Elsevier

Urology

Volume 66, Issue 6, Supplement 1, December 2005, Pages 35-63
Urology

Bladder tumor markers beyond cytology: International Consensus Panel on bladder tumor markers

https://doi.org/10.1016/j.urology.2005.08.064Get rights and content

Abstract

This is the first of 2 articles that summarize the findings of the International Consensus Panel on cytology and bladder tumor markers. The objectives of our panel were to reach a consensus on the areas where markers are needed, to define the attributes of an ideal tumor marker, and to identify which marker(s) would be suitable for diagnosis and/or surveillance of bladder cancer. Our panel consisted of urologists and researchers from Europe, Asia, and the United States who reviewed original articles, reviews, and book chapters on individual bladder tumor markers published in the English language mainly using the PubMed search engine. Panel members also met during 3 international meetings to write recommendations regarding bladder tumor markers. The panel found that the most practical use of noninvasive tests is to monitor bladder cancer recurrence, thereby reducing the number of surveillance cystoscopies performed each year. Markers also may be useful in the screening of high-risk individuals for early detection of bladder cancer. However, more prospective studies are needed to strengthen this argument. Case-control and cohort studies show that several markers have a higher sensitivity to detect bladder cancer. However, cytology is the superior marker in terms of specificity, although some markers in limited numbers of studies have shown specificity equivalent to that of cytology. Our panel believes that several bladder tumor markers are more accurate in detecting bladder cancer than prostate-specific antigen (PSA) is in detecting prostate cancer. However, bladder tumor markers are held to a higher standard than PSA. Therefore, use of bladder tumor markers in the management of patients with bladder cancer will require the willingness of both urologists and clinicians to accept them.

Section snippets

Detection

Bladder cancer may be diagnosed incidentally or because of symptoms. The main symptom of bladder cancer is hematuria, but in some patients, irritative symptoms are present from the very beginning. Incidental cancer is usually found on ultrasound performed for hematuria or irritative symptoms or for screening of symptoms unrelated to the urinary tract.

The clinical diagnosis of bladder cancer is usually made by flexible or rigid cystoscopy.4 Techniques of rigid and flexible cystoscopy are

Bladder tumor markers: why do we need them?

A noninvasive and accurate bladder tumor marker may be useful for bladder cancer screening and monitoring recurrence.

Ideal tumor marker

The attributes of an ideal tumor marker include technical ease of assaying, low intra-assay and interassay variability, and a high level of accuracy.2, 30

Good clinical practice in marker development

As in the setting of clinical trials research, there is a need to standardize different phases of tumor marker development and to develop general guidelines and protocols for broadly accepted (or at least broadly understood) principles of conducting and reporting translational marker studies.48, 49, 50, 51, 52 A number of leading scientists from a wide range of disciplines have chosen to focus on bladder cancer and the development of biomarkers to improve the diagnosis, prevention, and

Urine cytology: the standard noninvasive bladder tumor marker

Pathologic assessment of a randomly voided urine specimen is the standard noninvasive method in current use. Often called simply urine cytology, this approach is used primarily to monitor patients with a history of bladder cancer for the detection of new urothelial tumors. These new bladder neoplasms are traditionally called recurrences, but they are usually not at the same site as the index lesion and may not be the same grade or stage as the initial lesion. The pathologic interpretation of

Bladder tumor markers for diagnosis and monitoring recurrence

In this section, we will discuss various bladder cancer markers and tests that are commercially available or have shown potential to be clinically useful. Table I lists all of these tests and markers. The tumor markers are divided into 2 categories, soluble urine markers and cell-associated markers, based on whether urine specimens or exfoliated cells in urine are used in the assay.

Comparative analysis of bladder tumor markers (2000 to 2004)

Several studies have compared the sensitivity and specificity of a variety of markers with each other and with cytology. Most of the markers have a significantly higher sensitivity than cytology to detect bladder cancer. The sensitivity of many markers also varies with tumor grade, stage, and size. Some markers can detect bladder cancer recurrence before it can be detected by cystoscopy. Depending on the population, some markers show a specificity that is comparable to cytology in side-by-side

Standard Care for Bladder Cancer Detection and Surveillance

Cystoscopy and pathologic examination of biopsy specimens is the standard of care for the detection of bladder cancer. Periodic cystoscopies are the standard of care for surveillance. Surveillance schedules vary according to the risk factors of the disease.

Bladder Tumor Markers: Why Do We Need Them?

Screening of high-risk patients, but not the general population, using bladder tumor markers can offer early detection advantage and save medical costs. More studies are needed to identify accurate markers for bladder cancer screening.

Conclusion

Heterogeneity of bladder tumors to invade and metastasize and their frequent recurrence pose a challenge for physicians who treat patients with bladder cancer and for researchers who work on bladder cancer diagnosis, recurrence, and treatment-related areas. For most new bladder cancer cases, investigation begins when patients are symptomatic (eg, with hematuria or irritative voiding). This mode of detection is often inadequate for nearly 15% to 30% of these new cases with high-grade bladder

Acknowledgment

We acknowledge the editorial assistance of Cynthia Soloway and Dr. Adrienne Carmack for critically reviewing the manuscript.

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    This work was supported by Grant No. R01 CA-72821-06A2 from the National Cancer Institute/National Institutes of Health (VBL)

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