr. The cumulative incidence of disease-specific death at 5 yr was 8% (95% confidence interval [CI], 5–13%), 10% (95% CI, 5–17%), and 44% (95% CI, 35–56%) for those restaged with lower than T1, T1, and T2 disease, respectively. Immediate cystectomy was more likely in patients with cT1 disease at restaging than in those with disease lower than cT1, but there were no other obvious differences in clinical characteristics between those with and without immediate cystectomy. Survival was not statistically different for patients who underwent an immediate cystectomy versus those who were maintained on surveillance with deferred cystectomy if deemed appropriate. Of 333 patients who did not undergo immediate cystectomy, 59 had a deferred cystectomy, and the likelihood of deferred cystectomy was greater in those with T1 disease on restaging TUR (hazard ratio: 2.40; 95% CI, 1.43–4.01; p = 0.001).

Conclusions

Restaging TUR should be performed in patients diagnosed with cT1 bladder cancer to improve staging accuracy. Patients with T1 disease on restaging are at higher risk of progression and should be considered for early cystectomy.     

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.     

Infiltrative lamina propria invasion pattern as an independent predictor for cancer‐specific and overall survival of instillation treatment‐naïve stage T1 high‐grade urothelial bladder cancer

Objectives

To investigate established prognostic factors and relatively new histopathological tumor characteristics including metric substage and lamina propria invasion patterns in a large series of T1 high‐grade non‐muscle‐invasive bladder cancer.

Methods

Between 1989 and 2012, 322 patients with initial stage T1 high‐grade bladder cancer underwent transurethral resection, followed by re‐transurethral resection and a conservative approach with follow‐up regime alone or instillation treatment. Transurethral resection specimens were reassessed by two experienced urological pathologists for tumor grade according to the World Health Organization 1973 classification, metric T1 substage, lamina propria invasion pattern and associated carcinoma in situ. The median follow‐up period was 42 months (interquartile range 25–72 months). In addition to Kaplan–Meier analyses, uni‐ and multivariable Cox regression analyses were used to compare progression‐free survival, cancer‐specific survival and overall survival for the studied parameters comparing two subcohorts.

Results

While in patients after instillation treatment no examined feature was shown as an independent predictor for prognosis, there were predictive histopathological features in multivariable Cox regression analyses in instillation treatment‐naïve patients: associated carcinoma in situ (hazard ratio 2.278, 95% confidence interval 1.119–4.634, P = 0.023) and World Health Organization 1973 grade 3 (hazard ratio 2.950, 95% confidence interval 1.021–8.536, P = 0.046) for worse progression‐free survival, infiltrative lamina propria tumor pattern for worse cancer‐specific survival (hazard ratio 2.369, 95% confidence interval 1.034–5.429, P = 0.042) and overall survival (hazard ratio 1.049, 95% confidence interval 1.024–1.075, P = 0.001).

Conclusions

The results of the present T1 high‐grade bladder cancer series suggest that lamina propria invasion pattern is a promising parameter to predict the prognosis of T1 high‐grade bladder cancer in an instillation treatment‐naïve subcohort. Prospective multicenter evaluations are warranted. The need for instillation treatment in T1 high‐grade bladder cancer is clearly demanded.