Fluorescence cystoscopy in bladder cancer: what future?

Bladder transitional cell carcinoma, limited to the lamina propria, or superficial in 80% of the cases, is characterized by a high recurrence rate up to 70% in the three years following the first treatment. However, the constant evolution of the endoscopic techniques, useful to its diagnosis and treatment, contributed to reduce about by half this recurrence rate at three months. The actual development concerns new fluorescence detection methods, adapted to the standard endoscopic equipment. This new technique or fluorescence cystoscopy aims at improving the visual contrast between tumor and normal tissue in order to obtain a precise mapping of the diseased bladder. Thus, it allows to detect a carcinoma in situ (CIS) with a sensitivity around 80 to 90%. Its impact on the progression of the disease remains however to be demonstrated.     

Use of the holmium:YAG (Ho:YAG) laser for treatment of superficial bladder carcinoma

This is the first North American report describing the use of the holmium:YAG (Ho:YAG) laser to treat patients with superficial bladder carcinoma. Fifteen patients, with a total of 52 recurrent superficial bladder tumors, underwent endoscopic laser photoablation of their lesions. No intraoperative or delayed complications occurred. At follow-up cystoscopy performed 3 months after lasing, four patients (27%) were without disease; eight patients (53%) had out-of-field recurrences; and three patients (20%) were classified as having in-field recurrences. We conclude that using the Ho:YAG for endoscopic treatment of patients with superficial bladder tumors is both feasible and clinically useful and that the lack of perceived pain or discomfort during lasing, as well as the lack of need for an in-dwelling urethral catheter, makes it advantageous for selected patients over conventional electroresection techniques. © 1994 Wiley-Liss, Inc.     

Significance of fluorescence cystoscopy for diagnosis of superficial bladder cancer after intravesical instillation of delta aminolevulinic acid.

OBJECTIVES: Most lesions of superficial bladder cancer may be easily missed during conventional white light cystoscopy. The aim of this work was to evaluate the efficiency of endoscopic fluorescence diagnosis of superficial malignant bladder tumours following intravesical instillation of delta-aminoleviulenic acid. PATIENTS AND METHODS: 30 patients of suspected or previously diagnosed bladder cancer were subject of evaluation. All patients received 50 ml of a 3% delta-ALA solution intravesically, 2-3 h prior to diagnostic cystoscopy. Fluorescence excitation intraoperatively was achieved by a violet-blue light from a xenon light source. RESULTS: A clear strong red fluorescence colour was observed emitting from all malignant vesical lesions. A diagnostic sensitivity of 98% and specificity of 65% has been determined for this novel diagnostic modality. CONCLUSION: Fluorescence cystoscopy using delta-ALA is a reliable procedure that can be offered to all patients with suspected bladder cancer lesions.     

Hexyl aminolevulinate fluorescence cystoscopy: new diagnostic tool for photodiagnosis of superficial bladder cancer--a multicenter study

PURPOSE: We examined the sensitivity and specificity of Hexvix (PhotoCure ASA, Oslo, Norway) hexyl aminolevulinate (HAL) fluorescence cystoscopy in patients with superficial bladder cancer. MATERIALS AND METHODS: A total of 52 patients (38 men and 14 women) with a mean age of 72 years were investigated. HAL hydrochloride (100 mg dissolved in 50 ml phosphate buffer solution) (8 mM) was instilled into the bladder 1 hour prior to the endoscopic procedure. Cystoscopy was performed with the Storz D-light (Karl Storz, Tuttlingen, Germany) system, allowing inspection of the bladder wall under white and blue light (380 to 450 nm). RESULTS: A total of 422 biopsies obtained in fluorescing (165) and nonfluorescing (257) areas, including 5 random biopsies per patient, were analyzed to provide the best reference for the calculation of sensitivity and specificity. There were a total of 143 histologically verified tumors in 45 patients, including carcinoma in situ (CIS), Ta or T1 lesions. A total of 43 patients were diagnosed by fluorescence cystoscopy compared with 33 diagnosed by white light for 96% and 73% per-patient sensitivity, respectively. HAL cystoscopy was found particularly useful for finding CIS tumors. Of 13 patients with CIS tumors all except 1 were diagnosed or confirmed by HAL cystoscopy. HAL cystoscopy was well tolerated with no definite drug related adverse events reported, including effects on standard blood parameters. CONCLUSIONS: HAL fluorescence cystoscopy is a new, sensitive, promising diagnostic procedure that showed improved detection of bladder tumors, in particular CIS. The procedure is well tolerated and can easily be implemented in current clinical practice.     

Fluorescence cystoscopy: is it ready for use in routine clinical practice?

PURPOSE OF REVIEW: To review the recent literature on the use of fluorescence cystoscopy in the diagnosis and management of bladder cancer. RECENT FINDINGS: Recent advances have been made in fluorescence cystoscopy with the use of newer fluorescence agents (hexylester aminolevulinate and hypericin) and their application to flexible cystoscopy. Within several hours of intravesical administration of these agents, bladder tumors can be detected using fluorescence cystoscopy resulting in improved cancer detection and lower short-term recurrence rates than white light cystoscopy. Preliminary results with flexible fluorescence cystoscopy suggest that this technique can be used for office-based cystoscopy. SUMMARY: Significant advances have been made in the field of fluorescence cystoscopy. The currently available fluorescence agents in recent phase II and III trials outperform white light cystoscopy in terms of cancer detection and recurrence-free survival. Fluorescence cystoscopy should be considered as an adjunctive tool for the diagnosis and management of superficial bladder cancer.     

A comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of carcinoma in situ in patients with bladder cancer: a phase III, multicenter study

PURPOSE: We compared hexaminolevulinate (Hexvix) fluorescence cystoscopy with white light cystoscopy for detecting carcinoma in situ. MATERIALS AND METHODS: In this multicenter study 298 patients with known or suspected bladder cancer underwent bladder instillation with 50 ml 8 mM hexaminolevulinate for 1 hour. Cystoscopy was then performed, first using standard white light and then hexaminolevulinate fluorescence cystoscopy. Lesions or suspicious areas identified under the 2 illumination conditions were mapped and biopsied for histological examination. In addition, 1 directed biopsy was obtained from an area appearing to be normal. RESULTS: Of 196 evaluable patients 29.6% (58 of 196) had carcinoma in situ, including 18 with carcinoma in situ alone, and 35 with carcinoma in situ and concomitant papillary disease, which was only detected on random biopsy in 5. Of the 18 patients with no concomitant papillary disease carcinoma in situ was detected only by hexaminolevulinate fluorescence in 4 and only by white light in 4. In the group with concomitant papillary disease carcinoma in situ was found only by hexaminolevulinate fluorescence in 5 patients and only by white light in 3. The proportion of patients in whom 1 or more carcinoma in situ lesions were found only by hexaminolevulinate cystoscopy was greater than the hypothesized 5% (p=0.0022). Overall more carcinoma in situ lesions were found by hexaminolevulinate than by white light cystoscopy in 22 of 58 patients (41.5%), while the converse occurred in 8 of 58 (15.1%). Biopsy results confirmed cystoscopy findings. Of a total of 113 carcinoma in situ lesions in 58 patients 104 (92%) were detected by hexaminolevulinate cystoscopy and 77 (68%) were detected by white light cystoscopy, while 5 were detected only on directed visually normal mucosal biopsy. Hexaminolevulinate instillation was well tolerated with no local or systemic side effects. CONCLUSIONS: In patients with bladder cancer hexaminolevulinate fluorescence cystoscopy with blue light can diagnose carcinoma in situ that may be missed with white light cystoscopy. Hexaminolevulinate fluorescence cystoscopy can be used in conjunction with white light cystoscopy to aid in the diagnosis of this form of bladder cancer.     

Improved detection and treatment of bladder cancer using hexaminolevulinate imaging: a prospective, phase III multicenter study

PURPOSE: We determined if improved tumor detection using hexaminolevulinate (HAL) fluorescence cystoscopy could lead to improved treatment in patients with bladder cancer. MATERIALS AND METHODS: A total of 146 patients with known or suspected bladder cancer were assessed in this open, comparative, within patient, controlled phase III study. Patients received intravesical HAL for 1 hour and were assessed with standard white light cystoscopy and blue light fluorescence cystoscopy. All lesions were mapped onto a bladder chart and biopsies were taken from suspicious areas for assessment by an independent pathologist. An independent urologist blinded to the detection method used recommended treatment plans based on biopsy results and medical history according to European Association of Urology bladder cancer guidelines. Any differences in recommended treatment plans arising from the 2 cystoscopy methods were recorded. RESULTS: HAL imaging improved overall tumor detection. Of all tumors 96% were detected with HAL imaging compared with 77% using standard cystoscopy. This difference was particularly noticeable for dysplasia (93% vs 48%), carcinoma in situ (95% vs 68%) and superficial papillary tumors (96% vs 85%). As a result of improved detection, additional postoperative procedures were recommended in 15 patients (10%) and more extensive treatment was done intraoperatively in a further 10. Overall 17% of patients received more appropriate treatment at the time of the study following blue light fluorescence cystoscopy, that is 22% or 1 of 5 if patients without tumors were excluded. CONCLUSIONS: HAL imaging is more effective than standard white light cystoscopy for detecting bladder tumors and lesions. This leads to improved treatment in a significant number of patients (p <0.0001).     

Can transabdominal ultrasonography of the bladder replace cystoscopy in the followup of superficial bladder tumors?

Transabdominal ultrasonography of the bladder was performed on 100 patients 3 to 9 months after endoscopic resection of stage Pa or Pl transitional cell carcinoma of the bladder. In 81 patients there was a close correlation between the results of suprapubic ultrasonography and cystoscopy. In 19 patients the ultrasonography results were incorrect: 4 had false positive and 15 had false negative findings. Specificity for the diagnosis of recurrence was 90 per cent and sensitivity was 74 per cent. Transabdominal ultrasonography combined with cytology studies should be part of the diagnostic approach for recurrent superficial bladder tumors. When performed before cystoscopy these studies should reduce greatly without eliminating the frequency of this investigation.     

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.     

Clinical results of the transurethreal resection and evaluation of superficial bladder carcinomas by means of fluorescence diagnosis after intravesical instillation of 5-aminolevulinic acid

BACKGROUND AND OBJECTIVE: The high recurrence rate of superficial bladder carcinomas requires new approaches in diagnosis and therapy. Particularly, an improvement in detection, resulting in better resection of flat lesions, which are poorly or not detectable under white light, is necessary. The effectiveness of fluorescence diagnosis for detection and transurethral resection of bladder carcinomas was investigated in a prospective study. MATERIALS AND METHODS: From 120 patients, 347 biopsies were taken or tumors resected with the aid of fluorescence from 5-aminolevulinic acid. Urothelial carcinomas and dysplasias were detected in 124 cases. RESULTS: Of the lesions, 119 were fluorescence positive (N = 74 pTaG1/2; N = 9 pT1G1/2; N = 11 pT1G3; N = 7 carcinoma in situ; N = 6 p > T1; N = 12 dysplasia II), and 5 were falsely negative (N = 3 pTaG1/2; N = 1 pT1G1/2; N = 1 dysplasia II). The sensitivity of the fluorescence diagnosis (96.0%) was significantly higher than the 67.5% sensitivity of white-light cystoscopy (P < 0.0001). Taking the data for primary or recurrent tumor resection and secondary resection separately, the sensitivity was 100% and 80%, respectively, and was significantly higher than that of white-light cystoscopy, which was 80.8% and 20 %, respectively (P < 0.0001 and P < 0.0008). The lower sensitivity of fluorescence diagnosis in secondary transurethral resection is attributed to the higher rate of false-negative findings in areas of former resection. CONCLUSIONS: The high rate of false-positive findings limits the correct interpretation of fluorescence findings. In spite of this, fluorescence diagnosis is superior to white-light cystoscopy in every case. By means of better detection of urothelial neoplasias and dysplasias, as well as more thorough and extensive resection under fluorescence control, it should be possible to reduce the recurrence rate of superficial bladder carcinomas.     

Suprapubic ultrasonography in the follow-up of superficial bladder tumors

40 patients with superficial (grade 1-3, stage 0) transitional cell carcinoma of the bladder were followed using urinary cytology, cystoscopy and suprapubic ultrasonography. Sonography detected tumors as small as 2.5 mm, but missed lesions that developed in the dome as well as flat anomalies associated with positive urinary cytology. Although, not a definitive alternative to cystoscopy, suprapubic ultrasonography of the bladder can, in selected cases, be used to widen the interval between endoscopic controls.     

Comparative study between cystoscopy, urinary cytology, NMP-22 and a new method, bladder chek, in the follow-up of superficial bladder cell carcinoma

Objective: The goal of this work tries to evaluate the utility of the qualitative determination of NMP-22 in the evaluation of the superficial bladder carcinoma in asymptomatic patients, comparing it with its quantitative determination, the cytology and the cystoscopyMaterial and methodsA simple of urine just voided was taken in 88 asymptomatic patient follow-up for superficial bladder cell carcinoma. This dose was distributed in 3 parts, for performed cytology, for determination of NMP-22, and 4 drops of the third part are added to device bladder chek. Later, we performered cystoscopy and transurethral resection in patients with a suspicion of bladder cancerResults26 patients had tumor relapse and 62 patients were free of disease. The sensitivity for the bladder chek was of 28%, 34.62% for nmp-22, 34.62% for cytology and 100% for cystoscopy. The specificity was of 93.55%, 80.33%, 87.10% and 87.10% respectively. The sensitivity by degree was 25 in g1, 28.57 in g2 and 50 in g3 for Bladder chek; 29.41, 42.86and 50 for NMP-22; 23.53, 71.43 and 0 for cytology. The sensitivity by stages was 27.7 in Ta-1 and 50 in t2 for Bladder chek; 34.78 and 50 for NMP-22; 39.13 and 0 for the cytologyConclusionsThe low sensitivity of bladder chek invalidates it like alternative method to the cystoscopy in the follow-up of the superficial asymptomatic bladder cell carcinoma     

Diagnostik und Therapie des Harnblasenkarzinoms

Forty percent of patients with superficial bladder carcinoma progress towards muscle-invasive carcinoma despite initial therapy. Emergent technologies in the diagnostics and therapy of superficial bladder carcinoma including fluorescence cystoscopy are able to reduce recurrence and progression rates. Nevertheless to date no trial was able to show a benefit with regard to cancer-specific and overall survival using these new technologies. Lymph vessel invasion has been introduced as a new prognostic marker in muscle-invasive bladder carcinoma that can be easily incorporated into routine clinical practice. Furthermore adjuvant chemotherapy has been identified along with lymph node density as a statistically significant marker for survival in muscle-invasive bladder carcinoma which should be investigated in prospective clinical trials. In metastatic bladder carcinoma, vinflunine was approved as second-line chemotherapy for patients who failed cisplatin-based chemotherapy. This article critically reviews the emergent developments of the last 12-15 months and comments on their clinical efficacy for the treatment of bladder carcinoma.     

Clinically relevant improvement of recurrence-free survival with 5-aminolevulinic acid induced fluorescence diagnosis in patients with superficial bladder tumors

PURPOSES: Fluorescence diagnosis induced by 5-aminolevulinic acid enables more thorough transurethral resection of superficial bladder carcinoma compared with conventional white light. We performed a prospective, single institution, randomized trial to investigate whether the residual tumor rate and long-term tumor recurrence can be decreased by fluorescence diagnosis. MATERIALS AND METHODS: A total of 301 patients underwent transurethral resection of bladder tumors with white light or fluorescence diagnosis. Transurethral resection was repeated 5 to 6 weeks later to evaluate the residual tumor rate. To determine recurrence-free survival patient followup was performed every 3 months by white light cystoscopy and urine cytology. Recurrence-free survival was analyzed via Kaplan-Meier methods and multivariable Cox regression analysis. RESULTS: A total of 191 patients with superficial bladder carcinoma were available for efficacy analysis. The residual tumor rate was 25.2% in the white light arm versus 4.5% in the fluorescence diagnosis arm (p <0.0001). Median followup in the white light arm in 103 cases was 21.2 months (range 4 to 40) compared with 20.5 (range 3 to 40) in the 88 in the fluorescence diagnosis arm. Recurrence-free survival in the fluorescence diagnosis group was 89.6% after 12 and 24 months compared with 73.8% and 65.9%, respectively, in the white light group (p = 0.004). This superiority proved to be independent of risk group. The adjusted hazard ratio of fluorescence diagnosis versus white light transurethral resection was 0.33 (95% confidence interval 0.16 to 0.67). CONCLUSIONS: Fluorescence diagnosis is significantly superior to conventional white light transurethral resection with respect to the residual tumor rate and recurrence-free survival. The differences in recurrence-free survival imply that fluorescence diagnosis is a clinically relevant procedure for decreasing the number of tumor recurrences.     

The use of transabdominal ultrasound in the detection of early bladder tumours

We have studied the accuracy of transabdominal ultrasound (TAUS) in the diagnosis of early superficial bladder carcinoma. One hundred and twenty-six patients returning for check cystoscopy were scanned pre-operatively with the Technicare Autosector Scanner and the results compared with the endoscopic findings. Forty-four patients (37%) had a tumour recurrence. TAUS demonstrated a lesion in 50% of these with a false positive rate of 11%. The diagnostic accuracy was proportional to the tumour size (82% of patients with tumours above 5 mm were detected compared with 38% below 5 mm), but was not affected by grade, stage or position in the bladder. TAUS may prove a useful adjunct to cytology as a screening test for bladder cancer.     

Diagnosis of bladder carcinoma using protoporphyrin IX fluorescence induced by 5-aminolaevulinic acid

OBJECTIVE: To report the results of a clinical study investigating the diagnosis of malignant and dysplastic bladder lesions by protoporphyrin IX (PPIX) fluorescence and to compare them with those from earlier studies. PATIENTS AND METHODS: The study included 55 patients with suspected bladder carcinoma (at initial diagnosis or at tumour follow-up visits); 130 bladder biopsies from 49 patients were classified by pathological analysis. All patients received an intravesical instillation of 50 mL of a 3% 5-aminolaevulinic acid (ALA) solution a mean of 135 min before cystoscopy, which was then performed under white and blue light. Malignant/dysplastic lesions showing red fluorescence under blue-light excitation were noted and the increase in detection rate calculated. RESULTS: There were 63 benign and 67 malignant/dysplastic areas biopsied; 10 malignant/dysplastic lesions (four transitional cell carcinoma, two carcinoma in situ, four dysplasia) were not detected during routine white-light cystoscopy but were identified under blue light. Fluorescence cystoscopy improved the overall diagnosis of malignant/dysplastic bladder lesions by 18% over standard white-light cystoscopy. The improvement was greater for dysplastic lesions and carcinoma in situ (50%). However, the improvement over standard cystoscopy was less than that found by other groups. CONCLUSION: The ALA-based fluorescence detection system significantly enhanced the diagnosis of malignant/dysplastic bladder lesions. However, determining the optimum drug exposure time requires further investigation using well-characterized instrumentation and study protocols, which would then allow comparison of the results from different groups.     

Fluorescence detection of flat bladder carcinoma in situ after intravesical instillation of hypericin

PURPOSE: We determined the sensitivity and specificity of detecting flat bladder carcinoma in situ through fluorescent detection after intravesical hypericin instillations. MATERIALS AND METHODS: The study included 40 patients, of whom 26 presented with macroscopic visible tumor, 9 had a positive cytology without visible tumor and 5 underwent cystoscopy after bacillus Calmette-Guerin instillations (4) or radiotherapy (1). We instilled 40 ml. of a 8 microM. solution of hypericin intravesically for at least 2 hours. Fluorescence excitation with blue light was effective up to 16 hours after termination of the instillation. RESULTS: All visible papillary tumors showed red fluorescence. In addition, 134 flat fluorescent areas were detected. Analysis of 281 biopsies from flat bladder wall indicated 93% sensitivity and 98.5% specificity for detecting carcinoma in situ. Visible lesions resulting from radiotherapy, chemotherapy or immunotherapy did not show any fluorescent signs and, therefore, did not induce false-positive readings. There were no signs of photobleaching during inspection and resection. CONCLUSIONS: We report a simple yet comprehensive endoscopic method for early detection of bladder cancer, including carcinoma in situ. Hypericin induced fluorescence has a high sensitivity and specificity for detection of bladder transitional cell carcinoma, papillary and flat carcinoma in situ. When carcinoma in situ is suspected, this technique is highly recommended.     

Diagnostic efficacy of fluorescence cystoscopy for detection of urothelial neoplasms.

BACKGROUND AND PURPOSE: A major problem diagnosing bladder cancer using conventional white-light cystoscopy is that flat and tiny papillary neoplasms can be overlooked. Fluorescence cystoscopy is based on the detection of protoporphyrin IX (PpIX)-induced fluorescence in urothelial neoplasms through the topical administration of 5-aminolevulinic acid (ALA). The diagnostic efficacy of fluorescence cystoscopy in urothelial neoplasms was evaluated in this study. The focus of this investigation was to ascertain whether fluorescence cystoscopy could make a major contribution to staging and improving the choice of adjuvant therapy after transurethral resection. PATIENTS AND METHODS: A series of 62 patients with suspected bladder cancer were investigated by fluorescence cystoscopy. An intravesical instillation of ALA was conducted 2 hours prior to fluorescence. A total of 274 tissue samples were obtained from the fluorescing and nonfluorescing areas of the bladder. RESULTS: The sensitivity and negative predictive value of fluorescence cystoscopy were 98.0% and 94.7%, respectively, but the specificity was low (42.9%). Among a total of 148 lesions of urothelial neoplasm, 58 foci (dysplasia in 5, carcinoma in situ in 19, stage Ta in 15, T1 in 15, above T2 in 4) that were invisible under white-light cystoscopy were detected by fluorescence cystoscopy. The final histopathologic status was changed in 45% of patients (28/62) according to this technique. Among these patients, eight (13%) needed additional therapy, including a radical cystectomy in one patient and intravesical therapy in 10. CONCLUSIONS: The ALA-based fluorescence cystoscopy technique is a safe and simple procedure that enhances the detection of flat and papillary urothelial neoplasms. Moreover, it will be able to provide useful information that will enable proper staging and appropriate further treatment.     

Should fluorescence cystoscopy be used for transurethral resection in patients with high-grade T1 bladder cancer?

This Practice Point commentary discusses the study by Denzinger et al. in which patients with high-grade T1 (HGT1) bladder cancer were treated by transurethral resection with either white-light cystoscopy or fluorescence cystoscopy. Over a median follow-up duration >7 years, the recurrence-free survival was significantly improved in the fluorescence cystoscopy group. No difference was observed between the two groups, however, in the rate of progression to muscle-invasive disease, although the low number of progression events limited the power of this comparison. As such, a low threshold for radical cystectomy should be maintained in transurethrally resected HGT1 disease, regardless of the visualization technique used. Importantly, fluorescence cystoscopy represents a more costly and time-consuming procedure than does white-light cystoscopy. Larger clinical trials, as well as research at the molecular level, are needed to define the potential role of fluorescence cystoscopy in the treatment of HGT1 disease.     

Restaging transurethral resection of high risk superficial bladder cancer improves the initial response to bacillus Calmette-Guerin therapy

PURPOSE: This study was an evaluation of whether restaging transurethral resection (TUR) of superficial bladder cancer improves the early response to bacillus Calmette-Guerin (BCG) therapy. MATERIALS AND METHODS: A total of 347 patients with high risk superficial bladder cancer (high grade Ta and T1 tumors associated with carcinoma in situ) underwent a single transurethral resection (TUR, 132 patients) or restaging TUR (215 patients) before receiving 6 weekly intravesical BCG treatments. The patients were evaluated for response (presence or absence of tumor) at first followup cystoscopy, at 6 and 12 months after treatment, and evaluated for disease stage progression within 3 years of followup. RESULTS: Of the 132 patients who underwent a single TUR before BCG therapy, 75 (57%) had residual or recurrent tumor at the first cystoscopy and 45 (34%) later had progression, compared with 62 of 215 patients (29%) who had residual or recurrent tumors and 16 (7%) who had progression after undergoing restaging TUR (p = 0.001). CONCLUSIONS: Restaging TUR of high risk superficial bladder cancer improves the initial response rate to BCG therapy, reduces the frequency of subsequent tumor recurrence and appears to delay early tumor progression.