Clinical significance of urothelial dysplasia concomitant with superficial bladder cancer]

OBJECTIVE: Retrospective analysis was carried out to evaluate the prognostic value of urothelial dysplasia with superficial bladder cancer. PATIENTS AND METHODS: 62 patients with bladder cancer of pTa or pT1 who had been treated by transurethral resection (TUR-Bt), underwent random mucosal biopsies in the urinary bladder. The results of random biopsies were classified into 3 groups: negative group, dysplasia group and CIS group. The recurrence rate, progression rate and type of recurrences (true recurrence/new occurrence) were compared among the 3 groups. RESULTS: The results of random biopsies were as follows; negative group was found in 42 (68%), dysplasia group in 17 (27%) and CIS group in 3 (5%). There were no significant difference in the characteristics of the patients among the 3 groups. The recurrence rates at 1, 2 and 5 years after TUR-Bt were 3%, 12% and 21%, respectively, for negative group, and 37%, 51% and 67%, respectively, for dysplasia group (p < 0.01). For CIS group, 2 of 3 cases (67%) recurrenced within 1 year after TUR-Bt. Non of negative group progressed to muscle invasion, whereas 57% of dysplasia group invaded bladder muscle after 6 years post operatively (p < 0.001). No significant relationship was observed between the absence or presence of concomitant dysplasia and the rate of true recurrence. Dysplasia group revealed a higher rate (47.1%) of new occurrence than negative group (2.4%) (p = 0.0001). CONCLUSION: The presence or absence of concomitant dysplasia of superficial bladder cancer seems to be an important prognostic factor for future new ocurrence and progression after TUR-Bt.     

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.     

Risk of concomitant carcinoma in situ determining biopsy candidates among primary non-muscle-invasive bladder cancer patients: Retrospective analysis of 173 Japanese cases

Objectives:   To determine candidates for bladder biopsies among Japanese primary non-muscle-invasive bladder cancer patients according to the risk of concomitant carcinoma in situ (CIS).
Methods:   Between January 1992 and August 2006, 173 primary non-muscle-invasive bladder cancer cases underwent transurethral resection of the bladder tumor with bladder biopsies for the detection of CIS. Correlations between biopsy results and preoperative/pathological features were retrospectively analyzed.
Results:   Positive cytology was statistically associated with the presence of concomitant CIS in multivariate analysis ( P  < 0.01). Abnormal cystoscopic appearance outside the tumor almost achieved statistical significance in multivariate analysis among preoperative factors ( P  = 0.06). In our series, one (12.5%) of eight low-risk, 18 (24.7%) of 73 intermediate-risk and 41 (59.4%) of 69 high-risk cases had CIS in normal-looking sites, respectively. In cases with a single papillary tumor and negative cytology, one of 16 (6.3%) had concomitant CIS in their biopsy specimens at the normal-looking sites.
Conclusions:   All non-muscle-invasive bladder cancer patients with positive cytology are candidates for additional random biopsies. Targeted biopsies should be performed for all suspicious areas in the bladder mucosa. Random biopsies should be considered in cases with the macroscopic types of cancer for predicting intermediate- and high-risk cancer.     

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.     

Only metastasis to uterine corpus from superficial bladder cancer that of no original recurrence

We report a rare case of uterine corpus metastasis from superficial bladder cancer. A 78-year-old female presented with abnormal vaginal bleeding. She received transurethral resection of bladder tumor (TUR-Bt) two years previously, and the pathological findings were transitional cell carcinoma (TCC) grade 3 pT1. Eight courses of BCG instillation were performed postoperatively. There was no recurrence of bladder cancer when vaginal bleeding occurred. Cytology of vaginal discharge was class V, and transitional cell carcinoma suspected. Pathological finding of transvaginal uterine corpus biopsy was TCC. We diagnosed metastases to uterine corpus from bladder cancer.     

Two cases of the nephrogenic adenoma of the bladder

Nephrogenic adenoma is a relatively rare, benign tumor of the urinary tract. We experienced two cases of nephrogenic adenoma originating in the bladder. The first patient was a 61-year-old man. Two papillary tumors were found on the bladder. Transurethral resection of the bladder tumor (TUR-Bt) was performed. The second patient was a 72-year-old man who had a history of TUR-Bt for the bladder tumor and a history of left nephroureterectomy for left ureteral tumor. Cystoscopy showed a papillary tumor on the top of the bladder wall and TUR-Bt was performed. In both cases, the histopathological diagnosis was the nephrogenic adenoma. Our cases are the 40th and 41st cases of the nephrogenic adenoma of the bladder reported in the Japanese literature.     

Ablative and prophylactic effects of BCG Tokyo 172 strain for intravesical treatment in patients with superficial bladder cancer and carcinoma in situ of the bladder. Bladder cancer BCG Study Group]

We investigated the effects of intravesical instillation of BCG Tokyo 172 strain on patients with superficial bladder cancer and CIS of the bladder for tumor ablation and prophylaxis. This is the first controlled multicenter study for governmental approval of BCG Tokyo 172 strain for the treatment of superficial bladder cancer and CIS of the bladder. One hundred-fifty-seven patients (125 with Ta or T1, and 32 with CIS) were treated by 80 mg of BCG diluted in 40 ml of saline, once a week for 8 weeks. The dose and interval adopted in this multicenter study was determined by the previous Phase II study conducted by the same Study Group. Out of 125 superficial tumor Ta, T1, 83 (66.4%) showed complete disappearance of the tumor (CR) and 26 (20.8%) partial disappearance (PR), and out of 32 CIS, 27 (84.4%) showed CR and 2 (6.3%) PR. Among those patients showing CR, and PR who were treated with additional TUR-Bt, 98 patients were randomised for a controlled study of prophylactic BCG instillation. Prophylactic treatment consisted of 40 mg of BCG diluted in 40 ml of saline, monthly for 12 months. Forty-two patients were assigned to the treatment group, whereas the remaining 56 to the control group without any prophylactic instillation. Three cases showed tumor recurrence during the prophylactic phase. Twenty-five cases could not be treated for the whole course of prophylactic instillation mainly due to bladder irritable symptoms. Recurrent free curves were compared till 1050 days after the initiation of the study. However, there was no significant difference between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Photodynamic therapy for refractory superficial bladder cancer: long-term clinical outcomes of single treatment using intravesical diffusion medium

BACKGROUND: Diffuse superficial transitional-cell carcinoma (TCC) refractory to standard therapies poses a clinical dilemma. Photodynamic therapy (PDT), which uses an interaction between absorbed light and a retained photosensitizing agent to destroy tissue, has been used to treat diffuse superficial bladder TCC, although there are few reports of long-term outcomes. PATIENTS AND METHODS: A series of 34 patients, 29 with TCC carcinoma in situ (CIS) and 5 with multiple small papillary stage T(a) or T(1) lesions, received porfimer sodium (P) 48 hours before whole-bladder PDT with 630-nm laser light. A 0.02% soybean emulsion diffusion medium was instilled into the bladder, and the laser optical fiber was positioned under triplanar sonography prior to PDT. The mean follow-up was 52 months. RESULTS: At 3 months, a complete response (CR) in 14 (44%) of the 32 evaluable patients, a partial response (PR) in 4 (12%), and no response (NR) in 14 (44%). Four of the five patients with extensive papillary lesions did not respond. The NR rate for patients with CIS with or without resected papillary lesions was 37%. The mean time to recurrence in the CR group was 9.8 months, and five members of this group (36%) underwent cystectomy (mean time 20 months) for persistent/progressive disease (N = 3) or bladder contracture (N = 2). In the NR group, 6 (43%) underwent cystectomy (mean time 14 months) for persistent/progressive disease. Metastatic bladder cancer was the cause of death in only 4 of the 12 patients who have died. Of the remaining 22 patients, 15 are still alive and have an intact bladder, nine with no disease and six with only superficial disease. CONCLUSION: This is the first report of long-term results following whole-bladder PDT using diffusion medium for isotropic light distribution. More than half of the patients with TCC refractory to traditional intravesical therapy received benefit from a single PDT session. Patients with extensive flat papillary lesions do not appear to respond well. Patients who achieve a CR have less likelihood of and longer time interval before needing cystectomy for progressive disease than NR patients. Our PDT protocol is associated with minimal morbidity in these high-risk patients.     

Pathological characteristics and clinical course of bladder tumour developing after nephroureterectomy

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

OBJECTIVES

To determine the pathological features and clinical course of intravesical recurrence after nephroureterectomy (NU) for upper urinary tract (UUT) cancer.

PATIENTS AND METHODS

Among 325 patients undergoing NU with bladder cuff excision for UUT cancer, in this retrospective multi‐institutional study we evaluated 113 who developed bladder tumour after NU. Excluding patients with (i) perioperative systemic chemotherapy or radiotherapy for UUT cancer; (ii) a history of previous or synchronous bladder cancer at the time of NU; (iii) distant metastasis at the time of NU; (iv) a follow‐up of <1 year after the initial bladder cancer recurrence; or (v) missing data, 74 patients were included in this study. We compared the pathology between UUT cancer and the first bladder cancer recurrence, using Fisher’s exact test. Further intravesical recurrence and bladder cancer progression was analysed using the Kaplan‐Meier method, with the log‐rank test used to assess significance. A Cox proportional hazard model was used for multivariate analysis.

RESULTS

The grade of the first bladder cancer recurrence strongly correlated with that of the UUT tumour (P < 0.001) and the carcinoma in situ (CIS) lesion with the first bladder cancer recurrence correlated with high grade (grade 3) UUT tumour (P < 0.001). In all, 56 of the assessable 70 patients further developed intravesical recurrence at a median interval of 7 months after the first bladder cancer recurrence. There were no clinicopathological factors that predicted the second recurrence. Progression occurred in 14 patients, at a median interval of 25 months. A CIS lesion with the first bladder cancer recurrence was a risk factor for progression on multivariate analysis.

CONCLUSIONS

A large proportion of the patients who developed bladder tumour after NU had further intravesical recurrence, which indicated its refractory nature. Especially when a CIS lesion is detected in the initial intravesical recurrence, a careful follow‐up is mandatory to detect bladder cancer progression.     

Failure of intravesical interferon-alfa-2b for the treatment of patients with superficial bladder cancer previously failing intravesical BCG Therapy

Twelve patients with superficial bladder cancer who had failed one or two 6-week courses of intravesical bacillus Calmette-Guérin (BCG) therapy were treated with recombinant interferon-alfa-2b (rIFN-alfa-2b). Patients received 12 weekly instillations of rIFN-alfa-2b (100 MU) in 50 cc of normal saline. Those with an initial tumor-free response at the 3-month follow-up received maintenance rIFN-alfa-2b instillations (100 MU) monthly for an additional 9 months. Prior to rIFN-alfa-2b treatment, 6 patients had carcinoma in situ (CIS) with concurrent papillary tumor (pTa or pT I), and 6 had grades I or 2 pTa tumors. Patients were monitored every 3 months with urinary cytologies, cystoscopies, and biopsies when indicated. Median follow-up was 18 months (range 12 to 26 months). At the 3-month follow-up tumor recurrence was noted in 8 (66%) of 12 patients. An additional 3 (25%) patients had tumor recurrence at the 6-month follow-up period, and 3 (25%) patients also developed upper tract tumors during follow-up. Only 1 (8%) patient has maintained a continuous tumor-free response for 24 months. We are unable to demonstrate that rIFN-alfa-2b is likely to induce a tumor-free response in superficial bladder tumor patients who have failed intravesical BCG therapy, including those with CIS.     

Treatment of Bacillus Calmette-Guerin refractory superficial bladder cancer: further intravesical therapy

We here report our clinical experience with salvage therapy for patients with bacillus Calmette-Guerin (BCG)-refractory superficial bladder cancer and discuss current approaches to the disease, especially focusing on bladder preservation. First, we evaluated the efficacy of an initial 6-week course of intravesical BCG in 93 patients with carcinoma in situ (CIS) of the bladder. Of these, 91% achieved a complete response (CR) at the evaluation at 3 months. The 2- and 5-year recurrence-free rates were 71 and 67%, respectively (mean follow-up 39 months). These results support the intravesical BCG as a first-line therapy for CIS. Next, we assessed the efficacy of a second course of intravesical BCG for 16 patients who failed the initial induction course for CIS. Of these, 94% achieved CR at the evaluation at 3-month, and the 2- and 5-year recurrence-free rates were 62 and 46%, respectively (mean follow-up 28 months). None of the patients who received a second course had disease progression. Thus, a second course of BCG therapy seems to be a reasonable option for CIS patients failing the initial course. We also report our initial experience with intravesical gemcitabine therapy for 3 patients with BCG-refractory CIS of the bladder and 1 patient with recurrent multiple tumors. Gemcitabine (1500 mg in 100 ml saline) was given in the bladder for 1 hour twice weekly for a total of 12 treatments. The treatment was associated with minimal bladder irritation and systemic absorption, and was well tolerated except in a 90-year-old man who discontinued therapy because of grade 2 toxicity. Two patients achieved CR and maintained a tumor-free status beyond 14 months, suggesting that the intravesical gemcitabine is a promising salvage therapy for BCG-refractory superficial bladder cancer.     

经尿道膀胱肿瘤电切变性术的疗效

目的评估经尿道膀胱肿瘤电切变性术(TURD-Bt)的疗效和安全性。方法采用TURD-Bt治疗56例膀胱肿瘤,与32例行经尿道膀胱肿瘤电切术(TUR-Bt)进行对照研究。有和无肿瘤进展因素患者分别比较。结果随访时间TURD-Bt组(48.55±23.74)月,对照组(56.28±17.61)月。无肿瘤进展因素患者,TURD-Bt组无肿瘤复发,14例均生存;对照组3例(37.50%)复发,5例(62.5%)生存。有肿瘤进展因素患者,TURD-Bt组8例(19.05%)肿瘤复发,32例(76.19%)生存,肿瘤死亡3例(7.14%);TUR-Bt组18例(75.00%)复发(P0.05),12例(50.00%)生存(P0.01),8例(33.33%)肿瘤死亡(P0.05)。TURD-Bt组无特殊并发症发生。结论 TURD-Bt术可彻底切除和凝固变性膀胱肿瘤,疗效显著提高。手术安全可靠,操作过程预期可控制。对没有淋巴和远处转移的膀胱肿瘤,TURD-Bt可替代根治性TUR-Bt,保留膀胱。     

Beta-hCG producing urothelial carcinoma of the urinary bladder: a case report

A 74-year-old man visited our hospital presenting with pollakisuria. Cystoscopy revealed a bladder cancer with necrotic tissue. The patient was initially treated by transurethral resection of bladder tumor (TUR-Bt). Pathologically, the tumor was shown to be a carcinoma of bladder with human chorionic gonadotropin (hCG) positivity. After TUR-Bt, chemotherapy with M-VAC (methotrexate, vinblastine, adriamycine and cisplatin) was performed. This patient is still alive eight months after resection. To our knowledge, there are 37 cases of beta-hCG-producing urothelial carcinoma of the urinary bladder reported in the Japanese literature.     

A case of synchronous double primary cancers of prostate, and bladder in a hemodialysis patient: a case report

A 60-year-old male, who had been maintained on hemodialysis for 4 years, visited our hospital to receive living renal transplantation. He complained of macrohematuria, and preoperative examination showed elevation of psostate specific antigen (PSA). Cystoscopy revealed papillary tumors on the right lateral bladder wall. Transurethral resection of bladder tumor (TUR-Bt) was performed and histopathological examination showed transitional cell carcinoma, G2, pTa. The histologic diagnosis of the transrectal needle prostate biopsy specimen was moderately differentiated adenocarcinoma. Combined androgen blockade as a neoadjuvant therapy and radical prostatectomy were performed. A case of synchronous double primary cancers, comprised of adenocarcinoma of the prostate and transitional cell carcinoma of the urinary blader in a hemodialysis patient has never been previously reported in the Japanese literature.     

Are biopsies from the prostatic urethra useful in patients with superficial bladder carcinoma?

Fifty male patients entered a Mitomycin C trial for superficial bladder cancer and biopsies in the prostatic urethra were taken with a cold cup biopsy forceps. In one patient this procedure failed. In 21 of 49 patients no abnormalities were detected but in the remaining 28 patients (57.1%) histological changes were found in the prostatic urethra. In 13 of these patients (26.5%) the changes were either carcinoma in situ (CIS) or superficial bladder carcinoma. Carcinoma in situ in the prostatic urethra was found in nine patients (18%) and in all but one it was combined with CIS in the bladder. These results indicate that biopsies from the prostatic urethra must be taken routinely in order to plan adequate therapy.     

Evaluating the need for transurethral bladder biopsy at first follow up after intravesical BCG therapy for superficial bladder cancer: Preliminary data

IntroductionPatients with high-risk superficial transitional cell carcinoma (TCC) of the bladder have a lifelong risk of progression and require particular attention. Intravesical Bacillus Calmette-Guerin (BCG) is recommended as a first-choice adjuvant treatment to reduce the risk of progression of high-grade tumors and carcinoma in situ (CIS).ObjectivesTo evaluate the need for routine transurethral bladder biopsy from the site of previously resected tumor three months following intravesical BCG therapy, even if the urine cytology and cystoscopy were both negative.Subjects and methodsA prospective study was carried out on 45 patients of both genders presenting with superficial bladder cancer. All patients received a six-week course of intravesical BCG. The mean age of the patients was 59 (range 33–80) years. Three months following resection, urine cytology was negative in all patients. Cystoscopy was then performed and although it was negative for any suspicious lesions, a routine biopsy from the previous resection site was taken.ResultsThe indication for BCG instillation was T1G1 in 20 patients (44%), T1G2 in 12 patients (27%) and TaG2 in eight patients (18%). Three patients (7%) had a positive bladder biopsy for malignancy at follow-up despite the negative cystoscopy and cytology. There were no statistically significant differences between patients with positive and those with negative biopsies with regard to the stage and grade of the tumor before resection or the number of resected lesions. The original pathology of the three positive patients was T1G1 (two patients) and T1G2 (one patient). The pathology after BCG treatment was the same as before instillation, T1G1 (two patients) and T1G2 (one patient).ConclusionUntil more studies on larger numbers of patients are done, a routine biopsy from the site of previously resected tumor at the time of check cystoscopy may improve the detection of tumor recurrence.     

Clinical outcome of chemoradiotherapy for T1G3 bladder cancer

Abstract:   The aim of this study was to determine the clinical outcome of a bladder-sparing approach using chemoradiotherapy (CRT) for T1G3 bladder cancer.   Between May 2000 and August 2007, 11 patients with T1G3 bladder cancer and who were negative for macroscopic residual tumor were treated by CRT after transurethral resection of bladder tumor (TUR-Bt). Pelvic irradiation was given at a dose of 40 Gy in 4 weeks. Intra-arterial administration of cisplatin and systemic administration of methotrexate were carried out in the first and third weeks of radiotherapy. One month after CRT, response was evaluated by restaging TUR-Bt. For persistent tumor after CRT or tumor recurrence, patients received additional treatment. Median follow-up was 21.2 months. Complete response was achieved in 10 of 11 patients (90.9%). Local recurrence for the entire group of 11 patients was 22.1% at both 2 and 5 years. Tumor progression was 0% at 5 years. Disease-specific survival rates were 100% at 5 years. All of survivors retained functioning bladders. Bladder preservation by CRT is a curative treatment option for T1G3 bladder cancer and a reasonable alternative to intravesical treatment or early cystectomy.     

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.     

Case of tuberculous epididymitis caused by intravesical BCG therapy

Intravesical Bacillus Calmette-Guerin (BCG) therapy is commonly used against superficial urothelial carcinoma, especially carcinoma in situ (CIS). We report a case of tuberculous epididymitis that occurred during a course of intravesical BCG therapy. A 76-year-old man had received intravesical BCG therapy for multiple superficial bladder cancer and CIS in prostatic urethra after transurethral resection of bladder tumor (TUR-Bt). He recognized hard nodules in the left scrotum after 4 times intravesical BCG therapy. Skin fistula in scrotum occurred 5 months later. We performed left orchiectomy with scrotum skin resection. Histological diagnosis was tuberculous epididymitis. Postoperatively, he was administered chemotherapy consisting of isoniazid, refampin and ethambutol.     

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.