Staging Of Bladder Tumors Research Articles

Pretreatment p53 nuclear overexpression as a prognostic marker in superficial bladder cancer treated with Bacillus Calmette-Guérin (BCG).

Altered p53 gene product correlates with the stage and grade of bladder tumor, but its value as a predictor of BCG response has been disappointing. In order to revisit the prognostic value of pretreatment p53 nuclear overexpression for the BCG response, we studied a large cohort of consecutive patients with superficial bladder cancer treated with BCG. From 1988 to 2001, 102 patients with a history of multifocal, recurrent, and/or high-risk papillary transitional cell carcinoma or carcinoma in situ, were treated for the first time with BCG. p53 immunostaining was performed on paraffin-embedded tissues using monoclonal antibody DO7 and an automated immunostainer. Special attention was paid to the conditions of tumor fixation. p53 overexpression was defined as more than 20% tumor cells with p53-stained nuclei. Immunostaining was significantly higher for Ta/T1 G3 +/- Cis (p < 0.001), tumoral substage T1b (p = 0.001), grade 3 (p = 0.0001), and Cis (p = 0.002). Times to recurrence, progression and cancer death were shorter among patients with p53 overexpression (p = 0.03; p < 0.0001; p = 0.0003). In multivariate analysis, p53 overexpression was an independent predictor of recurrence (p = 0.0003) [RR = 0.15; 95%CI, 0.06 to 0.42]. Pretreatment p53 nuclear overexpression in superficial bladder tumors is associated with a high risk of disease recurrence, progression and cancer death after BCG therapy. Applying antibody DO7 with an automated immunostainer and stringent fixative conditions, p53 nuclear immunostaining yields clinically relevant information and may be a useful tool for selecting patients with superficial bladder cancer who might be resistant to BCG.

Association between glutathione S-transferase M1 and T1 polymorphisms and increased risk for bladder cancer in Korean smokers

We evaluated the relationship between polymorphisms in the GSTM1 and GSTT1 genes and smoking status in a case-controlled study of a Korean population. The GSTM1 and GSTT1 genotypes were determined using a polymerase chain reaction (PCR)-based method and prognostic factors, such as staging and grading were evaluated for 126 bladder cancer patients, and 204 control subjects. Smoking represented a high-risk factor (odds ratio (OR)=4.8, 95% confidence interval (CI)=2.9–8.0) for the patients with bladder cancer. The frequency of GSTM1 null individuals was higher than in the controls, but the differences were not statistically significant (OR=1.56, 95% CI=2.9–8.0). For Korean subjects who smoked more than 1 pack of cigarettes per year (PPY), the increased risk of bladder cancer was associated with the GSTM1 null genotype (OR=0.5, 95% CI=0.3–0.9). Low-stage bladder tumors were more common among the GSTM1 null genotypes (OR=2.3; 95% CI=1.1–5.5). This study suggests that in Korean subjects the GSTM1 null genotype may be associated with increased risk for bladder cancer, in a manner that appears to depend upon smoking status. And also, in bladder cancer patients the GSTM1 null genotype appears to be associated with a poorer prognosis with low stage bladder tumors.

Tumor suppressor role for myopodin in bladder cancer: loss of nuclear expression of myopodin is cell-cycle dependent and predicts clinical outcome

Myopodin is a dual compartment protein that displays actin-bundling activity and redistributes between the nucleus and the cytoplasm in a differentiation-dependent and stress-induced fashion. We evaluated myopodin expression in initiation and progression of bladder cancer. Normal urothelium expresses myopodin in the cytoplasm and nuclei. Invasive bladder tumors showed decreased nuclear myopodin expression as compared to superficial lesions. This loss of nuclear myopodin expression was significantly associated with histopathological stage, tumor grade and overall patient survival in bladder tumors contained in tissue microarrays. We identified a differential nuclear expression for myopodin among bladder cancer cell lines during cell-cycle. Myopodin was present in the nucleus during G1/S in cells derived from superficial and low-grade lesions but not in those derived from invasive tumors. Loss of nuclear myopodin expression could classify bladder tumors and bladder cancer cell lines based on their histopathology. Most importantly, patients with preserved nuclear myopodin expression showed a longer survival. Nuclear myopodin expression in the context of cell-cycle progression may prove useful for staging bladder tumors and suggest a tumor suppressor role of myopodin in bladder cancer.

Risk Factors for Patients With Pelvic Lymph Node Metastases Following Radical Cystectomy With En Bloc Pelvic Lymphadenectomy: The Concept of Lymph Node Density

We evaluated the clinical outcomes and risk factors for progression in a large cohort of patients with lymph node metastases following en bloc radical cystectomy and bilateral pelvic lymphadenectomy. From July 1971 through December 1997, 1,054 patients underwent radical cystectomy and bilateral pelvic-iliac lymphadenectomy for high grade, invasive transitional cell carcinoma of the bladder. Of these patients 244 (23%) with a median age of 66 years (range 36 to 90) had pathological lymph node metastases. Overall 139 of the 244 patients (57%) received some form of chemotherapy. At a median followup of greater than 10 years (range 0 to 28) outcomes data were analyzed in univariate analysis according to tumor grade, carcinoma in situ, primary bladder tumor stage, pathological subgroups, total number of lymph nodes removed and involved with tumor, and lymph node density (total number of positive lymph nodes/total number removed). In addition, the form of urinary diversion and the administration of chemotherapy were also evaluated. Multivariate analysis was then performed to analyze these variables independently. The incidence of positive lymph nodes increased with higher p stage and pathological subgroups. Of 669 patients 75 (11%) with organ confined primary tumors and 169 of 385 (44%) with extravesical tumor extension had involved lymph nodes. The median number of lymph nodes removed in the 244 lymph node positive cases was 30 (range 1 to 96), while the median number of positive lymph nodes was 2 (range 1 to 63). Overall recurrence-free survival at 5 and 10 years for the 244 patients with lymph node positive disease was 35% and 34%, respectively. Patients with lymph node positive disease and an organ confined primary bladder tumor had significantly improved 10-year recurrence-free survival compared with those with extravesical tumor extension (44% vs 30%, p = 0.003). The total number of lymph nodes removed at surgery was also prognostic. Patients with 15 or less lymph nodes removed had 25% 10-year recurrence-free survival compared with 36% when greater than 15 lymph nodes were removed. Recurrence-free survival at 10 years for patients with 8 or less positive lymph nodes was significantly higher than in those with greater than 8 positive lymph nodes (40% vs 10%, p <0.001). The novel concept of lymph node density was also a significant prognostic factor. Patients with a lymph node density of 20% or less had 43% 10-year recurrence-free survival compared with only 17% survival at 10 years when lymph node density was greater than 20% (p <0.001). On multivariate analysis the total number of lymph nodes involved, pathological subgroups of the primary bladder tumor, lymph node density and adjuvant chemotherapy remained significant and independent risk factors for recurrence-free and overall survival. Patients with lymph node tumor involvement following radical cystectomy may be stratified into high risk groups based on the primary bladder tumor, pathological subgroup, number of lymph nodes removed and total number of lymph nodes involved. Lymph node density, which is a novel prognostic indicator, may better stratify lymph node positive cases because this concept collectively accounts for the total number of positive lymph nodes (tumor burden) and the total number of lymph nodes removed (extent of lymphadenectomy). Future staging systems and the application of adjuvant therapies in clinical trials should consider applying lymph node density to help standardize this high risk group of patients following radical cystectomy.

Detection of mucin 7 gene expression in exfoliated cells in urine from patients with bladder tumor

Objectives To determine whether mucin (MUC) 7 gene expression can be used as a bladder tumor marker for transitional cell carcinoma in patients with bladder carcinoma. Methods Cells from the urine of 65 patients with bladder cancer, 15 patients with a negative bladder biopsy for bladder cancer, and 30 healthy volunteers were compared for the following parameters: tumor stage, grade, size, and number, urinary cytology, and expression of MUC7. Nested reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine MUC7 expression (348 base pairs). Results MUC7 in the urine samples of the control group was negative (no false-positive results, specificity 100%). Among the 15 patients with nonmalignant disease, MUC7 was negative in 13 (specificity 87%). In the 2 patients with positive MUC7, the histologic examination showed chronic inflammation. Among the 65 patients with bladder transitional cell carcinoma, MUC7 was positive in 44 (68%). Nested RT-PCR for MUC7 was positive in 25 (61%) of 41 with superficial stages (pTa and pT1) versus 16 (76%) of 21 patients with Stage pT2 or advanced stages. Nested RT-PCR for MUC7 was positive in 5 (42%) of 12 patients with grade 1 disease, 22 (65%) of 34 patients with grade 2 disease, and 17 (89%) of 19 patients with grade 3 disease. We demonstrated no correlation between MUC7 and the clinicopathologic features (tumor stage, grade, or size) of urinary bladder tumors. Conclusions Our results indicate that MUC7 is a potential marker for bladder cancer. This noninvasive detection method assesses urothelial cells from voided urine specimens using RT-PCR.

Value of Urethral Wash Cytology in the Retained Male Urethra After Radical Cystoprostatectomy

We determined the outcome in patients who underwent urethrectomy after cystectomy followed by routine urethral wash cytology versus those not followed by urethral wash cytology who presented with bleeding or urethral discharge. We retrospectively evaluated the outcome in post-cystectomy urethrectomy cases at our institution from 1994 to 2000. A total of 24 patients with a median age of 70.5 years underwent urethrectomy after cystectomy, including 17 due to asymptomatic, positive urethral wash cytology (group 1) and 7 who were not followed by urethral wash and presented with bleeding/urethral discharge (group 2). Median time from cystectomy to urethrectomy was 11.4 months (range 6.7 to 67.1). Median followup after cystectomy and urethrectomy was 37 and 27.7 months, respectively. Urethrectomy pathological evaluation showed pTis disease in cases 12 (50%), pT0 in 9 (37.5%) and pT1 in 3 (12.5%). Cystectomy pathology was organ confined (pT0, pTis and pT1-pT2b disease) in 12 cases (50%), nonorgan confined (pT3a-pT4) in 6 (25%) and pT any N1 in 5 (21%). Cystectomy pathology was unknown in 1 case. At the most recent followup there was no evidence of disease in 14 patients (58%), 5 (21%) were alive with disease, 3 (12.5%) were dead of disease, 1 (4%) was dead of other causes and disease status was unknown in 1 (4%). There was no statistical difference in survival in groups 1 and 2 when controlling for original bladder tumor stage. Cox regression analysis revealed that cystectomy pathology was the only statistically significant parameter of disease-free survival (p = 0.011), while urethrectomy pathology and followup method (urethral washing versus no washing) were not significant. There were no perioperative or postoperative complications and no patients died. There was no significant survival difference in patients followed and not followed with urethral washing. Longer followup and increased patient numbers are needed to determine the significance of these findings.

Conservative Elective Treatment of Upper Urinary Tract Tumors: A Multivariate Analysis of Prognostic Factors For Recurrence and Progression

We evaluate the safety and efficacy of conservative elective treatment of upper urinary tract tumors, and determine predictive factors for recurrence and progression to optimize indications of this type of treatment. Since 1984 we have performed a prospective study of conservative treatment of single, low grade and stage, less than 3 cm. upper tract tumors. The study includes 54 patients with a normal contralateral kidney who had been followed for more than 36 months. Open conservative surgery was performed in 31 cases and endourological surgery in 23. Minimum followup was 36 months, maximum 210 and mean 84.8. Univariate and multivariate analyses of recurrence and progression were performed in relation to age, sex, association with a bladder tumor, bladder tumor stage and grade, sequence of bladder tumor in relation to upper urinary tract tumor, number of previous bladder tumor recurrences, association with bladder carcinoma in situ, upper urinary tract tumor grade, stage, location, size and therapy, and upper urinary tract cytology. Of the 54 patients 19 (35%) had recurrence, which was bilateral recurrence in 4, and progression occurred in 9 (16%). At the end of analysis 44 (62.9%) patients were disease-free and alive at a mean time of 92.88 months, 13 (24%) died disease-free at a mean of 72.7 months and 7 (12.9%) died of disease at a mean of 97.85 months. Cause specific mortality occurred in 7 (12.9% cases). Among the 54 initially conservatively treated units 42 (77.7%) kidneys were ultimately preserved. On univariate and multivariate analysis tumor location in the renal pelvis and association with a previous multi-recurrent bladder tumor were variables significantly related to recurrence and progression, as well as bilateral recurrence. Conservative treatment is an optional approach for select upper urinary tract tumors. The strongest risk factors for recurrence and progression were association with a previous multi-recurrent bladder tumor and tumor location in the renal pelvis but these conditions were also the strongest risk factors for bilateral recurrence. Conservative treatment can also be recommended in these cases but only with compliant patients and close followup.

Correlation of Cystoscopy With Histology of Recurrent Papillary Tumors of the Bladder

We correlated individual urologist impressions of tumor stage and grade of recurrent papillary bladder tumors at cystoscopy with histological findings after transurethral resection to determine whether cystoscopy can reliably identify low grade, noninvasive papillary tumor for outpatient fulguration. A total of 144 recurrent papillary bladder tumors identified on outpatient flexible cystoscopy were classified as low grade and noninvasive (stage Ta grade 1), high grade and noninvasive (stage Ta grade 3) or invasive (stage T1). Voided urine cytology was also performed. The cystoscopic impression of each tumor was correlated with the final histological findings of tumor stage and grade after transurethral resection. Cystoscopy classified 97 tumors as stage Ta grade 1 and 47 as stage Ta grade 3 or stage T1. Cystoscopy correctly predicted the tumor stage and grade of 93% of stage Ta grade 1 and 99% of stage Ta grade 1 lesions associated with negative urine cytology. Urologists can usually identify noninvasive, low grade recurrent papillary tumors on followup cystoscopy that may be treated safely with outpatient fulguration.

The remnant urothelium after reconstructive bladder surgery.

The pathology of the remnant urinary tract in an increasing population of cystectomy patients with orthotopic and heterotopic bladder substitution due to primary bladder carcinoma, and its management is discussed. The incidence of urethral tumours in primary or recurrent bladder cancer in long-term studies is approximately 6% for male and 2% for female patients. Risk factors for urethral tumour occurrence are tumours at the bladder neck and recurrent multifocal tumours. CIS of the bladder not involving the bladder neck, and muscle invasive tumours with or without lymph node involvement are not significantly correlated with urethral cancer. Those patients at risk for urethral tumours need additional work-up (multiple urethral biopsies and/or urethral brushings, frozen section of the membranous urethra) before an orthotopic lower urinary tract reconstruction to the urethra should be considered. In a large series of male patients, the majority of patients with urethral tumours had a single conservative treatment session, and did not recur thereafter demonstrating the feasibility of a conservative approach for superficial urethral tumour recurrences in patients with an orthotopic neo-bladder to the urethra. The incidence of upper tract tumours following cystectomy and lower urinary tract reconstruction lies between 2.4-17%. In a group of 258 patients with an orthotopic bladder substitution, we have seen an incidence of 3.5%. Tumour multifocality, carcinoma in situ in the bladder and/or distal ureter, locally advanced bladder tumour stage, and invasion of the intramural ureter were seen as risk factors in some series. A tendency for a higher incidence can be seen in those series with longer follow-up. The median time between cystectomy and diagnosis of upper tract tumours lies between 8 and 69 months in most series. A longer observation period in larger numbers of patients with an orthotopic neo-bladder and longer survival rates in general after cystectomy may reveal an increase in the incidence of upper tract tumours over the next decade.

Functional analysis of the mismatch repair system in bladder cancer.

In bladder cancer the observed microsatellite instability indicates that mismatch repair deficiency could be a frequently involved factor in bladder cancer progression. To investigate this hypothesis we analysed extracts of seven bladder cancer cell lines and, as a novel approach, five clinical cancer samples for mismatch repair activity. We found that one cell line (T24) and three of the clinical samples had a reduced repair capacity, measured to ~20% or less. The T24 cell extract was unable to repair a G-G mismatch and showed reduced repair of a 2-base loop, consistent with diminished function of the MSH2-MSH6 heterodimer. The functional assay was combined with measurement for mutation frequency, microsatellite analysis, sequencing, MTT assay, immunohistochemical analysis and RT-PCR analysis of the mismatch repair genes MSH2, MSH3, MSH6, PMS1, PMS2 and MLH1. A >7-fold relative increase in mutation frequency was observed for T24 compared to a bladder cancer cell line with a fully functional mismatch repair system. Neither microsatellite instability, loss of repair nor mismatch repair gene mutations were detected. However, RT-PCR analysis of mRNA levels did detect changes in the ratio of expression of the Mut S and Mut L homologues. The T24 cell line had the lowest MSH6 expression level of the cell lines tested. Identical RT-PCR analysis of seventeen clinical samples (normal urothelium, 7; pTa low stage, 5; and pT1-4 high stage, 5) indicated a significant change in the expression ratio between MSH3/MSH6 (P< 0.004), MSH2/MSH3 (P< 0.012) and PMS2/MLH1 P< 0.005, in high stage bladder tumours compared to normal urothelium and low stage tumours. Collectively, the data suggest that imbalanced expression of mismatch repair genes could lead to partial loss of mismatch repair activity that is associated with invasive bladder cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com

Prognostic factors for survival and bladder recurrence in transitional cell carcinoma of the upper urinary tract.

Prognostic factors for survival in transitional cell carcinoma of the upper urinary tract have been extensively evaluated, but detailed analyses of patterns of bladder recurrence after surgery have been rare. The outcome and tumor recurrence of 93 patients with transitional cell carcinoma of the upper urinary tract surgically treated between 1975 and 1999 were reviewed, retrospectively. Disease-specific survival by pathologic stage and grade were analyzed by the Kaplan-Meier Prognostic factors for survival and bladder recurrence were examined by univariate and multivariate analysis. The 5-year disease-specific survival rates of the patients with pTa, T1 and T2 were 92.9%, 100% and 88.9%, respectively. However, that of the pT3 patients was 61.9% and the median survival of the pT4 cases was only 7 months. Bladder recurrence was seen in 40 cases and recurrences occurred within 1 year in 32 of these patients. The stage and grade of metachronous bladder tumors usually resembled those of primary tumors, but invasive recurrences were seen in 19% of recurrent cases with primary pTa, pT1 tumors. The significant prognostic factor for survival was pathologic stage (pT3, pT4), but no significant variables were detected for bladder recurrence by multivariate analysis. The prognosis of pT3, pT4 patients is poor and effective systemic adjuvant therapy is necessary. Invasive bladder recurrence occurred in 19% of patients with superficial primary tumors. As no significant prognostic variables for bladder recurrence were identified, careful follow up for bladder recurrence is important even if the primary tumors are non-invasive.

Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients.

To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes. All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients. A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node-negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node-negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node-negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P <.001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45%, respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P <.001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%). The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence. These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.

THE ROLE AND IMPACT OF PATHOLOGY REVIEW ON STAGE AND GRADE ASSESSMENT OF STAGES TA AND T1 BLADDER TUMORS: A COMBINED ANALYSIS OF 5 EUROPEAN ORGANIZATION FOR RESEARCH AND TREATMENT OF CANCER TRIALS

THE ROLE AND IMPACT OF PATHOLOGY REVIEW ON STAGE AND GRADE ASSESSMENT OF STAGES TA AND T1 BLADDER TUMORS: A COMBINED ANALYSIS OF 5 EUROPEAN ORGANIZATION FOR RESEARCH AND TREATMENT OF CANCER TRIALS

High-frequency endoluminal ultrasonography for staging transitional cell carcinoma of the bladder

Objectives. To assess the feasibility and limitations of endoluminal ultrasound (ELUS) for clinical staging of bladder tumors. Methods. From 1998 to 1999, 32 patients with transitional cell carcinoma of the bladder were evaluated by high-frequency ELUS using miniature ultrasound transducers (20 MHz, 5.1F or 7.2F) before transurethral resection. Clinical staging using ELUS was compared with the results of pathologic staging. Results. Seventeen (94%) of the 18 patients with superficial tumors on ELUS were confirmed by pathologic examination to have Stage pTa (n = 12) or Stage pT1 (n = 5) disease, and 11 (63%) of the 14 patients with muscle-invasive tumors on ELUS were confirmed by pathologic evaluation to have Stage pT2a (n = 2) or Stage pT2b (n = 9) disease. In all of the misdiagnosed patients, the tumor lacked a well-defined base and was larger than 2 cm in size. It was difficult to distinguish between Stage Ta and Stage T1 tumors because of the limited resolution of ELUS and between Stage T2a and Stage T2b tumors because of its low penetration. Conclusions. ELUS using a high-frequency (20 MHz), miniature ultrasound transducer is able to distinguish superficial tumors from those with muscle invasion. However, the lack of penetration of the sonographic beam places major limitations on the evaluation of the depth of the invasion in large (greater than 2 cm) tumors with a broad base.

Long-term follow-up of noninvasive bladder tumours (stage Ta): recurrence and progression.

To evaluate long-term recurrence-free and progression-free survival of noninvasive bladder tumours (stage Ta), and the significance of simple risk factors, including concomitant epithelial dysplasia. The study included 217 patients with primary noninvasive bladder tumour (stage Ta) who were followed routinely for up to 20 years. Voided urine cytology (VUC) and preselected site biopsies (PSB) were obtained prospectively to evaluate the significance of concomitant epithelial dysplasia. The mean follow-up was 84 months (maximum 238). Of all tumours, 39% did not relapse, a further 20% recurred infrequently (less than once a year) and 41% recurred frequently, amongst which the most frequent were multiple and early recurrent tumours; 42 (19%) tumours progressed to stage T1+ and 23 (11%) progressed further (stage T2+ or metastases). No grade 1 tumours became invasive. Positive VUC or PSB, a short recurrence-free period or multiplicity, and size > 3 cm were significant predictive factors. The treatment and surveillance of epithelium-confined bladder tumours are discussed. Concomitant dysplasia and early recurrence are associated with considerable risk of progression in the long-term follow-up in a group of otherwise low-risk superficial bladder tumours (stage Ta).

PROSTATIC TUMOR RELAPSE IN PATIENTS WITH SUPERFICIAL BLADDER TUMORS: 15-YEAR OUTCOME

Purpose We assessed the outcome of patients with superficial bladder tumors with relapse in the prostate and defined prognostic variables of survival. Materials and Methods A cohort of 186 men with superficial bladder tumors was followed for 15 years. Tumor relapse in the prostate was classified as noninvasive (prostatic urethra and ducts) or invasive (stroma) with intraurethral or direct prostatic invasion. Bladder tumor stage at the time of prostatic relapse was defined as confined or not confined to the bladder. The end point of the study was disease specific survival. The effects of covariates on survival were estimated on multivariate analysis. Results Of the 186 patients 72 (39%) had relapse in the prostate after a median followup of 28 months (range 3 to 216), including 45 (62%) with noninvasive prostatic tumor and 27 (38%) with stromal invasion. The survival rate was 82% in patients with prostatic urethra or duct involvement compared to 48% with stromal invasion. Intraurethral stromal invasion was associated with a 75% 15-year survival rate versus 9% for extravesical prostatic stromal invasion. Bladder tumor stage and prostatic stromal invasion were independent prognostic variables of survival. Conclusions The prostate is a frequent site of tumor relapse in patients with superficial bladder tumors followed for 15 years. Prostatic relapse may portend tumor invasion in the bladder and stromal invasion in the prostate, which significantly reduce survival.

Hydronephrosis as a prognostic indicator in bladder cancer patients.

Pathological stage is the standard measure of prognosis in patients who have undergone radical cystectomy for bladder cancer. Despite the development of new imaging techniques, clinical staging for bladder cancer continues to be inaccurate. We investigated whether the presence of unilateral or bilateral upper tract obstruction could accurately predict advanced cancer stage (extravesical extension, stage greater than p3b or N+). A retrospective study of 415 patients diagnosed with transitional cell carcinoma of the bladder who were treated with radical cystectomy between 1983 and 1993 was conducted. All patients were followed for survival. The criteria for analysis included hydronephrosis status (no obstruction, unilateral, bilateral) as well as pathological stage of the tumor. Of 415 patients 72% presented with no, 22.7% unilateral and 5.3% bilateral obstruction. Our results showed a significant correlation between hydronephrosis and advanced cancer stage (p <0.0001), and decreased patient survival (p <0.0001). More than 90% of patients with bilateral obstruction had disease with extravesical extension. Of the patients with unilateral obstruction a third had disease confined to the bladder with a significant proportion confined to the bladder mucosa. The presence of unilateral or bilateral hydronephrosis is a clinical datum that is already available to help accurately stage bladder tumors. The presence of bilateral obstruction is an ominous sign, while a significant proportion of patients presenting with unilateral obstruction have disease confined to the bladder.

HYDRONEPHROSIS AS A PROGNOSTIC INDICATOR IN BLADDER CANCER PATIENTS

Purpose Pathological stage is the standard measure of prognosis in patients who have undergone radical cystectomy for bladder cancer. Despite the development of new imaging techniques, clinical staging for bladder cancer continues to be inaccurate. We investigated whether the presence of unilateral or bilateral upper tract obstruction could accurately predict advanced cancer stage (extravesical extension, stage greater than p3b or N+). Materials and Methods A retrospective study of 415 patients diagnosed with transitional cell carcinoma of the bladder who were treated with radical cystectomy between 1983 and 1993 was conducted. All patients were followed for survival. The criteria for analysis included hydronephrosis status (no obstruction, unilateral, bilateral) as well as pathological stage of the tumor. Results Of 415 patients 72% presented with no, 22.7% unilateral and 5.3% bilateral obstruction. Our results showed a significant correlation between hydronephrosis and advanced cancer stage (p <0.0001), and decreased patient survival (p <0.0001). More than 90% of patients with bilateral obstruction had disease with extravesical extension. Of the patients with unilateral obstruction a third had disease confined to the bladder with a significant proportion confined to the bladder mucosa. Conclusions The presence of unilateral or bilateral hydronephrosis is a clinical datum that is already available to help accurately stage bladder tumors. The presence of bilateral obstruction is an ominous sign, while a significant proportion of patients presenting with unilateral obstruction have disease confined to the bladder.

Significance of Bladder Neck Involvement on Progression in Superficial Bladder Cancer

Objectives: To determine the significance of bladder neck involvement in predicting disease progression in superficial (stage Ta and T1) transitional cell carcinoma (TCC) of the urinary bladder. Patients and Methods: A series of 277 patients with newly diagnosed superficial TCCs of the bladder was reviewed, and disease progression (to T2 or worse) was considered. The significance of several risk factors including bladder neck involvement was assessed in univariate and multivariate analysis. Results: Progression occurred in 28 (10.1%) of 277 patients during a median follow-up period of 7.7 years. Nineteen died of bladder cancer. The following variables were found to be statistically significant at the univariate analysis (p < 0.05): irritative symptoms, urine cytology, tumor stage, involvement of the bladder neck, and tumor grade. Indeed, only involvement of the bladder neck, tumor stage, and grade retained their value as independent factors for progression at multivariate analysis. Patients were divided into three groups according to the number of independent risk factors they had. Groups having none, one, and two or three risk factors included 129, 99, and 49 patients with 5-year progression rates of 0.8, 4.6 and 27.5%, and 15-year rates of 4.0, 20.1 and 42.7%, respectively. Conclusion: Involvement of the bladder neck is a significant and independent risk factor for progression of superficial TCCs in addition to the histologic grade and stage. The combination of these three risk factors offers better prediction of progression in an individual patient.

High levels of transforming growth factor-alpha (TGF-alpha) mRNA may predict local relapses in early stage urinary bladder cancer.

Elevated expression of transforming growth factor-alpha (TGF-alpha) gene has been previously reported in some types of human neoplasms, but its role in the pathogenesis of bladder cancer has still not been investigated. In the present study, we analysed 28 samples of early stage bladder tumours for the presence of TGF-alpha mRNA using reverse transcription-polymerase chain reaction (RT-PCR). We detected TGF-alpha mRNA in 71% (20/28) of these samples. When we related the expression levels of TGF-alpha with local relapses of patients during a follow-up of 2 years, we found that a high TGF-alpha expression level in bladder cancer was significantly associated with local relapses in patients with early stage tumours. The appearance of early relapses in tumours with high TGF-alpha expression levels may suggest the existence of an additional marker in the prediction of local relapses in patients with superficial disease.