Liquid biopsy test appears better at detecting bladder cancer than urine cytology

In urogenital cancers, urine as a liquid biopsy for non-invasive cancer detection holds great promise for future clinical application. Their anatomical position allows for the local shedding of tumor DNA, but recent data indicate that tumor DNA in urine might also result from transrenal excretion. This study aims to assess the origin of tumor-associated DNA in the urine of 5 bladder and 25 cervical cancer patients. Besides natural voided urine, paired urine samples were collected in which contact with the local tumor was circumvented to bypass local shedding. The latter concerned nephrostomy urine in bladder cancer patients, and catheter urine in cervical cancer patients. Methylation levels of GHSR, SST, and ZIC1 were determined using paired bladder tumor tissues and cervical scrapes as a reference. Urinary methylation levels were compared to natural voided urine of matched controls. To support methylation results, mutation analysis was performed in urine and tissue samples of bladder cancer patients. Increased methylation levels were not only found in natural voided urine from bladder and cervical cancer patients, but also in the corresponding nephrostomy and catheter urine. DNA mutations detected in bladder tumor tissues were also detectable in all paired natural voided urine as well as in a subset of nephrostomy urine. These results provide the first evidence that the suitability of urine as a liquid biopsy for urogenital cancers relies both on the local shedding of tumor cells and cell fragments, as well as the transrenal excretion of tumor DNA into the urine.

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Biomarkers in Bladder Cancer Surveillance

Frontiers in Surgery ◽

10.3389/fsurg.2021.735868 ◽

2021 ◽

Vol 8 ◽

Author(s):

Sukumar S. Sugeeta ◽

Anand Sharma ◽

Kenrick Ng ◽

Arvind Nayak ◽

Nikhil Vasdev

Keyword(s):

Bladder Cancer ◽

Clinical Trials ◽

Prospective Studies ◽

Urine Cytology ◽

Cancer Surveillance ◽

Invasive Bladder Cancer ◽

Low Grade ◽

Protein Biomarkers ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

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 well as extracellular vesicles in the past decade.Methods: Using the PubMed/Medline search engines as well as Google Scholar, we performed an online search using the terms “bladder cancer,” “non-muscle invasive bladder cancer,” and “urine biomarkers” with filter for articles in English published up to May 2021. Systematic reviews and original data of clinical trials or observational studies which contributed to the development of the biomarkers were collated.Results: Biomarkers identified were divided into FDA-approved molecular biomarkers, protein biomarkers and gene-related biomarker with a table summarising the findings of each marker with the most relevant studies. The studies conducted were mainly retrospective. Due to the early stages of development, only a few prospective studies have been done for more recently developed biomarkers and limited meta-analyses are available.Therefore a detailed evaluation of these markers are still required to decide on their clinical use.Conclusion: Advancements of analytical methods in BC has driven the research towards non-invasive liquid-based biomarkers in adjunct to urine cytology. Further large prospective studies are required to determine its feasibility in a clinical setting as they are not effective when used in isolation as they have their limitation. With the ongoing pandemic, other than reduction in costs and increased accuracy, the need for biomarkers to cope with delay in cystoscopies in diagnosis and surveillance is crucial. Thus clinical trials with direct comparison is required to improve patient care.

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The pattern of urine cytology among patients with clinical diagnosis of bladder tumor in a tertiary hospital northwest Nigeria

International Surgery Journal ◽

10.18203/2349-2902.isj20194402 ◽

2019 ◽

Vol 6 (10) ◽

pp. 3521

Author(s):

Ahmed M. Umar ◽

Uzodimma E. Onwuasoanya ◽

Emmanuel U. Oyibo ◽

Adamu Dahiru ◽

Ismaila A. Mungadi

Keyword(s):

Bladder Cancer ◽

Clinical Diagnosis ◽

Bladder Tumour ◽

Tertiary Hospital ◽

Urine Cytology ◽

Female Ratio ◽

Non Invasive ◽

And Gender ◽

Low Sensitivity ◽

Age Range

Background: Urine cytology is a simple, safe, non-invasive and cheap investigation that is used as adjunct to cystoscopy in the diagnosis of bladder cancer. Its low sensitivity is a major limitation against its use as a sole diagnostic test for bladder cancer. The objective of this study was to determine the pattern of urine cytology seen in patients with clinical diagnosis of bladder tumour in our practice.Methods: This is a retrospective study of patients with clinical diagnosis of bladder tumour that had urine cytology in our centre. The age and gender of the patients, number of urine cytology per patient per year and cytologic diagnosis were analysed using the SPSS 20.Results: During the period under review, a total of 512 urine cytology was done for patients with clinical diagnosis of bladder tumour. The age range of the patients was 6 to 90 years with modal age of 60 years. 457 (89.3%) were males while 54 (10.5%) were females and 1 (0.2%) was unspecified. Male to female ratio was 8.5:1. The highest number of urine cytology was done in 2013 with 64 (12.5%) while the least number was 1 (0.2%) recorded in 2001 and 2003. Only 68 (13.3%) specimens were reported to be malignant while 245 (47.9%) were reported as negative representing the most common cytological diagnosis in the study.Conclusions: Although urine cytology is useful in the diagnostic workup of patients with bladder mass, it is unlikely it would supplant cystoscopy and biopsy in the diagnosis of bladder cancer.

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