Improved detection of urothelial carcinoma in situ with hexaminolevulinate fluorescence cystoscopy

PURPOSE: In this European multicenter study we compared hexaminolevulinate (HAL) fluorescence cystoscopy and standard white light cystoscopy for the detection of carcinoma in situ (CIS) in patients suspected of having high risk bladder cancer. MATERIALS AND METHODS: This study was a prospective controlled, within-patient comparison of standard and HAL fluorescence cystoscopy. Eligible patients received an intravesical instillation of 50 ml HAL 8 mM solution. Cystoscopy was performed using a D light system, which provided white and blue light at 375 to 440 nm. The bladder wall was inspected and mapped, first under white light, followed by blue light. All tumors and suspicious areas identified under white light and by red fluorescence were resected or biopsied. Histological findings were assessed by an independent central pathologist blinded to the identity of the biopsies. RESULTS: Of 211 evaluable patients 83 (39%) had CIS, of whom 18 (22%) were detected by HAL cystoscopy only, 62 (75%) were detected by standard and HAL cystoscopy, 2 (2%) were detected by standard cystoscopy only and 1 (1%) was detected by nonguided biopsy. Therefore, HAL cystoscopy identified 28% more patients with CIS than standard cystoscopy. The side effects of HAL instillation were negligible and no unexpected events were reported. CONCLUSIONS: HAL fluorescence cystoscopy improves the detection of bladder CIS significantly, which has consequences for clinical management and may improve the patient prognosis. The procedure is easily implemented as an adjunct to standard cystoscopy and it adds no significant risk of complications.     

A phase III, multicenter comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of superficial papillary lesions in patients with bladder cancer

PURPOSE: We compared hexaminolevulinate fluorescence cystoscopy with white light cystoscopy for detecting Ta and T1 papillary lesions in patients with bladder cancer. MATERIALS AND METHODS: A total of 311 patients with known or suspected bladder cancer underwent bladder instillation with 50 ml 8 mM HAL for 1 hour. The bladder was inspected using white light cystoscopy, followed by blue light (fluorescence) cystoscopy. Papillary lesions were mapped and resected for histological examination. RESULTS: Noninvasive pTa tumors were found in 108 of 196 evaluable patients (55.1%). In 31 patients (29%) at least 1 more tumor was detected by HAL than by white light cystoscopy (p<0.05). Six of these patients had no lesions detected by white light, 12 had 1 lesion detected by white light and more than 1 by HAL, and 13 had multiple Ta lesions detected by the 2 methods. Conversely at least 1 more tumor was detected by white light cystoscopy than by HAL cystoscopy in 10 patients (9%, 95% CI 5-16). Tumors invading the lamina propria (T1) were found in 20 patients (10.2%). At least 1 additional T1 tumor was detected by HAL but not by white light cystoscopy in 3 of these patients (15%), while at least 1 more T1 tumor was detected by white light cystoscopy than by HAL cystoscopy in 1 patient (5%, 95% CI 0-25). Detection rates for Ta tumors were 95% for HAL cystoscopy and 83% for white light cystoscopy (p=0.0001). Detection rates were 95% and 86%, respectively, for T1 tumors (p=0.3). HAL instillation was well tolerated with few local or systemic side effects. CONCLUSIONS: HAL fluorescence cystoscopy detected at least 1 more Ta and T1 papillary tumor than white light cystoscopy in approximately a third of the patients with such tumors. Whether this would translate to improved patient outcomes has yet to be determined.     

Flexible Cystoscopy Assisted by Hexaminolevulinate Induced Fluorescence: A New Approach for Bladder Cancer Detection and Surveillance?

OBJECTIVE: The aim of this study was the assessment of flexible cystoscopy assisted by hexaminolevulinate (HAL) fluorescence. METHODS: This study was a prospective controlled, within-patient comparison of flexible HAL cystoscopy with standard flexible cystoscopy, HAL rigid and standard white light rigid cystoscopy. Eligible patients received an intravesical instillation of 50 ml hexylaminolevulinate 8 mM solution. First flexible than rigid cystoscopy was performed in each patient using a Combilight PDD system (Richard Wolf, Germany), which provided standard white light and blue light at 375 to 440 nm, with mapping of all lesions detected. All tumors and suspicious areas identified under white light and by red fluorescence with flexible or rigid cystoscopy were then resected by TUR or biopsied. The specimen was assessed by an independent blinded pathologist. RESULTS: In the 45 patients studied 41 (91%) patients had exophytic tumors, of which 39 (95.1%) were detected by HAL flexible cystoscopy and 40 (97.5%) by HAL rigid cystoscopy. 17 (37.8%) patients had concomitant or carcinoma in situ only, which was identified by HAL flexible cystoscopy in 14 (82.3%), by HAL rigid cystoscopy in 15 (88.2%), by flexible standard in 11 (64.7%) and by standard white light rigid cystoscopy in 13 (76.7%) patients. CONCLUSION: HAL fluorescence flexible cystoscopy compared to HAL rigid cystoscopy showed almost equivalent results in detecting papillary and flat lesions in bladder cancer patients. Both procedures were superior to standard white light flexible cystoscopy.     

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).     

Hexaminolevulinate photodynamic diagnosis in non-muscle invasive bladder cancer: experience of the BLUE group

ObjectivesPhotodynamic diagnosis (PDD) with hexaminolevulinate has been recently used to improve detection of non-muscle invasive bladder cancer. Our main purpose was to quantify the benefit of PDD vs. conventional white light cystoscopy (WL) in our area.Material and methodsFluorescence-guided cystoscopy using hexaminolevulinate was performed at the time of the transurethral resection (TUR) in 305 patients from 7 Spanish hospitals. All lesions found with WL and PDD were numbered and recorded in an online database. Each lesion was sent separately for pathology analysis. Random biopsies were also obtained in 148 patients.ResultsA total of 1659 lesions were biopsied: 522 were identified with PDD and WL, 237 only with PDD, 19 only with WL and 881 random biopsies. Of the 600 tumors, PDD detected 563, WL 441 and random biopsies 29 (20 CIS). The mean overdetection rate for PDD over WL was 31.9% for all types of lesions, but it was 209% for carcinoma in situ (CIS). Sensitivity was 93.8% for PDD and 78.2% for WL. Specificity was 81.5% for PDD and 90.5% for WL. In 23% of patients, PDD detected at least one additional neoplastic lesion compared to WL.ConclusionsHexaminolevulinate fluorescence cystoscopy improves detection and resection of non-muscle invasive bladder cancer, especially of CIS. Sensitivity of PDD is higher than WL, but specificity is lower. In our study, random biopsies were able to detect some CIS not visible under PDD.     

Comparison of hexaminolevulinate based flexible and rigid fluorescence cystoscopy with rigid white light cystoscopy in bladder cancer: results of a prospective Phase II study

INTRODUCTION AND OBJECTIVE: Several studies have shown that rigid fluorescence cystoscopy (RFC) with hexaminolevulinate (HAL) is superior to standard rigid white light (RWLC) cystoscopy in diagnosing bladder tumours, with a clinically relevant impact on the patient's management. These studies, however, have been done with rigid cystoscopes. We carried out a study to evaluate whether the technique of fluorescence cystoscopy with HAL was also feasible with a specially designed flexible fluorescence cystoscope (FFC). METHODS: 20 patients with known or suspected bladder cancer were included in a comparative within patient controlled Phase II study. All patients signed informed consent. All patients received 50 ml of HAL (Hexvix) 8 mM 1h prior to transurethral resection. Using a D-light-C system (Storz, Germany), FFC and RFC were performed followed by RWLC. All lesions visible during these three cystoscopies were mapped, taped and resected. RESULTS: In these 20 patients (mean age 71 years (49-89), 3 females) mean HAL instillation time was 81 min. Overall 27 histologically confirmed lesions were found in 19 patients. Detection rates in these 19 patients were 14 with FFC, 17 with RFC and 15 with RWLC. Of the 27 lesions 19 were detected with FFC, 23 with RFC and 20 with RWLC. Overall fluorescence intensity using the flexible system was 76% (30-147%) as compared to RFC using a visual analogue score. No side effects were noted which were attributable to HAL. CONCLUSION: The use of FFC is feasible and seems to be comparable to RWLC and slightly inferior to RFC. Larger studies should determine the role of flexible fluorescence cystoscopy.     

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.     

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.     

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.     

A comparison of white-light cystoscopy and narrow-band imaging cystoscopy to detect bladder tumour recurrences

OBJECTIVE

To determine whether narrow‐band imaging (NBI) cystoscopy enhances the detection of non‐muscle‐invasive bladder tumours over standard white‐light imaging (WLI) cystoscopy, as surveillance WLI is the standard method used to diagnose patients with recurrent bladder tumours, but they can be missed by WLI cystoscopy, possibly accounting for early recurrences.

PATIENTS AND METHODS

We evaluated 427 patients for recurrent bladder tumours by WLI cystoscopy, followed by NBI cystoscopy as a further procedure, using the same video‐cystoscope. Recurrent tumours visualized by WLI or NBI cystoscopy were mapped, imaged, biopsied and subsequently treated by transurethral resection (TUR) or fulguration. Biopsies or TUR specimens obtained by WLI and NBI were examined separately for presence of tumour.

RESULTS

In all, 103 patients (24%) had tumour recurrences; 90 (87%) were detected by both WLI and NBI and another 13 (100%) only by NBI cystoscopy. NBI detected extra papillary tumours or more extensive carcinoma in situ in 58 (56%) patients found to have recurrences. The mean number of recurrent tumours visualized on WLI cystoscopy was 2.3, vs to 3.4 seen on NBI cystoscopy (P = 0.01).

CONCLUSION

NBI cystoscopy improved the detection of recurrent non‐muscle‐invasive bladder tumours over standard WLI cystoscopy.     

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 detection of bladder tumors with 5-amino-levulinic acid

BACKGROUND: Preliminary data suggest that photodiagnosis by fluorescence detection of protoporphyrin IX, a biosynthetic product of the photosensitizer 5-amino-levulinic acid (ALA), is superior to conventional cystoscopy in bladder tumor detection. PATIENTS AND METHODS: We instilled 1.5 g of ALA into the bladders of 52 patients with suspect bladder lesions 1 to 4 hours prior to transurethral resection or biopsy. Red fluorescence was induced by violet-blue light (wavelength 380-450 nm). RESULTS: In 13 patients (25%), significant tumors were detected by fluorescence that were missed on conventional cystoscopy. In the present series, ALA photodetection had a sensitivity of 94.6% (compared with 76% for cystoscopy) and a specificity of 43%. CONCLUSION: Fluorescence diagnosis with ALA may become a standard procedure for bladder tumor detection and resection, especially in endoscopically difficult situations (carcinoma in situ, multifocal tumors, multiple prior resections, or previous drug instillation therapy).     

窄光成像膀胱镜在膀胱肿瘤诊断中的应用

目的 探讨窄光成像诱导光动力学检查对膀胱肿瘤早期诊断的应用价值. 方法 应用高清窄光成像膀胱镜系统对28例血尿患者进行膀胱镜检,术中分别对普通光下及窄光下的可疑部位膀胱黏膜组织活检,普通光组取样35处,窄光组取样79处(含普通光35处,普通光镜下疑似者窄光均显示镜下疑似,不重复取样)送病理检查.比较窄光取样组和普通光取样组肿瘤检出敏感性.结果 窄光取样组活检病理报告尿路上皮癌32处(21例),其中原位癌11处,腺性膀胱炎5处(2例),良性病变(炎性病变)3处(2例),正常黏膜4处(3例).普通光取样组尿路上皮癌17处(15例),腺性膀胱炎2处(1例),无原位癌.活检病理阳性32处,窄光组病理阳性32处,肿瘤检出率100%(32/32);普通光组病理阳性17处.肿瘤检出率53%(17/32);膀胱肿瘤及原位癌检出率2组比较差异有统计学意义(P<0.01).共取样79处,其中窄光组阳性32处,敏感性41%(32/79);普通光组阳性17处,敏感性22%(17/79),2组肿瘤取样敏感性比较差异有统计学意义(P<0.01). 结论 窄光成像膀胱镜能提高对膀胱肿瘤特别是原位癌的诊断敏感性,降低术中残存率,减少膀胱肿瘤复发危险性.     

Blue light cystoscopy for the diagnosis of bladder cancer: Results from the US prospective multicenter registry

Introduction

Blue light cystoscopy (BLC) using hexaminolevulinate (HAL/Cysview/Hexvix) has been previously shown to improve detection of non–muscle-invasive bladder cancer (NMIBC). Herein, we evaluated the detection of malignant lesions in a heterogenous group of patients in the real world setting and documented the change in risk category due to upstaging or upgrading.

Fluorescence and white light cystoscopy for detection of carcinoma in situ of the urinary bladder

ObjectivesTo understand the additional benefits of HAL compared with conventional cystoscopy at the patient level and to explore relationships of urine cytology and CIS.MethodsWe reanalyzed pooled data from 3 phase III studies comparing hexaminolevulinate (HAL, Hexvix) fluorescence cystoscopy with white light (WL) cystoscopy for detecting CIS.ResultsOf 551 patients, 174 had at least one CIS lesion detected by HAL, WL, or random biopsy. The CIS detection rate of HAL was 0.87 vs. 0.75 for WL (P = 0.006). By multivariate Poisson regression, female patients had fewer CIS lesions (P < 0.0001) while older patients (≥65) had a higher number of CIS lesions detected by HAL (P = 0.04). HAL was less likely to detect CIS in patients previously treated with chemotherapy or BCG (P = 0.01 and 0.03, respectively), after adjusting for age. CIS was unifocal in 44% and multifocal in 56%. Multifocal CIS was associated with positive cytology more frequently than unifocal (65% vs. 45%; P = 0.016) whereas a negative cytology was more frequently associated with unifocal CIS. Patients with positive urine cytology had twice as many CIS lesions detected by HAL as patients with negative urine cytology (P = 0.02).ConclusionsHAL cystoscopy had a higher CIS detection rate than WL cystoscopy. The average number of CIS lesions detected was associated with baseline clinical characteristics. Cytology was positive more frequently in multifocal CIS suggesting that HAL may be particularly useful in this setting to optimize detection of the extent of CIS.     

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.     

5-氨基乙酰丙酸诱导荧光膀胱镜在膀胱肿瘤诊断中的应用（附31例报告）

目的：研究5-氨基乙酰丙酸（5-ALA）诱导荧光光动力学对膀胱肿瘤的早期诊断价值。方法：对血尿患者行5-ALA诱导荧光膀胱镜检查及活组织检查,以5-ALA膀胱灌注,2h后采用D-light光源系统进行膀胱镜检,对荧光阳性区域及白光下肉眼可见异常但荧光阴性区域进行活检,活检后行经尿道膀胱肿瘤电切术。结果：31例患者中有4例荧光阴性且普通光肉眼观阴性者未活检。余27例患者共取活检96处,其中荧光阳性区域取活检89处（包括普通光肉眼观阴性区域35处）,切缘取活检7处。病理检查结果显示：尿路上皮癌65处,阳性率为73．03％（65／89）,非肿瘤性病变24例,假阳性率为27％（24／89）,切缘活检7处为阴性。荧光下阳性而白光下阴性的肿瘤位点11处,切缘活检7处均为阴性。结论：5-ALA诱导荧光光动力学诊断对膀胱肿瘤有较高价值,能发现早期肿瘤,同时进行电切将更彻底。     

Fluorescence cystoscopy in the management of bladder cancer: a help for the urologist!

As a disease characterized by a nature polymorphic and fluctuant in its evolution, superficial transitional cell carcinoma of the bladder remains a perpetual therapeutic challenge, and raises a great interest in the development of new diagnostic and surveillance techniques. This paper reviews 10 years of experience of fluorescence cystoscopy, a simple technique perfectly adapted to the current endoscopic equipment. Its principle is to enhance the visual contrast between benign and malignant cells. Three photosensitizing agents are available, two prodrugs: delta-aminolevulinic acid or hexaminolevulinate, and a natural substance: hypericin. With a detection rate of over 90% for carcinoma in situ and a real potential for detecting small tumors overlooked by standard cystoscopy, fluorescence cystoscopy may be clearly recommended in clinical practice. This technique favors a standardization of superficial bladder cancer endoscopic management and is susceptible to have a real impact on the disease recurrence and progression rate.     

Clinical experience with intravesical instillations of 5-aminolevulinic acid (5-ALA) for the photodynamic diagnosis using fluorescence cystoscopy for bladder cancer

PURPOSE: To report our clinical experience with intravesical instillations of 5-aminolevulinic acid (5-ALA) for the photodynamic diagnosis of bladder cancer and to assess any side-effects of the diagnostic method. MATERIALS AND METHODS: Photodynamic diagnosis was performed in 18 patients of which 14 were men and 4 women with a median age of 71 years (range 44-84), 7 were primary cases and 11 were recurrent cases with bladder cancer. Two to two and half hours prior to endoscopy 1.5 g 5-ALA dissolved in 50 ml of 8.4% sodium hydrogen carbonate (NaHCO3) solution was instilled intravesically. For fluorescence excitation a blue light source (D-LIGHT System, Karl Storz Endoscopy Japan K. K.) was used. Under white and fluorescence light guidance, tumor locations were recorded, cold cup biopsies were taken and tumors were resected. The levels in images of the 5-aminolevulinic acid-induced fluorescence were compared with the pathological results. The area under the receiver operative characteristic (ROC) curve (AUC) in blue light endoscopy was also compared with that in white light endoscopy. RESULTS: Among the 129 specimens obtained by transurethral biopsy 45 were obtained from polypoid lesion and 84 from non-polypoid lesion, and among the 76 malignant diseases 36 were obtained from polypoid lesion and 40 from non-polypoid lesion (including 19 carcinoma in situ), and 21 patients with dysplasia were detected pathologically, with a sensitivity of 89.5% and specificity of 58.5% with a predictive accuracy of 77.0%. The AUC in blue light endoscopy was more than that in white light endoscopy in not only all cases (p = 0.010) but also in cases with non-polypoid lesion (p = 0.007) and recurrent cases (p = 0.002). Duration of 5-ALA instillation with a median time of 80 (range 30-150) min. did not seem to affect the accuracy of photodynamic diagnosis. Procedures were well tolerated by all patients with mild bladder irritability but no systemic side effect. CONCLUSION: Photodynamic diagnosis with intravesically applied 5-ALA is more effective than observation by conventional cystoscopy in detecting bladder cancer without additional risk or complication, and is expected to become a golden standard in the detection program.     

Reduced bladder tumour recurrence rate associated with narrow‐band imaging surveillance cystoscopy

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b What’s known on the subject? and What does the study add? Narrow‐band imaging cystoscopy is a new imaging modality developed to enhance conventional standard white‐light cystoscopy to evaluate bladder tumors. The current paper suggests that fulguration of low‐risk papillary bladder tumours using NBI cystoscopy results in fewer subsequent tumour recurrences than fulguration using standard cystoscopy. How, or if, NBI cystoscopy will become integrated into routine management of non‐invasive bladder tumours remains for further study.

OBJECTIVE

To evaluate frequency of recurrences among patients with papillary bladder tumours followed sequentially with conventional white‐light (WLI) cystoscopy and narrow‐band imaging (NBI) cystoscopy.

PATIENTS AND METHODS

A cohort of 126 patients with recurrent low‐grade papillary bladder tumours were followed every 6 months for 3 years by conventional WLI cystoscopy, and then over the next 3 consecutive years by NBI cystoscopy. Recurrent tumours detected were treated by outpatient fulguration or transurethral resection. We compared the tumour recurrence rate during follow‐up with WLI and NBI cystoscopy, using patients as their own controls.

RESULTS

Of the 126 patients, 94% had tumour recurrences during WLI cystoscopy vs 62% during NBI cystoscopy. The mean number of recurrent tumours was 5.2 with WLI cystoscopy vs 2.8 with NBI cystoscopy, and the median recurrence‐free survival time was 13 vs 29 months (P= 0.001).

CONCLUSION

Compared with follow‐up with WLI cystoscopy, NBI cystoscopy was associated with fewer patients having tumour recurrences, fewer numbers of recurrent tumours, and a longer recurrence‐free survival time.