The prognostic value of E-cadherin, alpha-, beta-, and gamma-catenin in urothelial cancer of the upper urinary tract

OBJECTIVES: To determine the value of loss of the expression of E-cadherin and cadherin-associated molecules as useful markers for both prognosis and bladder recurrence in patients with upper urinary tract cancer. MATERIALS AND METHODS: In 61 paraffin-embedded nephroureterectomy specimens, the expression of E-cadherin and alpha-, beta-, and gamma-catenin was examined by immunohistochemical staining. To evaluate the prognostic significance, Kaplan-Meier survival curves were calculated and compared by the log-rank test. A multivariate test was performed to detect prognostic markers. RESULTS: Normal expression was found in 32 cases (52.5%) for E-cadherin, 41 cases (67.2%) for alpha-catenin, 42 cases (68.9%) for beta-catenin, and 31 cases (50.8%) for gamma-catenin. The expression patterns of E-cadherin and alpha-, beta- and gamma-catenin were significantly correlated with each other. Survival analysis showed a significant difference between normal and aberrant expression in each staining. Multivariate analysis revealed that tumor stage and the expression of E-cadherin were independent prognostic factors for cause-specific survival. In contrast, there was no significant correlation between the expression of E-cadherin and alpha-, beta-, and gamma-catenin and bladder recurrence. CONCLUSION: Our data suggest E-cadherin may be a good prognostic marker for patients with upper urinary tract cancer.     

The prognostic value of E-cadherin and the cadherin-associated molecules alpha-, beta-, gamma-catenin and p120ctn in prostate cancer specific survival: a long-term follow-up study

OBJECTIVES: To determine the value of loss of expression of E-cadherin and cadherin associated molecules as prognostic markers for prostate cancer patients in a long-term follow-up study. METHODS: Sixty-five prostate cancer specimens, obtained from patients with different stages of prostate cancer who underwent a radical prostatectomy or TUR-P between 1987 and 1991, were used for immunohistochemical analysis of the expression pattern of E-cadherin, alpha-, beta-, gamma-catenin and p120(ctn). Clinical records of these patients were studied for follow-up data and the prognostic value of expression of these adhesion molecules was determined by Kaplan-Meier survival analyses and multivariable proportional hazard regression analysis. RESULTS: Normal staining patterns were found in 36 cases (55.4%) for E-cadherin, 37 cases (56.9%) for alpha-catenin, 40 cases (61.5%) for beta-catenin, 25 cases (38.5%) for gamma-catenin, and 40 cases (61.5%) for p120(ctn). Overall, a strong correlation was found between the expression of E-cadherin and other cadherin-associated molecules. The 5-year survival rates for each staining were as follows: E-cadherin (normal 79.2%, aberrant 26.8%), alpha-catenin (normal 79.2%, aberrant 26.8%), beta-catenin (normal 73.1%, aberrant 27.3%), gamma-catenin (normal 86.4%, aberrant 37.1%), and p120(ctn) (normal 72.8%, aberrant 30.0%). There was a significant difference in survival between normal and aberrant expression in each staining (log rank P < 0.0001). The proportional hazard regression model including tumor stage and Gleason score revealed alpha-catenin expression as the best prognostic marker for patients with prostate cancer. CONCLUSIONS: Our data revealed a strong correlation between E-cadherin expression and other cadherin-associated molecules. Among these markers, alpha-catenin seems the best prognostic marker for prostate cancer specific survival. Larger studies are needed to confirm this result.     

The significance of E-cadherin and alpha-, beta-, and gamma-catenin expression in surgically treated non-small cell lung cancers of 3 cm or less in size

OBJECTIVES: Expression of the cell-cell adhesion molecules E-cadherin and alpha-, beta-, and gamma-catenin seems closely related to tumor invasiveness. The relationship between the expression and clinicopathologic characteristics in surgically resected non-small cell lung cancers of 3 cm or less in size was studied. The relationship to patient survival was analyzed. METHODS: A total of 115 patients with surgically resected lung cancers of 3 cm or less in size were enrolled in this study. Expression of E-cadherin and alpha-, beta-, and gamma-catenin was immunohistochemically measured. The chi(2) test was used to correlate this expression with clinicopathologic parameters. Their influence on patient survival was evaluated with the Cox proportional hazards model. RESULTS: There was a positive correlation between E-cadherin and catenin expression in lung cancers. In general, E-cadherin and catenin expression were greater in tumors that were either bronchioloalveolar carcinomas or adenocarcinomas, well differentiated, early stage, peripheral, and without vascular or pleural invasion. By using multicovariate analysis of patient survival, only early-stage and peripheral tumors were significantly favorable prognostic factors. Further analysis of the group of patients with early-stage disease showed that higher alpha-, beta-, or gamma-catenin expression was a favorable prognostic indicator. CONCLUSION: Expression of alpha-, beta-, or gamma-catenin can be used as a prognostic indicator in patients with surgically resected stage I non-small cell lung cancers of 3 cm or less in size.     

Expression status of E-cadherin and alpha-, beta-, and gamma-catenins in thymoma

BACKGROUND: A loss or dysfunction of E-cadherin or catenins, which maintain tissue integrity, is associated with an invasive phenotype of various solid tumors. Therefore, we analyzed the expression of E-cadherin and alpha-catenin, beta-catenin, and gamma-catenin in thymoma tissue specimens to investigate its clinical significance. METHODS: The expressions of E-cadherin and alpha-catenin, beta-catenin, and gamma-catenin in thymoma tissues were evaluated in 21 patients, including 9 epithelial predominant type, 5 lymphocytic predominant type, and 7 mixed type patients based on an immunohistochemical analysis using monoclonal antibodies, and the relationship between the expression status and clinicopathologic features was investigated. RESULTS: Reduced expressions were observed in 11 patients (52%) for E-cadherin, 10 (45%) for alpha-catenin, 6 (27%) for beta-catenin, and 10 (45%) for gamma-catenin. Such an expression status (reduced or preserved) of the molecules closely correlated with each other. The expression of E-cadherin was well preserved in 5 of 5 patients with lymphocyte predominant type whereas E-cadherin was reduced in 11 of 17 patients with other histologic subtypes. All of the 9 cortex type thymomas (B1 to 3) showed preserved expression of beta-catenin. There was no significant relationship among the expressions of the molecules and the Masaoka stage classification (I versus others). CONCLUSIONS: The status of expressions for these molecules may affect the degree of lymphoid infiltration while not affecting the degree of invasiveness in thymoma.     

Cell-cell adhesion molecules and signaling intermediates and their role in the invasive potential of prostate cancer cells

PURPOSE: The highly variable natural history of prostate carcinoma may be reflected in heterogeneity of invasive potential between tumors. MATERIALS AND METHODS: We have examined two prostate cancer cell lines of low invasive potential (CAHPV10 and PZHPV7) and three cell lines of high invasive potential (DU-145, PC-3, LNCapFGC), to determine whether specific adhesion molecule profiles correlated with their invasive behavior. RESULTS: Using an in vitro invasion assay, we demonstrated that DU-145, LNCapFGC and PC-3 cells were highly invasive compared with CA-HPV-10 and PZ-HPV-7 cells. LNCapFGC cells expressed high levels of E-cadherin, alpha-, beta- and gamma-catenin, desmoglein, desmoplakin and GSK3beta using immunoblotting. This was, in general, comparable to immunohistochemical staining. PC-3 cells had no E-cadherin or alpha-catenin, but expressed a high level of the HGF/SF receptor c-Met. In contrast, DU-145 cells were found to express E-cadherin and low levels for all other protein molecules, except c-Met. The DU-145 cell line also lacked alpha-catenin expression. In CA-HPV-10 and PZ-HPV-7 cells, there was no detection of APC, PECAM-1, P-cadherin or Wnt-1. DU-145, LNCapFGC and PC-3 cells formed cell-cell aggregates, which were reduced by inclusion of anti-E-cadherin antibody and the motogen HGF/SF. CONCLUSION: These results show that prostate cancer cells exhibit a diverse expression of cell-cell adhesion molecules and their signaling intermediates. The expression of these adhesion molecules bears an important relationship with the invasive phenotype of these cells.     

Cadherin-11 is expressed in detrusor smooth muscle cells and myofibroblasts of normal human bladder

OBJECTIVES: It has recently been found that detrusor smooth muscle cells and myofibroblasts are coupled via gap junctions. However, gap junctions cannot account for strong physical interaction between cells, which has prompted the search for intercellular adhesion molecules. Cadherin-11 is a candidate for such a molecule, since it mediates the interaction of dermal myofibroblasts in contractile wound granulation tissue. We therefore hypothesised that the physical adhesion between detrusor smooth muscle cells and myofibroblasts is mediated by cadherin-11. The aim of this study was to test this hypothesis. METHODS: Bladder biopsies from eight radical cystectomy specimens were snap-frozen, sectioned, and stained for E-cadherin; cadherin-11; alpha-catenin; beta-catenin; gamma-catenin; and smooth muscle cell/myofibroblast markers connexin-43, vimentin, desmin, smooth muscle actin, and smoothelin. Specimens were analysed by using binocular epifluorescent and confocal laser-scanning microscopy. RESULTS: Specific positive membranous expression of all adhesion complex molecules except E-cadherin was detected in detrusor suburothelial tissue. All biopsies showed a similar punctate pattern of expression for cadherin-11 within bundles of smooth muscle cells and a suburothelial layer of cells. Cadherin-11 was specifically located at the cell membrane, in distinct linear domains. CONCLUSIONS: To our knowledge this is the first time evidence has been provided for cadherin-mediated smooth muscle and suburothelial myofibroblast cell-cell interaction in the human bladder. Cadherin-11 most probably plays an important role in the intercellular physical coupling of detrusor smooth muscle cells and also of myofibroblasts.     

The Prognostic Value of E-Cadherin, α-, β-, and γ-Catenin in Urothelial Cancer of the Upper Urinary Tract

Objectives

To determine the value of loss of the expression of E-cadherin and cadherin-associated molecules as useful markers for both prognosis and bladder recurrence in patients with upper urinary tract cancer.

Materials and methods

In 61 paraffin-embedded nephroureterectomy specimens, the expression of E-cadherin and α-, β-, and γ-catenin was examined by immunohistochemical staining. To evaluate the prognostic significance, Kaplan-Meier survival curves were calculated and compared by the log-rank test. A multivariate test was performed to detect prognostic markers.

Results

Normal expression was found in 32 cases (52.5%) for E-cadherin, 41 cases (67.2%) for α-catenin, 42 cases (68.9%) for β-catenin, and 31 cases (50.8%) for γ-catenin. The expression patterns of E-cadherin and α-, β- and γ-catenin were significantly correlated with each other. Survival analysis showed a significant difference between normal and aberrant expression in each staining. Multivariate analysis revealed that tumor stage and the expression of E-cadherin were independent prognostic factors for cause-specific survival. In contrast, there was no significant correlation between the expression of E-cadherin and α-, β-, and γ-catenin and bladder recurrence.

Conclusion

Our data suggest E-cadherin may be a good prognostic marker for patients with upper urinary tract cancer.     

E-cadherin immunostaining of bladder transitional cell carcinoma, carcinoma in situ and lymph node metastases with long-term followup

PURPOSE: We analyze the expression of E-cadherin in bladder transitional cell carcinoma, areas of carcinoma in situ and lymph node metastases, and determine the value of E-cadherin immunoreactivity for predicting disease progression and survival of patients with bladder transitional cell carcinoma. MATERIALS AND METHODS: The study group consisted of 77 patients who underwent radical cystectomy. Formalin fixed paraffin sections were processed with a hot, citric acid antigen retrieval method, followed by immunostaining with anti-E-cadherin monoclonal antibody and a standard avidin biotin complex technique. E-cadherin expression was also evaluated in carcinoma in situ sections (18) and in regional lymph node metastases (17). RESULTS: Loss of normal membrane E-cadherin immunoreactivity was found in 59 (77%) patients. Abnormal expression of E-cadherin was associated with muscle invasive disease (p = 0.010) and lymph node metastasis (p = 0.044). Of the 18 carcinoma in situ specimens 15 (83%) and of the 17 metastatic lymph nodes 13 (76%) had abnormal E-cadherin expression. Concordance rates of E-cadherin status in carcinoma in situ areas and metastatic lymph nodes with the primary tumors were 85% and 88%, respectively. At a median followup of 128 months, abnormal E-cadherin expression was significantly associated with disease progression (p = 0.0219) and bladder cancer specific survival (p = 0.037). E-cadherin expression and pathological stage but not grade were independent predictors of disease progression (p = 0.042, 0.047 and 0.158, respectively). CONCLUSIONS: In bladder cancer altered E-cadherin expression is associated with the degree of invasiveness, lymph node metastasis and increased risk of death from bladder cancer. Furthermore, E-cadherin status is an independent predictor of disease progression in patients treated with cystectomy for transitional cell carcinoma of the bladder.     

Correlation of cyclooxygenase-2 expression with molecular markers,pathological features and clinical outcome of transitional cell carcinoma of the bladder

PURPOSE: We investigated the relationship between cyclooxygenase-2 (COX-2) expression and molecular alterations commonly found in transitional cell carcinoma (TCC) of the bladder and determined whether COX-2 immunoreactivity is associated with cancer stage, progression and survival in patients undergoing radical cystectomy. MATERIALS AND METHODS: Immunohistochemical staining for COX-2 was done in archival tumor specimens from 80 patients who underwent radical cystectomy. Immunoreactivity was categorized as positive (reactivity in greater than 10% tumor cells) or negative. Microvessel density, E-cadherin, pRB, p16, p21, p53 and transforming growth factor (TGF)-beta1 and its receptors (types I and II) were also studied because evidence suggests a biological association between COX-2 and alteration of these molecules. RESULTS: COX-2 was over expressed in 62 patients (78%). COX-2 over expression was associated with muscle invasive pathological stage (p = 0.022), TGF-beta1 over expression (p = 0.004), decreased E-cadherin expression (p < 0.001), and altered expression of pRB (p = 0.003) and p16 (p = 0.006). At a median followup of 101 months COX-2 over expression was associated with disease progression (p = 0.038) and bladder cancer specific survival (p = 0.042). However, when adjusted for the effects of standard pathological features, only lymph node metastasis was associated with bladder cancer progression (p = 0.027) and mortality (p = 0.042). CONCLUSIONS: COX-2 is commonly expressed in patients with bladder TCC. Using the cutoff of 10% abnormal COX-2 expression is associated with the degree of invasiveness, alterations in TGF-beta1 and pRB/p16 pathways, and loss of cell adhesion. While COX-2 expression has limited prognostic value in patients with bladder TCC, it may serve as a target for therapy with selective COX-2 inhibitors.     

Cadherins and catenins in clival chordomas: correlation of expression with tumor aggressiveness

The local invasiveness and occasional rapid growth of chordomas, despite optimal treatment, highlight the need to develop ways to predict their biologic behavior. Alterations in adhesion proteins have been shown to participate in proliferation, invasiveness, and metastasis in epithelial tumors. We therefore analyzed the expression of E-cadherin, N-cadherin, as well as their cytosolic binding proteins alpha-catenin, beta-catenin, and gamma-catenin, in 51 paraffin archived and 17 cryopreserved chordoma specimens. In the majority of chordomas, E-cadherin and N-cadherin expression was inversely correlated, whereas beta-catenin and gamma-catenin expression was directly correlated. By multivariate analysis, N-cadherin up-regulation correlated with a diminished recurrence-free survival, and E-cadherin down-regulation strongly correlated with increased probabilities of death as determined by the Kaplan-Meier log-rank test. There was a 3.28-fold increased probability of having a tumor recurrence and a 10.98-fold increased probability of dying when, respectively, N-cadherin was up-regulated and E-cadherin down-regulated. These results suggest that changes in the relative expression of the cadherin-catenin complex reflect chordoma aggressiveness; and that decreased expression of E-cadherin and increased expression of N-cadherin may underlie the transition from a less to a more aggressive tumor phenotype.     

膀胱癌合并上尿路积水患者行根治术的预后分析

目的 探讨术前合并上尿路积水对根治性膀胱切除患者预后的影响.方法 回顾性分析从2003年1月至2010年5月期间126例行根治性膀胱切除术患者的资料,上尿路积水39例(31.0%),单因素分析上尿路积水对膀胱癌患者术后无复发生存率的影响,多因素分析上尿路积水、病理T分期和盆腔淋巴结转移情况等因素对膀胱癌根治术患者术后预...     

Lokal fortgeschrittenes oder metastasiertes Harnblasenkarzinom Aktuelle Aspekte in der Therapie

The prognostic factors for infiltrating tumors established by the TNM system in 1997 include: Depth of infiltration, degree of differentiation, status of lymph nodes distant metastases. Of the additional factors investigated, only tumor size and hydronephrosis appear to be of prognostic significance. In the scope of molecular markers, the loss of expression of the epithelial cell-cell adhesion molecule E-cadherin signals an unfavorable clinical course. In cases of carcinoma of the urinary bladder without metastases (T2-4,N0,M0), radical cystectomy is the therapy of choice. A preceding neoadjuvant systemic regimen of chemotherapy with three cycles of M-VAC (methotrexate, vinblastine, adriamycin, cisplatin) significantly improves the survival rate. In patients with locally advanced urinary bladder carcinoma, however, adjuvant systemic chemotherapy with M-VAC after cystectomy and lymphadenectomy offers no advantages for survival. Quality of life in patients with metastatic bladder cancer disease is improved by new cytotoxic drugs, i.e. gemcitabine or taxanes.     

The role of p53, bcl-2 and E-cadherin expression in predicting biochemical relapse for organ confined prostate cancer in Taiwan

PURPOSE: We evaluated the prognostic significance of p53, bcl-2 and E-cadherin immunoreactivity for organ confined prostate cancer after radical prostatectomy. MATERIALS AND METHODS: The medical records on 70 pT2 prostatic adenocarcinomas were analyzed retrospectively. Radical prostatectomy specimens were stained using antip53 (DO7), antibcl-2 (124) (Dako, Glostrup, Denmark) and antiE-cadherin (HECD-1) (R & D Systems, Abingdon, United Kingdom) antibodies. Biochemical relapse was defined as 2 consecutive elevations in serum prostatic specific antigen (PSA) higher than 0.2 ng/ml. The prognostic significance of Gleason grade, PSA, and p53, bcl-2 and E-cadherin expression was assessed. RESULTS: While p53 immunoreactivity was identified in 16 patients (22.9%), only 3 tumors (4.3%) expressed bcl-2. Aberrant E-cadherin expression was noted in 39 tumors (55.7%). At a median followup of 36.5 months 21 patients (30%) experienced biochemical relapse. There was a significantly higher biochemical failure rate in patients with abnormal bcl-2 and E-cadherin expression (log rank test p = 0.024 and 0.003, respectively). On multivariate analysis bcl-2 and E-cadherin contributed independently to the prediction of PSA relapse (p = 0.017 and 0.005, respectively). CONCLUSIONS: We noted that bcl-2 and aberrant E-cadherin expression are independent factors predicting biochemical relapse in stage pT2 prostatic cancers.     

Detailed analysis of histopathological parameters in radical prostatectomy specimens and PCA3 urine test results

BACKGROUND: Due to the drawbacks of serum prostate-specific antigen, there is an ongoing search for new diagnostic and prognostic prostate cancer (PCa) markers. PCA3 has proven to be of value in the diagnosis of PCa. However, so far few attempts have been made to investigate the prognostic value of PCA3. Our objective was to further investigate the prognostic value of PCA3. METHODS: In this study we correlated the PCA3 score in urinary sediments after digital rectal examination in 62 men with the classical prognostic parameters assessed in radical prostatectomy specimens (i.e. Gleason score, pathological tumor stage and total tumor volume) and moreover, with the expression of three immunohistochemical markers for PCa biological aggressiveness (i.e. E-cadherin, alpha-catenin and EZH2). The results from this study serve as a reflection on and a valuable adjunct to recently published results. RESULTS: We did not find a significant correlation of the PCA3 score with the classical prognostic parameters assessed in radical prostatectomy specimens or the expression of the immunohistochemical markers for PCa biological aggressiveness. However, we did observe a trend for a higher PCA3 score in significant PCa versus insignificant PCa, aberrant E-cadherin staining versus normal E-cadherin staining and increased EZH2 staining versus normal EZH2 staining. CONCLUSIONS: In this study we could not prove the prognostic value of PCA3. Further research with large numbers of men and adequate follow-up is needed to provide a definitive answer to the question if PCA3 is not only a diagnostic but also a prognostic PCa marker.     

Prognostic factors of outcome after radical cystectomy for bladder cancer: a retrospective study of a homogeneous patient cohort

PURPOSE: Pathological predictors of outcome for patients undergoing radical cystectomy for bladder cancer are needed as few data are available in the literature. We retrospectively analyzed a homogeneous and contemporary series of patients treated with radical surgery as monotherapy for bladder cancer to identify the independent predictors of survival. MATERIALS AND METHODS: We evaluated 369 of 535 patients with bladder cancer treated with radical cystectomy, pelvic node dissection and urinary diversion by the same staff at a single institution between February 1982 and February 1994. Patients treated with radiation therapy and/or chemotherapy, and those who did not undergo formal pelvic node dissection were excluded from study. The end point of univariate and multivariate analyses was the overall 5-year survival. RESULTS: Univariate analysis revealed that tumor stage, nodal involvement, ureteral obstruction, and vascular, lymphatic and perineural invasion were prognostic predictors of survival (p <0.05). However, only tumor stage (p <0.0000) and nodal involvement (p <0.0000) were independent prognostic variables of survival on multivariate analysis. CONCLUSIONS: Tumor stage and nodal involvement are the only independent predictors of survival to be used to select the optimal therapy after radical cystectomy, stratify patients in controlled trials and evaluate new prognostic factors.     

Costs of radical cystectomy

OBJECTIVE: The total costs of radical cystectomy comprise a significant part of the total costs of bladder cancer treatment. The aims of this study were to determine the costs of cystectomy, with and without complications, and to investigate related prognostic factors. MATERIAL AND METHODS: The clinical records and relevant economic files of 70 consecutive patients operated on between 1994 and 1998 were studied. Uni- and multivariate analyses were performed on 22 variables of possible prognostic significance to high total costs. RESULTS: The total (median) costs for 53 uncomplicated and 17 complicated cystectomies were 181,096 and 290,625 SEK, respectively. The preoperative variables (patient characteristics) had no or minimal prognostic significance for high total costs. High peri-operative blood loss was the most important factor associated with high total hospital costs for radical cystectomy. CONCLUSIONS: Total costs may be very high for a cystectomy with complications. Peri-operative blood loss was the most important factor associated with high total hospital costs for radical cystectomy due to bladder cancer. If the amount of bleeding can be influenced then substantial reductions in the total costs of cystectomy would seem possible.     

Prognostic significance of vascular invasion in patients with bladder cancer who underwent radical cystectomy

BACKGROUND: The objective of this study was to determine whether vascular invasion (i.e. lymphatic and blood vessel invasion) could be a useful prognostic predictor in patients with locally invasive transitional cell carcinoma (TCC) of the bladder who underwent radical cystectomy. METHODS: This series included 114 consecutive patients undergoing radical cystectomy for primary TCC of the bladder between November 1989 and July 2003. Several clinicopathological characteristics of these patients were analyzed, focusing on the association between vascular invasion and disease recurrence after radical cystectomy. RESULTS: Lymphatic and blood vessel invasions were detected in 55 (48.2%) and 33 (29.8%) specimens, respectively. Lymphatic invasion was significantly associated with pathological stage, tumor grade, lymph node metastasis, blood vessel invasion and disease recurrence, whereas blood vessel invasion was significantly related to pathological stage, lymph node metastasis, lymphatic invasion and disease recurrence. Recurrence-free survival in patients with lymphatic invasion was significantly lower than that in those without lymphatic invasion, and a similar significant difference in recurrence-free survival was observed between patients with and without blood vessel invasion. However, multivariate analysis using the Cox proportional hazards model showed that only pathological stage and lymph node metastasis could be used as independent predictors for disease recurrence after radical cystectomy. CONCLUSIONS: Despite a significant association between several prognostic parameters, vascular invasion was not an independent predictor of disease recurrence; therefore, if there are other conventional parameters available, there might not be any additional advantage to considering the presence of vascular invasion when predicting the prognosis of patients undergoing radical cystectomy for TCC of the bladder.     

Immunohistochemical studies of p53, Ki-67, E-cadherin and beta-catenin on renal pelvic and ureteral cancers

PURPOSE: We reviewed prognosis and bladder recurrence of 31 patients with renal pelvic and ureteral cancer concerning clinicopathological and immunohistochemical factors. METHODS: The patients consisted of 19 males and 12 females. The median age was 69 years, ranging from 43 to 84 years. Median follow-up period was 79 months. Immunohistochemistry for p53, Ki-67, E-cadherin and beta-catenin was performed on sections from tumor tissue. RESULTS & CONCLUSIONS: The overall 5-year cause-specific survival rate was 77.4%. Univariate analysis indicated tumor number, grade, infiltrating pattern, lymphatic involvement to be significant prognostic factors. Moreover, multivariate analysis with Cox's proportional hazard model revealed tumor number and lymphatic involvement to be independent prognostic factors for cause-specific survival rate. The overall 5-year bladder recurrence free rate was 60.9%. Univariate analysis revealed expression of E-cadherin to be a significant factor for bladder recurrence free rate.     

Effectiveness of neoadjuvant chemotherapy for the patients with locally invasive bladder cancer

OBJECTIVE: To know the survival and prognostic factors of the patients who received radical cystectomy with or without neoadjuvant cisplatin-based chemotherapy. METHODS: Between 1977 and 2001, 201 patients underwent radical cystectomy at Yokohama City University and Yokosuka Kyosai Hospital whose tumor were clinically diagnosed as locally invasive bladder cancer (T2-4NxM0). Survival rates and 9 prognostic factors (Age, Size, Multiplicity, Type, Grade, p-stage, n,neoadjuvant chemotherapy, adjuvant chemotherapy) were analysed by Kaplan-Meier methods and Cox-proportional hazard model. RESULTS: The independent prognostic factors of these patients were size, multiplicity, type, grade, p-stage, n, neoadjuvant by univariate analysis. Of these 7 factors, n, neoadjuvant, p-stage and size are significant by multivariate analysis. Survival of the patients who received neoadjuvant cisplatin-based chemotherapy followed cystectomy is better than cystectomy only group by Kaplan-Meier method. CONCLUSIONS: From these rusults, neoadjuvant cisplatin-based chemotherapy play some role for survival of the patients with invasive bladder cancer.     

A study of the morbidity,mortality and long-term survival following radical cystectomy and radical radiotherapy in the treatment of invasive bladder cancer in Yorkshire

OBJECTIVES: To study the morbidity of radical cystectomy and radical radiotherapy in the treatment of patients with invasive carcinoma of the bladder and to report the long-term survival following these treatments. PATIENT AND METHODS: 398 patients with invasive carcinoma of the bladder treated between 1993 and 1996 in the Yorkshire region were studied. Of 398 patients studied, 302 patients received radical radiotherapy and 96 underwent radical cystectomy. A retrospective review of patients' case notes was performed to construct a highly detailed database. Crude estimates of survival differences were derived using Kaplan-Meier methods. Log-rank tests (or, where appropriate, Wilcoxon tests) were used to test for the equality of these survivor functions. These functions were produced as all-cause survival. The proportional hazards regression modelling was used to assess the impact of definitive treatment on survival. A backwards-stepwise approach was used to derive a final predictive model of survival, with likelihood ratio tests to assess the statistical significance of variables to be included in the model. RESULTS: The patients undergoing radiotherapy were significantly older (mean age: 71 years versus 66 years), but no difference was identified in the distribution of American Society of Anaesthesiologists (ASA) grades in the two treatment groups. The stage distribution of cases in the treatment groups was not significantly different. Significant treatment delays were observed in both treatment groups. The median time from being seen in the clinic to transurethral resection of bladder tumour (TURBT) and subsequent radical treatment (cystectomy or radiotherapy) was 4.3 and 9 weeks, respectively. Age was the most significant independent factor accounting for treatment delays (p < 0.001). The 30-day and 3-month treatment-associated mortality for radical cystectomy and radiotherapy was 3.1% and 8.3% and 0.3% and 1.65%. Of the patients who received radiotherapy, 57 (18.8%) were subsequently subjected to a salvage cystectomy. For these 57 patients, 30-day and 3-month mortality after the salvage cystectomy were 8.8% and 15.7%. Gastrointestinal complications were the major source of early morbidity after primary and salvage cystectomy. Bowel leakage occurred in 3% following radical and 8.7% after salvage cystectomy. Bowel complications (leakage and obstruction) were the major cause of death following salvage cystectomy. No specific cause was predominant in those undergoing radical cystectomy with intestinal anastomotic leakage and urinary leakage accounting for one death each. Exacerbation of co-morbid conditions accounted for the remaining causes of mortality. Urinary leakage occurred in 4% following both forms of cystectomy. Recurrent pyelonephritis and intestinal obstruction were responsible for the majority of complications in the follow-up period. Bladder and gastrointestinal complications accounted for the majority of complications following radical radiotherapy. Some degree of irritative bladder and rectal were noted commonly. Severe bladder problems, which rendered the bladder non-functional or required surgical correction, occurred in 6.3% of patients. 2.3% of patients underwent surgery for bowel obstruction related to radiotherapy induced bowel strictures. Following radiotherapy, 43.6% of patients had a recurrence in the bladder at varying intervals post-treatment. Of these, 40% had > or =T2 disease. The 5-year survival following radiotherapy (with or without salvage cystectomy) was 37.4% while 36.5% of patients were alive 5 years after radical cystectomy. There was no statistically significant difference in the overall 5-year survival figures between the two primary treatments. Tumour stage, ASA grade and sex were the only independent predictors of 5-year survival on multivariate analysis. CONCLUSIONS: This retrospective regional study shows that there is no significant difference in the 5-year survival of patients with invasive bladder cancer treated with either radical radiotherapy or radical cystectomy. All forms of radical treatment for bladder cancer are associated with a significant treatment-associated morbidity and mortality. Gastrointestinal complications were responsible for the majority of complications. The treatment-associated mortality at 3 months was two- or three-fold higher than the 30-day mortality; emphasising its importance as an indicator of the true risks of cystectomy. The clinical T stage, the sex and the ASA grade of the patient were the only independent predictors of survival. The data in this series suggests that radical radiotherapy and radical cystectomy should be both considered as valid primary treatment options for the management of invasive bladder cancer.