Carcinoma in situ as a prognostic factor for G3pT1 bladder tumours

G3pT1 bladder cancer has traditionally been regarded as a superficial tumour with a high risk of progression. We have studied 37 patients with initial G3pT1 bladder tumours treated between January 1981 and December 1985. They were divided into 2 groups according to the association with carcinoma in situ (Cis) at the time of diagnosis. Clinical behaviour was analysed at 5 years. The first group (without Cis) showed progression and recurrence rates similar to those of low grade, low stage bladder tumours. The second group (with Cis) had a similar rate of recurrence but their progression rate was 65%.     

Prognostic Significance of p53 Protein Accumulation in Stage pT1 Transitional Cell Carcinoma of the Bladder

Objective: Mutations in the tumour suppressor gene p53 results in the production of a mutant type, dysfunctional p53 protein which can readily be detected in the cell nucleus by immunohistochemical staining. This study aims to investigate the association of nuclear p53 protein accumulation with the clinical outcome of stage pT1 transitional cell carcinoma of the bladder which is renowned for high rates of recurrence and progression. Methods: TUR samples of the tumours from fifty-two patients with primary stage T1 bladder cancer were analyzed immunohistochemically using the standard avidin-biotin peroxidase method for nuclear p53 accumulation. Status of p53 immunostaining was correlated with tumour recurrence, disease progression and three-year survival of each patient. Results: The rate of tumour recurrence in pT1 bladder cancer was 36% in patients with tumours stained negatively for p53 protein and 78% in patients with tumours stained positively for p53 protein. Disease progression was seen in 15% of p53 (-) patients and in 56% of p53 (+) patients. Conclusions: In stage pT1 bladder tumours p53 nuclear accumulation indicates higher rates of tumour recurrence and disease progression. Accordingly, in patients who have pT1 bladder tumours with nuclear p53 accumulation, institution of more aggressive therapy should be considered and early radical therapeutic modalities should be offered to these patients.     

Intravesical Bacillus Calmette-Guerin treatment improves patient survival in T1G3 bladder tumours

OBJECTIVE: To study the clinical and pathological factors that affect recurrence, progression and survival in pT1G3 bladder tumours treated conservatively. MATERIAL AND METHODS: From January 1979 to December 1996, 80 patients were conservatively treated for pT1G3 bladder tumours. All patients were studied for potential prognostic factors such as: age, sex, previous tumour recurrence, tumour size, multiple tumours, carcinoma in situ, and intravesical instillations. A longitudinal, retrospective, observational and analytical study was conducted to evaluate four different types of events: recurrence, progression, overall survival, and disease-specific survival. The chi(2) (Fischer exact test) and student t tests were used to assess the prognostic value of the qualitative and quantitative variables. Estimations of the survival distributions were calculated according to the Kaplan-Meier method and compared with the Log rank test. Multivariate analysis of the data was performed with Cox proportional hazard models. RESULTS: Among the 80 patients, 67 (84%) were men and 13 (16%) were women, with median age of 65.5 years. The median tumour size was 20 mm, most had single tumour (58.8%) and carcinoma in situ was found in six patients (7.5%). Thirty patients were treated with transurethral resection (TUR) of the bladder tumour and 50 patients were treated with TUR followed by BCG. The two groups of patients were comparable and followed up during a median time of 61 and 65 months, respectively (p=0.454). Kaplan-Meier estimators and Log rank tests demonstrated that patients with TUR alone recurred (p<0.0001), progressed (p<0.040) and died (overall survival: p<0.009; disease-specific p<0.040) earlier than patients who received intravesical instillations of BCG. The results were confirmed with Cox models and odds-ratios are presented. CONCLUSION: In this study, BCG adjuvant immunotherapy was the only factor affecting recurrence, progression and survival. Conservative treatment using TUR followed by BCG may improve disease-specific survival.     

Aurora kinase B is an independent protective factor in superficial bladder tumours with a dysfunctional G1 checkpoint

OBJECTIVES

To investigate the clinical role of Aurora kinases (essential for regulating mitosis) in human bladder pathogenesis, by quantifying Aurora kinase A and B, phospho‐Aurora A, and phospho‐Rb and p53 in bladder tumours, analysing the correlations between expression and clinicopathological features.

PATIENTS AND METHODS

We evaluated levels of Aurora A, B, phospho‐Aurora A, phospho‐Rb and p53 in 73 superficial bladder tumours using tissue microarrays and immunohistochemistry, and correlated expression with pathological variables and clinical outcome.

RESULTS

None of the Aurora proteins, when analysed alone, significantly predicted either tumour recurrence or progression. In tumours with an aberrant G1 checkpoint, assessed by phospho‐Rb and p53 status, expression of neither Aurora A nor its phosphorylated form predicted either tumour recurrence or progression. Surprisingly, high expression of Aurora B in tumours with an aberrant G1 checkpoint significantly protected from tumour recurrence. On multivariate analysis, Aurora B was the only significant factor that predicted tumour recurrence in the presence of either phospho‐Rb or mutated p53. This difference was not evident in tumours with an intact G1 checkpoint.

CONCLUSIONS

High expression of Aurora B in superficial bladder tumours with an aberrant G1 checkpoint significantly protects patients from tumour recurrence. The potential application of nonspecific Aurora kinase inhibitors in non‐muscle‐invasive bladder cancer might be detrimental.     

Superficial (pT2a) and deep (pT2b) muscle invasion in pathological staging of bladder cancer following radical cystectomy

PURPOSE: We compared and evaluated clinical outcomes in patients with pathological superficial (pT2a) and deep (pT2b) invasion of bladder muscle with transitional cell carcinoma following radical cystectomy and urinary diversion. MATERIALS AND METHODS: From 1971 to 2001, 311 of 1,359 patients (23%), including 244 males (78%) and 67 females, were found to have pathological muscle invasive (pT2) bladder cancer following radical cystectomy. Of this group 147 patients (47%) had pT2a (superficial) and 164 (53%) had pT2b (deep) muscle invasive tumors. Overall 242 patients had no evidence of lymph node metastasis, including 127 with pT2a (86%) and 115 with pT2b (70%). A total of 69 patients (22%) had lymph node involvement, including 20 with pT2a (14%) and 49 with pT2b (30%). At a median followup of 14.3 years (range 0 to 30.1) clinical outcomes were determined, including recurrence-free and overall survival, and local vs distant recurrence. RESULTS: In the 311 patients with pT2 tumors 10-year recurrence-free and overall survival rates were 72% and 47%, respectively. There was a significantly higher risk of node positive disease with pT2b vs pT2a tumors (30% vs 14%, p <0.001). No significant difference was observed in 10-year recurrence-free survival in patients with pT2a node negative vs pT2b node negative tumors (84% vs 72%, p = 0.091). When comparing pT2a node positive vs pT2b node positive tumors, no significant difference was observed in 10-year recurrence-free survival (50% vs 48%, p = 0.84). Recurrence-free survival was significantly higher in patients with pT2 lymph node negative tumors than in those with pT2 lymph node positive tumors (79% vs 49%, p <0.001). Furthermore, these differences remained significant when stratified by pT2a and pT2b node negative vs positive disease. Local pelvic recurrence developed in 10 of 311 patients (3%) with pT2 disease, while 69 (22%) had distant metastatic disease. In patients with recurrence the local or distant recurrence site was not associated with tumor stage (pT2a vs pT2b p = 0.24) or lymph node status (node negative vs positive p = 0.37). CONCLUSIONS: In muscle invasive (pT2) bladder cancer treated with radical cystectomy there is a higher risk of lymph node positive disease in deep muscle (pT2b) vs superficial (pT2a) invasion. However, no apparent difference was observed in recurrence-free survival between pT2a (superficial) vs pT2b (deep) muscle invasive tumors when controlling for lymph node status. Recurrence-free survival is significantly improved in patients with pT2 lymph node negative tumors compared to survival in those with pT2 lymph node positive tumors. Patients with muscle invasive (pT2), lymph node negative tumors have excellent clinical outcomes following cystectomy, while those with muscle invasive (pT2), lymph node positive tumors have higher recurrence rates and should be considered for adjuvant treatment protocols.     

Management of T1G3 tumours of the bladder

T1G3 tumours are the most aggressive superficial tumours of the bladder, with a high risk of recurrence and progression. Complete endoscopic resection of the tumour is the first diagnostic and therapeutic step in T1G3 management. A second resection should be done at 1 month to avoid residual tumour and misdiagnosis of a muscle infiltrative cancer. As a result of treatment by instillations of Calmette and Guérin bacillus following endoscopic resection, a 5-year survival rate of 80% has been reported, with 50 to 60% of bladder preservation. BCG is the only conservative treatment that has proven effectiveness on both tumour recurrence and progression. Long term protocols seem to give the best results. Endovesical chemotherapy is not commonly used as its impact on progression has not been demonstrated. Radical cystectomy can be chosen as first line treatment in patients with particularly aggressive tumours. Long term and close surveillance should be achieved in every patient.     

Evaluation of P53 protein overexpression, Ki67 proliferative activity and mitotic index as markers of tumour recurrence in superficial transitional cell carcinoma of the bladder

OBJECTIVES: To confirm the interrelationship between p53, ki67, mitotic index with others known prognostic factors such us stage, grade, multifocality, tumour size, history of recurrence in transitional cell carcinoma (TCC) of the bladder and to determine the prognostic impact of p53, Ki67 and mitotic index in predicting recurrence in superficial bladder cancer. METHODS: Two hundred and fourteen patients with apparently superficial TCC of the bladder underwent TURBT and the 192 histologically Ta-T1 were divided into 104 primary lesions (group 1, mean follow-up 26 months) and 88 recurrent tumours (group 2, mean follow-up 28 months). Data concerning focality, tumour size, number of recurrences and recurrence-free survival were considered in each patients. All samples were immunohistochemically stained with p53 and Ki67 monoclonal antibodies. Mitotic index (MI) was calculated on haematoxylin and eosin stained sections. RESULTS: Recurrence-free survival was significantly lower in superficial recurrent tumours (group 2) compared with primary tumours (group 1). P53 staining was correlated with grade and stage for both 5 and 20% positivity thresholds. Ki67 and MI were significantly different over strata defined by stage, grade and focality in both patients groups but only Ki67 showed a correlation with p53 status. Recurrence-free survival could not be predicted either by p53 status or MI. A 20% cut-off level of Ki67 staining resulted a good predictor of recurrence in group 1 Ta-T1/G1-G2 tumours (p = 0.03). Only Ki67 and multifocality were found to be independent prognostic factors of recurrence in multivariate analysis. Stratifying Ta-T1/G1-G2 patients according to these variables, Ki67 provided a useful tool to predict early recurrence in monofocal lesions from both groups. CONCLUSIONS: P53 and MI despite a fairly good correlation with traditional prognostic factors in bladder TCC seem to play no role in the prediction of tumoural recurrence. A Ki67 index over 20% predicts those single well-differentiated (Ta-T1/G1-G2) tumours which are likely to recur within one year of treatment.     

Evaluation of multiple recurrence events in superficial bladder cancer patients treated with intravesical bacillus Calmette-Guérin therapy using the Andersen-Gill's model

To evaluate factors affecting recurrenceafter intravesical bacillus Calmette-Guérin(BCG) therapy (Tokyo 172 strain), we revieweddata for 101 patients with superficial bladdercancer (pTa [n = 80] and pT1 [n = 21]) treatedbetween 1985 and 1999. The median follow-upperiod was 58.9 months. Factors affecting thefirst tumour recurrence were evaluated usingCox's proportional hazards model and thoseaffecting multiple recurrence withAndersen-Gill's model. The 5-yearrecurrence-free rate was 63% for all 101patients. The recurrence frequency, defined astimes per 100 patient-months of follow-up,greatly decreased from 7.3 ± 9.6 (SD) beforethe instillation to 2.6 ± 5.6 after thetherapy (p < 0.0001). Patients with pT1tumours tended to have earlier recurrence thanthose with pTa tumours (p = 0.06). Multivariateanalysis using Cox's proportional hazards modelrevealed that a history of bladder cancer andpathological stage were independent factorsaffecting the first tumour recurrence after theBCG therapy. When multiple endpoints ofrecurrence were evaluated using theAndersen-Gill's model, number of tumours aswell as a history of bladder cancer andpathological stage demonstrated significantlinks to tumour recurrence after the BCGtherapy. The 5-year progression-free and 5-yearsurvival rates were 89.3% and 85.3% for allthe 101 patients, respectively. Becauseintravesical recurrence may involve multipleevents during the clinical course of patientswith bladder cancer, the Andersen-Gill's modelappears useful for evaluation of riskfactors.     

A clinical study of recurrence and progression of grade 3 superficial bladder tumor]

Forty-one patients who had grade 3, superficial, transitional cell carcinoma of the bladder were treated with transurethral resection of bladder tumor between January, 1986 and April, 1998. The clinicopathological studies were conducted on intravesical recurrence, disease progression, and prognosis using multivariate analyses. Intravesical recurrence was found in 18 patients (43.9%), and the recurrence-free rate was 77.0% for 1 year. The 3- and 5-year recurrence-free rates were 57.7% and 38.5% for patients with stage pTa disease, and 36.3% and 36.3% for patients with stawe pT1-disease. There was a significant difference between the recurrence-free rates in the patients with stage pTa disease and those with stage pT1 disease (p < 0.01). Disease progression was observed after a mean period of 14.2 months after treatment in 6 patients (14.6%) with pT1 tumors. Three of these patients died of cancer. In the multivariate analyses with clinical and pathological factors, bladder irritability, urine cytology after initial treatment, and tumor multiplicity were the factors contributing to a high risk for recurrence. Intravesical instillation with Calmette-Guerin bacillus was found to prevent recurrence. These results suggest that radical surgery should be performed in a timely manner in patients with G3-stage pT1 tumors because they have a higher risk of recurrence and progression as compared to patients with G3-stage pTa tumors.     

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

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

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.     

A re-staging transurethral resection predicts early progression of superficial bladder cancer

OBJECTIVE: To determine whether pathology on a re-staging transurethral resection (TUR) predicts the early progression of superficial bladder cancer. PATIENTS AND METHODS: In all, 710 patients presenting with multiple superficial bladder cancers were evaluated by re-staging TUR and followed for 5 years. Tumours were classified by stage as confined to mucosa (Ta) or invading submucosa (T1), and by grade (low- or high-grade). Pathology on re-staging TUR was correlated with the endpoints of tumour recurrence and stage progression. RESULTS: Of the 710 patients, 490 (69%) had a recurrence and 149 (21%) progressed over 5 years. Eighty patients had high-grade invasive (T1G3) cancer on re-staging TUR and 61 (76%) progressed to muscle invasion (median time to progression 15 months), compared with 88 of 630 (14%) who had no evidence of tumour (T0) or other than T1 tumours detected on re-staging TUR. CONCLUSION: A re-staging TUR identifies patients with superficial bladder cancer who are at high risk of early tumour progression.     

Clinical significance of interobserver differences in the staging and grading of superficial bladder cancer

OBJECTIVE: To assess the reliability of the histological diagnosis of bladder cancer by assessing the interobserver variability of staging and grading in pTa/pT1 tumours and evaluating the clinical significance of discrepancies. MATERIALS AND METHODS: All sections from 301 superficial bladder carcinomas were reviewed by one pathologist. The prognostic relevance of grade and stage from both the initial and review diagnosis were determined in 128 patients for whom there was long-term follow-up information. RESULTS: There were significant interobserver differences in both the grading and staging of tumours. From a total of 235 tumours that were initially considered pT1, the reviewer classified 35% as pTa, 56% as pT1, 6% as pT1- (at least pT1), and 3% as pT2-4. In 39% of all biopsies there were interobserver differences in tumour grade. The prognostic significance of grade and stage differed between the initial pathology report and the reviewer's diagnosis. The reviewer's staging allowed a better estimate of the risk of subsequent tumour progression than the initial staging. Progression was significantly more common in 49 tumours in which the reviewer agreed with stage pT1 than in 29 tumours that were down-staged from pT1 to pTa (P = 0.0116). However, the initial tumour grade (P = 0.0386) but not the reviewer's grade (P = 0.2645) was significantly linked to progression. CONCLUSIONS: These results show that grading and staging by different pathologists have varying prognostic implications. If possible, biopsies from bladder tumours should be independently evaluated by two different pathologists before radical therapy is administered.     

The optimum timing of radical cystectomy for patients with recurrent high-risk superficial bladder tumour

OBJECTIVE: To establish the optimum time of radical cystectomy (RC) for patients with recurrent high-risk superficial bladder tumours after the failure of intravesical therapy. PATIENTS AND METHODS: Among 318 patients with transitional cell carcinoma treated with RC and with no neoadjuvant therapy, there were 46 with clinical stage Ta, T1 or Tis refractory to transurethral resection associated with intravesical therapy. These patients had at least one of: (i) high-risk superficial bladder tumours after failure of two consecutive induction courses of intravesical therapy; (ii) superficial bladder tumours with prostatic stromal invasion; (iii) superficial bladder tumours with mucosa/ducts involvement after failure of one course of intravesical therapy; (iv) uncontrolled superficial tumours with transurethral resection associated or not with intravesical therapy. Progression and cause-specific survival of these patients were compared to those with muscle-invasive tumours. Univariate and multivariate analyses of predictive factors for cause-specific survival were also used in patients with superficial tumours. The incidence of significant prognostic factors was compared in both superficial and muscle-invasive tumours, as were the progression pattern and survival. RESULTS: The progression-free and cause-specific survival of patients with superficial tumours was 54% and 67%, respectively, with no significant difference from those with muscle-invasive tumours. In multivariate analysis, positive lymph-nodes and prostatic stromal invasion were significant and independent variables for survival. The incidence of positive lymph nodes was 15% vs 30% (P < 0.05) and of stromal invasion was 32% vs 1.5% (P < 0.001) in patients with superficial and muscle-invasive tumours, respectively. Accounting for the progression pattern in patients with superficial tumours, extravesical urothelial recurrence prevailed over local or distant recurrences (30% vs 15%), whereas in patients with muscle-invasive tumours the opposite occurred (5% vs 33%, respectively). The cause-specific survival of patients with superficial tumour and prostatic stromal invasion was one of three, and in those who developed extravesical urothelial recurrence was 28.5%. CONCLUSION: In patients with recurrent high-risk superficial bladder cancer after intravesical therapy, our criteria for RC were inappropriate, and patients had a survival rate similar to those with muscle-invasive tumours. RC might have been used too late, as there was a high incidence of prostatic stromal invasion and extravesical urothelial recurrence after RC. Both events seem to be responsible of the low cause-specific survival. Predictive factors for progression are needed to indicate early RC in patients with recurrent high-risk superficial tumours. From a previous analysis the pathological pattern of the clinical lack of response (T1, G3, bladder carcinoma in situ and prostate involvement) to intravesical therapy evaluated at 3 months might be important for predicting progression, and an early RC at that time might be useful.     

The long-term outcome in patients with superficial transitional cell carcinoma of the bladder: a single-institutional experience.

OBJECTIVE: To determine the natural history of transitional cell carcinoma (TCC) of the bladder, and to identify factors which place patients at lifelong risk of developing progression and dying from bladder carcinoma. PATIENTS AND METHODS: The long-term outcome was evaluated retrospectively in 231 patients with superficial bladder TCC, assessed for the first time within a 6-year period from 1981 to 1986, with a median follow-up of 108 months. Of 231 patients, 217 (94%) were initially treated by transurethral or segmental resection. RESULTS: Recurrence developed in 141 of 217 (65%) patients; the duration of the interval free of recurrence was significantly less for patients with initial G3 tumours than that for those with G1 (P<0.01) and for pT1 compared with pTa disease (P<0.01). The disease progressed in 42 of 231 (18%) patients. Differences in the progression-free interval between patients with G1 and G3 tumours, and with pTa and pT1 disease, were statistically significant (P<0. 005 and P<0.001, respectively). In 27 of 231 patients (12%), TCC of the bladder was the cause of death, whilst 118 (51%) died from unrelated causes. There were no deaths among patients with initial pTaG1 tumours, compared with 10 of 26 (38%) deaths in those with pT1G3 disease at presentation. CONCLUSION: The long-term prognosis is good for patients with pTaG1 tumours, whilst pT1G3 is a potentially aggressive disease. Lifelong endoscopic surveillance is mandatory in patients in whom new tumours are very active, at least in those of younger age. Routine cystoscopy can possibly be discontinued in patients with low-grade, low-stage disease in whom a low liability of recurrence has been shown during follow-up.     

Pathological stage review is indicated in primary pT1 bladder cancer

Study Type – Diagnosis (case series)
Level of Evidence 4

OBJECTIVE

To evaluate the effect of a pathology review on the clinical outcome of patients with primary pT1 bladder cancer (BC), as the clinical course of such patients is variable.

PATIENTS AND METHODS

The slides of 164 primary (first diagnosis) pT1 bladder tumours from two university hospitals were reviewed by one pathologist for stage and grade (World Health Organization 1973 and 2004). Patients were initially managed conservatively with bacille Calmette‐Guérin (BCG). Uni‐ and multivariate analyses compared the predictive value of age, gender, hospital, carcinoma in situ (CIS), tumour‐size, reviewed grade and reviewed stage.

RESULTS

With a mean follow‐up of 6.4 years, there was disease progression in 48 (29%) patients and 26 (16%) died from BC. Associated CIS was found in 55 (34%) patients. After reviewing the slides, 24 (15%) tumours were downstaged to pTa, 134 (82%) remained pT1 and six (4%) were upstaged to ≥pT2. The grade review resulted in 74 G2, 90 G3, 37 low‐grade and 127 high‐grade lesions for the two systems used. In multivariate analyses, reviewed stage (both P < 0.001) and CIS (P = 0.017 and 0.023) had independent significance for progression and disease‐specific survival, respectively.

CONCLUSION

A stage review is indicated in pT1 BC, as almost 20% of pT1 tumours were up‐ or downstaged, and the reviewed stage predicted the patient’s prognosis. Hence, pathology review identified patients with different prognoses who might benefit from other treatment strategies than BCG. We confirmed that CIS is an unfavourable sign in pT1 bladder cancer.     

The fate of G3pT1 bladder cancer

Poorly differentiated (G3) cancers are known to have a worse prognosis than other superficial bladder tumours. In the period 1976 to 1987, 53 patients with G3pT1 disease were treated by radical radiotherapy with a 5-year survival rate of 64%. Thirteen patients (25%) developed an invasive tumour during the follow-up period. The presence of secondary carcinoma in situ was associated with a poor prognosis. These results are better than those reported for transurethral resection alone and suggest that radiotherapy is the treatment of choice in G3 superficial tumours.     

p53 expression predicts progression and poor survival in T1 bladder tumours

OBJECTIVES: Histological grade (G) is the only parameter proved to have prognostic value for progression in T1 transitional cell carcinoma (TCC) of the bladder, although it is considered inaccurate to make clinical decisions on individuals. The aim of the present study was to evaluate the prognostic relevance of p53 expression in T1 TCC of the bladder. METHODS: Clinical records of 207 patients with T1 TCC of the bladder were reviewed for clinical parameters reported to influence the evolution of superficial bladder cancer. Among these 207 patients, 40 developed muscle-invasive disease (20 G2 and 20 G3). A retrospective case-control study was then carried out comparing the latter 40 tumours with 40 control tumours matched by grade, sex, age, number and size of the tumours, chemical exposure and presence of carcinoma in situ. p53 immunostaining with monoclonal antibody was performed in these two groups. RESULTS: Histological grade was the only clinical parameter that influenced evolution. p53 expression correlated with tumour progression, since it was observed in 21 out of 24 p53-positive tumours and in only 20 of 56 p53-negative tumours (p<0.0001), showing a specificity of 93. 5% and a sensitivity of 53%. p53 expression correlated as well with patient survival, being 39% in patients with p53-positive tumours and 80% in patients with p53-negative tumours at 60 months (p<0. 0001). CONCLUSIONS: p53 protein expression has prognostic value for survival and progression in T1 bladder tumours and can be used for early detection of poor-prognosis T1 bladder tumours.     

Results of adjuvant intravesical Bacillus Calmette-Guérin therapy for grade 3 superficial bladder cancer

To examine the incidence of recurrence, progression and survival in patients with grade 3 superficial bladder cancer after transurethral resection (TUR) and adjuvant intravesical instillation of Bacillus Calmette-Guérin (BCG), we retrospectively studied 39 patients with grade 3 superficial bladder cancer. Nineteen patients with high-grade superficial bladder cancer (pTa, pT1) and 5 patients with grade 3 carcinoma in situ (CIS) received intravesical instillation of BCG after transurethral resection of the bladder tumor (BCG group and CIS-BCG group). The Tokyo 172 strain BCG was given for 8 weeks, as a rule, in a dose of 80 mg in 40 ml of saline instilled into the bladder. As a control, 15 patients with grade 3 superficial bladder cancer who did not receive BCG therapy after TUR were compared (non-BCG group). Of the BCG group (n=19), 4 patients (21.1%) had recurrent tumor and 3 had invasive progression after BCG therapy and died as a result of tumor progression, while in the non-BCG group (n=15), 8 cases (53.3%) developed recurrence, only one case had progression and died of cancer. In the CIS-BCG group (n=5), 3 patients (60.0%) had recurrent tumor and 2 had invasive progression. Univariate analysis (Logrank test) demonstrated that tumor size and adjuvant instillation of BCG were associated with tumor recurrence except for carcinoma in situ, but tumor progression and survival did not differ significantly. Our results suggest that BCG therapy prevents grade 3 superficial bladder cancer (pT1, pTa) recurrence.     

Follow-up guidelines for nonmetastatic renal cell carcinoma based on the occurrence of metastases after radical nephrectomy.

OBJECTIVE: To define guidelines for the follow-up management of nonmetastatic renal cell carcinoma (RCC), by assessing tumour recurrences and the clinical course in patients who had undergone radical nephrectomy. PATIENTS AND METHODS: The records of 187 patients with pT1-3, N0-X, M0 RCC who underwent radical nephrectomy between 1982 and 1997 were reviewed prospectively. Clinicopathological variables were compared with the time of first recurrence, site of metastasis and reason for diagnosis. RESULTS: Metastases were diagnosed in 98 sites in 56 of the 187 patients (30%). The risk for developing metastases increased with stage; 80% of the patients had their metastases diagnosed within 3 years (median 14.5 months) after nephrectomy. The time to first diagnosis was longer for patients with pT1 tumours and for those with skeletal metastases. The cause-specific 5-year survival rate for pT1 tumours was 95%, for pT2 87% and for pT3 tumours 37%. All patients with diploid pT1-2 RCC survived, having a survival advantage over those with aneuploid pT1-2 tumours (P=0.018). Also, pT1-2 tumours of < 5 cm were associated with better survival rates. Among 74 patients with pT3 tumours, 45 got metastases; DNA ploidy in these tumours did not influence survival. Of 30 patients with lung metastases, 28 were diagnosed during follow-up, while 25 of 26 other metastatic sites were diagnosed because of symptoms. CONCLUSIONS: The risk for tumour progression depends mainly on stage; these results indicate no need for follow-up in patients with diploid pT1-2 tumours or with aneuploid pT1 tumours of < 5 cm. For patients with aneuploid pT1-2 tumours of > 5 cm and pT3 tumours, follow-up is indicated.