Recurrence, progression and survival in bladder cancer. A retrospective analysis of 232 patients with greater than or equal to 5-year follow-up

A retrospective study of 232 bladder tumours with minimum follow-up 5 years is presented. The carcinoma was superficial in 66%, muscle-invasive in 31% and could not be staged in 3%. Primary treatment was mainly transurethral resection for superficial tumour, but was cystectomy or radiotherapy in 22 of 29 T1 G3. Of the superficial tumours, 71% recurred. Progression to higher T stage occurred in 15% of Ta and 29% of T1 tumours, and half of these patients died of bladder cancer. The corrected 5-year survival rates in grades 1, 2A, 2B and 3-4 were 96, 84, 64 and 43%, and in stages Ta, T1, T2 and T3 they were 94, 69, 40 and 31%. All patients with T4 tumour died within 4 years. Among the 45 patients with 40 Gy irradiation + cystectomy, the corrected 5-year survival rate was 83% in superficial and 64% in muscle-invasive tumours, and among the 38 with radical radiotherapy the rates in T1-3 were 46, 36 and 13%. Transurethral resection was successful in most Ta cases. Most T1 tumours were, like T2-4, of higher grade than Ta. Prognosis was worse in T1 than in Ta. After progression to muscle-invasive disease, even during close follow-up the outlook was poor, as poor as for patients with primary muscle-invasive disease.     

Radical transurethral resection and chemotherapy in the treatment of muscle-invasive bladder cancer: a long-term follow-up

OBJECTIVE: To evaluate the treatment of patients with muscle-invasive bladder cancer (T2-T4a) by radical transurethral resection (TUR) and cisplatin-methotrexate systemic chemotherapy. PATIENTS AND METHODS: Fifty patients with transitional cell carcinoma (TCC) of the bladder (nine T2, 36 T3 and five T4a) were treated by 'complete' TUR of the bladder tumour followed by 2-6 cycles of cisplatin (70 mg/m2) and methotrexate (40 mg/m2) chemotherapy. The median (range) tumour size was 3 (1-7 cm). In six patients, attempted TUR at the dome of the bladder led to intraperitoneal perforation; the tumour was excised by partial cystectomy in these patients. The latest follow-up results from 57 patients treated by radical TUR and methotrexate alone, reported previously, are included. RESULTS: At the first evaluation cystoscopy immediately after completing chemotherapy, 38 patients were tumour-free, eight had persistent muscle-invasive TCC and four had Ta, T1+CIS disease. With an overall median follow-up of 47 months, 10 additional patients relapsed with muscle-invasive carcinoma in the bladder after a median interval of 15.6 months; three patients developed Ta, T1 tumours, three Ta, T1 + CIS, and six CIS only. Six of the 10 recurrent invasive tumours were at the same site, but four were at a different site in the bladder. Although during follow-up 12 patients developed superficial recurrence that required endoscopic treatment, the bladder was preserved (free of muscle-invasive cancer) in 37 of 50 patients. In 30 of these 37, this was achieved with no need for salvage radiotherapy or cystectomy. Six patients died from metastatic TCC with no tumour in the bladder. CONCLUSION: In this selected group of patients, muscle-invasive bladder cancer was controlled by TUR and systemic chemotherapy, preserving normal bladder function in 60% of patients without apparently comprising overall survival.     

Urinary CYFRA 21.1 is not a useful marker for the detection of recurrences in the follow-up of superficial bladder cancer

OBJECTIVES: The objective of this prospective study is to establish an appropriate cutoff value of urinary CYFRA 21.1 assay and to assess its utility combined with voided cytology and/or haemoglobin dipstick in the follow-up of patients with superficial bladder cancer. METHODS: From December 2000 to November 2003, 446 patients in follow-up for superficial bladder cancer (Ta-T1) after transurethral resection of the bladder (TURB) were included in a prospective study. Voided urine specimens were collected 7-14 d before cystoscopy and/or TURB for CYFRA 21.1 (one sample), haemoglobin dipstick (one sample), and cytology (three samples). All samples were processed for CYFRA 21.1 and haemoglobin dipstick according to manufacturer instructions. A control group (n=185) was obtained from patients in follow-up after transurethral resection of superficial disease (without recurrences within the following 6 mo). There were 125 recurrent transitional tumours detected by cystoscopy (34 TaG1; 53 TaG2/T1G1-2; 23 Ta-1G3/Tis, and 15 T2-4). Receiver operator characteristic (ROC) curves were constructed and cutoff values were chosen. Sensitivity, specificity, PPV (positive predictive value), NPV (negative predictive value), and their 95% confidence intervals were calculated. RESULTS: ROC curve analysis based on the previously reported cutoff value of 4ng/ml for CYFRA 21.1 demonstrated a sensitivity and specificity of 43% and 68%, respectively. At a cutoff value of 1.5ng/ml, sensitivity was 73.8% with a low specificity (41%). Further lowering of the cutoff point below 1.5ng/ml did not demonstrate a significant increase in sensitivity. Therefore, this value was chosen as the most sensitive CYFRA 21.1 cutoff point during the rest of the study. Specificity increased when all the patients treated with pelvic radiotherapy or with UTI, urethral catheterisation, and intravesical instillations within 3 previous months were not included in our analysis. CYFRA 21.1 plus cytology and the combination of CYFRA 21.1, cytology, and haemoglobin dipstick demonstrated the highest overall sensitivities, and detected 91.3% of Ta-1G3 tumours and 93.3% of T2-4 tumours. However, there were one muscle-invasive tumour, two T1G3/Tis, three T1G2, and nine T1G1 neoplasms with negative combination of cytology and CYFRA 21.1 (1,5ng/ml). All these tumours were smaller than 2cm in size; most were single tumours. Nevertheless, there were 16 tumours larger than 0.5cm (0.5-2cm), and multiple neoplasms were endoscopically detected in 14 patients. Similar results were obtained through the combination of CYFRA 21.1 (cutoff: 1.5ng/ml), cytology, and haemoglobin dipstick. CONCLUSIONS: In our experience the low sensitivity of urinary CYFRA 21.1, even using lower cutoff values and/or a combination with cytology and/or haemoglobin dipstick, makes its application not very useful as a surveillance tool for superficial bladder carcinoma.     

Analysis of clinical characteristics, management and survival of patients with Ta T1 bladder tumours in Sweden between 1997 and 2001

OBJECTIVE: To analyse the management and outcome of patients with Ta T1 urinary bladder cancer in a population-based national database. MATERIAL AND METHODS: Between 1997 and 2001, 94% of all newly diagnosed cases of urinary bladder cancer were registered in the Swedish National Bladder Cancer Register. Data were analysed regarding gender, healthcare region, stage and grade for patients with Ta T1 tumours. The choice of initial treatment in different regions was reviewed. Survival was analysed by calculating relative survival. RESULTS: Out of 9859 registered patients, there were 4442 Ta tumours and 2139 T1 tumours. The median age at diagnosis was 72 and 73 years for patients with Ta and T1 tumours, respectively. Seventy-six percent of the patients were men. The choice of treatment varied between different healthcare regions. A significant trend towards an increased use of intravesical therapy was seen over time. Significantly fewer older than younger patients received such therapy. There was also a tendency towards more intensive therapy in men. The bladder cancer relative 5-year survival rate was 93% for Ta and 75% for T1 tumours. Survival was similar for men and women. CONCLUSIONS: Our analysis revealed a regional variation in the treatment of bladder cancer. A large group of patients, even those at high risk, were still undertreated. However, the recent publication of guidelines may have contributed to an increased use of intravesical treatment. Urologists tended to treat TaG3 and T1G3 tumours more aggressively than T1G2 tumours. Therapeutic aggressiveness decreased as the age of the patients increased. The survival rate of patients with bladder cancer in Sweden seems to remain at the levels previously reported for the 1980s.     

Intravenous urography in patients with transitional cell carcinoma of the bladder. The incidence and implications of ureteral obstruction.

In order to study the value of excretory urography in the diagnosis of transitional cell carcinoma of the bladder, and also the incidence and implications of ureteral obstruction, 100 consecutive patients were studied. Of 73 patients with superficial tumours (stages Tis, Ta, T1) only 1 (1,4%) had hydronephrosis as a result of the bladder tumour. However, 2 further patients had hydronephrosis secondary to synchronous ureteral tumours. Of the 27 patients with muscle-invasive tumours, 10 (37%) had hydronephrosis at the time of diagnosis. Four patients who had normal upper tracts initially, developed hydronephrosis during follow-up: 1 due to progression of a superficial tumour to stage T3, 1 due to the development of an ureteral tumour, and 2 due to fibrosis of the intramural ureter after transurethral resection of superficial tumours. The presence of ureteral obstruction at the time of diagnosis most often implies a muscle-invasive tumour, but the possibility of a synchronous ureteral tumour must also be considered. Fibrous strictures of the distal ureter can occur after transurethral resection of superficial bladder tumours.     

Does cystoscopy correlate with the histology of recurrent papillary tumours of the bladder?

OBJECTIVE: To correlate the cystoscopic appearance of recurrent papillary bladder tumours with the histology after transurethral resection, and thus ascertain whether cystoscopy can reliably identify low-grade, noninvasive papillary tumours suitable for outpatient fulguration. PATIENTS AND METHODS: In all, 150 recurrent papillary tumours of the bladder identified at outpatient flexible cystoscopy were classified as either low-grade and noninvasive (TaG1), high-grade and noninvasive (TaG3), or invasive (TIG3) tumours, and correlated with urine cytology and histology of tumour stage and tumour grade after transurethral resection. RESULTS: Cystoscopy classified 84 of the 150 papillary tumours as TaG1 and 66 as either TaG3 or T1G3. Cystoscopy correctly predicted the histology of 78 of 84 (93%) TaG1 tumours, 71 of 72 (98%) TaG1 tumours associated with a negative urine cytology, and 92% of TaG3 or T1G3 tumours. CONCLUSIONS: A skilled urologist can identify noninvasive, low-grade recurrent papillary bladder tumours on follow-up cystoscopy that do not require biopsy and that may be treated by outpatient fulguration alone.     

Outcome of very large superficial bladder tumours: a 10-year experience

OBJECTIVES: To determine the biological behaviour of very large superficial bladder tumours (pTa, pT1) and evaluate the impact of the initial tumour weight on long-term prognosis. MATERIAL AND METHODS: Of 1569 patients who presented with bladder tumours over a 10-year period, 1070 of the tumours were superficial. Fifty-nine patients had very large tumours (resected weight >or= 15 g). Case notes were analysed to determine recurrence, progression and survival. Median follow-up was 60 months (range 1-156 months). Histological slides were reviewed for all tumours initially reported as pT1 to determine the presence of uninvolved muscle. Statistical analysis was performed using the Kaplan-Meier method to calculate progression and survival estimates. RESULTS: The overall progression and recurrence rates for very large superficial bladder tumours were 18% and 68%, respectively. The progression rates for Ta, T1, G1, G2 and G3 tumours were 4%, 28%, 0%, 20% and 50%, respectively, with highest progression rates being seen for pT1G2 and pT1G3 tumours. The progression rate was significantly influenced by initial stage (p=0.01) and grade (p=0.03). Tumour weight did not affect either recurrence, progression or cause-specific survival. There were no differences in progression and survival rates in patients with tumour weights of 15-30 and >30 g (p=0.80 and 0.07, respectively). The review of histology slides of T1 tumours showed that 7/10 cases (70%) with progression had no muscle or an inadequate amount of muscle for definitive staging. Upper urinary tract tumours were seen in only two patients (3.4%). CONCLUSIONS: Large size is not an adverse prognostic factor for patients with a superficial bladder tumour. However, these cases are difficult to stage. In view of the high rates of progression and disease-specific mortality, we recommend that very large pT1G2 bladder tumours should be considered as high-risk tumours and targeted for aggressive treatment, including early re-resection, to rule out any occult invasive disease.     

Primary Ta high grade bladder tumors: Determination of the risk of progression

PurposeTaG3 bladder cancer is an under-investigated disease and because of its rarity it is commonly studies together with T1G3 disease. We sought to exclusively study TaG3 disease and to determine the factors associated with disease progression.Material and methodWe retrospectively studied patients with primary TaG3 bladder cancer. Progression to ≥pT1 and pT2 were analyzed using Cox and competing-risk regression analyses.ResultsOf 3,505 consecutive patients with nonmuscle invasive bladder cancer, 285 patients had primary TaG3 without concomitant carcinoma in-situ. Progression to ≥pT1 occurred in 21 patients (7.4%). In a multivariable competing-risk regression analysis, intravesical Bacillus Calmette-Guerin (BCG) was significantly associated with a lower risk of progression to ≥pT1 (HR 0.23, 95%CI 0.08–0.64, P = 0.005). Recurrence in the first year of diagnosis was significantly associated with an increased risk of stage progression to ≥pT1 (HR 7.81, 95%CI 2.50–24.44, P < 0.001). Progression to ≥T2 was observed in 9 patients (3.2%). In univariable competing-risk regression analyses, intravesical BCG was significantly associated with a lower risk of progression to ≥pT2 (HR 0.11, 95%CI 0.04–0.47, P = 0.003). On the other hand, recurrence in the first year of diagnosis was significantly associated with an increased risk of stage progression to ≥T2 (HR 7.12, 95%CI 1.50–33.77, P = 0.013). In a subgroup of 199 patients who were treated with BCG, there was no statistically significant association between tumor recurrence in the 1^st year of diagnosis and stage progression to ≥pT1 (P = 0.14) or ≥pT2(P = 0.19).ConclusionPatients with TaG3 bladder cancer are considered high risk but if appropriately treated with BCG that risk is considerably mitigated. Our data support that TaG3 without concomitant carcinoma in-situ should not be considered as aggressive as T1G3 as it has a lower risk of progression to muscle-invasive bladder cancer. Recurrence in the first year after diagnosis is the strongest predictor of progression to muscle-invasive bladder cancer.     

Long-term outcome of bladder papillary urothelial neoplasms of low malignant potential

OBJECTIVE: To evaluate the long-term outcome of bladder papillary urothelial neoplasms of low malignant potential (PUNLMP). PATIENTS AND METHODS: Of 475 consecutive patients with newly diagnosed bladder tumours between 1976 and 1993, 330 (69%) had superficial (Ta and T1) tumours and 53 (11%) were diagnosed as having PUNLMP. Fifty patients (mean age at presentation 57.2 years, range 26-83; male-to-female ratio 6 : 1) who were followed for> 5 years or until they died, were included in the present study. All histological slides were reviewed, and fulfilled the diagnostic criteria of the 1998 World Health Organization/International Society of Urological Pathology classification system. RESULTS: The mean (median, range) follow-up was 11.7 (10.8, 1.3-24.4) years. During the follow-up, 30 patients (60%) had local recurrences. The 2, 5 and 10-year recurrence-free rates were 66%, 51% and 36%, respectively. No patients developed high-grade or muscle-invasive (>/= T2) carcinomas, or upper urinary tract tumours, or died from the disease. At the last follow-up, 34 patients (68%) had been disease-free for> 5 years. CONCLUSIONS: Despite a high recurrence rate, PUNLMP carries a very low malignant potential. We agree with the use of the term 'papillary urothelial neoplasms of low malignant potential' instead of 'superficial bladder carcinoma (cancer)' for these tumours.     

Prognosis of muscle-invasive bladder cancer: difference between primary and progressive tumours and implications for therapy

OBJECTIVE: To evaluate the difference in prognosis between progressive and primary muscle-invasive bladder cancer. MATERIALS AND METHODS: From 1986 to 2000, 74 patients with progressive muscle-invasive bladder cancer were identified. Eighty-nine patients with primary muscle-invasive bladder cancer were frequency matched for stage to these patients with progressive disease. Baseline data including patient and tumour characteristics were collected at the time of diagnosis of the muscle-invasive tumour. Duration of survival was defined as time from muscle-invasive bladder cancer diagnosis until disease-specific death. Kaplan-Meier curves were drawn to determine the difference in prognosis between the two study groups. To adjust for potential residual confounding due to differences in treatment, 4 subgroups (T2/3, T4, N+ and M+) were constructed according to the TNM classification. In order to see whether age and gender had any effect on outcome, the four stage groups, age and gender were entered in a Cox's proportional hazard regression model. RESULTS: The 3-year bladder cancer-specific survival was 67% in the primary group and 37% in the progressive group (log rank p=0.0015). Kaplan-Meier curves comparing the different stage groups showed a better prognosis for the patients with primary, i.e. pT2/3 or N+, tumours at baseline. Cox regression analysis demonstrated that age and gender had no influence on bladder cancer-specific survival. CONCLUSIONS: Patients with muscle-invasive bladder cancer and a history of superficial bladder cancer have a worse prognosis than patients with primary muscle-invasive bladder cancer.     

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.     

Should follow-up cystoscopy in bacillus Calmette-Guérin-treated patients continue after five tumour-free years?

Background

It is not known how long follow-up cystoscopy in tumour-free bacillus Calmette-Guérin (BCG)-treated patients should continue.

Objective

Determine the incidence of late recurrences and progression after a tumour-free period of >5 yr after BCG treatment.

Design, setting, and participants

Data on 542 patients with non-muscle-invasive bladder cancer treated with BCG between 1986 and 2003 were analysed. Of 542 patients, 204 patients (37.6%) were tumour-free for ≥5 yr. The median tumour-free period was 105.5 mo (range: 60-252 mo).

Measurements

To compare the tumour-free group with patients who were not tumour-free for 5 yr, traditional variables (tumour grade, tumour stage, age, gender, tumour number and size, primary or recurrent tumour, BCG strain, previous chemotherapy, previous upper tract tumour, number of earlier resections, and European Organisation for Research and Treatment of Cancer recurrence and progression risk groups) were analysed using the Fisher exact test for dichotomous variables, the Mantel-Haenszel chi-square test for ordered categorical variables, and the Mann-Whitney U-test for continuous variables. Kaplan-Meier curves for time to recurrence were constructed using Statistica software (StatSoft, Tulsa, Oklahoma, USA). Differences between groups were tested with the log-rank test. For continuous variables, Cox proportional hazard regression was performed to find significant effect on the time to recurrence.

Results and limitations

Twenty-two of 204 patients (10.8%) had a recurrence after being tumour-free for ≥5 yr. The Kaplan-Meier estimated risk for recurrence was 12.5% at 10 yr and 20.5% at 15 yr. Among patients with TaG1-TaG2 before BCG, 11 of 79 patients (13.9%) had recurrences, including three patients with invasive extravesical tumours. Among the bladder recurrences were seven TaG1 s and one carcinoma in situ (CIS). Among the 125 patients with TaG3/CIS/T1 before BCG, 11 patients (8.8%) had recurrences, including 2 patients with invasive ureter tumours. The bladder recurrences were one T2, four CIS, and four TaG1. Late recurrences were 8.5 times more common among patients with recurrent tumours before BCG compared with patients treated after their first tumour episode. The study was retrospective and nonrandomised but unselected and population-based.

Conclusions

A tumour-free period of 5 yr after BCG treatment is a good prognostic sign, but recurrences after >10 yr are not unusual. Literature data and the present report support cystoscopy follow-up for ≥10-15 tumour-free years, at least among patients with recurrent tumours and/or high-grade lesions before BCG treatment.     

Protein expression patterns of ezrin are predictors of progression in T1G3 bladder tumours treated with nonmaintenance bacillus Calmette-Guérin

Background

Bacillus Calmette-Guérin (BCG) is a standard treatment for reducing tumour recurrence and delaying progression of high-risk, non–muscle-invasive bladder tumours. However, it is not clear yet which patients are more likely to be responders to BCG.

Objective

To evaluate the role of ezrin expression in bladder cancer (BCa) progression in T1G3 bladder tumours treated with BCG.

Design, setting, and participants

Ezrin protein expression patterns were analysed on tumour specimens belonging to 92 patients with T1G3 non–muscle-invasive BCa undergoing nonmaintenance BCG treatment. Re-resection was not performed. The median follow-up was 90.5 mo (range: 3.0–173.0). A specific tissue array was created containing three representative cores of each of the tumour specimens belonging to these patients.

Measurements

Ezrin protein expression patterns were assessed by immunohistochemistry on this tissue array. Proliferation rates were assessed by means of Ki67 staining. Recurrence, progression into muscle-invasive tumours, and disease-specific overall survival (OS) rates were analysed using univariate and multivariate tests.

Results and limitations

Among the 92 patients analysed, 40 recurred (43.5%), 17 progressed (18.5%), and 14 died of the disease (15.2%). Log-rank survival analyses revealed that an ezrin membrane expression <20% was significantly associated with increased progression (p = 0.009) and shorter disease-specific OS (p = 0.006). Multivariate analyses showed that ezrin was an independent prognostic marker of progression (p = 0.031) and disease-specific survival (p = 0.035). Interestingly, the low ezrin membrane expression correlated with high proliferation rates (p = 0.033).

Conclusions

Immunohistochemistry analyses revealed that the membrane expression of ezrin is associated with the clinical outcome of patients with T1G3 tumours undergoing BCG treatment. Protein expression patterns of ezrin were associated with tumour progression in T1G3 disease. The differential expression of ezrin distinguished patients responding to BCG from those who may require a more aggressive therapeutic approach.     

Patterns of primary care and survival in 336 consecutive unselected Norwegian patients with bladder cancer.

The outcome of 336 unselected patients diagnosed as having bladder cancer in 1985 in a southern health region of Norway was studied. Two hundred and forty patients had superficial bladder cancer (Tis, Ta and T1). Seventy-four had T2-3 and 17 had T4 bladder tumours at the time of diagnosis (the T-category was unknown in five cases). In 46 of 248 evaluable cases (19%) 12 or more months had elapsed between the onset of symptoms and the histological confirmation of the diagnosis. The information received from the initial routine histology report was inadequate in 51 of 240 (21%) of the patients with superficial bladder cancer. Among the 91 patients with muscle-infiltrating tumours the primary treatment varied considerably, and only 15 patients underwent total cystectomy as the initial treatment. Only 46 in whom muscle-infiltrating tumours were diagnosed initially were referred to the regional uro-oncological unit during the course of the disease. The cancer-corrected, four-year survival was 86% and 42% for superficial and muscle infiltrating bladder cancer, respectively. The comparable figures for crude survival were 64% and 34%, respectively. The lack of optimal standard treatment of muscle-infiltrating bladder cancer warrants the introduction of clinical trials to assess both curative and palliative regimens as well as to study prognostic factors such as proliferation and immunohistochemical parameters by uro-oncological units. Scandinavian Cancer Registries should consider the optional recording of the T category on the case record forms for newly diagnosed cases of bladder cancer.     

The value of a second transurethral resection in evaluating patients with bladder tumours

OBJECTIVES: To evaluate the usefulness of a second transurethral resection for superficial and muscle-invasive bladder tumours. METHODS: A review of the literature relevant to repeat resection for bladder tumours was conducted using Medline Services. RESULTS: Transurethral resection of the bladder has two shortcomings: underestimating clinical stage, and overlooking other lesions. A second transurethral resection, when performed 2-6 weeks after the initial resection, corrects clinical staging errors in 9-49% of cases and detects residual tumour in 26-83% of cases. A second resection is particularly warranted for T1 tumours since 2-28% of them prove to be muscle-invasive, thus requiring a change in management. For muscle-invasive tumours, a second resection may be performed only if bladder sparing is being considered, as it helps to exclude the presence of tumour sites contra-indicating conservative treatment. CONCLUSIONS: A second transurethral bladder resection may be warranted for T1 tumours, and for invasive tumours when a bladder preservation is planned.     

High expression of karyopherin-α2 defines poor prognosis in non-muscle-invasive bladder cancer and in patients with invasive bladder cancer undergoing radical cystectomy

Background

Conventional clinicopathologic risk factors have failed to accurately predict the prognosis of patients with bladder cancer (BC).

Objective

To evaluate karyopherin-α2 (KPNA2) expression as a progression marker in patients with non–muscle-invasive BC (NMIBC) treated by conservative methods and as a prognostic marker in patients with invasive BC undergoing radical cystectomy (RC).

Design, setting, and participants

Two different tissue microarrays were constructed, one with 234 primary Ta/T1 tumours from patients treated by transurethral resection of the bladder and one with 377 tumours from RC patients.

Intervention

KPNA2 expression based on immunohistochemistry.

Measurements

Risk of progression of Ta/T1 patients to muscle-invasive BC was estimated in clinical follow-up to progression or a minimum of 53 mo. Risk of recurrent disease and death following RC was estimated in clinical follow-up of a minimum of 24 mo in patients alive.

Results and limitations

A high KPNA2 expression in Ta/T1 patients was significantly correlated with a higher risk of progression that was independent of conventional risk factors in multivariate analysis. In patients undergoing RC, a high KPNA2 expression was an independent predictor of poor prognosis. A high KPNA2 expression was correlated with a higher risk of visceral metastasis rather than lymphatic spread.

Conclusions

KPNA2 expression is a marker for progression of NMIBC and a prognostic marker in patients undergoing RC.     

Transitional cell carcinoma of the bladder in patients under 40 years of age

There are conflicting reports about the natural history and prognosis of bladder tumours in patients under 40 years of age. A review of 156 patients younger than 40 treated at our Department between 1960 and 1991 with transitional cell carcinoma of the bladder revealed that 89.1% had superficial (Ta/T1) disease and the remaining 10.9% presented with invasive disease. Slightly more than half of the patients with superficial disease had multiple tumours. The follow-up of 97 patients over a period of 12–372 months revealed that there was a recurrence rate of 10.3% and 38.4% for Ta and T1 tumours, respectively (p<0.01). Further analysis comparing patients under 30 to those between 30 and 40 years revealed recurrence rates of 7.5% and 22%, respectively (p<0.05). Progression rates for Ta and T1 tumours are 3.5% and 19.3% (p<0.05). In the invasive disease group 8 patients were lost for follow-up, 2 died of the disease and the remaining 7 are alive, with a mean follow-up of 3.6 years. We conclude that while transitional cell carcinoma of the bladder in patients under 30 behave less aggressively, the behaviour of the disease in patients 30 to 40 years old is similar to the older age group and should be monitored closely, especially when risk factors for recurrence and progression are present.     

Comparison of the bladder tumour antigen test with photodynamic diagnosis in patients with pathologically confirmed recurrent superficial urinary bladder tumours

OBJECTIVE: To verify the sensitivity of the bladder tumour antigen (BTAstat, Bard Urological, Covington, GA) test against the sensitive procedure of photodynamic diagnosis (PDD), in which 5-aminolaevulinic acid (5-ALA, a precursor of fluorescent porphyrins) is absorbed by the tumour and detected by ultraviolet cystoscopy, in the early diagnosis of urinary bladder tumours. PATIENTS AND METHODS: Forty-three patients (31 men and 12 women, age range 21-87 years) were assessed after transurethral resection of their bladder tumour using the BTAstat test and PDD. Sixty-nine biopsies from suspect areas of bladder mucosa were taken during cystoscopy under ultraviolet light and all suspect lesions electrocoagulated. RESULTS: Thirty-five patients (81%) had a positive BTAstat test; in these patients PDD detected malignant lesions (17 Ta1G1-2, two T1G2, two T1G3 and 14 Tis). In eight patients (19%) the BTAstat was negative but PDD detected three malignant lesions (two Tis and one TaG1). CONCLUSIONS: PDD is valuable for detecting bladder malignancy and can identify small lesions not detected by the BTAstat test.     

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

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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).     

Recurrence and progression in stage T1G3 bladder tumour with intravesical bacille Calmette-Guérin (Danish 1331 strain)

OBJECTIVE: To report recurrence and progression rates in patients with T1G3 superficial bladder carcinoma treated with intravesical bacille Calmette-Guérin (BCG, Danish 1331 strain) after complete transurethral resection. PATIENTS AND METHODS: Data from the records of 111 patients with T1G3 bladder carcinoma treated between January 1991 and December 1999 were analysed for recurrence, progression, salvage therapy and survival. RESULTS: Of the 111 patients with T1G3 bladder tumours, 69 had intravesical BCG therapy, 20 radical cystectomy and 22 only transurethral resection (TUR). Of the 69 patients receiving BCG therapy 37 (54%) had no recurrence, and 24 (35%) had a recurrence that was not muscle-invasive (Ta/T1) and were treated with TUR only. The remaining eight (12%) progressed to muscle invasion and had salvage cystectomy. During the follow-up six patients died, four from disease and three from other causes, while the remaining 63 are alive and well. Of the other 42 patients, 15 are alive after radical cystectomy and 18 after TUR. CONCLUSION: This series further confirms the benefits of intravesical BCG (Danish 1331) in an adjuvant setting; furthermore, this treatment facilitates bladder preservation by reducing recurrences and delaying the progression in many patients.