Iatrogenic tumor cell implantation in bladder cancer

J82 monolayer cell cultures and 647 V multicellular tumor spheroids were incubated in Resectal, urine (pH 5.5; 7.5) and distilled water for 5-30 min. In the case of both monolayers and tumor spheroids inhibition of tumor cell growth was achieved by incubation in distilled water. Transurethral resection (TUR) of a primary superficial bladder cancer was performed in 133 patients (Ta, T1). In 60 of these patients selected biopsies of apparently normal bladder mucosa were taken at the same time. There was no significant difference in tumor recurrence between the groups with biopsy and without biopsy. However, all patients with dysplasia in the selected mucosal biopsies developed a tumor recurrence. Between 1969 and 1984 bladder wall perforation occurred in 12 patients during TUR of Ta, T1 bladder cancer. None of the patients who experienced bladder wall perforation developed extraperitoneal or intraperitoneal metastases. Although our clinical results suggest that iatrogenic tumor cell implantation during TUR of a bladder cancer is rather unlikely, this event could be prevented by the use of distilled water during and after TUR.     

Significance of random bladder biopsies in superficial bladder cancer

OBJECTIVES: We investigated to what extent biopsies of normal-appearing urothelium taken from patients with superficial bladder cancer (Ta, T1, Tis) showed malignant disease and whether those findings had impact on therapeutical decisions. PATIENTS AND METHODS: 1033 consecutive patients presenting with Ta, T1 or Tis (carcinoma in situ) superficial bladder tumors at increased risk for recurrence underwent multiple random biopsies from normal-appearing urothelium during transurethral resection (TUR). Patients with small, primary, singular tumors (smaller or equal to 1cm) were excluded from random biopsies. RESULTS: No tumor was found in the random biopsies of 905 patients (87.6%). 128 patients (12.4%) showed urothelial bladder cancer in their random biopsies (Tis: 74, Ta: 41, T1: 12, T2: 1). In 14 patients, where transurethral resection of the primary tumor revealed no signs of malignancy, urothelial bladder cancer was detected in the random biopsy material: Ta 8 patients, Tis 5 patients and T1 one patient. 21 patients with Ta tumors and 29 patients with T1 disease showed concomitant Tis. Upstaging of the primary, resected tumor by histological examination of the random biopsy material occurred in 75 patients (7%). Altogether, due to the random biopsy results therapy was altered in 70 patients (6.8%) of our series: It changed intravesical chemotherapy to BCG in 45, provoked a second TUR in 48 and cystectomy in 15 patients. CONCLUSIONS: While the clinical significance of random biopsies is still controversial, random biopsy results had strong impact on therapeutical decisions in our series. Regarding random bladder biopsies a simple tool for the urologist to identify high risk groups of patients, we recommend them as part of the routine management of superficial bladder cancer.     

The significance of urothelial dysplasia as diagnosed by cup biopsies

A prospective study was carried out in which four quadrant cold cup biopsies of the bladder were taken from patients with either a bladder tumour (57) or irritative bladder symptoms (44), and a control group (23). Five histopathological patterns were recognized: normal urothelium, mild, moderate and severe dysplasia, and carcinoma in situ (CIS). In the control group, 22 of the 23 patients had normal urothelium, giving a 4% incidence of mild dysplasia. Of the 57 patients with all stages and grades of transitional cell carcinoma, 38 (67%) had dysplastic urothelium. This association is significant (P less than 0.01, chi-squared). Thirty-seven patients had Ta or T1 tumours, and 24 (65%) of these had dysplasia, including four (11%) with CIS. Twenty patients had T2-T4, Grade 111 tumours and 14 (70%) of these had dysplasia, including five (25%) with CIS. There was no statistical difference between these two groups. The recurrence rate was evaluated for all patients presenting with a first bladder tumour. Seventy-three percent of patients with normal cup biopsies remained recurrence free during a mean follow-up of 3 years (s.d. 1.15 years). Of patients with dysplastic urothelium, 72% remained recurrence free over a mean follow-up of 3.25 years (s.d. 1.23 years). Hence, the presence of dysplasia did not predict the likelihood of tumour recurrence. Thirty patients had dysuria or suprapubic pain for which there was no explanation. Sixteen (53%) had dysplasia on cup biopsy including three (10%) with CIS (P less than 0.01, chi-squared). It seems clear, therefore, that the dysplasia was the cause of these symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Value of random mucosal biopsies in the management of superficial bladder cancer.

115 newly diagnosed patients with Ta-T1, G1-G2 superficial transitional cell carcinoma of the bladder underwent four quadrant biopsies of normal-looking bladder mucosa, in addition to the endoscopic treatment of the primary tumour or tumours. In 88 (77%) patients all the biopsies were normal; in the other 27 (23%) at least one biopsy revealed dysplasia or carcinoma in situ or G1-G2 carcinoma. 88 patients presented with a single tumour, of which 14 (16%) had abnormal biopsies compared to 13 (48%) of the 27 presenting with multiple tumours. The difference between the 2 groups was statistically significant (p < 0.01). The incidence of freedom from new tumours at 5 years was 68% in patients with normal biopsies compared to 33% in patients with abnormal biopsies (p = 0.002). In patients presenting with multiple tumours and in those with single tumours and abnormal biopsies, the incidence of freedom from new tumours was significantly lower than in those presenting with single tumours and normal mucosal biopsies (p = 0.002). The study shows that the exercise of performing random mucosal biopsies is particularly useful in patients presenting with single tumours, in order to identify those who are more likely to develop new tumours over the longer term. Such patients could be offered early prophylactic intravesical chemotherapy. The study did not substantiate tumour implantation as a factor for new tumour development in superficial bladder cancer.     

Frequency of positive biopsies after visual disappearance of superficial bladder cancer marker lesions.

INTRODUCTION AND OBJECTIVES: In phase II trials in superficial bladder cancer, marker lesions have been used to test the ablative activity of intravesical chemo- or immunotherapy. These studies provide important knowledge about drug activity and toxicity without exposing hundreds of patients in phase III trials to drugs which ultimately may not be successful in preventing tumour recurrence or progression. After treatment a deep biopsy was necessary at the site of the marker lesion even in the absence of any visual tumour. The question is if this biopsy, in the absence of any visual tumour, should be done. MATERIAL AND METHODS: The ablative effect of MMC, epirubicin, and quarter dose BCG instillations was evaluated in three different studies on a papillary marker lesion. Patients with multiple, primary or recurrent superficial bladder tumours were included. All visible Ta-T1 lesions were resected except for one marker lesion not exceeding 1 cm. TIS was excluded. In the last study, patients with T1 G3 tumours or multiple tumours >10 were also excluded. If the marker lesion disappeared completely, a deep biopsy was performed at the scar in order to prove histological disappearance of the tumour. RESULTS: 185 patients were evaluated. No visual tumours were seen in 110 patients and a TUR was performed in 101 of them. It revealed only 3 Ta lesions. In the 9 others no biopsy was performed but follow-up cystoscopy revealed no lesions. CONCLUSIONS: In the absence of any visual tumors, TUR and deep biopsy at the site of the scar of the marker lesion only rarely revealed (3 out of 110) the histological presence of a tumour. Therefore, this biopsy can be omitted in new marker lesion protocols in patient with Ta-T1, G1 G2 papillary superficial bladder tumours at intermediate risk for recurrence and low risk for progression.     

Should Bladder Biopsies be Performed Routinely after Bacillus Calmette-Guérin Treatment for High-Risk Superficial Transitional Cell Cancer of the Bladder?

OBJECTIVE: After endoscopic resection of high-grade superficial urothelial neoplasms (Ta, T1 or Tis), adjuvant bacillus Calmette-Guérin (BCG) therapy is performed routinely to avoid recurrence and/or progression. Vesical biopsies often are performed to assess the efficacy of treatment. The aim of our study was to evaluate the usefulness of these biopsies. MATERIALS AND METHODS: During this retrospective bi-centre study, 130 patients who had undergone vesical high-grade tumour resection were included. There were 40 Ta associated with Tis in three cases, 87 T1 associated with Tis in 13 cases, and three isolated Tis. After BCG treatment, the following parameters were studied: cytoscopic findings, urine cytology and the histologic results of systematised biopsies. RESULTS: Urine cytology was positive (high-grade) for 26 patients and negative (normal or low-grade) for 104 patients. For the 26 patients with positive cytology, vesical flexible cystoscopy findings were considered suspicious in 18 patients and normal in eight patients. As for the 104 patients who presented negative cytology, cystoscopic findings were considered negative in 76 patients and suspicious in 28 patients. In the present study, the sensitivity of cytology and cystoscopy in the detection of recurrence after BCG treatment was 56% and 87.5%, respectively; specificity was 56% and 81.6%, respectively. When the two examinations were combined, sensitivity was 100%, and specificity was 76%. CONCLUSIONS: After BCG therapy, the association of negative flexible cystoscopy findings and normal urine cytology made it possible to avoid routine biopsies. Patients could therefore avoid the morbidity of this procedure.     

Bladder tumors. Indications for and results of routine biopsies of the macroscopically healthy mucosa (with a study of surface antigens)

The routine biopsy of macroscopically normal mucosa has demonstrated the frequency of anomalies (hyperplasia, dysplasia or carcinoma in situ) associated with bladder tumours. 75 patients with urothelial bladder cancer were investigated by a total of 163 endoscopic examinations which, apart from resection of the tumour, included biopsies of macroscopically healthy mucosa. The frequency and severity of the lesions increased with the grade and the stage of the tumour: in cases with stage O/Ta lesions, the percentage of anomalies increased from 15% with grade 1 to 53% with grade 3. At stage A (T1), anomalies were present in 8 out of 10 cases and consisted of carcinoma in situ in one half of cases. Similar figures were obtained for stages B/C (T2, T3). Lesions which may persist in the absence of a visible tumour respond dramatically to intravesical BCG chemotherapy. Analysis of the surface antigens did not reveal any clear correlation between the antigenic status of the tumour and that of the non-tumoural mucosa. These results clarify the indications for biopsies in macroscopically healthy mucosa, which should be limited to follow-up endoscopies and treatment of grade 3 tumours.     

Significance of bladder biopsies in Ta,T1 bladder tumors: a report from the EORTC Genito-Urinary Tract Cancer Cooperative Group. EORTC-GU Group Superficial Bladder Committee.

OBJECTIVES: We investigated to what extent biopsies of normal-appearing urothelium taken from patients with Ta,T1 bladder cancer showed malignant disease: carcinoma in situ, or papillary tumor. We also investigated biopsies underlying the papillary tumor, adjacent to the tumor, and from suspicious-appearing mucosa. METHODS: In EORTC protocol 30863 (low-risk tumors), 393 patients underwent a biopsy of normal-appearing urothelium. In protocol 30911 (intermediate- and high-risk tumors), multiple biopsies were taken from normal- appearing urothelium in 602 patients. RESULTS: No abnormalities were found in the random biopsies of 376 (95.6%) patients with low-risk tumors and in 532 (88.4%) patients with intermediate- and high-risk tumors. Six (1.5%) patients with low-risk tumors and at least 21 (3.5%) patients with higher-risk tumors showed carcinoma in situ in their random biopsies. None of the patients in the low-risk group and 1 (0.2%) patient in higher-risk group had an invasive tumor (T2). CONCLUSIONS: This analysis indicates that biopsies of normal-appearing urothelium in Ta,T1 bladder cancer patients show no abnormalities in about 90% of the patients. Performing such biopsies does not contribute to the staging or to the choice of adjuvant therapy after transurethral resection.     

Treated history of noninvasive grade 1 transitional cell carcinoma. The National Bladder Cancer Group.

A total of 178 patients with grade 1 noninvasive (stage Ta) bladder tumors followed from 1 to 10 years (median 58 months) was prospectively evaluated by cystoscopy, transurethral resection, mucosal biopsies, cytology, size and number of tumors at diagnosis, recurrences, progression in grade and stage, number of negative or positive cystoscopies and death from all causes. Histopathological and cytological studies were confirmed by a Central Pathology Laboratory using the criteria for grade 1 as described previously. Of the patients 122 (68.5%) had a single tumor. Three-quarters of the patients had tumors of less than 2 cm., 95% had mild or no urothelial dysplasia and 1 had positive cytology results. There were 419 recurrent tumors in 109 patients (61%). Patients with multiple tumors were at a significantly greater risk for recurrences (p < 0.001). Size of tumor significantly affected the rate of recurrence in the first 2 years after initial diagnosis in single tumor patients only. Of the multiple tumor patients 90% experienced a recurrence compared to 46% of the single tumor patients. Of the 1,112 cystoscopies performed in 122 single tumor patients 18% were positive, compared to 33% of the 686 cystoscopies performed in 56 multiple tumor patients. A total of 29 patients had a change in grade, 5 having grade 3 and 24 having grade 2 tumors. Progression to stage T1 occurred in 5 patients and to stage T2 or greater in 3. Of the 36 patients who died, 1 died of obstruction due to bladder cancer. Experimental evidence supports the opinion that the cells of stage Ta, grade 1 tumors are different in several ways from normal urothelium. There are little data to support the use of the term papilloma to describe stage Ta, grade 1 tumors without reservation. The data demonstrate that the tumor diathesis being expressed ceases with time and for unknown reasons. Multiple tumor patients with stage Ta, grade 1 disease might be included in chemotherapy trials only with stratification and a control arm of transurethral resection/fulguration alone.     

Is bladder biopsy necessary at three or six months post BCG therapy?

The standard of practice set by the SWOG investigation of BCG therapy for superficial bladder cancer has been to evaluate response at 3 months with cystoscopy and bladder biopsy. This study is to determine if all patients require a biopsy post therapy at 3 or 6 months. We reviewed the charts of 43 patients who had received a 6-weekly course of BCG (Connaught strain) for high grade or recurrent Ta, T1, or Tis transitional cell carcinoma of the bladder. The patients with Ta recurrent, T1 or Tis disease received maintenance therapy. All patients were followed through 6 months. At 3 months, 32/43 patients had negative cystoscopies. All 32 patients had corresponding negative biopsies. Eight patients had visible papillary tumors, while three patients had erythematous lesions, which were biopsy negative. At 6 months, eight different patients had visible lesions on cystoscopy that were biopsy proven superficial bladder cancer. The positive predictive value at 3 and 6 months post BCG therapy was 72.6% and 100%, respectively. The false positive rate was 7% at the 3-month checkpoint. Bladder biopsy is not necessary at the 3 or 6 month period following BCG therapy in the face of negative cystoscopic findings.     

Clinical study of prognostic factors of superficial bladder cancer treated with intravesical bacillus Calmette-Guerin

Intravesical instillation of Tokyo 172 strain Bacillus Calmette-Guérin (BCG) was performed in 96 patients with initial superficial bladder cancer (Ta and T1) after transurethral resection (TUR) of tumour as a prophylaxis against tumour recurrence. The recurrence rate of tumours was estimated by the person-years method, comparing it with that of historical controls. There were statistically significant decreases in recurrent tumours following BCG therapy. To clarify the efficacy of intravesical BCG therapy, the prognostic significance of several factors was evaluated in patients with bladder cancer treated with TUR and instillation of BCG. The prophylactic effects were statistically better for those with multiple tumours, grade 3 lesions or Ta lesions than for control patients. No correlation between purified protein derivative (PPD) responsiveness and favourable results could be observed. Our results suggest that intravesical BCG instillation can alter the biological behaviour that affects the recurrence of superficial bladder cancer, especially for multiple, high grade or Ta tumours.     

Transurethral resection of 1250 bladder tumours

A total of 1250 bladder tumours were subjected to transurethral resection (891 curative, 107 palliative operations, 252 TUR biopsies). Complication rate was 9.9%, mortality rate 0.8%. In patients with primary tumours the 1-year recurrence rate after TUR was 23.8%, the 3-year rate was 36.6%, with an increase in proportion to stage. The 5-year survival rate was 66.5%. Within five years 9% of the patients died from tumour generalization, also with a rising tendency in proportion to stage. TUR as a curative method is suitable mainly for the removal of Ta and T1, under circumstances also of T2 G1-G2 tumours.     

Recurrence, progression and success in stage Ta grade 3 bladder tumors treated with low dose bacillus Calmette-Guerin instillations

PURPOSE: Bacillus Calmette-Guerin (BCG) therapy is considered to be an effective prophylactic and therapeutic agent for high risk superficial transitional cell carcinoma of the bladder. Nevertheless, in a select uncommon population of stage Ta grade 3 superficial lamina-free tumors the results of this treatment have not yet been well established. We evaluated recurrence and progression rates, and the success of BCG therapy in a population with stage Ta grade 3 transitional cell carcinoma of the bladder. MATERIALS AND METHODS: Of the 605 patients treated at our institution from 1982 to 1996 for the histopathological diagnosis of primary bladder cancer 32 (5.3%) with stage Ta grade 3 noninvasive primary bladder tumor were treated with intravesical instillations of 75 mg. Pasteur strain BCG in 50 ml. saline weekly for 6 weeks. At a followup of 2 to 13 years (mean 58.4 months) patients were evaluated with urinary cytology, cystoscopy, transurethral resection and random mucosal biopsies. Recurrence, grade and stage progression, death and causality were analyzed. RESULTS: Of the 32 patients 9 (28%) responded positively to BCG without recurrence, while disease recurred as stage Ta in 8 (25%) and T1 in 7 (22%), and progressed to muscle layer infiltration in 8 (25%). Four patients (12%) died of bladder cancer. The number of tumors at primary resection, gross examination, the mitotic index or an association with carcinoma in situ did not appear to be predictive factors of progression to muscle invasion. Urine cytology (I to II versus III to IV) appeared to correlate highly with progression and BCG response (p<0.001) with excellent sensitivity (1) but low specificity (0.67). CONCLUSIONS: Our study demonstrates the high progression potential of stage Ta grade 3 tumors, since nearly 50% recurred and 25% progressed to invasive disease. These results may be closely compared with the results of previous trials of stage T1 grade 3 disease. We suggest that recurrence should be detected at an early stage using long-term followup with strict observance of the surveillance protocols during a minimum 5-year tumor-free period.     

DNA/RNA ratio in bladder cancer: a factor indicating the recurrence rate?

Flow cytometry (FCM) was used to monitor 24 patients receiving intravesical mitomycin C (MMC) therapy. The patients were selected for MMC therapy because of multiple low stage bladder tumours which had not been cleared by previous endoscopic management. The response to treatment was monitored with cystoscopy, cytology, mucosal biopsies and flow cytometry. Follow-up was for a minimum of 12 months and 19 patients (79%) remained free of tumour. Four patients developed recurrences 6 months after therapy (16.5%) and one showed no response. There were no partial responders. The flow patterns of the four patients who developed recurrence showed an increased RNA/DNA ratio; this was detected after the third MMC instillation and remained throughout the follow-up period. The patients who did not develop recurrence demonstrated either a 1:1 or decreased RNA/DNA ratio. The increased RNA/DNA ratio appears to precede cystoscopic, urine cytology or biopsy evidence of recurrence. If this is confirmed in a larger series it could be used to select patients at high risk for recurrence who would be suitable for alternative therapy.     

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.     

Significance of multiple biopsies obtained from bladder mucosa in renal pelvic and ureteral carcinoma

PURPOSE: We reviewed significance of multiple biopsies obtained from bladder mucosa in 59 patients of renal pelvic and ureteral carcinoma treated at Osaka Police Hospital between 1990 and 2003. MATERIALS & METHODS: The patients consisted of 41 males and 18 females. The median age was 68 years, ranging from 42 to 91 years. Multiple biopsies were carried out in principle to examine the following 5 cystoscopically normal-appearing bladder mucosal sites: (1) trigone, (2) posterior wall, (3) left lateral wall, (4) right lateral wall and (5) dome. Positive case of multiple biopsies was defined as patients having abnormalities in at least one biopsy specimen such as bladder tumor (BT) or dysplasia. Median follow-up period was 54 months. RESULTS & CONCLUSIONS: Of the 59 patients, 6 had positive multiple biopsies. Among them 3 had carcinoma n situ (CIS), and others had dysplasia. 4 patients with positive multiple biopsies had past or concurrent history of BT and received adjuvant intravesical instillation therapy. Positive rate of multiple biopsies significantly differed between patients with and without past and/or concurrent BT (4/15: 27% vs 2/44: 5% p = 0.03), indicating that multiple biopsies were useful to detect abnormal lesion accompanied with past and/or concurrent BT. 3-year bladder recurrence free rate was 61%. Postoperative bladder recurrence rate did not significantly differ between positive (1/6 17%) and negative (20/53: 38%) cases of multiple biopsies. Univariate analysis indicated stage (p = 0.03) and venous involvement (p = 0.02) to be significant prognostic factors for bladder recurrence free rate, but not multiple biopsies, although multivariate analysis with Cox's proportional hazard model revealed no independent prognosticators. Low recurrence rate of patients with positive multiple biopsies was possibly due to adjuvant intravesical instillation therapy to prevent bladder recurrence.     

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.     

Prognostic significance of mucosal aneuploidy in stage Ta/T1 grade 3 carcinoma of the bladder.

In a prospective series of 71 patients with newly detected grade 3, stages Ta and T1 bladder carcinoma tumor characteristics, including the results of deoxyribonucleic acid (DNA) analysis as well as morphological and DNA characteristics of the grossly normal urothelium, were investigated and related to progression-free survival. The mean duration of followup was 57 months, with a minimum of 24 months. Of the 71 patients 24 underwent primary cystectomy, and 47 were conservatively treated with transurethral resection alone, or followed by instillation therapy or irradiation therapy. Of the cystectomy and conservatively treated patients 2 (8%) and 16 (34%), respectively, died of bladder carcinoma. Among the 47 conservatively treated patients tumor progression could not be predicted by the initial characteristics of tumor stage, papillary or nonpapillary growth, tumor multiplicity, tumor size, existence of 1 or multiple aneuploid cell populations, S phase value, carcinoma in situ and atypia or aneuploidy in the mucosal biopsies. Neither was progression predicted by the recurrence rate during year 1 of observation. However, a change to or persistent mucosal aneuploidy and a change to or persistent morphological abnormality of the mucosa during year 1 of observation were predictive for tumor progression (p = 0.001 and 0.045, respectively). When compared in stepwise regression analysis (Cox's proportional hazard model), DNA aneuploidy in the mucosa at 12 months after diagnosis was a highly significant predictor, whereas morphology added no further prognostic information. Therefore, progression is related to gross chromosomal abnormalities of the mucosa. High risk patients can be identified by evaluation of the grossly normal mucosa, which should be done as part of the initial diagnosis and during followup in conservatively treated patients with stages Ta and T1, grade 3 bladder carcinoma.     

CA-50 as tumour marker in transitional bladder carcinoma

Monoclonal antibody CA-50 is a useful tumour marker in gastrointestinal carcinoma. We report an assessment of its value in bladder cancer patients. We found raised levels in 2 of 2 patients with infiltrating carcinoma and in 8 of 35 with superficial carcinoma. The recurrence rate was higher in patients with raised levels, since 6 of 8 with elevated levels and 15 of 27 with normal values had a recurrence within 6 months. T1 and T3 carcinoma had a mean CA-50 level higher than normal. G3 tumours had a mean level slightly above normal. A statistically significant difference emerged when comparing Ta with T1 + T3 carcinomas. A longer study, with serial determinations, could assess the role of CA-50 as a prognostic indicator in bladder cancer.     

Urothelial atypia concomitant with primary bladder tumour. Incidence in a consecutive series of 500 unselected patients

A consecutive series of 500 primary bladder tumours from a single clinic is presented, with distribution of the tumours according to T category and histologic type and grade. Mucosal biopsies were obtained from pre-selected sites at initial cystoscopy or initial transurethral resection of the tumour in 396 cases. In 54% of the patients with grade III tumour there was concomitant urothelial atypia, either carcinoma in situ (urothelial atypia grade III, 30%) or urothelial atypia grade II (24%). In 30% of the patients with invasive grade II bladder tumour and in 14% of those with noninvasive grade II tumour there was concomitant urothelial atypia, mostly grade II. Since concomitant urothelial atypia predicts new tumour growth after successful transurethral surgery or radiotherapy, mucosal biopsies should be performed at preselected sites during initial cystoscopy or transurethral tumour resection in order to identify high-risk patients.