Surveillance guidelines based on recurrence patterns after radical cystectomy for bladder cancer: the Canadian Bladder Cancer Network experience

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Radical cystectomy with pelvic lymph node dissection is recognized as the standard of care for carcinoma invading bladder muscle and for refractory non‐muscle‐invasive bladder cancer. Owing to high recurrence and progression rates, a two‐pronged strict surveillance regimen, consisting of both functional and oncological follow‐up, has been advocated. It is also well recognized that more aggressive tumours with extravesical disease and node‐positive disease recur more frequently and have worse outcomes. This study adds to the scant body of literature available regarding surveillance strategies after radical cystectomy for bladder cancer. In the absence of any solid evidence supporting the role of strict surveillance regimens, this extensive examination of recurrence patterns in a large multi‐institutional project lends further support to the continued use of risk‐stratified follow‐up and emphasizes the need for earlier strict surveillance in patients with extravesical and node‐positive disease.

OBJECTIVES

• ? To review our data on recurrence patterns after radical cystectomy (RC) for bladder cancer (BC).
• ? To establish appropriate surveillance protocols.

PATIENTS AND METHODS

• ? We collected and pooled data from a database of 2287 patients who had undergone RC for BC between 1998 and 2008 in eight different Canadian academic centres.
• ? Of the 2287 patients, 1890 had complete recurrence information and form the basis of the present study.

RESULTS

• ? A total of 825 patients (43.6%) developed recurrence.
• ? According to location, 48.6% of recurrent tumours were distant, 25.2% pelvic, 14.5% retroperitoneal and 11.8% to multiple regions such as pelvic and retroperitoneal or pelvic and distant.
• ? The median (range) time to recurrence for the entire population was 10.1 (1–192) months with 90 and 97% of all recurrences within 2 and 5 years of RC, respectively.
• ? According to stage, pTxN+ tumours were more likely to recur than ≥pT3N0 tumours and ≤pT2N0 tumours (5‐yr RFS 25% vs. 44% vs. 66% respectively, P < 0.001). Similarly, pTxN+ tumours had a shorter median time to recurrence (9 months, range 1–72 months) than ≥pT3N0 tumours (10 months, range 1–70 months) or ≤pT2N0 tumours (14 months, range 1–192 months, P < 0.001).

CONCLUSIONS

• ? Differences in recurrence patterns after RC suggest the need for varied follow‐up protocols for each group.
• ? We propose a stage‐based protocol for surveillance of patients with BC treated with RC that captures most recurrences while limiting over‐investigation.

     

Outcomes of pT0N0 at radical cystectomy: The Canadian Bladder Cancer Network experience

Introduction:

Radical cystectomy is the standard treatment for muscle invasive bladder cancer. We assessed clinical outcomes in patients found to have no evidence of disease (i.e., pT0N0) following radical cystectomy.

Methods:

We collected and pooled a database of 2287 patients who underwent radical cystectomy between 1993 and 2008 in eight centres across Canada. Of this number, 135 patients were found to have pT0N0 bladder cancer at the time of cystectomy. Survival data and prognostic variables were analyzed using Kaplan-Meier method and Cox proportional hazard regression analysis.

Results:

Median patient age was 66 years with a mean follow-up of 42 months. Clinical stage distribution was Tis 8.9%, Ta 1.5%, T1 20.7%, T2 45.2%, T3 5.2%, and T4 5.2%. The five-year recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) were 83%, 96%, and 88%, respectively. The 10-year RFS, DSS and OS were 66%, 92%, and 70%, respectively. On Cox proportional regression analysis, no variables were associated with disease recurrence and only patient age was associated with overall survival.

Interpretation:

Patients with pT0N0 pathology after cystectomy have excellent outcomes with high five- and 10-year RFS, DSS and OS. However, there is still a risk of tumour recurrence in this patient population and thus postoperative surveillance is still required.     

The best treatment for high-grade T1 bladder cancer is cystectomy

OBJECTIVES: To evaluate the role of initial cystectomy in the management of high-grade T1 bladder cancer. METHODS: A selected review of the literature was performed to evaluate outcomes with intravesical therapy vs. initial cystectomy in this patient population, with a focus on identifying risk factors for failure of conservative therapy. RESULTS: Many studies in the literature fail to include central pathologic review and re-TUR clinical staging, and there are no randomized studies comparing outcomes with these two initial approaches. Retrospective studies of patients with high-grade T1 tumors treated with initial intravesical therapy suggest that approximately 30% of patients will ultimately require cystectomy, and 30% will die of their disease with or without cystectomy. The risk of progression continues for the life of the patient, and late recurrence and progression is common. Initial clinical and pathologic factors can be identified that predict a high risk of progression and are reasonable indicators for initial cystectomy. CONCLUSION: Radical cystectomy can provide a very high cure rate for these patients and should be considered early in the treatment plan.     

Radical cystectomy for bladder cancer: the case for early intervention

There are no prospective studies comparing early cystectomy versus cystectomy after failed conservative management in patients with high-risk superficial bladder cancer. In the absence of clinically proven biomarkers for predicting tumor biology and the response to therapy, the treatment decision must be individualized based on the high-risk features outlined herein. Assuming that all patients can be treated effectively with bladder-sparing regimens and safely salvaged at the time of failure or progression is dangerous. Data support the negative impact of a delay in cystectomy and argue for improvements in the timing of cystectomy despite the clinical absence of muscle invasion. Accordingly, high-risk patients with non-muscle invasive disease require vigilant follow-up and should be informed from the onset of the risk for progression and the possible need for cystectomy. Repeat resection before intravesical therapy in the patient with T1 tumor is advised and should help to improve, but will not completely eliminate, the problem of clinical under-staging. Among patients with CIS and recurrent high-grade non-muscle invasive tumors, repeat biopsies following intravesical therapy are encouraged to ensure treatment response. Although there is debate regarding the timing of early cystectomy for patients with high-risk non-muscle invasive bladder cancer, there is little doubt that, for muscle invasive disease, prompt cystectomy influences the effectiveness of this therapy choice. An unnecessary delay in the performance of radical cystectomy in patients with organ-confined bladder cancer compromises outcomes and risks potentially avoidable deaths from disease.     

Radical cystectomy versus alternative treatments for muscle-confined bladder cancer

Of the 100 patients with muscle-confined transitional cell cancer of thebladder and ASA score 3, 59 underwent radical cystectomy (RC) and41 received non-cystectomy alternative treatments (AT). Median follow-upwas 30.8 and 30.5 months in RC and in AT groups, respectively. Disease-freeand overall survivals were significantly longer in RC group than AT group.Salvage cystectomy was required in approximately 25% of the patients whoreceived AT. AT was associated with higher rate of cancer-related morbidityand cancer progression than RC. Every patient with invasive bladdercancer should be given a chance for cystectomy.     

Invasive T1 bladder cancer: indications and rationale for radical cystectomy

Invasive T1 bladder cancers are potentially lethal tumours with varying degrees of aggressiveness and progression. The management of invasive tumours can be very difficult and includes bladder-sparing with transurethral resection and intravesical therapy, or a more aggressive approach with radical cystectomy. Certain clinical and pathological factors might provide some risk stratification for invasive T1 tumours, and might better direct the physician towards an earlier cystectomy for some patients. This review provides a rationale for a radical cystectomy in patients with high-risk, invasive T1 bladder cancer.     

Radical cystectomy in regionally advanced bladder cancer.

The distinction pathologically of invasive tumors confined to the muscularis propria from those that penetrate the bladder wall and invade the perivesical fat or adjacent organs is a critical prognostic determinant. Nodal metastases are evident in approximately one half of patients with tumors pathologically staged as P3b or greater. Five-year survival rates after radical cystectomy with or without preoperative irradiation for stage P3b tumors range from 17% to 46%. Long-term survival is the exception when bladder cancer invades the pelvic sidewall or adjacent structures, yet cystectomy can provide palliation and accurate staging and can be considered in the context of combination therapy. Supravesical diversion can provide palliation when there is nodal disease above the bifurcation or pelvic fixation. The optimal role of adjuvant chemotherapy in the treatment of regionally advanced bladder cancer is yet to be defined. Tannock has delineated the many serious pitfalls inherent in interpreting nonrandomized trials of new therapies (see also his article elsewhere in this issue). Randomized trials are currently under way to determine if survival can be improved with adjuvant or neoadjuvant chemotherapy and the most efficacious timing of chemotherapy administration. Clinicians should generally resist the tendency to treat all patients with these regimens until it is clear that we are truly improving the outcome of therapy and the quality of life for our patients.     

T1G3 bladder cancer – Indications for early cystectomy

Objectives: To review our experience with early radical cystectomy in patients with T1G3 Transitional Cell Carcinoma of bladder (TCC). Patients and methods: Thirty patients, who underwent early radical cystectomy over a 10-year period for clinical stage T1G3 TCC bladder, were studied. Of these 21 (70%) had radical cystectomy without treatment with intravesical chemo/immunotherapy. The number of tumours, presence or absence of Carcinoma In-Situ (CIS) and the pathological stage of the cystectomy specimen were recorded in each patient. Disease specific survival was determined in the subgroups using Kaplan-Meier estimates. Results: Seventeen patients underwent radical surgery for a single tumour without concomitant CIS (Group A). The other 13 had multiple tumours with or without concomitant CIS or a single tumour with CIS (Group B). The disease was upstaged after cystectomy in 1 (6%) patient in Group A compared to 7 (55%) in Group B, (p = 0.009). Nine (53%) had pT0 disease in Group A compared to 0% in Group B, (p = 0.0017). The 5-year cancer specific survival rates were 92% in Group A and 82% in Group B. Conclusions: In patients with multiple T1G3 tumours with or without associated CIS, or in those with single T1G3 tumour with associated CIS the incidence of the disease being already muscle invasive at the time of clinical diagnosis is 55%. Early radical cystectomy should be advocated in this group. Conversely, for a single T1G3 tumour without associated CIS, conservative bladder preserving strategy with immuno-chemotherapy and close surveillance is justified. This revised version was published online in August 2006 with corrections to the Cover Date.     

Radical cystectomy in septuagenarian patients with bladder cancer

Introduction: Clinical results of radical cystectomy performed on elderly bladder cancer patients over 70 years old were assessed to determine whether age is one of the critical points for the application of this type of surgery. Materials: From January 1992 to December 2002, 41 radical cystectomy performed in septuagenarian population were compared with 197 performed in patients less than 70 years of age. Results: The early and late complication rate for septuagenarians was 29.7% and 12%, compared with 26.9% and 9.6% for patients younger than 70 years respectively. The overall mortality rate for septuagenarians was 4.9%, compared with 8.6% for patients younger than 70 years. There was no significant difference between the two groups with regard to pathologic stage or length of hospital stay. The 5-year overall survival rate for septuagenarians was 53% compared with 59% for patients younger than 70 years. Conclusions: When indicated after adequate preoperative assessment and optimization of the patient, radical cystectomy is a safe procedure in the septuagenarians and patient should not be denied surgery dependent on chronologic age.     

保留前列腺远端包膜在全膀胱切除肠代膀胱术中的应用

目的探讨膀胱癌患者根治性全膀胱切除术中保留前列腺远端包膜的价值.方法56例患者均为男性,平均年龄62岁.其中膀胱移行细胞癌53例,鳞状细胞癌3例;原发肿瘤40例,复发肿瘤16例.浅表性肿瘤27例,浸润性肿瘤29例.常规盆腔淋巴清扫术后,行保留前列腺远端包膜的全膀胱前列腺切除术.分别应用去管化回结肠或回肠作原位代膀胱20例和36例.随访观察手术效果和生活质量.结果回结肠代膀胱和回肠代膀胱的平均手术时间分别为350和380 min,术中出血量分别为580和540 ml.病理报告pT1N028例,pT2N025例,pT3N+3例.平均随访42个月(4～102个月),3例T3N+者分别于术后8、11、19个月死于癌肿,死于其他病变者5例.随访1年时,两种代膀胱白天控尿率分别为94%(17/18)和100%(30/30),夜间排尿1～2次后,保持干燥者占96%(46/48).术后最大尿流率分别为(15.8±2.6)ml/s和(14.7±3.2)ml/s.随访5年以上者28例,肿瘤特异5年生存率T1N0为94%(15/16),T2N0为83%(10/12).术前勃起功能正常31例中,术后维持正常勃起23例(74%).结论保留前列腺远端包膜的膀胱癌肠代膀胱术,能有效保留神经和括约肌功能,提高术后控尿和勃起能力,不影响肿瘤切除原则,值得临床推广应用.     

Radical cystectomy for invasive bladder cancer: contemporary results and remaining controversies

The impact of stage progression of superficial cancer to invasive disease is profound. However, the optimal-timed management of invasive bladder cancer is still controversial. Pelvic lymph node dissection and radical cystectomy are considered to be the optimal therapy regarding local tumor control and ultimate cure of cancer, whereas chemotherapy offers the only viable but limited option for patients with distant metastasis or locally advanced disease. Identification of conventional and molecular prognostic factors to predict cancer-specific survival following radical cystectomy is one important step to identify candidates that may benefit from early cystectomy or adjunct chemotherapy. With this background, the results of historic and contemporary radical cystectomy series for carcinoma of the bladder are reviewed.     

Radical cystectomy for primary neuroendocrine tumors of the bladder: the university of southern california experience

PURPOSE: Primary neuroendocrine tumors of the bladder are rare and they include small and large cell variants. We reviewed our experience with treating these tumors with radical cystectomy to evaluate their histopathological characteristics and clinical outcomes. MATERIALS AND METHODS: From August 1971 to June 2004, 2,005 patients underwent radical cystectomy for primary bladder cancer at our institution, of whom 25 (1.2%) had neuroendocrine tumors of the bladder, including small cell carcinoma in 20 and large cell carcinoma in 5. Pure neuroendocrine-type histology was identified in 16 cases, including 1 with small and large cell features, while the remaining 9 had mixed histology, that is transitional cell carcinoma in 8 and adenocarcinoma in 1. Multi-agent chemotherapy was administered to 14 patients. RESULTS: Median patient age was 68 years (range 40 to 82) and 19 patients were male (76%). A total of 19 patients (76%) had lymph node involvement, of whom 2 had small liver metastases found intraoperatively, while only 4 (16%) had organ confined tumors and 2 (8%) had extravesical, node negative disease. These tumors tended to have a flat, ulcerative gross appearance with lymphovascular invasion, carcinoma in situ and necrosis present microscopically. Median followup was 11.8 years (range 18 days to 15.1 years). Five-year overall and recurrence-free survival was 10% and 13%, respectively. There was no significant survival difference between small and large cell carcinoma. Mixed histologies tended to do better than pure neuroendocrine tumors, although this did not attain statistical significance (p = 0.064). Patients receiving multimodality therapy had significantly better overall (p = 0.051) and recurrence-free (p = 0.003) survival than those treated with cystectomy alone. CONCLUSIONS: Neuroendocrine tumors of the bladder usually present with advanced pathological stage and portend a poor prognosis. Adjuvant chemotherapy protocols may provide improved survival compared with cystectomy alone.