Radical cystectomy for urothelial carcinoma of the bladder: an analysis of perioperative and survival outcome

OBJECTIVE

To review the outcomes in a large group of patients treated with radical cystectomy (RC) for urothelial cancer (UC) of the bladder, by one surgical team.

PATIENTS AND METHODS

In all, 504 patients had RC for UC of the bladder between 1992 and 2007; 432 met the inclusion criteria and were analysed for survival and disease recurrence.

RESULTS

Of the 432 patients, (mean age 69 years; mean follow‐up 38 months, range 1–172), 240 (56%) and 179 (41%) had an ileal conduit and orthotopic neobladder for urinary diversion, respectively. The mortality rate within 30 days of RC was 2%; 105 (24%) patients developed local and/or distant recurrence with a mean interval of 13.6 months. The overall survival, recurrence‐free survival (RFS) and disease‐specific survival (DSS) at 5 years was 58%, 64% and 74%, respectively, and 43%, 62% and 68% at 10 years. The 5‐year RFS and DSS for those with organ‐confined, node‐negative tumours was 81% and 91%, compared to 46% and 56% in those with extravesical extension and lymph node‐negative tumours. The RFS and DSS of patients with lymph node metastasis at 5 years was 29% and 40%, respectively.

CONCLUSION

Our study reaffirms that RC with bilateral pelvic lymph node dissection offers a reasonable possibility of disease control at 5 years, with a DSS of 74%. However, there is a need for an earlier diagnosis and effective systemic therapy if additional gains in survival are to be delivered.     

Sex differences in bladder cancer outcomes among smokers with advanced bladder cancer

Study Type – Aetiology (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Smoking is well described among the most important risk factors for bladder cancer. It is also known that higher quantity of tobacco exposure is associated with higher bladder cancer risk and that smoking cessation is known to be associated with lower risk of bladder cancer. Furthermore, among patients with non‐muscle invasive bladder cancer, smoking cessation decreases the risk of tumour recurrence. On the other hand, the effect of smoking on tumour stages at presentation and especially on prognosis is not well studied. The current study describes the presentation and outcome of 564 patients (64% smokers, 36% non‐smokers) treated with radical cystectomy. Patients with smoking history have more advanced outcome at the time of radical surgery and significantly worse outcome after surgery when compared to non‐smokers, although the effect of smoking was not significant when survival was studied in multivariable analysis including classic prognostic parameters such as tumour grade, stage and adjuvant chemotherapy. Finally, there was a surprising finding that history of smoking affected outcome among male patients but such effect was not noted among female patients.

OBJECTIVE

? To study the effect of smoking on bladder cancer presentation and outcome in a large cystectomy population.

PATIENTS AND METHODS

? A database including 546 patients from the University Health Network (Toronto, Canada) and Turku University Hospital (Turku, Finland) was studied. ? In addition to the association of smoking with clinicopathological parameters, the effect of smoking on survival was analyzed. ? Categorical data were analyzed by the chi‐squared test and numerical data were analyzed by Student's t‐test. ? The Kaplan–Meier method, log‐rank test and a proportional hazards model were used to estimate the effect of smoking on survival.

RESULTS

? In total, 352 patients (64%) were smokers and 194 (36%) were non‐smokers. ? Smokers had more frequently advanced tumours and nodal metastasis. ? The 10‐year disease‐specific survival (DSS) was 52% vs 66% for smokers and non‐smokers, respectively (P= 0.039). ? Smokers also had significantly worse overall survival (10‐year overall survival 37% vs 62%; P= 0.015). ? Smoking affected significant DSS among men (P= 0.012), although no effect was observed among women. ? In a univariate model smoking was associated with a hazard ratio (HR) of 1.4 (95% confidence interval, CI, 1.0–1.9) for bladder cancer specific mortality and 1.4 (95% CI, 1.1–1.8) for overall mortality. ? In a multivariate model, smoking did not impact on DSS (HR, 1.1; 95% CI, 0.8–1.6; P= 0.41). ? In addition to advanced stage and nodal metastasis, female sex was an independent risk factor for DSS (HR, 1.6; 95% CI, 1.1–2.3; P= 0.007).

CONCLUSIONS

? Smokers appear to have worse outcomes after radical cystectomy for bladder cancer; however, it does not appear to be an independent prognostic factor for survival. ? Smoking affected survival only among men. ? Women had poorer survival but smoking was not a contributing factor to this.     

Predicting survival after radical cystectomy for bladder cancer

Accurate prediction is essential for patient counselling, appropriate selection of treatments and determination of eligibility for clinical trials. In this review we assess the available determinants of oncological outcome after radical cystectomy (RC) for transitional cell carcinoma of the urinary bladder. We reviewed previous publications to provide guidelines in terms of criteria, limitations and clinical value of available tools for predicting patient outcome after RC. Our findings suggest that while individual surgical, patient and pathological features provide useful estimates of survival outcome, the inherent heterogeneity of tumour biology and patient characteristics leads to significant variation in outcome. By incorporating all relevant continuous predictive factors for individual patients, integrative predictive models, such as nomograms or artificial neural networks, provide more accurate predictions and generally surpass clinical experts at predicting outcomes. Nonetheless, there is a clear need for the development and validation of molecular biomarkers and their incorporation into multivariable predictive tools. Significant progress has been made in identifying important molecular markers of disease and the development of multifactorial tools for predicting the outcome after RC.     

Management of muscle-invasive bladder cancer in Victoria, 1990-1995

BACKGROUND: The management and outcomes of muscle-invasive bladder cancer are described in this article. METHODS: A retrospective survey of medical practitioners involved in the management of bladder cancer was conducted. The survey obtained at least 5 years of follow-up data on all patients. The sample was taken from the public and private health sectors in Victoria. All were cases of muscle-invasive bladder cancer diagnosed between 1990 and 1995. The main outcome measures included reported management by staging, treatment and survival. RESULTS: Completed questionnaires were returned for 743 (89.6%) of 829 cases. Of these, 523 (70.4%) were men, and the mean age was 72.7 years. More than 75% of the cases (560) presented with macroscopic haematuria. The majority (696, 94%) had transitional cell carcinoma. A variety of treatments were given in various sequences, with 231 cases (31.1%) having initial surveillance. Eventually, 303 cases (40.8%) proceeded to 'definitive' management with either radiotherapy (132, 17.8%) or cystectomy (171, 23.0%). In addition, chemotherapy was given to 254 patients (34.2%) at some time. Most patients (613, 82.5%) have subsequently died; 402 (54%) died from bladder cancer. Crude 5-year survival was 13.0%, and disease-specific survival was 27.7%. Multivariate analysis identified the following predictors of greater disease-specific survival: grade 1 or 2 histopathology (P = 0.0003), T2 primary (P < 0.0001), N0 disease (P = 0.04), M0 disease (P < 0.0001), radiation dose in BED(10) >70 Gy and cystectomy (P < 0.0001). CONCLUSION: Muscle-invasive bladder cancer in Victoria typically occurs in elderly patients, and a notable proportion of these patients do not proceed onto 'definitive' treatment. Disease stage, cystectomy and the use of high doses of radiation are associated with better outcomes. Chemotherapy was given to approximately one-third of patients at some point in their disease management. Our data are similar to population-based data from North America, and provide a baseline against which potential changes in management of bladder cancer can be compared.     

Post-chemotherapy surgery in patients with unresectable or regionally metastatic bladder cancer

PURPOSE: We update our experience with post-chemotherapy surgery in patients with unresectable or lymph node positive bladder cancer. METHODS: Of 207 patients with unresectable or regionally metastatic bladder cancer 80 (39%) underwent post-chemotherapy surgery after treatment with a cisplatin based chemotherapy regimen. We assessed the impact of surgery on achieving a complete response to chemotherapy and on relapse-free survival. RESULTS: No viable cancer was present at post-chemotherapy surgery in 24 of the 80 cases (30%), pathologically confirming a complete response to chemotherapy. Of the 24 patients 14 (58%) survived 9 months to 5 years. Residual viable cancer was completely resected in 49 patients (61%), resulting in a complete response to chemotherapy plus surgery, and 20 (41%) survived. Post-chemotherapy surgery did not benefit those who failed to achieve a major complete or partial response to chemotherapy. Only 1 of the 12 patients (8%) who refused surgery remains alive. CONCLUSIONS: Post-chemotherapy surgical resection of residual cancer may result in disease-free survival in some patients who would otherwise die of disease. Optimal candidates include those in whom the pre-chemotherapy sites of disease are restricted to the bladder and pelvis or regional lymph nodes, and who have a major response to chemotherapy.     

Treatment and outcome of invasive bladder cancer in patients after renal transplantation

PURPOSE: Optimal management and clinical outcome of bladder cancer in renal transplant recipients are not well-defined. We analyzed single institution treatment strategies and outcomes of these patients. MATERIALS AND METHODS: We retrospectively reviewed the University of California, San Francisco transplant database which contains information on 6,288 renal transplants performed between 1964 and 2002. The United Network for Organ Sharing database and Israel Penn International Transplant Tumor Registry were also queried to characterize the global nature of bladder cancer in renal transplant recipients. RESULTS: The United Network for Organ Sharing database (1986 to 2001) contained information on 31 patients who were found to have bladder cancer (0.024% prevalence) and the Israel Penn International Transplant Tumor Registry (1967 to 2001) contained information on 135 patients representing 0.84% of all reported malignancies. We identified 7 renal transplant recipients with bladder cancer at our institution. Invasive transitional cell carcinoma developed in 5 patients at a median of 2.8 years after transplant. Three patients underwent uncomplicated radical cystectomy and preservation of the renal allograft. Overall survival at 48 months was 60%. CONCLUSIONS: Bladder cancer after renal transplantation is not common. For patients who present with invasive disease, traditional extirpative surgery should be considered. Moreover, the allograft is rarely the source of transitional cell carcinoma and can be preserved. In our experience the cancer and urinary outcomes compare favorably with nontransplant patient outcomes after treatment.     

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.     

Current status of molecular markers for prognostication and outcome in invasive bladder cancer

What's known on the subject? and What does the study add? Currently, prognostication of patients with invasive BC is hampered owing to the inadequacy of standard clinicopathological risk factors to predict accurately individual treatment outcomes. This review provides a comprehensive albeit brief overview on current studies elucidating the potential role of different molecular markers to close this gap of evidence. It focusses on biostatistical considerations in the interpretation of study results which are essential to provide meaningful clinical conclusions for an individual patient.

OBJECTIVE

• ? To improve prognostication and the management of patients with invasive bladder cancer (BC).

METHODS

• ? Standard clinicopathological risk factors are not reliably enough to accurately predict outcomes in patients after radical treatment and guide clinicians for recommending selectively the use of adjuvant therapies.
• ? With detailed insights into the molecular pathology of BC, biomarkers have come to the fore of researchers as a potential tool to close this gap of evidence.
• ? However, their definitive role in the diagnostic and therapeutic management of patients with invasive BC has not clearly been addressed so far.

RESULTS

• ? Invasive BC are an extremely heterogenenous group of malignancies which are characterized by multiple genetic alterations involved in the carcinogenesis and development of metastatic spread. Thus, it is questionable whether any single marker will provide superior prognostication compared with a combination of markers.
• ? Current studies evaluating the predictive value of a multitude of markers have used high‐throughput technologies and investigated the gain in predictive accuracy within new nomograms which encompass well‐established clinicopathological and novel putative molecular parameters. p53 overexpression was found to be associated with increased risk of recurrence in urothelial and non‐urothelial cancer. In pT1 disease, the combination of p53, p21 and p16 as well as epigenetic alterations of myopodin expression has been shown to provide improved prognostication, and this might help to advocate more selectively the use of early radical treatment.
• ? After the bladder‐sparing approach, p53 and p21 overexpression indicate decreased probability of long‐term bladder preservation. Additionally, altered retinoblastoma expression is associated with improved survival after adjuvant chemotherapy.
• ? To provide meaningful conclusions for individual prognosis and the need of adjuvant treatment, biostatistical pitfalls in the analysis and interpretation of results have to be taken into account.

CONCLUSIONS

• ? Different molecular markers have the potential to improve prognostication of patients with invasive BC and provide improved evidence for targeted therapy in the neoadjuvant, adjuvant and metastatic setting.
• ? However, in order to advocate their routine clinical use on a sound scientific basis prospective data are still necessary.

     

T1G3期膀胱癌诊治策略

膀胱癌是我国泌尿系统最常见的恶性肿瘤，新发病例中75％的病变局限于黏膜和固有层，临床分期属于T1期。其中10％的肿瘤病理分级属于G3级。把临床分期T1、病理分级G3的膀胱移行上皮癌统称为T1G3期膀胱癌。研究发现，T1G3期膀胱癌患者疾病进展和死亡的风险比其他T1期肿瘤患者高出10倍，其生物学行为复杂、临床预后较差，临床诊治相对较为棘手。目前国际上对于这类疾病多采取经尿道膀胱肿瘤电切联合膀胱灌注BCG保留膀胱、或根治性膀胱切除术的方式进行治疗。但何时选择保留膀胱的治疗方案、何时选择根治性膀胱切除术，还需要根据患者的具体临床风险因素进行综合分析，并制定最佳的治疗方案。作者在认真学习并总结国际上关于T1G3期膀胱癌最新治疗指南的基础上，对这类疾病的诊断与治疗的最新理念及方法进行综合分析，供广大泌尿外科同道参考。     

Correlation between clinical and pathological staging in a series of radical cystectomies for bladder carcinoma

OBJECTIVE: To analyse the rate of concordance between the clinical and pathological Tumour-Nodes-Metastasis staging systems in a homogeneous series of patients who had undergone radical cystectomy for locally advanced or recurrent multifocal superficial bladder carcinoma. PATIENTS AND METHODS: The clinical data of 156 patients who had undergone radical cystectomy and bilateral iliaco-obturator lymphadenectomy for bladder cancer in our department were analysed retrospectively. RESULTS The clinical stage of the primary tumour was carcinoma in situ in three patients (1.9%), cT1 in 67 (42.9%), cT2 in 70 (44.9%), cT3 in five (3.2%) and cT4 in nine (5.8%). Clinical lymph node involvement was detected in 19 patients (12.2%). The differences between clinical and pathological stages were statistically significant (P < 0.001), the concordance was moderate (kappa = 0.27, P < 0.001). Of the 70 patients with < or = cT1, 40 (57%) were reconfirmed as having pathological stage < or = T1; of the 70 with cT2, 16 (23%) had pT2 carcinoma. Of the 140 patients with clinically organ-confined (< or =T2) neoplasms, 70 (50%) had been understaged after radical cystectomy. The clinical and pathological systems were statistically overlapping for locally advanced cases only. Pathological lymph node involvement was diagnosed in 45 patients (28.8%); this was foreseen with pelvic computed tomography in 19 (12%) only (P < 0.001). All patients designated cN+ were also pN+. CONCLUSION: These data confirm the high risk of clinical understaging of both local extension of the primary tumour and lymph node involvement.     

Patients with bladder and lung cancer: a long-term outcome analysis

OBJECTIVES: To report on patient characteristics, stage of disease and long-term outcome and prognosis of patients with dual bladder and lung cancers, as there is an established increased risk of smoking-related second primary cancers, especially lung cancer, developing in patients with bladder cancer. PATIENTS AND METHODS: We reviewed our hospital tumour registry database from 1990 to 2002, and identified 27 patients who had both bladder and lung cancers among 1038 with bladder cancer and 2427 with lung cancer. Seventeen patients had bladder cancer detected before lung cancer (group 1), and the remaining 10 had lung cancer diagnosed first (group 2). RESULTS: Group 1 and 2 were comparable in terms of patients' characteristics, mean interval between cancer detection and their use of tobacco. Group 1 patients had a tendency towards more invasive lung cancer at diagnosis than had group 2 patients (11/17 vs 2/10 stage >/= IIB, respectively; P = 0.082). The mean follow-up was 49.8 and 64.5 months for groups 1 and 2, respectively (not significant). The mean (sd) interval to death from the date of diagnosis of lung cancer was 18 (17) months for group 1 and 65 (42) months for group 2 (P < 0.05). CONCLUSIONS: Patients with bladder and lung cancer who have lung cancer detected first have a lower lung cancer stage and higher overall survival rate than patients diagnosed with bladder cancer first.     

Ribonucleotide reductase subunit M1 expression in resectable,muscle‐invasive urothelial cancer correlates with survival in younger patients

OBJECTIVE

To assess whether high ribonucleotide reductase subunit M1 (RRM1) expression in patients with resected, muscle‐invasive (T2–4NxM0) urothelial carcinoma (UC) correlated with longer overall survival (OS). RRM1 is the primary cellular target of gemcitabine and previous studies in resected early‐stage lung cancer have shown a survival benefit for patients with high expression.

PATIENTS AND METHODS

In all, 84 radical cystectomy specimens with muscle‐invasive UC were identified from existing tissue microarrays. The patients' medical records were retrospectively reviewed to confirm pathology and stage. Specimens were analysed for RRM1 expression using automated quantitative analysis. The median value of RRM1 was established a priori as the threshold for high and low expression.

RESULTS

The median age of the patients was 69 years. Stages were nearly equally distributed: 30%, 38%, and 32% for stage II, III, and IV, respectively. Most were high grade (99%) with no nodal involvement (69%). The median (range) OS was 2.0 (0–13.1) years. Tumoral RRM1 levels did not correlate with OS for the entire cohort, but when adjusted for age, high tumoral RRM1 expression in younger patients (aged <70 years) correlated with increased survival. Younger patients with high RRM1 expression had a median OS of 10.6 years compared with 1.6 years in older patients (P= 0.001). There was no difference in OS among low RRM1 expressors: 2.3 vs 1.6 years in younger and older patients, respectively (P= 0.22).

CONCLUSIONS

Our results suggest that high RRM1 expression may be prognostic for improved survival in patients with muscle‐invasive UC aged <70 years.