Comparison of Screening Methods in the Detection of Bladder Cancer

Ramakumar, Sanjay; Bhuiyan, Jalaluddin; Besse, Jennifer A.; Roberts, Sigrid C.; Wollan, Peter C.; Blute, Michael L.; O’Kane, Dennis J.

doi:10.1016/s0022-5347(01)61899-8

Cited by 306 publications

(138 citation statements)

References 30 publications

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“…The costs involved for PCR-based telomerase assays have been calculated previously and amount to approximately Euro 15 for each test. 52 With regard to our own study, this assumption is vague, as no economic data have been collected. Nevertheless, these characteristics should render both hTERT and hTR analysis cost-effective compared to cytology.…”

Section: Discussionmentioning

confidence: 97%

Quantitative evaluation of telomerase subunits in urine as biomarkers for noninvasive detection of bladder cancer

Weikert

Krause

Wolff

et al. 2005

Intl Journal of Cancer

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The aim of our study was to prospectively evaluate the potential diagnostic value and clinical applicability of quantitative analysis of telomerase subunits gene expression in urine for noninvasive detection of bladder cancer. Expression levels of human telomerase reverse transcriptase (hTERT) and human telomerase RNA (hTR) were analyzed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in urine samples from 163 subjects with bladder cancer and 237 controls (163 individuals with benign genitourinary diseases; 74 healthy subjects). The sensitivity, specificity and optimal cutoffs were determined and compared to the corresponding values obtained by voided urine cytology. Quantitative urinary hTR analysis detects bladder cancer with an overall sensitivity of 77.0%, whereas hTERT analysis reached a sensitivity of 55.2%. The majority of undetected tumors were small, lowgrade pTa lesions. Both hTR and hTERT proved to be significantly more sensitive than cytology (34.5%; p < 0.001). Specificities for hTR, hTERT and cytology were 72.1%, 85.0% and 92.7%, respectively, in the total study population and 96.9%, 89.2% and 100%, respectively, in healthy subjects. Higher diagnostic accuracy was achieved by hTR than by hTERT analysis (p < 0.05). The specificity of hTR increased to 85.0% in the total population if urinary leukocyte contamination was excluded. These data suggest that quantitative hTR analysis is the most accurate telomerase-based test for bladder cancer detection and has the potential to replace cytology as a noninvasive biomarker for disease diagnosis and follow-up. ' 2005 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 97%

Quantitative evaluation of telomerase subunits in urine as biomarkers for noninvasive detection of bladder cancer

Weikert

Krause

Wolff

et al. 2005

Intl Journal of Cancer

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“…18 Our study concurs with several others and confirms marked improvement of sensitivity by incorporating ImmunoCyt/uCytt with cytology. Most studies reported results comparable or better 44-74% (65%) 57-90% (72%) BTA trak 21,26,30À32 58-78% (67%) 63-84% (75%) NMP22 21,22,27,28,31,33 53-74% (64%) 55-80% (70%) Telomerase 4,17,22 65-70% (68%) 89-99% (94%) Microsatellites 16 -(74%) -(82%) FISH 17 -(81%) -(96%) ImmunoCyt/ uCytt 6,7,11,13À15,18,20,21 53-100% (90%) 64-95% (74%)…”

Section: Discussionmentioning

confidence: 98%

ImmunoCyt/uCyt+™ improves the sensitivity of urine cytology in patients followed for urothelial carcinoma

et al. 2005

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ImmunoCyt/uCytt is a fluorescent test combining three monoclonal antibodies. In this study, it has been tested as a complement to cytology in the detection of urothelial carcinoma in urine. It has been performed simultaneously with standard cytology and cystoscopy on 870 urine analyses from one hospital. In 136 cases, one or more bladder tumors were found. Overall sensitivity of cytology, ImmunoCyt/uCytt and combined analyses reached 29, 74 and 84%, respectively, and overall specificity was 98, 62 and 61%. The negative predictive value of cytology, ImmunoCyt/uCytt and both analyses was 88, 93 and 95%, respectively, and the positive predictive value was 70, 26 and 29%. The sensitivity of cytology for low malignant potential neoplasms, low-and high-grade papillary carcinomas was 6, 18 and 53%, while it reached 71, 79 and 93% when combined with ImmunoCyt/uCytt. The sensitivity of cytology for stages Ta, T1, T2 and over and Tis tumors was12, 67, 47 and 50%, while it reached 78, 83, 79 and 100% when combined with ImmunoCyt/uCytt. In the absence of tumor on cystoscopy but with positive ImmunoCyt/uCytt, 18% of patients developed a tumor, 2-6 months later. Of the 109 cases diagnosed as suspicious for malignancy by cytology, a tumor was present in 30 cases and ImmunoCyt/uCytt was positive in 22 (73%) of them. In conclusion, ImmunoCyt/uCytt may be used to postpone cystoscopies in patients followed for bladder cancer and may help to save cytologist and pathologist screening Keywords: urothelial carcinoma; cytology; ImmunoCyt/uCytt; immunofluorescence; urinary bladder; recurrence Superficial bladder cancers are defined as tumors limited to the mucosa (Tis, Ta) or invading into the lamina propria (T1), without muscle invasion. 1 They represent more than 80% of urothelial carcinomas and more than 50% will recur. 1-3 Patients with bladder cancer are followed with regular cytologies and cystoscopies. Cytology is very specific but this test is limited by its low sensitivity ranging from 16 to 60%. 4 Cytology is most useful at detecting highgrade (HG) cancer, whereas its sensitivity for lowgrade (LG) urothelial tumors is low and merely reaches 17%. 4 Furthermore, criteria used in urinary cytology to detect tumor cells are largely subjective and the ability to detect cancer cells is dependent on the experience of cytologists or pathologists. For instance, atypical cells and papillary aggregates may be found in either reactive or neoplastic conditions. 5 Furthermore, LG urothelial carcinomas do not always exfoliate in aggregates and the cell characteristics are often so subtle that they might not be recognizable even by an experienced cytologist. 5 Standard practice in the follow-up of patients with bladder cancer requires cystoscopies at regular intervals, but this technique is invasive, costly and causes discomfort to the patient. It is thus estimated that by improving the sensitivity of cytology, fewer follow-up cystoscopies would be needed. Furthermore, improved sensitivity would help cytologists and pathologists to save time c...

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“…Sensitivities for urine samples have ranged between 0% and 100% ( Rahat et al, 1999;Ramakumar et al, 1999;Yokota et al, 1998;Yoshida et al, 1997). The reasons for these widely divergent ®ndings remain unclear, particularly because methodical di erences, such as in the treatment of the samples, are not apparent.…”

Section: Urine Samplesmentioning

confidence: 99%

Telomerase: Its clinical relevance in the diagnosis of bladder cancer

Müller

2002

Oncogene

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More than 50 years ago, Papanicolaou recognized the importance of a non-invasive technique for the diagnosis and follow-up of patients with carcinoma of the urinary bladder. Cystoscopy, however, has remained the`gold standard' since no currently available non-invasive method can compete with cystoscopy's sensitivity and speci®city. The detection of the ribonucleoprotein telomerase or the telomerase subunits human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) in urine samples o er new diagnostic perspectives. The present article presents a review of publications in the literature and evaluates their clinical relevance. The experimental studies reported to date are very promising and show that telomerase exactly ful®ls the requirements for a good diagnostic marker for carcinoma of the urinary bladder. The diagnostic application remains in an experimental stage and telomerase is still several steps away for routine use as a clinical parameter. The remaining steps leading to its routine clinical application will be discussed.

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Comparison of Screening Methods in the Detection of Bladder Cancer

Cited by 306 publications

References 30 publications

Quantitative evaluation of telomerase subunits in urine as biomarkers for noninvasive detection of bladder cancer

Quantitative evaluation of telomerase subunits in urine as biomarkers for noninvasive detection of bladder cancer

ImmunoCyt/uCyt+™ improves the sensitivity of urine cytology in patients followed for urothelial carcinoma

Telomerase: Its clinical relevance in the diagnosis of bladder cancer

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