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.     

Narrow-band imaging flexible cystoscopy in the detection of recurrent urothelial cancer of the bladder

OBJECTIVE

To investigate whether narrow‐band imaging (NBI) flexible cystoscopy improves the detection rate of urothelial carcinomas (UCs) of the bladder. NBI is an optical image enhancement technology in which the narrow bandwidth of light is strongly absorbed by haemoglobin and penetrates only the surface of tissue, increasing the visibility of capillaries and other delicate tissue surface structures by enhancing contrast between the two.

PATIENTS AND METHODS

Between November 2005 and May 2007 at the Queen Elizabeth Hospital, Birmingham, NBI flexible cystoscopy was performed on 29 patients with known recurrences of UC of the bladder after initial conventional white‐light imaging (WLI) flexible cystoscopy with the same instrument (Olympus Lucera sequential RGB endoscopy system).

RESULTS

Subjectively, NBI provided a much clearer view of bladder UCs and in particular their delicate capillary architecture. Objectively, NBI detected 15 additional UCs in 12 of 29 patients (41%), as compared with WLI. The mean (sd ) difference was 0.52 (0.74) UCs per patient (P < 0.001, Wilcoxon signed‐rank test).

CONCLUSIONS

Even in the few patients studied there is strong evidence that NBI differs from WLI in the number of UCs it detects, with a significantly increased detection rate. We feel that further evaluation of NBI flexible cystoscopy in more patients will show this technique to be highly valuable in the detection of both new and recurrent bladder UCs, and this work is continuing in our unit.     

Narrow‐band imaging cystoscopy to evaluate bladder tumours – individual surgeon variability

Study Type – Diagnosis (exploratory cohort)
Level of Evidence 2b

OBJECTIVE

To assess individual urologist variability using narrow‐band imaging (NBI) cystoscopy to evaluate bladder tumours.

PATIENTS AND METHODS

In all, 50 patients underwent white‐light and NBI cystoscopy to evaluate for recurrent bladder tumours. Endoscopic images in each patient were independently viewed by four urologists assessing presence or absence of tumour. Their findings were correlated with biopsy results.

RESULTS

In all, 26 patients had recurrent tumour and 24 had benign histology. There were no significant differences among urologists detecting recurrent tumour or in determining final pathology.

CONCLUSIONS

There does not appear to be a ‘learning curve’ for adapting to NBI‐surveillance cystoscopy in patients with bladder cancer.     

Urothelkarzinom der Harnblase

Background

Transurethral resection of transitional cell carcinoma of the bladder provides a definitive surgical treatment and supplies tissue for histological evaluation. Superficial low-grade carcinomas with a small risk of progression are treated properly with fulguration alone. To justify fulguration as a definitive treatment of papillary bladder tumours, one must be able to safely distinguish low-grade, noninvasive tumours from those that are high grade and potentially invasive.

Material and methods

A total of 160 patients with a transitional cell carcinoma at cystoscopy underwent transurethral resection of the tumour. The macroscopic appearance of the tumour, the aspect with bimanual palpation and the perioperative urine cytology were compared with the histological report.

Results

In our study we were able to safely distinguish low-grade tumours from high-grade tumours. All noninvasive tumours could be identified visually as such.

Conclusion

Urologists skilled in the evaluation of urine cytology can distinguish low-grade noninvasive tumours of the bladder from high-grade and potentially invasive tumours by means of appearance at cystoscopy and perioperative urine cytology.     

Thulium laser resection via a flexible cystoscope for recurrent non‐muscle‐invasive bladder cancer: initial clinical experience

OBJECTIVE

To present our initial experience of thulium laser resection via a flexible cystoscope for recurrent non‐muscle‐invasive bladder cancer (ThuRBT), as transurethral resection for bladder tumour (TURBT) is regarded as the reference standard for treating this disease, but alternative laser resection or ablation is suitable especially for recurrent tumours.

PATIENTS AND METHODS

From January 2005 to October 2005, 32 patients with early recurrent bladder tumour (recurrent within a year after TURBT) were treated with ThuRBT via a flexible cystoscope. The follow‐up included urine analysis, ultrasonography and cystoscopy every 3 months.

RESULTS

All patients were treated successfully with ThuRBT in one session, with no bladder haemorrhage, obturator nerve reflex or vesicle perforation. Randomized biopsies taken after surgery on and adjacent to the resection surface revealed no residual tumours. The mean (range) tumour diameter was 1.5 (0.5–3) cm and the mean operative duration was 25 (15–35) min. During the first year of follow‐up, local and heterotopic recurrences were found in three and six patients, respectively. The accumulated recurrence rates at 3, 6 and 12 months were 9%, 22% and 28%, respectively.

CONCLUSIONS

ThuRBT is a reliable therapy with minimal morbidity and invasiveness for selected patients with bladder cancer.     

Does cystoscopy correlate with the histology of recurrent papillary tumours of the bladder?

OBJECTIVE: To correlate the cystoscopic appearance of recurrent papillary bladder tumours with the histology after transurethral resection, and thus ascertain whether cystoscopy can reliably identify low-grade, noninvasive papillary tumours suitable for outpatient fulguration. PATIENTS AND METHODS: In all, 150 recurrent papillary tumours of the bladder identified at outpatient flexible cystoscopy were classified as either low-grade and noninvasive (TaG1), high-grade and noninvasive (TaG3), or invasive (TIG3) tumours, and correlated with urine cytology and histology of tumour stage and tumour grade after transurethral resection. RESULTS: Cystoscopy classified 84 of the 150 papillary tumours as TaG1 and 66 as either TaG3 or T1G3. Cystoscopy correctly predicted the histology of 78 of 84 (93%) TaG1 tumours, 71 of 72 (98%) TaG1 tumours associated with a negative urine cytology, and 92% of TaG3 or T1G3 tumours. CONCLUSIONS: A skilled urologist can identify noninvasive, low-grade recurrent papillary bladder tumours on follow-up cystoscopy that do not require biopsy and that may be treated by outpatient fulguration alone.     

Treatment changes and long‐term recurrence rates after hexaminolevulinate (HAL) fluorescence cystoscopy: does it really make a difference in patients with non‐muscle‐invasive bladder cancer (NMIBC)?

Study Type – Therapy (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? HAL fluorescence cystoscopy is known to improve tumour detection in NMIBC cases and to have a potentially favourable impact concerning the recurrence rates. The present trial assessed the advantages of HAL cystoscopy with regard to postoperative treatment changes and 2 years' recurrence rates, subjects that are poorly evaluated in the literature.

OBJECTIVES

• ? To evaluate in a prospective, randomized study the impact of hexaminolevulinate blue‐light cystoscopy (HAL‐BLC) on the diagnostic accuracy and treatment changes in cases of non‐muscle invasive bladder cancer (NMIBC) compared with standard white‐light cystoscopy (WLC).
• ? To compare the long‐term recurrence rates in the two study arms.

PATIENTS AND METHODS

• ? In all, 362 patients suspected of NMIBC were included in the trial based on positive urinary cytology and/or ultrasonographic suspicion of bladder tumours and underwent transurethral resection of bladder tumours.
• ? A single postoperative mytomicin‐C instillation was performed in all cases, intravesical chemotherapy for intermediate‐risk patients and BCG instillations for high‐risk cases.
• ? The follow‐up protocol consisted of urinary cytology and WLC every 3 months for 2 years.
• ? Only first‐time recurrences after the initial diagnosis were considered.

RESULTS

• ? In the 142 patients with NMIBC in the HAL‐BLC series, tumour detection rates significantly improved for carcinoma in situ, pTa andoverall cases.
• ? In 35.2% of the cases, additional malignant lesions were found by HAL‐BLC and consequently, the recurrence‐ and progression‐risk categories of patients and subsequent treatment improved in 19% of the cases due to fluorescence cystoscopy.
• ? In all, 125 patients in the HAL‐BLC group and 114 of the WLC group completed the follow‐up.
• ? The recurrence rate at 3 months was lower in the HAL‐BLC series (7.2% vs 15.8%) due to fewer ‘other site’ recurrences when compared with the WLC series (0.8% vs 6.1%).
• ? The 1 and 2 years recurrence rates were significantly decreased in the HAL‐BLC group compared with the WLC group (21.6% vs 32.5% and 31.2% vs 45.6%, respectively).

CONCLUSIONS

• ? HAL‐BLC was better than WLC for detecting NMIBC cases and improved tumour detection rates.
• ? HAL‐BLC significantly modified the postoperative treatment of cases.
• ? The 3 months, 1 and 2 years recurrence rates were significantly improved in the HAL‐BLC arm.

     

NBI技术结合电子软膀胱镜在膀胱肿瘤早期诊断中的应用研究

目的：评估窄带成像（NBI）技术结合电子软膀胱镜（简称NBI膀胱镜）在膀胱肿瘤早期诊断中的应用价值。方法：2009年1月～5月对85例早期膀胱肿瘤或癌前病变患者,首先使用标准白光（WLI）膀胱镜进行观察,接着使用NBI膀胱镜进行观察,均记录观察到的乳头状肿瘤个数,最后取活组织检查并进行病理学诊断。对比NBI膀胱镜与WLI膀胱镜在膀胱肿瘤早期诊断中的检出率。结果：NBI技术能够提供更加清晰的膀胱肿瘤的图像,特别是肿瘤组织与正常膀胱黏膜的边界。85例中包括乳头状Ta期膀胱肿瘤76例,原位癌6例,重度不典型增生3例。使用WLI膀胱镜：Ta期膀胱肿瘤76例检查出肿瘤个数为178,原位癌检查出2例,重度不典型增生检查出1例;使用NBI膀胱镜：Ta期膀胱肿瘤76例检查出肿瘤个数214,原位癌检查出6例,重度不典型增生检查出3例;检出率分别提高了20．2％,200％,200％。结论：与WLI膀胱镜相比,NBI膀胱镜的应用能更清晰的显示肿瘤组织与正常膀胱黏膜的边界,提高早期膀胱癌及癌前病变的诊出率,降低漏诊率。     

窄波成像电子膀胱软镜在膀胱肿瘤诊断中的应用价值

目的 研究窄波成像(NBI)电子膀胱软镜在膀胱肿瘤诊断中的应用价值.方法 临床疑似膀胱肿瘤患者31例,采用Olympus ExeraⅡ电子膀胱软镜系统,分别在NBI和普通白光(WLI)视野下检查,顺序采用随机化法,观察时间相同.分别取2种视野下膀胱内所见可疑病灶活检,比较2种检查方法膀胱肿瘤诊断准确率.结果 31例患者中,经病理检查确诊为膀胱尿路上皮癌28例(90%),其中Tis 3例、Ta 15例、T1 7例、T2 3例;低级别癌20例、高级别癌8例;多发病灶16例、单发病灶12例.WLI下共取活检73处,癌组织61处,阳性率84%,确诊膀胱癌23例;NBI下共取活检91处,癌组织80处,阳性率88%,确诊膀胱癌28例.NBI发现癌组织较WLI多19处,2组检出准确率比较,差异有统计学意义(P＜0.05). 结论 NBI诊断膀胱肿瘤的准确率明显高于WLI电子膀胱软镜.     

Should follow-up cystoscopy in bacillus Calmette-Guérin-treated patients continue after five tumour-free years?

Background

It is not known how long follow-up cystoscopy in tumour-free bacillus Calmette-Guérin (BCG)-treated patients should continue.

Objective

Determine the incidence of late recurrences and progression after a tumour-free period of >5 yr after BCG treatment.

Design, setting, and participants

Data on 542 patients with non-muscle-invasive bladder cancer treated with BCG between 1986 and 2003 were analysed. Of 542 patients, 204 patients (37.6%) were tumour-free for ≥5 yr. The median tumour-free period was 105.5 mo (range: 60-252 mo).

Measurements

To compare the tumour-free group with patients who were not tumour-free for 5 yr, traditional variables (tumour grade, tumour stage, age, gender, tumour number and size, primary or recurrent tumour, BCG strain, previous chemotherapy, previous upper tract tumour, number of earlier resections, and European Organisation for Research and Treatment of Cancer recurrence and progression risk groups) were analysed using the Fisher exact test for dichotomous variables, the Mantel-Haenszel chi-square test for ordered categorical variables, and the Mann-Whitney U-test for continuous variables. Kaplan-Meier curves for time to recurrence were constructed using Statistica software (StatSoft, Tulsa, Oklahoma, USA). Differences between groups were tested with the log-rank test. For continuous variables, Cox proportional hazard regression was performed to find significant effect on the time to recurrence.

Results and limitations

Twenty-two of 204 patients (10.8%) had a recurrence after being tumour-free for ≥5 yr. The Kaplan-Meier estimated risk for recurrence was 12.5% at 10 yr and 20.5% at 15 yr. Among patients with TaG1-TaG2 before BCG, 11 of 79 patients (13.9%) had recurrences, including three patients with invasive extravesical tumours. Among the bladder recurrences were seven TaG1 s and one carcinoma in situ (CIS). Among the 125 patients with TaG3/CIS/T1 before BCG, 11 patients (8.8%) had recurrences, including 2 patients with invasive ureter tumours. The bladder recurrences were one T2, four CIS, and four TaG1. Late recurrences were 8.5 times more common among patients with recurrent tumours before BCG compared with patients treated after their first tumour episode. The study was retrospective and nonrandomised but unselected and population-based.

Conclusions

A tumour-free period of 5 yr after BCG treatment is a good prognostic sign, but recurrences after >10 yr are not unusual. Literature data and the present report support cystoscopy follow-up for ≥10-15 tumour-free years, at least among patients with recurrent tumours and/or high-grade lesions before BCG treatment.     

Applying narrow-band imaging in complement with white-light imaging cystoscopy in the detection of urothelial carcinoma of the bladder

ObjectivesTo investigate the value of narrow-band imaging (NBI) flexible cystoscopy in the detection of urothelial carcinoma (UC) of the bladder.Materials and methodsClinical data of 179 patients with suspected UC, who presented with gross hematuria, were collected at China PLA General Hospital from January 2009 to August 2010. These patients underwent white-light imaging (WLI) cystoscopy followed by NBI. The tumors were visualized, imaged, and recorded. Suspected UCs were biopsied or treated by transurethral resection, and then sent for pathologic examination. Detection results for NBI and WLI were compared.ResultsWLI and NBI confirmed UC in 143 patients; a total of 285 tumors were detected. The patient-level detection rates for NBI and WLI were 97.9% (140/143) and 88.8% (127/143), respectively (P = 0.002). The patient-level false-positive detection rates for NBI and WLI were 21.8% (39/179) and 29.1% (52/179), respectively (P = 0.12). NBI detected a total of 59 additional tumors (17.2%; 34pTa, 17pT1, 3pT2, and 5pTis) in 44 of 143 patients (30.8%). NBI found 1 additional tumor in 34 cases, 2 additional tumors in 6 cases, 3 additional tumors in 3 cases, and 4 additional tumors in 1 case. The mean ± SD (range) number of identified UCs per patient was 1.97 ± 0.67 (1–5) for NBI and 1.78 ± 0.53 (1–4) for WLI (P = 0.01). The tumor-level detection rates for NBI and WLI were 96.8% and 79.3%, respectively (P < 0.001).ConclusionsCompared with WLI, NBI improves UC detection. It has a higher rate of detection and a comparative rate of false-positive detection. NBI is simple and requires no dyeing. It can be conveniently applied to complement WLI.     

Surveillance of patients with bladder carcinoma using fluorescent in-situ hybridization on bladder washings

OBJECTIVES

To compare the sensitivity and specificity of the UroVysion^TM (Abbott Laboratories Inc., Downers Grove, IL, USA) fluorescent in‐situ hybridization (FISH) assay to that of urinary cytology obtained from bladder irrigation during cystoscopic surveillance in patients with bladder carcinoma.

PATIENTS AND METHODS

The medical records were retrospectively reviewed for 41 consecutive patients screened at the authors’ institution between August 2000 and December 2006 for recurrence of pathologically confirmed bladder cancer. All 162 cytology examinations and 141 FISH assay results obtained from bladder washing were included. Recurrence was determined by cystoscopy, bladder biopsy and upper‐tract imaging. Sensitivity, specificity, positive predictive and negative predictive values were assessed using a chi‐square distribution with one degree of freedom.

RESULTS

There were 24 men and 17 women (male to female ratio 0.59), the mean (range) age was 56 (33–73) years and the mean follow‐up 30 (2–57) months. At the initial diagnosis, 35 of the 41 patients (85%) had superficial tumours (stage ≤ T1), while six (15%) had muscle‐invasive tumours (stage ≥T2). Twenty‐six (63%) had low‐grade and 15 (37%) had high‐grade tumours. In 16 of 141 (11%) of the FISH assays and 16 of 162 (10%) of the cytological samples that were collected from bladder irrigations, there were too few cells for an adequate analysis. The FISH assay correctly correlated with subsequent cystoscopy, bladder biopsy or upper‐tract imaging in 110/125 (88%) cases but not in 15/125 (12%). Cytology correctly correlated with the subsequent evaluation in 112/146 (77%) cases but did not in 34/146 (23%). When the FISH was compared with cytology in this setting, the sensitivity was 77% (30/39) vs 74% (37/50; P > 0.1), the specificity was 93% (80/86) vs 78% (75/96; P < 0.01), the positive predictive value was 83% (30/36) vs 64% (37/58; P < 0.05), and the negative predictive value was 90% (80/89) vs 85% (75/88; P > 0.1), respectively.

CONCLUSION

The UroVysion FISH assay obtained from bladder washings during cystoscopic surveillance of patients with a history of bladder cancer provides a similar specificity but greater sensitivity than that of cytology for detecting bladder cancer recurrences. Given the better specificity and similar sensitivity of UroVysion compared with urine cytology obtained from bladder washings, a reasonable approach might be to use the UroVysion assay as the primary marker for recurrence, with urine cytology used as a complementary examination.     

Narrow‐band imaging cystoscopy to evaluate the response to bacille Calmette‐Guérin therapy: preliminary results

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b

OBJECTIVE

To evaluate whether narrow‐band imaging cystoscopy (NBIC) can identify bladder tumour suspected on follow‐up white‐light cystoscopy (WLC) after intravesical bacille Calmette‐Guérin (BCG) therapy, as BCG causes an intense reaction in the bladder, appearing as red lesions on WLC, which might be residual tumour or BCG‐induced inflammation.

PATIENTS AND METHODS

Sixty‐one patients with high‐risk non‐muscle‐invasive bladder tumours were evaluated 3 months after starting induction BCG therapy. All patients had abnormal erythematous lesions on WLC, suspected to be residual carcinoma in situ. After WLC, they were evaluated by NBIC, urine cytology and biopsy, followed by transurethral resection of all visible lesions.

RESULTS

Of the 61 patients, 22 (36%) had residual tumour. NBIC correctly identified tumour in 21 patients, but another 10 had unnecessary biopsy (NBIC positive, negative biopsy). Only one of 30 patients who had negative NBIC findings had tumour. NBIC outperformed urine cytology in detecting residual tumour after BCG therapy.

CONCLUSION

NBIC appears to better identify patients who have suspected residual tumour on follow‐up WLC at 3 months after BCG therapy.     

Routine follow-up cystoscopy in detection of recurrence in patients being monitored for bladder cancer

BACKGROUND AND AIMS: Cystoscopy and urine cytology are the standard tools for monitoring superficial bladder cancer. The sensitivity of cystoscopy is, however, limited to the tumours that can be visualised, and the sensitivity of cytology is relatively low in low-stage/low-grade tumours. Therefore, new tumour markers have been developed. BTA stat has been reported to have high sensitivity in detecting both primary and recurrent bladder tumours, and may have the potential to detect tumours that cannot be visualised by routine cystoscopy including recurrences in upper tract. The objective of the study was to analyse the reliability of routine follow-up cystoscopy by further investigating patients with positive marker status, BTA stat Test and urine cytology, but negative cystoscopy. MATERIAL AND METHODS: 446 consecutive patients being followed for bladder cancer were analysed in a prospective multicenter study. A voided urine sample was obtained prior to cystoscopy and split for culture, cytology and BTA stat testing. In the case of positive marker status, BTA stat Test or urine cytology, but negative cystoscopy patients were further investigated by i.v. urography or renal ultrasound and random biopsies. The sensitivity of routine follow-up cystoscopy is reported. RESULTS: Of 446 patients 131 (29.4%) had a bladder cancer recurrence at routine cystoscopy. Of the remaining 315 patients not having recurrent tumour at cystoscopy, 56 patients (17.8%) had positive BTA stat Test result, 6 (1.9%) had positive cytology and 5 were positive by both tests. Nine recurrences that were missed at routine follow-up cystoscopy were detected by further investigations making the total number of bladder confined recurrent tumours 140 (140/446, 31.4%). Five of these 9 recurrences were high grade lesions (1 T1G3, 4 CIS), of which 4 were detected by positive cytology. The overall sensitivity of cystoscopy was 93.6%. CONCLUSIONS: We found that routine follow-up cystoscopy may miss over five percent of the recurrent tumours. Although cystoscopy remains the gold standard for bladder cancer follow-up, it is suggested that even with negative cystoscopy patients with positive marker status, BTA stat Test and especially urine cytology, should be considered at risk for coexisting, and in some case even high grade recurrence.     

Mechanisms of recurrence of Ta/T1 bladder cancer

INTRODUCTION

Bladder cancer recurrence occurs via four mechanisms - incomplete resection, tumour cell re-implantation, growth of microscopic tumours, and new tumour formation. The first two mechanisms are influenced by clinicians before and immediately after resection; the remaining mechanisms have the potential to be influenced by chemopreventive agents. However, the relative importance and timing of these mechanisms is currently unknown. Our objective was to postulate the incidence and timing of these mechanisms by investigating the location of bladder cancer recurrences over time.

PATIENTS AND METHODS

The topographical locations of tumours and their recurrences were analysed retrospectively for 169 patients newly-diagnosed with Ta/T1 bladder cancer, with median follow-up of 33.8 months. Tumours were assigned to one or more of six bladder sectors, and time to recurrence and location of recurrences were recorded.

RESULTS

Median time to first tumour recurrence was 40 months. Median times between subsequent recurrences were 6.6, 7.9, 8.0 and 6.6 months for recurrences 1 to 2, 2 to 3, 3 to 4, and 4 to 5, respectively. The risk of first tumour recurrence in any given bladder sector increased by nearly 4-fold if the primary tumour was resected from that sector (P < 0.001); this association was not significant for subsequent recurrences. The proportion of tumour recurrences in multiple bladder sectors increased from 13% for the first recurrence to 100% for recurrence seven onwards.

CONCLUSIONS

First tumour recurrence appears different to subsequent recurrences; incomplete resection and tumour cell re-implantation may dominate at this time-point. Only later does genuine new tumour formation appear to increase in importance. This has important implications for clinical trials, especially those involving chemopreventive agents.     

Clinical and Cost Effectiveness of Hexaminolevulinate-guided Blue-light Cystoscopy: Evidence Review and Updated Expert Recommendations

Context

Non–muscle-invasive bladder cancer (NMIBC) is associated with a high recurrence risk, partly because of the persistence of lesions following transurethral resection of bladder tumour (TURBT) due to the presence of multiple lesions and the difficulty in identifying the exact extent and location of tumours using standard white-light cystoscopy (WLC). Hexaminolevulinate (HAL) is an optical-imaging agent used with blue-light cystoscopy (BLC) in NMIBC diagnosis. Increasing evidence from long-term follow-up confirms the benefits of BLC over WLC in terms of increased detection and reduced recurrence rates.

Objective

To provide updated expert guidance on the optimal use of HAL-guided cystoscopy in clinical practice to improve management of patients with NMIBC, based on a review of the most recent data on clinical and cost effectiveness and expert input.

Evidence acquisition

PubMed and conference searches, supplemented by personal experience.

Evidence synthesis

Based on published data, it is recommended that BLC be used for all patients at initial TURBT to increase lesion detection and improve resection quality, thereby reducing recurrence and improving outcomes for patients. BLC is particularly useful in patients with abnormal urine cytology but no evidence of lesions on WLC, as it can detect carcinoma in situ that is difficult to visualise on WLC. In addition, personal experience of the authors indicates that HAL-guided BLC can be used as part of routine inpatient cystoscopic assessment following initial TURBT to confirm the efficacy of treatment and to identify any previously missed or recurrent tumours. Health economic modelling indicates that the use of HAL to assist primary TURBT is no more expensive than WLC alone and will result in improved quality-adjusted life-years and reduced costs over time.

Conclusions

HAL-guided BLC is a clinically effective and cost-effective tool for improving NMIBC detection and management, thereby reducing the burden of disease for patients and the health care system.

Patient summary

Blue-light cystoscopy (BLC) helps the urologist identify bladder tumours that may be difficult to see using standard white-light cystoscopy (WLC). As a result, the amount of tumour that is surgically removed is increased, and the risk of tumour recurrence is reduced. Although use of BLC means that the initial operation costs more than it would if only WLC were used, over time the total costs of managing bladder cancer are reduced because patients do not need as many additional operations for recurrent tumours.     

Narrow-band imaging flexible cystoscopy in the detection of primary non-muscle invasive bladder cancer: a “second look” matters?

Objective  

We investigated whether narrow-band imaging (NBI) was superior to white light imaging (WLI) for detecting primary non-muscle invasive bladder cancer (NMIBC) in a randomized imaging sequence modality, as the increased detection rate by NBI maybe result from the “second look” inspection of the bladder.     

Aurora kinase B is an independent protective factor in superficial bladder tumours with a dysfunctional G1 checkpoint

OBJECTIVES

To investigate the clinical role of Aurora kinases (essential for regulating mitosis) in human bladder pathogenesis, by quantifying Aurora kinase A and B, phospho‐Aurora A, and phospho‐Rb and p53 in bladder tumours, analysing the correlations between expression and clinicopathological features.

PATIENTS AND METHODS

We evaluated levels of Aurora A, B, phospho‐Aurora A, phospho‐Rb and p53 in 73 superficial bladder tumours using tissue microarrays and immunohistochemistry, and correlated expression with pathological variables and clinical outcome.

RESULTS

None of the Aurora proteins, when analysed alone, significantly predicted either tumour recurrence or progression. In tumours with an aberrant G1 checkpoint, assessed by phospho‐Rb and p53 status, expression of neither Aurora A nor its phosphorylated form predicted either tumour recurrence or progression. Surprisingly, high expression of Aurora B in tumours with an aberrant G1 checkpoint significantly protected from tumour recurrence. On multivariate analysis, Aurora B was the only significant factor that predicted tumour recurrence in the presence of either phospho‐Rb or mutated p53. This difference was not evident in tumours with an intact G1 checkpoint.

CONCLUSIONS

High expression of Aurora B in superficial bladder tumours with an aberrant G1 checkpoint significantly protects patients from tumour recurrence. The potential application of nonspecific Aurora kinase inhibitors in non‐muscle‐invasive bladder cancer might be detrimental.     

Evaluation of an orthotopic rat bladder urothelial cell carcinoma model by cystoscopy

OBJECTIVES

To enable preclinical testing of intravesical therapies against non‐muscle‐invasive bladder cancer (NMIBC) in an orthotopic rat bladder tumour model, augmented by the use of serial cystoscopy for in vivo tumour assessment and follow‐up.

MATERIALS AND METHODS

Fischer F344 rats had a 16‐G transurethral cannula placed. The bladder mucosa was conditioned with an acid rinse, followed by a 1‐h instillation of 1.5 × 10⁶ AY‐27 rat bladder urothelial cell carcinoma (UCC) cells (day 0). Cystoscopy (1 mm) was done on day 0 (control) and at 3, 4, 5, 6, 7, 10, 13 and 17 days. At the scheduled times the rats were killed after cystectomy (four at each time) for histopathological examination of the bladder.

RESULTS

Overall, tumour establishment was >80%, with predominantly carcinoma in situ preceding or concomitant with invasive tumour growth. All tumours were formed at 3–5 days, and remained non‐muscle‐invasive up to 5 days. From 6 days, tumours progressed to muscle‐invasive disease in 40% of the rats. Visibility at cystoscopy was excellent and tumours were apparent in >90% of rats from 5 days on, with a specificity and sensitivity of >90%. Cystoscopy could not distinguish NMIBC from muscle‐invasive disease.

CONCLUSIONS

This is a reliable model of orthotopic rat bladder UCC, with early high‐grade NMIBC growth, immediately followed by muscle‐invasive growth, i.e. the recommended time to start intravesical therapy would be 5 days after tumour cell inoculation. Tumour growth can easily be monitored by cystoscopy, but cannot be used to distinguish NMIBC from muscle‐invasive bladder cancer.