Stellen wir die Indikation zur radikalen Zystektomie immer zeitgerecht?

INTRODUCTION: The aim of this study was to examine how the survival rates for patients with muscle-invasive bladder carcinoma are influenced by the tumor stage at initial presentation. PATIENTS AND METHODS: This study examined the clinical course of 452 patients who underwent radical cystectomy for bladder carcinoma from 1992 to 2004. The patients were divided into three groups according to the histological results of the initial and final transurethral tumor resection (TURB). In group 1 (n=114) patients who presented with a superficial bladder carcinoma which had a high likelihood of progressing underwent radical cystectomy. Group 2 included (n=92) patients who displayed a superficial tumor stage when they first presented and developed progressive muscle-invasive bladder carcinoma under conservative treatment. Group 3 (n=246) comprised patients who were already at the muscle-invasive tumor stage in the course of primary TURB. The histopathological characteristics of all transurethral tumor resections and radical cystectomy were recorded. Progression-free survival rates and overall survival rates in the three groups were then compared. RESULTS: The average patient age at cystectomy was 64.3 (35-80) years, and the average follow-up period was 49 months. Progression-free survival and overall survival of all 452 patients were 56.1 and 53.6%, respectively, after 5 years. The best outcome was a progression-free 5-year survival rate of 78.4% with organ-confined, lymph node-negative tumors (n=213). This result was statistically significant (p<0.01) compared with the progression-free 5-year survival rate of 42.3% for non-organ-confined, lymph node-negative tumors (n=112). Lymph node-positive patients (n=127) achieved a progression-free 5-year survival rate of 29.0% regardless of the tumor infiltration. Group 1 patients achieved a progression-free survival rate of 71.3% and an overall survival rate of 69.1% after 5 years. Group 2 patients achieved a progression-free survival rate of 52.9% and an overall survival rate of 51.4% after 5 years. Group 3 patients achieved a progression-free survival and overall survival of 50.2% and 47.1%, respectively, after 5 years. There was no significant difference between groups 2 and 3 with regard to their progression-free or overall survival rates (p>0.45). However, both groups displayed significantly poorer progression-free and overall survival rates compared with group 1 (p<0.01). CONCLUSION: Our results show that patients with superficial bladder carcinoma with tumor progression to muscle invasion do not have a better prognosis after radical cystectomy than patients presenting initially with muscle-invasive bladder carcinoma. Survival rates in this group can only be improved by singling out patients on the basis of risk factors at an earlier stage and carrying out cystectomy. Due to these results we must expect that waiting for a muscle invasion in patients with superficial bladder carcinoma with a high risk profile results in a significant impairment of prognosis.     

新辅助动脉化疗在肌层浸润性大体积膀胱癌保留膀胱治疗中的价值

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

根治性经尿道电汽化术切除侵犯肌层膀胱肿瘤的疗效评估

目的评估根治性经尿道膀胱肿瘤电汽化术(根治性TUVBT)治疗膀胱肿瘤的中长期疗效. 方法已侵犯肌层的膀胱肿瘤患者39例.采用根治性TUVBT治疗14例,获随访12例,时间34～66个月,平均44.6个月.参照根治性经尿道膀胱肿瘤电切术的手术原则,汽化切除肿瘤至膀胱壁外脂肪层.采用膀胱部分切除术治疗25例,获随访22例,时间30～96个月,平均50.7个月.两组术后常规10-羟基喜树碱膀胱灌注化疗2年. 结果根治性TUVBT组术后肿瘤复发率33.3%(4/12);膀胱部分切除术组复发率31.8%(7/22),死亡率4.5%(1/22).两组比较,差异无显著性意义(P>0.05). 结论对已侵犯肌层的膀胱肿瘤,根治性TUVBT可作为外科治疗的一种选择,尤其适用于年老体弱或不愿意接受根治性膀胱全切术或开放手术者.     

Long-term results of intravesical bacillus Calmette-Guérin therapy for stage T1 superficial bladder cancer

OBJECTIVES: To examine in a prospective study the incidence of recurrence and progression in patients with Stage T1 bladder carcinoma after complete transurethral resection of the bladder tumor and adjuvant immunotherapy with bacillus Calmette-Guérin (BCG). METHODS: Between July 1987 and April 1999, 126 patients presenting to our clinic with a superficial urothelial carcinoma of the bladder (Stage pT1, grade 1-3) received adjuvant intravesical immunotherapy with BCG after complete transurethral resection of the bladder tumor. In the case of recurrence of superficial tumor (pTa, pT1, or carcinoma in situ), patients received a second cycle of BCG. For muscle-invasive tumor progression (pT2, pT3, or pT4), radical cystectomy was recommended. Six of the patients (5%) presented with Stage pT1,G1 tumor, 74 (59%) with Stage pT1,G2 tumor, and 46 patients (36%) with Stage pT1,G3 tumor. Median follow-up was 53 months (range 3 to 144). RESULTS: One hundred eight patients (86%) remained tumor-free with a retained bladder during the follow-up after one or two 6-week cycles of BCG. Twenty-four patients (19%) had a recurrence of superficial tumor, 13 (10%) had muscle-invasive progression after the first BCG cycle, and an additional 4 (3%) had progression after the second BCG cycle. Six patients (5%) underwent radical cystectomy, and 9 patients (7%) died as a result of tumor progression. The tumor-free survival rate of all patients was 89% (112 of 126). CONCLUSIONS: Adjuvant immunotherapy with BCG after complete transurethral resection of the bladder tumor represents a highly effective primary treatment for Stage T1 carcinoma of the bladder. Even in Stage pT1,G3 tumor, immediate radical cystectomy does not appear necessary.     

Predicting extravesical extension of bladder carcinoma: a novel method based on micrometer measurement of the depth of invasion in transurethral resection specimens

OBJECTIVES: Patients with bladder cancer and extravesical extension (Stage T3 or greater) have worse survival than those with organ-confined cancer. We sought to determine whether the depth of invasion in transurethral resection of the bladder (TURB) specimens will predict extravesical extension in patients treated by radical cystectomy. METHODS: We studied 90 patients diagnosed with invasive bladder carcinoma between 1979 and 1984. The 1997 TNM (tumor, lymph node, metastasis) system was used for pathologic staging. The mean patient age was 65 years (range 44 to 78). The male/female ratio was 5:1. All patients had invasive bladder cancer at TURB. Muscle invasion was identified in 35 patients (39%) and lamina propria invasion was present in 55 patients (61%) in the TURB specimens. The depth of invasion in the TURB specimens was measured by an ocular micrometer. All patients were treated by radical cystectomy. The median interval from TURB to cystectomy was 44 days (range 2 to 159). Extravesical extension (Stage T3 or greater) at cystectomy was present in 39 patients (43%). RESULTS: The depth of invasion was associated with final pathologic stage (Spearman correlation r = 0. 58, P <0.001). The overall accuracy of the depth of invasion for the prediction of extravesical extension, measured by the area under the receiver operating characteristic curve, was 0.81 (standard error 0. 045). The mean depth of invasion among patients with extravesical extension at cystectomy was 4.0 mm compared with 2.2 mm for those without extravesical extension. On the basis of a 4.0-mm cutoff point, the sensitivity, specificity, positive predictive value, and negative predictive value for extravesical extension were 54%, 90%, 81%, and 72%, respectively. CONCLUSIONS: Patients with a bladder cancer depth of invasion greater than 4 mm in the TURB specimens, as measured by micrometer, are likely to have extravesical extension, and more aggressive treatment should be considered.     

Long-term follow up of patients with invasive bladder carcinoma receiving combined cisplatin-based intra-arterial chemotherapy and radiotherapy

OBJECTIVES: Combined cisplatin-based intra-arterial chemotherapy and radiotherapy is an effective treatment for patients with locally invasive bladder carcinoma. We report long-term follow-up data regarding definitive treatment of locally invasive bladder carcinoma, regardless of whether bladder preservation was possible. METHODS: The follow-up data from 24 patients (18 males and six females; aged, 31-85 years; median, 73 years) with invasive bladder carcinoma, between 1993 and 2003, was examined. The clinical stages of the patients ranged T2-T4, all N0M0, and involved 13 patients at T2 (T2a, T2b), seven patients at T3 and four patients at T4. Combined cisplatin-based intra-arterial chemotherapy and radiotherapy was performed. RESULTS: The 5-year overall survival rate and cancer-specific survival rate for all patients were 81.6% and 85.6%, respectively. When the patients were divided into complete response (CR) of 10 patients and non-CR groups of 14 patients, the 5-year overall survival rate for the CR group was 87.5%, while that of the non-CR group was 78.6% (P = 0.58). The tumor grade of the CR group was significantly lower than that of the non-CR group (P = 0.01). When the non-CR group was divided into radical cystectomy and non-radical cystectomy groups, the 5-year overall survival rate for the radical cystectomy group (100%) was higher than that of the non-radical cystectomy group (70%). CONCLUSION: This combined chemo-radiotherapy was effective for local invasive bladder carcinoma, leading to the possibility of bladder preservation using this therapy.     

TURBT联合膀胱内BCG灌注治疗肌层浸润性膀胱癌疗效分析

目的 探讨选择性经尿道膀胱肿瘤电切术(transurethral resection of bladder tumor,TURBT)治疗经选择的肌层浸润性膀胱尿路上皮癌患者保留有功能性膀胱的可行性.方法 回顾性分析大连医科大学附属第二医院2006年至2011年间323例行TURBT治疗的膀胱尿路上皮癌患者的临床资料,选择术前影像学检查无明显膀胱外浸润,肿瘤单发,直径5 cm以下,局限于膀胱顶壁、底壁及侧壁,距输尿管口1 cm以上,不伴有原位癌,肿瘤创缘及基底部活检为阴性的T2期患者为研究对象,接受选择性TURBT伴膀胱内灌注BCG的保膀胱治疗.术后膀胱镜密切随访5~10年,运用统计学分析生存率、疾病特异生存率和无复发生存率评价疗效.结果 入组31例患者,5年总体生存率、疾病特异生存率和无复发生存率分别为87%、93%和58%.复发15例,浅表性复发6例,8例接受延迟膀胱癌根治术.23例保留有功能性膀胱,死亡6例.结论 选择性TURBT治疗肌层浸润性膀胱癌在少部分经严格选择的患者中是合理可行的,术后患者应终生接受膀胱镜严密随访.     

T2a transitional cell carcinoma of the bladder: long-term experience with intravesical immunoprophylaxis with bacillus Calmette-Guerin

PURPOSE: In this prospective study we evaluate the effect of combined transurethral resection of early muscle invasive bladder cancer and immunotherapy with bacillus Calmette-Guerin (BCG) in patients unfit for radical cystectomy or refusing more aggressive therapies. MATERIALS AND METHODS: A total of 22 patients with a mean age 73.6 years were included in the study. Inclusion criteria were histologically proven muscle invasive transitional cell carcinoma of the bladder with a tumor-free second resection and negative staging examinations in patients unfit for radical cystectomy or refusing more aggressive therapies. All patients received 6 weekly instillations of 120 mg. BCG starting 14 to 21 days after the last transurethral resection of the tumor. Followup at 3 months included cystoscopy, urinary cytology, ultrasound of the abdomen and chest x-ray. Every 6 months computerized tomography of the abdomen and bone scans were performed. RESULTS: The overall 5-year survival rate was 69.1%, while the disease specific 5-year survival rate was 94%. One muscle invasive recurrence was noted at 69 months, which was again treated with the same regimen but ultimately led to radical cystectomy 21 months later. One patient died of progressive recurrence in the upper urinary tract. The 5-year recurrence-free survival rate was 46.5%. The only severe complication was BCG pneumonitis. CONCLUSIONS: The data show encouraging results for transurethral resection of bladder tumor with intravesical BCG therapy in select patients with T2a bladder cancer who are not candidates for radical cystectomy.     

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.     

Neo-adjuvant chemotherapy in invasive bladder cancer

In patients with locally advanced muscle-invasive bladder cancer, neo-adjuvant chemotherapy was designed to treat micrometastatic disease present in up to 50% of patients at the time of diagnosis. Early chemotherapy has been combined with local therapy based on the reasoning that treatment of small volume disease would result in a better outcome. Another reason for giving neo-adjuvant chemotherapy is in an attempt to save the bladder. In selected patients, bladder preservation can be achieved with the use of chemotherapy plus radiotherapy, partial cystectomy, or transurethral resection of the bladder (TURB). Neo-adjuvant chemotherapy and bladder preservation remain controversial topics, as radical cystectomy is still considered to be the gold standard of treatment for muscle-invasive bladder cancer. The true success of bladder-preserving treatment by chemotherapy with or without RT will require validation in prospective randomized trials.     

Prävalenz von Lymphknotenmetastasen beim nicht muskelinvasiven Blasenkarzinom

OBJECTIVE: To study clinical and histopathologic parameters after cystectomy and lymphadenectomy in non-muscle-invasive transitional cell carcinoma (TCC) of the bladder and their association with the prevalence of lymph node metastases (N+). PATIENTS AND METHODS: Of 866 patients treated with radical cystectomy and lymphadenectomy, 219 had non-muscle-invasive TCC of the bladder. The prevalence of N+ was related to parameters such as gender, age, number of transurethral resections of the bladder (TURBs), intervals between first TURB and cystectomy, adjuvant therapy, maximum histopathologic tumor stage and grade at TURB, and tumor upstaging in the cystectomy specimen by univariate and multivariate analysis. RESULTS: A total of 33 patients (15%) had N+. By multivariate analyses, tumor upstaging and the number of TURBs were independent predictors of N+ at cystectomy. The number of TURBs increased the prevalence of N+ from 8% (one TURB) to 24% (two to four TURBs). Tumor upstaging in the cystectomy specimen increased the prevalence of N+ from 4% to 36%. CONCLUSION: Inappropriate delay and staging errors of"high risk" non-muscle-invasive TCC of the bladder contribute to an increased prevalence of N+ and should be avoided. In our series, the number of TURBs and tumor upstaging in the cystectomy specimen were independent predictors for N+ by multivariate analysis.     

Initial conservative treatment for grade 3 Ta-1 superficial bladder cancer

We retrospectively investigated the therapeutic outcomes of our series of 7 Ta and 62 T1 bladder cancers with grade 3 (G3) malignancy in 61 men and 8 women having a mean age of 66.2 years. Following transurethral resection of bladder tumor (TURBT), 35 and 6 patients received intravesical instillations of bacillus Calmette-Guerin (BCG) and anthracycline-derivants, respectively, whereas 15 received no adjuvant therapy. Five and 2 patients received systemic and local chemotherapy with irradiation, respectively, and six underwent radical cystectomy for invasive potential. The 5-year nonrecurrence, progression-free, and overall (cancer-specific) survival rates were 66, 82%, and 76 (88%), respectively, after a median follow-up of 52 months. The 5-year non-recurrence rates were 24% in non-adjuvant, 85% in BCG, 0% in anthracycline-derivants, 65% in systemic and local chemoradiation therapy, and 68% in cystectomy. The 5-year progression-free and overall (cancer-specific) survival rates of the patients treated with BCG instillation were 91% and 94 (100)%. There were no significant differences in the 5-year non-recurrence and progression-free rates between 12 patients with carcinoma in situ (CIS) and 23 patients without CIS. Complete TUR of all visible tumors and a reliable histopathological diagnosis of appropriate specimens bearing the muscle layer are mandatory for assessment of recurrence. G3 Ta-1 bladder cancers and CIS showed a high risk of recurrence, and required aggressive treatment. Since BCG therapy following TURBT significantly reduced the risk of recurrence and progression, adjuvant BCG therapy is considered to be the most promising initial conservative treatment for G3 Ta-1 bladder cancers.     

Grading the invasive component of urothelial carcinoma of the bladder and its relationship with progression-free survival

Although grading is valuable prognostically in pTa and pT1 papillary urothelial carcinoma, it is unclear whether it provides any prognostic information when applied to the invasive component in muscle-invasive carcinoma. The authors analyzed 93 cases of muscle-invasive urothelial carcinoma of the bladder treated with radical cystectomy for which follow-up information was available. Each case was graded using the Malmstr?m grading system for urothelial carcinoma, applied to the invasive component. Pathologic stage, lymph node status, and histologic invasion pattern were also recorded and correlated with progression-free survival. Thirty-four cases (37%) were pT2, 40 (43%) were pT3, and 19 (20%) were pT4. Of the 77 patients who had a lymph node dissection at the time of cystectomy, 34 (44%) had metastatic carcinoma to one or more lymph nodes. The median survival for pT2, pT3, and pT4 stages was 85, 24, and 29 months, respectively (p = 0.0001). Lymph node-negative and lymph node-positive patients had a median survival of 63 and 23 months, respectively (p = 0.0001). Fifteen patients (16%) were graded as 2b and 78 patients (84%) were graded as 3. Median survival of patients graded as 2b was 34 months compared with 31 months for patients graded as 3 (p value not significant). Three invasive patterns were recognized: nodular (n = 13, 14%), trabecular (n = 39, 42%), and infiltrative (n = 41, 44%). The presence of any infiltrative pattern in the tumor was associated with a median survival of 29 months, compared with 85 months in tumors without an infiltrative pattern (p = 0.06). Pathologic T stage and lymph node status remain the most powerful predictors of progression in muscle-invasive urothelial carcinoma. In this group of patients histologic grade, as defined by the Malmstr?m system and as applied to the invasive component, provided no additional prognostic information. An infiltrative growth pattern may be associated with a more dismal prognosis.     

Recurrence, progression and survival in bladder cancer. A retrospective analysis of 232 patients with greater than or equal to 5-year follow-up

A retrospective study of 232 bladder tumours with minimum follow-up 5 years is presented. The carcinoma was superficial in 66%, muscle-invasive in 31% and could not be staged in 3%. Primary treatment was mainly transurethral resection for superficial tumour, but was cystectomy or radiotherapy in 22 of 29 T1 G3. Of the superficial tumours, 71% recurred. Progression to higher T stage occurred in 15% of Ta and 29% of T1 tumours, and half of these patients died of bladder cancer. The corrected 5-year survival rates in grades 1, 2A, 2B and 3-4 were 96, 84, 64 and 43%, and in stages Ta, T1, T2 and T3 they were 94, 69, 40 and 31%. All patients with T4 tumour died within 4 years. Among the 45 patients with 40 Gy irradiation + cystectomy, the corrected 5-year survival rate was 83% in superficial and 64% in muscle-invasive tumours, and among the 38 with radical radiotherapy the rates in T1-3 were 46, 36 and 13%. Transurethral resection was successful in most Ta cases. Most T1 tumours were, like T2-4, of higher grade than Ta. Prognosis was worse in T1 than in Ta. After progression to muscle-invasive disease, even during close follow-up the outlook was poor, as poor as for patients with primary muscle-invasive disease.     

Outcome of Patients Who Refuse Cystectomy after Receiving Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer

Objectives

To determine the outcome of patients who refuse cystectomy after receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer.

Methods

Between 1995 and 2001, 63 patients were evaluated who declined to undergo a planned cystectomy, because they achieved a complete clinical response to neoadjuvant cisplatin-based chemotherapy. Patient, tumor, and treatment features were assessed prospectively, and correlated in univariate and multivariate analyses with overall survival. The median follow-up was 86 mo and all patients were followed for more than 5 yr.

Results

Forty patients (64%) survived, with 54% of them having an intact functioning bladder. The number and size of invasive tumors were strongly associated with overall survival. The most significant treatment variable predicting better survival was complete resection of the invasive tumor on re-staging transurethral resection before starting chemotherapy. Of 23 patients (36%) who subsequently died of disease, 19 (30%) relapsed with invasive cancer in the bladder. Over 90% of surviving patients had solitary, small, and low-stage invasive tumors completely resected, and 83% survived without relapses in the bladder.

Conclusions

Selected patients with muscle-invasive bladder cancers may survive after transurethral resection and neoadjuvant chemotherapy, and tumor features can identify which patients responding completely to chemotherapy may survive without cystectomy.     

Radical transurethral resection and chemotherapy in the treatment of muscle-invasive bladder cancer: a long-term follow-up

OBJECTIVE: To evaluate the treatment of patients with muscle-invasive bladder cancer (T2-T4a) by radical transurethral resection (TUR) and cisplatin-methotrexate systemic chemotherapy. PATIENTS AND METHODS: Fifty patients with transitional cell carcinoma (TCC) of the bladder (nine T2, 36 T3 and five T4a) were treated by 'complete' TUR of the bladder tumour followed by 2-6 cycles of cisplatin (70 mg/m2) and methotrexate (40 mg/m2) chemotherapy. The median (range) tumour size was 3 (1-7 cm). In six patients, attempted TUR at the dome of the bladder led to intraperitoneal perforation; the tumour was excised by partial cystectomy in these patients. The latest follow-up results from 57 patients treated by radical TUR and methotrexate alone, reported previously, are included. RESULTS: At the first evaluation cystoscopy immediately after completing chemotherapy, 38 patients were tumour-free, eight had persistent muscle-invasive TCC and four had Ta, T1+CIS disease. With an overall median follow-up of 47 months, 10 additional patients relapsed with muscle-invasive carcinoma in the bladder after a median interval of 15.6 months; three patients developed Ta, T1 tumours, three Ta, T1 + CIS, and six CIS only. Six of the 10 recurrent invasive tumours were at the same site, but four were at a different site in the bladder. Although during follow-up 12 patients developed superficial recurrence that required endoscopic treatment, the bladder was preserved (free of muscle-invasive cancer) in 37 of 50 patients. In 30 of these 37, this was achieved with no need for salvage radiotherapy or cystectomy. Six patients died from metastatic TCC with no tumour in the bladder. CONCLUSION: In this selected group of patients, muscle-invasive bladder cancer was controlled by TUR and systemic chemotherapy, preserving normal bladder function in 60% of patients without apparently comprising overall survival.     

Bladder Preservation in Selected Patients with Muscle-Invasive Bladder Cancer by Complete Transurethral Resection of the Bladder Plus Systemic Chemotherapy: Long-Term Follow-up of a Phase 2 Nonrandomized Comparative Trial with Radical Cystectomy

Background

Many phase 2 bladder-sparing programmes using transurethral resection of the bladder (TURB) plus chemotherapy or radio-chemotherapy have been undertaken, but some controversies remain.

Objective

To determine the efficacy of complete TURB plus three cycles of cisplatin-based chemotherapy in selected patients with muscle-invasive bladder cancer (MIBC).

Design, setting, and participants

A phase 2 nonrandomized trial was designed that included patients with MIBC who underwent complete TURB with positive biopsies of the tumour bed. Patients with negative biopsies of the tumour bed, with macroscopically residual tumour, with hydronephrosis, or with distant metastasis were excluded from this trial. Patients included in this trial were offered three cycles of systemic chemotherapy or radical cystectomy (RC). Clinical response (cR) was denoted by either no tumour or the presence of Ta1–Tis bladder tumour at 3-mo evaluation; clinical non-response (cNR) was denoted by cases of muscle-invasive tumour or distant metastasis. Of 146 patients who entered this trial, 75 choose the bladder-sparing programme and 71 chose RC.

Measurements

At 5 yr and 10 yr, the cancer-specific survival (CSS) rate was 64.5% and 59.8%, respectively, with no significant difference compared to the RC arm (p = 0.544). The progression-free survival with bladder preserved was 52.6% and 34.5%, respectively. In multivariate analysis, cR was the only predictive factor for survival (p = 0.001) and bladder preservation (p = 0.000).

Results and limitations

This was not a randomized trial, and patients were included over 16 yr. However, no modifications were made to the therapy schedule except from chemotherapy schemes considered standard at the time.

Conclusions

Patients with microscopic residual cancer after complete TURB seem to be good candidates for the bladder-sparing programme using three cycles of systemic chemotherapy, with CSS comparable to RC.     

The role of adjuvant chemotherapy for locally advanced bladder cancer

The incidence of locally advanced bladder cancer is estimated at 5 new cases per 100,000 of the population annually in North America and most European countries. Radical cystectomy for muscle-invasive organ-confined tumors and locally advanced disease, which is defined as extravesical tumor growth or involvement of regional lymph nodes, is the preferred treatment in Japan, the United States, and in some countries of Europe. The clinical outcome of radical cystectomy has improved remarkably over the past 20 years as a result of advances in operative technique and perioperative care. Nevertheless, at least 50% of patients with invasive bladder cancer are expected to develop progressive disease within the first 2?years when treated with radical cystectomy alone. In order to improve the fate of muscle-invasive and locally advanced disease, the administration of additional therapy to definite treatment has been studied in various forms, such as neoadjuvant and adjuvant systemic chemotherapy as well as combined radio-chemotherapy. Prolonged progression-free survival for patients suffering from locally advanced bladder cancer by administration of adjuvant systemic chemotherapy has been suggested by three randomized studies, published by Skinner, Freiha and Stöckle since 1991. These studies demonstrated a disease-free survival benefit of 17–50% within the first 3–5?years when applying adjuvant systemic chemotherapy after radical cystectomy. Patients who most likely benefit from adjuvant chemotherapy are those with limited node-positive disease, extravesical tumor, and direct invasion into adjacent viscera, such as prostate, uterus, or vagina. This review will summarize past, current, and future aspects of systemic adjuvant chemotherapy for transitional cell carcinoma of the bladder.     

Updated results of bladder-sparing trimodality approach for invasive bladder cancer

PurposeTo update long-term results with selective organ preservation in invasive bladder cancer using aggressive transurethral resection of bladder tumor (TURBT) and radiochemotherapy (RCT) and to identify treatment factors that may predict overall survival (OS).Materials and methodsBetween 1990 and 2007, a total of 74 patients with T2-T4 bladder cancer were enrolled in 2 sequential bladder-sparing protocols including aggressive TURB and RCT. From 1990 to 1999, 41 patients were included in protocol no. 1 (P1) that consisted of three cycles of neoadjuvant methotrexate, cisplatin, and vinblastine (MCV) chemotherapy prior to re-evaluation and followed by radiotherapy (RT) 60 Gy in complete responders. Between 2000 and 2007, 33 patients were entered in protocol no. 2 (P2) that consisted of concurrent RCT 64, 8 Gy with weekly cisplatin. In case of invasive residual tumor or recurrence, salvage cystectomy was recommended. Primary endpoints were OS, overall survival with bladder preservation (OSB), and late toxicity.ResultsThe mean follow-up for the whole series was 54 months (range 9–156), 69 months for patients in P1 and 36 months for patients in P2. The actuarial 5-year OS and OSB for all series were 72% and 60%, respectively. Distant metastases were diagnosed in 11 (15%) patients. Grade 3 late genitourinary (GU) and intestinal (GI) complications were 5% and 1.3%, respectively. There were no significant differences in the incidence of superficial recurrences (P = 0.080), muscle-invasive relapses (P = 0.722), distant metastasis (P = 0.744), grade ≥2 late complications (P = 0.217 for GU and P = 0.400 for GI), and death among the 2 protocols (P value for OS = 0.643; P value for OSB = 0.532).ConclusionThese data confirm that trimodality therapy with bladder preservation represents a real alternative to radical cystectomy in selected patients, resulting in an acceptable rate of the long-term survivors retaining functional bladders.     

The value of bladder-conserving strategies in muscle-invasive bladder carcinoma compared with radical surgery

PURPOSE OF REVIEW: Patients with muscle-invasive bladder cancer will practically all develop progression, often associated with severe side effects including pain, dysuria or macrohematuria. Recent reports demonstrate multimodality bladder-sparing approaches as primary treatment for muscle-invasive bladder cancer. RECENT FINDINGS: Bladder-conserving strategies include thorough transurethral resection of the bladder tumor, external beam radiation therapy and chemotherapy. It has been shown that survival rates are similar to those of radical cystectomy series; additionally, a substantial number of patients survive with an intact bladder. The high costs, close cooperation between clinical specialists and a highly compliant patient need to be taken into consideration, however. SUMMARY: Nowadays, the good long-term results after radical cystectomy with the creation of an orthotopic neobladder make the substantial advantage of a bladder-preserving strategy questionable when the patient's quality of life is addressed. Multimodality bladder-conserving strategies are a therapeutic option for selected patients; however, radical cystectomy remains the gold standard of treatment.