Multiple Chromatographic Analysis of Urine in the Detection of Bladder Cancer (original) (raw)

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.

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.

A SIDE BY SIDE COMPARISON OF CYTOLOGY AND BIOMARKERS FOR BLADDER CANCER DETECTION

The Journal of …, 2004

Purpose: The identification of accurate bladder tumor markers/tests could improve diagnosis, recurrence monitoring and treatment in patients with bladder cancer. In this study we compared the efficacy of the hyaluronic acid (HA)-hyaluronidase (HAase), BTA-Stat (Bard/Bion Diagnostics, Redmond, Washington), Hemastix (Bayer Corp., Elkhart, Indiana) (hematuria detection) and UBC-Rapid (IDL Biotech, Borlä nger, Sweden) tests, and cytology to detect bladder cancer. The HA-HAase test measures urinary HA and HAase levels, BTA-Stat detects complement factor-H and H related protein in urine, the Hemastix hemoglobin dipstick detects hematuria and UBC-Rapid detects cytokeratin 8 and 18 fragments in urine.

Liquid Biopsy Biomarkers in Urine: A Route towards Molecular Diagnosis and Personalized Medicine of Bladder Cancer

Journal of Personalized Medicine, 2021

Bladder cancer (BC) is characterized by high incidence and recurrence rates together with genomic instability and elevated mutation degree. Currently, cystoscopy combined with cytology is routinely used for diagnosis, prognosis and disease surveillance. Such an approach is often associated with several side effects, discomfort for the patient and high economic burden. Thus, there is an essential demand of non-invasive, sensitive, fast and inexpensive biomarkers for clinical management of BC patients. In this context, liquid biopsy represents a very promising tool that has been widely investigated over the last decade. Liquid biopsy will likely be at the basis of patient selection for precision medicine, both in terms of treatment choice and real-time monitoring of therapeutic effects. Several different urinary biomarkers have been proposed for liquid biopsy in BC, including DNA methylation and mutations, protein-based assays, non-coding RNAs and mRNA signatures. In this review, we s...

Considerations on implementing diagnostic markers into clinical decision making in bladder cancer

Urologic Oncology: Seminars and Original Investigations, 2010

Bladder cancer is a common disease that is often detected late and has a high rate of recurrence and progression. Cystoscopy is the main tool in detection and surveillance of bladder cancer but is invasive and can miss some cancers. Cytology is frequently utilized but suffers from a poor sensitivity. There are several commercially available urine-based tumor markers currently available but their use is not recommended by guideline panels. Markers such as the Urovysion FISH assay and the NMP22 BladderChek test are approved for surveillance and detection in patients with hematuria. The added benefit of these markers and other commercially available markers (e.g. Ucytϩ, BTA stat) has not been well investigated though it appears these markers are insufficiently sensitive to replace cystoscopy. Additional studies are needed to determine the clinical scenarios where bladder markers are best utilized (screening, surveillance, early detection, evaluating cytologic atypia) and what impact they should have on clinical decision making. Furthermore, a variety of issues and barriers can affect the movement of clinical tests from research to clinical practice. This article addresses some of the challenges facing research and medical communities in the delivery and integration of markers for bladder cancer diagnosis. Moreover, we attempt to outline criteria for the clinical utility of new bladder cancer diagnostic markers.

A Novel Urine-Based Assay for Bladder Cancer Diagnosis: Multi-Institutional Validation Study

European Urology Focus, 2016

Background: CellDetect is a unique histochemical stain enabling color and morphological discrimination between malignant and benign cells based on differences in metabolic signature. Objective: The objective of the present study was to validate the performance of this assay in a controlled, blinded, multicenter study. Design, setting, and participants: The study, conducted in nine hospitals, included patients with documented history of bladder cancer, monitored for urothelial carcinoma (UCC) or scheduled for bladder cancer surgery. Outcome measurements and statistical analysis: Cystoscopy and/or biopsy were used as a reference standard to determine sensitivity and specificity. Smears were stained by CellDetect and interpreted by two cytologists blinded to the patient's final diagnosis. The findings were compared with those of standard urine cytology and BTA stat. Results and limitations: Two hundred and seventeen voided urine specimens were included. Ninety-six (44%) were positive by histology and 121 (56%) were negative by either cystoscopy or histology. The overall sensitivity of CellDetect was 84%. Notably, the sensitivity for detecting lowgrade nonmuscle-invasive bladder cancer tumors was greater than this of BTA stat (78% vs 54%) and more than twofold higher compared with standard cytology (33%, p 0.05). The specificity was 84% in patients undergoing routine surveillance by cystoscopy. At a median follow-up of 9 mo, 21% of the patients with positive CellDetect and negative reference standard developed UCC, which was significantly higher compared with the 5% of the true negative cases. Limitations include the lack of instrumental urine samples and the lack of patients with nongenitourinary cancers in the study population. Conclusions: This study validates the performance of CellDetect as a urine-based assay to identify UCC in patients with history of bladder cancer. The high sensitivity was maintained across all cancer grades and stages without compromising the assay specificity. Further studies are required to test whether this novel stain can be incorporated in routine bladder cancer surveillance as a noninvasive alternative to cystoscopy. Patient summary: Surveillance of bladder cancer requires frequent invasive procedures. In the present study, we validate the ability of a novel biomarker to accurately identify early-stage tumors in urine specimens for the noninvasive monitoring of patients with history of bladder cancer.

Novel urinary biomarkers for the detection of bladder cancer: A systematic review

Cancer treatment reviews, 2018

Urinary biomarkers for the diagnosis of bladder cancer represents an area of considerable research which has been tested in both patients presenting with haematuria and non-muscle invasive bladder cancer patients requiring surveillance cystoscopy. In this systematic review, we identify and appraise the diagnostic sensitive and specificity of reported novel biomarkers of different 'omic' class and highlight promising biomarkers investigated to date. A MEDLINE/Pubmed systematic search was performed between January 2013 and July 2017 using the following keywords: (bladder cancer OR transitional cell carcinoma OR urothelial cell carcinoma) AND (detection OR diagnosis) AND urine AND (biomarker OR assay). All studies had a minimum of 20 patients in both bladder cancer and control arms and reported sensitivity and/or specificity and/or receiver operating characteristics (ROC) curve. QUADAS-2 tool was used to assess risk of bias and applicability of studies. The search protocol was ...

The clinical relevance of urine-based markers for diagnosis of bladder cancer

The aim of the present study was to evaluate the diagnostic relevance of urinary fibronectin (FN), telo-merase (RTA), and cytokeratin 20 (CK20) mRNA in comparison with voided urine cytology (VUC). The study included 132 patients with bladder cancer, 60 patients with benign bladder lesions, and 48 healthy individuals. All were subjected to urine cytology, estimation of fibronectin by ELISA, RTA by TRAP, and CK20 mRNA by conventional RT–PCR in urothelial cells from voided urine. The best cutoff point for FN was determined by receiver operating characteristic curve (41.7 ng/mg protein) revealed the highest sensitivity for malignant (80%) followed by the benign (70%) than the healthy individuals (4.1%) at P \ 0.001. Also, RTA and VUC showed significant difference among the three investigated groups (P \ 0.001). The overall sensitivity (89.3%) and specificity (98.4%) were the highest for CK20 mRNA. Combined sensitivity of VUC with FN, RTA, and CK20 mRNA together (98.4%) was higher than either the combined sensitivity of VUC with any of them or than that of the biomarker alone. Accordingly, when the diagnostic efficacy was considered, CK20 mRNA had the highest sensitivity and specificity compared to all investigated markers. Keywords Fibronectin Á Relative telomerase activity Á Cytokeratin 20 mRNA Á Voided urine cytology Á Bladder cancer