Multiple biopsies of normal‐looking urothelium in patients with superficial bladder cancer: Are they necessary?

BACKGROUND: The objective of the study presented here was to assess the usefulness and indications of multiple biopsies of normal-appearing urothelium in patients with superficial bladder cancer. METHODS: Between December 1996 and December 2002, multiple biopsies of normal-appearing bladder mucosa were performed in 100 patients with superficial bladder transitional cell carcinoma. Biopsy specimens were taken from seven different sites in females and nine different sites in males. RESULTS: In eight of 100 patients, bladder cancers were detected in the biopsy specimens. Three cases were Ta and five were Tis. All of the five patients with carcinoma in situ (CIS) in their biopsy specimens had multiple papillary broad-base tumors and positive urinary cytology. The detection ratio of CIS in patients with these findings was 17.9% (5/28). No concomitant CIS was detected in the 72 patients who had a solitary tumor, pedunculated tumor(s), or negative urinary cytology. CONCLUSION: Multiple mucosal biopsies of normal-appearing urothelium are not necessary for all patients with superficial bladder cancer. They are, however, necessary for patients with multiple papillary broad-base tumors and positive urinary cytology.     

Discrepancies between cytology, cystoscopy and biopsy in bladder cancer detection after Bacille Calmette-Guerin intravesical therapy

Objectives:   To evaluate discrepancies in the detection of Bacille Calmette-Guerin (BCG)-resistant bladder cancer by cystoscopy, bladder biopsy and urinary cytology.
Methods:   Between January 1992 and August 2006, 127 bladder cancer patients underwent a cycle of eight weekly BCG instillations. Four weeks after the last BCG instillation, urinary cytological analysis and cystoscopy with targeted biopsy in addition to eight–nine selected-site biopsies were performed.
Results:   Biopsy-proven cancer was found in 11/27 (40.7%), 5/42 (11.9%), and 11/58 (19.0%) of positive, suspicious, and negative cytology cases, respectively. Abnormal and normal cystoscopic findings correlated with a biopsy-proven cancer in 13/53 (24.5%) and 14/74 (18.9%) cases, respectively. The combination of a macroscopic cystoscopic suspicion and a positive cytology missed malignant cases in 15.9% of the cases. In 100 cases without biopsy-proven cancer, the rates of denuded urothelium at biopsy in the cases with positive and non-positive cytology were 7/16 (43.8%) and 16/84 (19.0%), respectively
Conclusions:   According to our study, routine biopsy is recommended in the evaluation of BCG treatment, even if the timing, limitations and disadvantages of the procedure should be taken into account.     

Clinical outcome of high-grade non-muscle-invasive bladder cancer: A long-term single center experience

Objectives:   To report on the long-term clinical outcome of high-grade (G3) non-muscle-invasive bladder cancer (NMIBC) patients treated at a single institution.
Methods:   A retrospective analysis of 93 patients with NMIBC treated between January 1991 and September 2005 was performed. Patients were divided into three groups on the basis of treatment they received after transurethral resection (TUR) of the bladder. Forty-seven patients received adjuvant intravesical epirubicine after TUR of the bladder (Group 1). Twenty-four patients received intravesical bacillus Calmette–Guérin (BCG) (Group 2). A radical cystectomy (RC) was performed on twenty-two patients (Group 3).
Results:   Median follow up was 68.7 months. Overall, thirty patients (33%) experienced tumor recurrence. The survival rates of Group 3 were significantly higher than the 71 patients undergoing conservative therapy (Group 1 and 2). There was no statistically significant difference between Group 1 and 2, but treatment failure in patients treated with epirubicine was significantly higher than in those with BCG. Cases without concomitant carcinoma in situ (CIS) showed statistically significantly higher survival rates than those with concomitant CIS.
Conclusions:   RC provides excellent survival rates in patients with high-grade NMIBC. Adjuvant therapy with BCG after a complete TUR of the bladder may be an effective treatment for high-grade NMIBC. If a conservative treatment is preferred to RC, co-existence of a concomitant CIS should be considered with caution.     

Clinical Evaluation of Random Biopsy of Urinary Bladder in Patients with Superficial Bladder Cancer

Background Superficial bladder cancer has a tendency to recur in the urinary bladder. One reason for recurrence is the presence of concomitant carcinoma in situ (CIS) or dysplasia. However, the usefulness of random biopsy of the urinary bladder has been unclear.
Methods Between September 1990 and March 1996, 83 patients with superficial bladder cancer underwent mucosal biopsy of 6 different sites in the urinary bladder with macroscopically normal findings (random biopsy). The relationship between a positive biopsy (CIS or dysplasia) and the tumor characteristics was examined. The disease-free survival of the patients according to the biopsy results was determined.
Results The positive biopsy rate was 24.1% (CIS, 14.5% dysplasia, 9.6%). The incidence of positive biopsy in patients with high-grade (C3), pT1 tumors, 3 or more and non-papillary wide-based tumors was significantly higher than that in patients with 1 or 2 tumors, low-grade (G1, G2), pTa tumors and papillary tumors (P< 0.05). In patients with a single papillary tumor, positive biopsy was found in 9.5%. The disease-free survival in patients with a positive biopsy did not differ from that in patients with a negative biopsy, because intravesical bacillus Calmette-Guérin was instilled in patients with a positive biopsy.
Conclusion Our results indicate that random biopsy is useful for detecting concomitant CIS or dysplasia and in the choice of drugs for intravesical instillation.     

Clinical impact of bladder biopsies with TUR-BT according to cytology results in patients with bladder cancer: a case control study

Background

There seems to be no consensus concerning taking bladder biopsies during transurethral resection of bladder tumor (TUR-BT). We investigate the clinical significance of bladder biopsy with TUR-BT and the relationship between urinary cytology and the biopsy results.

Methods

We reviewed a total of 424 patients with non-muscle invasive bladder cancer treated with TUR-BT between 1998 and 2005. Of the total, 293 patients also underwent a bladder biopsy. Biopsies from suspicious-appearing urothelium (N = 59) and those from normal-appearing urothelium (N = 234) were evaluated separately.

Results

Bladder cancer was observed in 23 cases (39.0%) who underwent a biopsy of suspicious-appearing urothelium. Among these 23 cases, 9 cases with visible tumor resection had carcinoma in situ (CIS) only in the biopsies from suspicious-appearing urothelium. Urinary cytology was negative in 3 of the 9 cases. Bladder cancer was observed in 26 cases (11.1%) who underwent a biopsy of normal-appearing urothelium. Of them, 5 cases with visible tumors had CIS only in the multiple biopsies from normal-appearing urothelium. Urinary cytology was positive in all of the 5 cases. No upstaging or upgrading cases were found in these patients by the addition of these two types of biopsy. Furthermore, therapy was not altered in these patients. With or without bladder biopsy was not a significant factor for tumor recurrence in either the univariate or multivariate analysis.

Conclusions

Based on the results, it is concluded the multiple biopsies from normal-appearing urothelium are not necessary in patients with negative cytology results because of the low detection rate and lack of influence on therapeutic decisions. Meanwhile, biopsy of suspicious-appearing urothelium is needed in patients with negative cytology results in order to detect CIS due to staging properties. This result supports a recent EAU guideline.     

Clinical outcomes of bacillus Calmette-Guérin instillation therapy for carcinoma in situ of urinary bladder

Objectives:   We analyzed the clinical outcomes of instillation therapy with Bacillus Calmette-Guerin (BCG) to treat carcinoma in situ (CIS) and searched for prognostic factors that could predict disease progression.
Methods:   Between January 1995 and January 2001, 185 patients (male, 155; female, 30) diagnosed with bladder CIS underwent weekly BCG instillations (80 mg of Tokyo 172 strain) for eight weeks. Primary, concomitant, and secondary CIS was found in 62 (33.5%), 60 (32.4%) and 63 (34.1%), patients, respectively. Seventy-five (40.5%) and 64 (34.6%) patients had limited and extensive CIS, respectively. The median follow up period was 37.5 months (range 4–95 months).
Results:   The overall complete response rate was 86.5%. The five-year progression-free survival rate was 78.5%. Several factors, such as age (<60 or ≥60 years), gender, previous transurethral resection, type of CIS, and CIS extension (three or more positive sites out of four to six biopsy sites was defined as extensive), were examined by multivariate analysis to predict progression. The extension of CIS was the only independent prognostic factor. The five-year recurrence-free rate of complete responders ( n  = 160) was 66.0%. Radical cystectomy was performed in 10 patients (6.3%) during follow up incomplete responders, of whom seven had invasive bladder cancer. Extravesical involvement was identified in 30 patients (16.2%) among whom, 21 (11.3%) had upper urinary tract recurrence and nine (4.9%) had prostatic involvement.
Conclusion:   Therapy with BCG is effective against CIS, the extent of which might be a prognostic factor. Disease progression including extravesical involvement should be carefully monitored over the long-term after BCG therapy.     

The value of the UroVysion assay for surveillance of non-muscle-invasive bladder cancer

OBJECTIVE: Patients with non-muscle-invasive bladder cancer are traditionally followed by repeat cystoscopy and urine cytology. A fluorescence in situ hybridisation technique called UroVysion((R)) (UV) is now available for clinical diagnosis of urothelial cancer cells. The aim of the present study was to compare UV analysis with routine follow-up methods. METHODS: We studied an unselected cohort of patients undergoing cystoscopy follow-ups at two Swedish centres in 2004-2005. All patients were investigated by cystoscopy, cytology, and UV assay. The UV assay was evaluated with regards to sensitivity, specificity, and positive predictive value for tumour recurrence. RESULTS: In all, 159 cases were analysed. UV had a 30% overall sensitivity for the 27 biopsy-proven recurrences and 70% sensitivity for high-risk tumours (pT1 and carcinoma in situ [CIS]). The specificity of UV was 95%. UV detected all six CIS cases in the study and was predictive in two additional patients who developed CIS within 1 yr of inclusion. Cytology was positive in four of those eight CIS cases and atypical in the other four. CONCLUSIONS: The UV assay cannot replace cystoscopy for surveillance of patients with non-muscle-invasive bladder cancer, but it may be valuable as a supplement to traditional measures for detecting CIS. Before any conclusions can be drawn regarding the efficacy of novel markers of bladder cancer, they must be studied in bladder cancer patients undergoing endoscopic surveillance.     

Management of concomitant ureteral carcinoma in situ at radical cystectomy

OBJECTIVE: We conducted a retrospective study to evaluate and define the management of concomitant ureteral carcinoma in situ (CIS) at radical cystectomy. METHODS: For 158 consecutive patients, who underwent radical cystectomy for invasive bladder cancer, ureteral CIS missed by preoperative examinations were evaluated by intraoperative analysis of frozen sections or postoperative histological analysis. The median follow-up period was 3.4 years. RESULTS: In total, 15 concomitant ureteral CIS were diagnosed by intraoperative (n=9) or postoperative analysis (n=6). Additional ureteral resection achieved no malignancies in the final ureteral margins of eight patients. During the follow-up period, five patients (3.6%) suffered from tumor recurrence in the upper urinary tract in total, as did three (20%) among the 15 patients with ureteral CIS missed by preoperative examinations. No recurrence was identified in the eight patients with no malignancy in the final ureteral margins after additional resection. Furthermore, multivariate analysis indicated that the presence of bladder CIS was a risk factor for the presence of concomitant ureteral CIS. CONCLUSIONS: Detection of concomitant ureteral CIS by intraoperative studies, in combination with complete resection of ureteral CIS, might be beneficial for patients with risk factors such as bladder CIS.     

Results of Transurethral Resection Plus Adjuvant Intravesical Chemotherapy for Superficial Bladder Cancer

Background : We analyzed the results of conservative therapy for superficial bladder cancer to determine the risk factors for recurrence and progression.
Methods : Between May 1984 and February 1997, 111 patients with primary superficial bladder cancer were treated by a transurethral resection with or without intravesical instillation of chemotherapy, or for patients with concomitant carcinoma in situ (CIS), bacillus Calmette-Guerin. We examined the relationship between tumor stage, grade, incidence of concomitant CIS and recurrence-free survival according to pathologic findings and the drugs instilled.
Results : The incidence of concomitant CIS in pTI, grade 3 tumors was significantly higher than that in pTa, grade 1 tumors (42% vs. 3%, P= 0.006). The 5-year recurrence-free survival rate of all patients was 73%. There was no significant difference in recurrence-free survival and pathologic stage, tumor grade, presence of concomitant CIS, or drugs used for instillation. However, the recurrence-free survival in patients with 5 tumors was significantly lower than in patients with less than 5 tumors. Of the 111 patients, only 3 patients demonstrated disease progression and underwent a radical cystectomy, while 1 patient with a pTI b, grade 3 tumor developed a tumor in the ureter. No patient died of bladder cancer.
Conclusion : Our results indicate that the prognosis of superficial bladder cancer patients with a high-stage, high-grade (pTI, grade 3) tumor is favorable when treated by a transurethral resection and intravesical instillation. Bacillus Calmette-Guerin therapy is useful to prevent the recurrence of tumors with concomitant CIS.     

Clinical outcome of tumor recurrence for Ta, T1 non-muscle invasive bladder cancer from the data on registered bladder cancer patients in Japan: 1999–2001 report from the Japanese Urological Association

Objective:   To characterize the clinical outcome in a large contemporary series of Japanese patients with newly diagnosed Ta, T1 non-muscle invasive bladder cancer who underwent transurethral bladder tumor resection with or without intravesical chemotherapy or Bacillus Calmette-Guérin (BCG) therapy.
Methods:   We developed a database incorporating newly diagnosed non-muscle invasive bladder cancer data and outcomes from a Japanese bladder cancer registry between 1999 and 2001 and identified a study population of 3237 consecutive patients who had complete data based on pathological features. Median patient age was 69.9 years.
Results:   The 1-year, 3-year, and 5-year overall recurrence-free survival rates were 77.0%, 61.3%, and 52.8%, respectively. In multivariate analyses, the multiplicity of bladder tumors, tumor size greater than 3 cm, pathological stage T1, tumor grade G3, and the absence of adjuvant intravesical instillation were independent risk factors for tumor recurrence. Overall, 1710 patients (52.8%) received intravesical instillation; chemotherapy in 1314 (76.8%) and BCG treatment in 396 (23.2%). In patients treated with intravesical chemotherapy in which an anthracycline chemo-agent was used in 90.5% of the cases, multivariate analyses demonstrated that male gender, multiple bladder tumors, a tumor size greater than 3 cm, and pathological stage T1 were associated with tumor recurrence.
Conclusions:   The accumulation and analysis of data from the Japanese National Bladder Cancer Registry made it possible to determine the clinical characteristics, management trends, and survival rates for the period studied. Further study with a dataset created from longer follow-up data would be warranted to analyze tumor progression and disease survival.     

Independent predictors of contralateral metachronous upper urinary tract transitional cell carcinoma after nephroureterectomy: Multi-institutional dataset from three European centers

Objectives:   To identify the variables predictive of contralateral metachronous upper urinary tract transitional cell carcinoma (UUT-TCC) after nephroureterectomy (NFU) for non-metastatic UUT-TCC.
Methods:   Clinical and pathological data of 234 patients who had undergone NFU for UUT-TCC from 1989 to 2005 in three European urological centers were retrospectively collected and analyzed.
Results:   The median follow-up duration for the whole cohort was 34 months. Contralateral metachronous UUT-TCC was detected in 14 patients (6%). Three patients were treated by NFU, while seven patients underwent ureterectomy and reimplantation and four patients were treated by endoscopic resection plus bacillus Calmette–Guérin instillations within the UUT through a nephrostomic tube. On univariate analysis, a prior history of bladder TCC before NFU was the only factor predictive of the occurrence of contralateral UUT-TCC. Specifically, the 5-year probabilities of being free from contralateral UUT-TCC were 96.6% for the patients with de novo UUT-TCC, and 91.1% and 55.3% for those having non-muscle-invasive and muscle invasive bladder TCC before the UUT cancer, respectively. All survival differences were statistically significant (no history of bladder TCC vs history of non-muscle-invasive bladder TCC, log rank P value 0.015; history of non-muscle-invasive bladder TCC vs history of muscle-invasive bladder TCC, log rank P value 0.035).
Conclusions:   In our multicenter dataset of patients who had undergone NFU for UUT-TCC, contralateral metachronous UUT-TCC occurred in 6% of the patients. A prior history of bladder TCC before NFU was the only variable predictive of UUT recurrence at univariate analysis.     

Bladder sparing approach for initial T1G3 bladder cancer: Do multifocality,size of tumor or concomitant carcinoma in situ matter? A long‐term analysis of 132 patients

OBJECTIVES: In T1 bladder cancer (BC) multifocality, size of tumor (> or =3 cm) and concomitant carcinoma in situ (CIS) are used to stratify patients' risk. We compared the long-term results in patients with initial T1G3 bc treated with transurethral resection of the bladder (TURB), bacille Calmette-Guérin (BCG) instillations and repeat resection with special regard to these clinical risk factors. The aim was to determine if they influence the outcome in the bladder sparing approach for initial T1G3 bc. METHODS: One hundred and thirty-two consecutive patients with initial T1G3 and no prior history of BC were identified. All patients completed six weekly adjuvant BCG instillations followed by control TURB. Follow-up consisted of cystoscopy with bladder wash cytology every 3 months for 2 years and every 6 months thereafter. RESULTS: Forty-two percent of patients had residual disease, 65% developed recurrence of any stage and 41% had progression to muscle-invasive disease. Cancer-specific survival was 89% and 78% at 5 and 10 years, respectively. Only CIS was significantly correlated with all end points on multivariate analysis. While the presence of one or two risk factors was not related to recurrence, progression or cancer-related death, the presence of all three risk factors predicted the latter. CONCLUSIONS: While no guideline has been established for the decision between cystectomy and bladder sparing, concomitant CIS and the presence of all three risk factors together seem to predict an adverse oncological outcome in the bladder sparing approach.     

Role of routine transurethral biopsy and isolated upper tract cytology after intravesical treatment of high‐grade non‐muscle invasive bladder cancer

Objectives: To investigate whether random bladder, and prostatic urethral biopsies and individual upper tract cytologies (restaging) provide useful clinical information in addition to cystoscopy and bladder cytology in assessing initial intravesical therapy response for high‐grade non‐muscle invasive bladder cancer. Methods: We retrospectively reviewed records of all patients who underwent restaging at our institution after treatment for high‐grade non‐muscle invasive bladder cancer (Ta, T1 and Tis) between January 2000 and October 2009. A total of 78 patients undergoing 116 consecutive restagings were included. The presence of intravesical cancer at restaging was assessed by cystoscopy, bladder wash cytology and random bladder biopsies, whereas ureteral and prostatic urethral disease was determined using upper tract barbotage cytology and prostatic urethral biopsies. Results: Indication for intravesical treatment was carcinoma in situ in 86, high‐grade T1 in 16 and high‐grade Ta in 14 cases. A total of 48 patients had primary disease and 68 had recurrence. Overall, 59 of 116 (50.9%) restagings showed positive bladder or prostatic biopsy and/or a positive cytology localized to the upper tract. Of the total number of recurrences, 12.9% (15 of 116) showed a negative cystoscopy and negative bladder cytology, and would have been missed on routine surveillance. A total of 23 of 116 (19.8%) restagings showed evidence of prostatic urethral and or ureteral disease. Conclusion: Roughly 25% of high‐grade non‐muscle invasive bladder cancer early recurrences after induction intravesical therapy would go unnoticed without the addition of random and directed prostate biopsies, and isolated upper tract cytologies to standard cystoscopy and bladder cytology.     

The sensitivity and clinical implications of periodical bladder biopsy following transurethral resection of superficial bladder transitional cell carcinoma

The role of the periodical bladder biopsy after transurethral resection (TUR-Bt) of superficial bladder cancer (sBT) was evaluated. Sixty-four patients (85 TURs) with sBT who underwent TUR-Bt between 1993 and 1998 were divided into 14 (22 TURs) who had carcinoma in situ (CIS) at the first TUR (group A), and 50 (64 TURs) who had papillary tumors without concomitant CIS (group B). Post-TUR intravesical instillation was performed with bacillus Calmette-Guerin for the majority of group A, and mitomycin C for the majority of group B. The first biopsy was performed at 3 months postoperatively, and the second biopsy was done at 8 to 12 months postoperatively. The mean observation time was 4 years and 6 months. Residual cancer was detected in 7 out of 34 biopsies (20.6%) in group A, and 19 out of 94 (20.2%) in group B. Every residual lesion in group A was CIS with negative cytology. In group B, with exclusion of 11 recurrent papillary tumors, the detection rate was only 8/83 (9.6%). In both groups, even in the cases with no sign of disease in biopsies, the recurrence immediately after the termination of the biopsy protocol was common. The progression of the cancer was more frequent in group A (4 patients), than in group B (2 patients) (p < 0.01, log-rank test), and no case in group B showed local progression. The periodical biopsy may have a certain, but limited advantage over conventional examinations. A less invasive and more sensitive method in awaited.     

Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ-confined TCC at radical cystectomy

OBJECTIVES: Carcinoma in situ (CIS) is a nonpapillary, high-grade, potentially aggressive, and unpredictable manifestation of transitional cell carcinoma (TCC) of the bladder. The aim of this study was to assess whether presence of concomitant CIS has a detrimental effect on cancer control after radical cystectomy. METHODS: The records of 812 consecutive patients who underwent radical cystectomy and pelvic lymphadenectomy for bladder TCC at three US academic centres were reviewed. Ninety-nine of 812 (12%) patients had CIS only at radical cystectomy and were excluded from the analyses. RESULTS: Three hundred thirty of the 713 (46.3%) patients had concomitant CIS at radical cystectomy. Patients with TCC involvement of the urethra were more likely to have concomitant CIS than not (61% vs. 40%, p=0.018). Concomitant CIS was significantly more common in patients with lower cystectomy stages and higher tumour grades. In univariate, but not multivariate, analysis, patients with concomitant CIS versus those without were at increased risk of disease recurrence (p=0.0371). In patients with organ-confined disease, concomitant CIS was an independent predictor of disease recurrence (p=0.048 and p=0.012, respectively) but not bladder cancer-specific mortality (p=0.160 and p=0.408, respectively) after adjusting for the effects of standard postoperative features. CONCLUSIONS: Concomitant CIS in the cystectomy specimen is common, and patients with concomitant CIS are at increased risk of urethral TCC involvement. The presence of concomitant CIS appears to confer a worse prognosis in patients with non-muscle-invasive TCC treated with radical cystectomy.     

Bladder cancer develops 6 years earlier in current smokers: Analysis of bladder cancer registry data collected by the cancer registration committee of the Japanese Urological Association

Objectives:   It is generally recognized that cigarette smoking is the most important risk factor for bladder cancer. The present study was undertaken to examine the relationships between smoking history of bladder cancer patients and the age of onset of bladder cancer and tumor characteristics.
Methods:   The present study examined the data for 5959 cases (4728 males and 1231 females) collected in the bladder cancer database of the Japanese Urological Association from 1999 to 2001. Patients were divided by smoking history into three categories as current non-smokers, current smokers and unknown smoking history. Relationship between smoking history and the age at diagnosis of bladder cancer, gender, T stage, grade, tumor size, tumor number and initial symptoms was analyzed
Results:   In both males and females the onset of bladder cancer is about 6 years (6.1 years in males and 5.9 years in females) earlier for current smokers than for current non-smokers. At the time of diagnosis, tumor stage was significantly higher in the current smokers group. The current smokers group tended to have larger tumor size.
Conclusions:   The finding of 6-year-earlier onset of bladder cancer among current smokers is of great importance to both health care and medical economics. It is essential to make people better informed concerning the need to quit smoking.     

Clinical significance of immediate urine cytology after transurethral resection of bladder tumor in patients with non‐muscle invasive bladder cancer

Objectives: To assess the clinical significance of immediate urine cytology (IUC) after transurethral resection of bladder tumor (TURBT) for non‐muscle invasive bladder cancer (NMIBC). Methods: We reviewed the records of 174 patients who underwent IUC after TURBT for NMIBC. IUC was obtained just before Foley catheter removal after TURBT. The relationship between IUC and tumor stage, grade, size and multiplicity, as well as preoperative urine cytology and immediate intravesical epirubicin therapy, were assessed. The relationship between a positive IUC and cancer recurrence was also assessed. Multivariate Cox proportional hazards regression analysis was carried out, including IUC, tumor stage, tumor grade, tumor size, tumor multiplicity, preoperative urine cytology and immediate intravesical epirubicin therapy. Results: IUC was positive in 76 patients (43.7%) and negative in 98 patients (56.3%). In the positive IUC group, tumor stage and grade were higher (P = 0.001, <0.001), tumor size was larger (P = 0.001), tumor multiplicity was higher (P = 0.002) and positive preoperative cytology was more likely (P = 0.006) than in the negative IUC group. In the positive IUC group, the cancer recurrence rate was 72.3% and that of the negative IUC group was 30.6% (P < 0.001). In a multivariate Cox proportional hazards regression analysis, positive IUC (HR 1.83, P = 0.019), tumor size (HR 1.72, P = 0.045), tumor multiplicity (HR 3.63, P = 0.015), preoperative urine cytology (HR 1.23, P = 0.043) and immediate intravesical epirubicin therapy (HR 0.171, P = 0.001) were independent prognostic factors for cancer recurrence. Conclusion: These data suggest that IUC after TURBT for NMIBC can be an independent prognostic factor to predict cancer recurrence.     

Bacillus Calmette-Guerin versus epirubicin for primary, secondary or concurrent carcinoma in situ of the bladder: results of a European Organization for the Research and Treatment of Cancer--Genito-Urinary Group Phase III Trial (30906)

PURPOSE: We compared the efficacy and side effects of intravesical instillations of bacillus Calmette-Guerin (BCG) and epirubicin in patients with carcinoma in situ (CIS) of the bladder. MATERIALS AND METHODS: Patients with primary, secondary or concurrent CIS of the bladder were randomized to 81 mg BCG-Connaught (6 weekly instillations) or 50 mg epirubicin (8 weekly instillations). When a complete response (CR), defined as no Ta/T1 or CIS on biopsy and negative cytology, was obtained, patients in the 2 groups received maintenance instillations at months 3, 6, 12, 18, 24, 30 and 36. When no complete response was observed, the original treatment was repeated, followed again by cystoscopy and biopsies plus cytology. RESULTS: A total of 168 patients were randomized between March 1993 and April 1999 to receive BCG (84) or epirubicin (84), while 4 on epirubicin and 3 on BCG were ineligible. The majority (52%) had concurrent CIS. Primary and secondary CIS was found in 23% and 24% of cases, respectively. The overall CR rate was 56% for epirubicin and 65% for BCG (p = 0.21, 90% CI 21.5 to -2.9). When tumor was found following 2 instillation courses, further treatment was left to the investigator (BCG in 29 cases and epirubicin in 37). Time to bladder tumor recurrence after CR was longer in patients treated with BCG vs epirubicin (median 5.1 vs 1.4 years). CIS recurrences were more frequently observed in complete responders to epirubicin (45% vs 16%). No differences in time to progression or duration of survival were observed. Side effects were more frequently seen in patients on BCG with 26 on BCG and 8 on epirubicin stopping treatment due to side effects. CONCLUSIONS: No significant difference in CR rates could be demonstrated with intravesical instillations of epirubicin or BCG. Time to recurrence was significantly longer in patients treated with BCG after having achieved a CR. More CIS recurrences were found in patients treated with epirubicin. For time to progression and survival longer followup is warranted. Side effects were more frequent in patients on BCG.     

Significance of the BTA Test in Bladder Cancer: A Multicenter Trial

Background :
The BTA test is a latex agglutination assay for the qualitative detection in the urine of analytes that are associated with bladder tumor. We compared the results of the BTA test with those of voided urine cytology (VUC) in patients with bladder cancer.
Methods :
A multicenter trial was performed at 6 institutions. A total of 132 patients with histologically diagnosed bladder cancer were enrolled. Urine samples were split for BTA and VUC testing.
Results :
The sensitivities of the BTA test and VUC were 57.6% and 37.9%, respectively; this difference was significant ( P < 0.001). The BTA test had much higher sensitivity for small, solitary, superficial tumors than did VUC.
Conclusion :
The BTA test is simple to perform, gives rapid results, and is far more sensitive than VUC for detection of bladder cancer. The BTA test has the potential to become an additional tool for detecting bladder cancer.