Biomarkers for non-muscle invasive bladder cancer: Current tests and future promise (original) (raw)

Bladder cancer biomarkers and their role in surveillance and screening

International Journal of Urology, 2009

Early detection of bladder cancer and its recurrences is essential for improved prognosis and long-term survival. The detection and follow-up of these patients is currently based on cystoscopy, which is expensive and invasive, and , in most cases, cytology, which is non-invasive but not very sensitive. During recent years, many urine-based tests have been developed and tested in different patient populations. In this review we discuss new developments for biomarkers in bladder cancer that have potential use in surveillance and screening. In almost all publications authors compare sensitivity of the test with a concomitantly executed cystoscopy, for example, determine cross-sectional sensitivity. However, it has also been shown that false positive test results may be followed by a positive cystoscopy in the near future, showing that cystoscopy itself does not provide 100% sensitivity. This suggests that for a proper evaluation of urine-based tests, longitudinal studies should be carried out and the results communicated to the urologist.

Biomarkers for Bladder Cancer Diagnosis and Surveillance: A Comprehensive Review

Diagnostics

Bladder cancer (BC) ranks as the sixth most prevalent cancer in the world, with a steady rise in its incidence and prevalence, and is accompanied by a high morbidity and mortality. BC is a complex disease with several molecular and pathological pathways, thus reflecting different behaviors depending on the clinical staging of the tumor and molecular type. Diagnosis and monitoring of BC is mainly performed by invasive tests, namely periodic cystoscopies; this procedure, although a reliable method, is highly uncomfortable for the patient and it is not exempt of comorbidities. Currently, there is no formal indication for the use of molecular biomarkers in clinical practice, even though there are several tests available. There is an imperative need for a clinical non-invasive testing for early detection, disease monitoring, and treatment response in BC. In this review, we aim to assess and compare different tests based on molecular biomarkers and evaluate their potential role as new mol...

Urine Markers for Detection and Surveillance of Non–Muscle-Invasive Bladder Cancer

European Urology, 2011

Context: Bladder cancer diagnosis and surveillance includes cystoscopy and cytology. The limitation of urinary cytology is its low sensitivity for low-grade recurrences. As of now, six urine markers are commercially available to complement cystoscopy in the detection of bladder cancer. Several promising tests are under investigation. Objective: In this nonsystematic review, we summarize the existing data on commercially available and promising investigational urine markers for the detection of bladder cancer. Evidence acquisition: A PubMed search was carried out. We reviewed the recent literature on urine-based markers for bladder cancer. Articles were considered between 1997 and 2011. Older studies were included selectively if historically relevant. Evidence synthesis: Although different studies have shown the superiority of urine markers regarding sensitivity for bladder cancer detection as compared with cytology, none of these tests is ideal and can be recommended unrestrictedly. Conclusions: Urine markers have been studied extensively to help diagnose bladder cancer and thereby decrease the need for cystoscopy. However, no marker is available at present that can sufficiently warrant this. Several urinary markers have higher but still insufficient sensitivity compared with cytology. Urinary cytology or markers cannot safely replace cystoscopy in this setting. To identify an optimal marker that can delay cystoscopy in the diagnosis of bladder cancer, large prospective and standardized studies are needed.

Urinary markers in the detection of bladder cancer: whatʼs new?

Current Opinion in Urology, 2006

Bladder cancer is one of the most common genitourinary malignancies and is a potentially life-threatening diagnosis. For many patients, however, the diagnosis of bladder cancer entails a lifetime of vigilant, costly, and invasive surveillance for recurrent and/or progressive disease. In the context of relative limitations of the current standard of cystoscopy and cytology, there has been burgeoning activity in the development of novel molecular urine-based markers for bladder cancer detection.

Biomarkers in Bladder Cancer Surveillance

Frontiers in Surgery, 2021

Aim: This is a narrative review with an aim to summarise and describe urinary biomarkers in the surveillance of non-muscle-invasive bladder cancer (NMIBC). It provides a summary of FDA-approved protein biomarkers along with emerging ones which utilise genetic, epigenetic and exosomal markers. We discuss the current limitations of the available assays.Background: Current guidelines advice a combination of cystoscopy, imaging,and urine cytology in diagnosis and surveillance. Although cytology has a high specificity, it is limited by low sensitivity particularly in low grade tumours. There are six FDA-approved urinary assays for diagnosis and surveillance of bladder cancer. They have shown to improve sensitivity and specificity to be used alongside cytology and cystoscopy but have a lower specificity in comparison to cytology and false positives often occur in benign conditions. Recent developments in laboratory techniques has allowed for use of markers which are RNA-, DNA-based as wel...

Biomarkers for bladder cancer management: present and future

American journal of clinical and experimental urology, 2014

Accurate and sensitive detection of bladder cancer is critical to diagnose this deadly disease at an early stage, estimate prognosis, predict response to treatment, and monitor recurrence. In past years, laboratory diagnosis and surveillance of urinary bladder cancer have improved significantly. Although urine cytology remains the gold standard test, many new urinary biomarkers have been identified. Furthermore, recent advances in genomic studies of bladder cancer have helped to refine our understanding of the pathogenesis of the disease, the biological basis for outcome disparities, and to inform more efficient treatment and surveillance strategies. In this article, the established diagnostic tests, newly identified biomarkers and genomic landscape of bladder cancer will be reviewed.

Biomarkers for detection, treatment decision and prognosis of the urinary bladder cancer

Currently, there is no perfect test for the detection of bladder cancer. Even the gold standard cystoscopy is increasingly being demonstrated to miss both Tis and papillary bladder cancer. The oldest urine-based biomarker, cytology, has high specificity but has low sensitivity and significant variability in performance. Stage and grade of transitional cell carcinoma are currently the most useful tools for taking therapeutic decisions and evaluating the prognosis of bladder cancer patients. During the last two decades, the better understanding of the molecular mechanisms involved in carcinogenesis and tumor progression has provided a large number of molecular markers of bladder cancer, with a potential diagnostic and prognostic value. Markers that distinguish among bladder cancer, normal urothelium, and benign urothelial conditions are potentially diagnostic, prognostic, and therapeutic targets. Currently, there are many research bladder tumor markers, but only a few are commercially available. The ideal urinary bladder tumor test is still unavailable, but the eventual "gold standard" will consist of multiple assays that analyze nucleic acids and proteins for detection. In addition, these tests would also reveal to the clinician both prognostic information and therapeutic targets for personalized medical treatment.

Urinary Biomarkers in Bladder Cancer

British Journal of Medical and Surgical Urology, 2009

Purpose of review To provide a current comprehensive review of the available urinary biomarkers for the detection and surveillance of bladder cancer. Recent findings The limitations of urine cytology and invasive nature of cystoscopic evaluation have led to a growing search for an ideal, cost-effective biomarker with acceptable sensitivity and specificity. Current FDA approved biomarkers such as UroVysion fluorescent in situ hybridization, Immunocyt, and nuclear matrix protein 22 do not have the specificity, and thus positive predictive value to warrant their cost as a routine adjunct or replacement for cystoscopy. Several promising commercially available assays such as Cxbladder, Assure MDx, and Xpert BC may perform better than cytology in select populations. Novel genomic, epigenetic, inflammatory, and metabolomic-based assays are being analyzed as potential urinary biomarkers. Summary Urinary biomarkers with high sensitivity and specificity are an unmet need in bladder cancer. Several new assays may meet these criteria and future research may justify use in clinical practice.

Bladder tumor markers: a review of the literature

The International Journal of Biological Markers, 2008

Bladder cancer is among the top eight most frequent cancers. Its natural history is related to a combination of factors that impact on its aggressiveness. Cystoscopy and urine cytology are the currently used techniques for the diagnosis and surveillance of non-invasive bladder tumors. The sensitivity of urine cytology for diagnosis is not high, particularly in low-grade tumors. The combination of voided urine cytology and new diagnostic urine tests would be ideal for the diagnosis and follow-up of bladder cancer. However, in order to have some clinical utility, new diagnostic and/or prognostic markers should achieve better predictive capacity that the currently used diagnostic tools. None of the markers evaluated over the last years showed remarkable sensitivity or specificity for the identification of any of the diverse types of bladder cancer in clinical practice. The limitations of the known prognostic markers have led to the research of new molecular markers for early detection of bladder cancer. This research focused in particular on the discovery of biomarkers capable of reducing the need for periodic cystoscopies or, ideally, offering a non-invasive examination instead. In this review, we will examine various new markers of bladder cancer and their value in the diagnosis and follow-up of non-muscleinvasive bladder cancer. When compared with urine cytology, which showed the highest specificity, most of these markers demonstrated an increased sensitivity.