Urinary biomarkers for diagnosis of bladder cancer: A systematic review and meta-analysis

Roger Chou, John L. Gore, David Buckley, Rongwei (Rochelle) Fu, Kate (Katie) Gustafson, Jessica C. Griffin, Sara Grusing, Shelley Selph

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Background: Urinary biomarkers may be a useful alternative or adjunct to cystoscopy for diagnosis of bladder cancer. Purpose: To systematically review the evidence on the accuracy of urinary biomarkers for diagnosis of bladder cancer in adults who have signs or symptoms of the disease or are undergoing surveillance for recurrent disease. Data Sources: Ovid MEDLINE (January 1990 through June 2015), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and reference lists. Study Selection: 57 studies that evaluated the diagnostic accuracy of quantitative or qualitative nuclear matrix protein 22(NMP22), qualitative or quantitative bladder tumor antigen (BTA), fluorescence in situ hybridization (FISH), fluorescent immunohistochemistry (ImmunoCyt [Scimedx]), and Cxbladder (Pacific Edge Diagnostics USA) using cystoscopy and histopathology as the reference standard met inclusion criteria. Case-control studies were excluded. Data Extraction: Dual extraction and quality assessment of individual studies. Overall strength of evidence (SOE) was also assessed. Data Synthesis: Across biomarkers, sensitivities ranged from 0.57 to 0.82 and specificities ranged from 0.74 to 0.88. Positive likelihood ratios ranged from 2.52 to 5.53, and negative likelihood ratios ranged from 0.21 to 0.48 (moderate SOE for quantitative NMP22, qualitative BTA, FISH, and ImmunoCyt; low SOE for others). For some biomarkers, sensitivity was higher for initial diagnosis of bladder cancer than for diagnosis of recurrence. Sensitivity increased with higher tumor stage or grade. Studies that directly compared the accuracy of quantitative NMP22 and qualitative BTA found no differences in diagnostic accuracy (moderate SOE); head-to-head studies of other biomarkers were limited. Urinary biomarkers plus cytologic evaluation were more sensitive than biomarkers alone but missed about 10% of bladder cancer cases. Limitation: Restricted to English-language studies; no search for studies published only as abstracts; statistical heterogeneity present in most analyses; few studies for qualitative NMP22, quantitative BTA, and Cxbladder; and methodological shortcomings in almost all studies. Conclusion: Urinary biomarkers miss a substantial proportion of patients with bladder cancer and are subject to false-positive results in others. Accuracy is poor for low-stage and low-grade tumors. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO registration number: CRD42014013284)

Original languageEnglish (US)
Pages (from-to)922-931
Number of pages10
JournalAnnals of Internal Medicine
Volume163
Issue number12
DOIs
StatePublished - Dec 15 2015

Fingerprint

Urinary Bladder Neoplasms
Meta-Analysis
Biomarkers
Neoplasm Antigens
Cystoscopy
Fluorescence In Situ Hybridization
Information Storage and Retrieval
Health Services Research
MEDLINE
Signs and Symptoms
Case-Control Studies
Neoplasms
Language
Immunohistochemistry
Databases
Recurrence
nuclear matrix protein 22

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Urinary biomarkers for diagnosis of bladder cancer : A systematic review and meta-analysis. / Chou, Roger; Gore, John L.; Buckley, David; Fu, Rongwei (Rochelle); Gustafson, Kate (Katie); Griffin, Jessica C.; Grusing, Sara; Selph, Shelley.

In: Annals of Internal Medicine, Vol. 163, No. 12, 15.12.2015, p. 922-931.

Research output: Contribution to journalArticle

@article{27617d1ec7244a79904724ade544c1e2,
title = "Urinary biomarkers for diagnosis of bladder cancer: A systematic review and meta-analysis",
abstract = "Background: Urinary biomarkers may be a useful alternative or adjunct to cystoscopy for diagnosis of bladder cancer. Purpose: To systematically review the evidence on the accuracy of urinary biomarkers for diagnosis of bladder cancer in adults who have signs or symptoms of the disease or are undergoing surveillance for recurrent disease. Data Sources: Ovid MEDLINE (January 1990 through June 2015), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and reference lists. Study Selection: 57 studies that evaluated the diagnostic accuracy of quantitative or qualitative nuclear matrix protein 22(NMP22), qualitative or quantitative bladder tumor antigen (BTA), fluorescence in situ hybridization (FISH), fluorescent immunohistochemistry (ImmunoCyt [Scimedx]), and Cxbladder (Pacific Edge Diagnostics USA) using cystoscopy and histopathology as the reference standard met inclusion criteria. Case-control studies were excluded. Data Extraction: Dual extraction and quality assessment of individual studies. Overall strength of evidence (SOE) was also assessed. Data Synthesis: Across biomarkers, sensitivities ranged from 0.57 to 0.82 and specificities ranged from 0.74 to 0.88. Positive likelihood ratios ranged from 2.52 to 5.53, and negative likelihood ratios ranged from 0.21 to 0.48 (moderate SOE for quantitative NMP22, qualitative BTA, FISH, and ImmunoCyt; low SOE for others). For some biomarkers, sensitivity was higher for initial diagnosis of bladder cancer than for diagnosis of recurrence. Sensitivity increased with higher tumor stage or grade. Studies that directly compared the accuracy of quantitative NMP22 and qualitative BTA found no differences in diagnostic accuracy (moderate SOE); head-to-head studies of other biomarkers were limited. Urinary biomarkers plus cytologic evaluation were more sensitive than biomarkers alone but missed about 10{\%} of bladder cancer cases. Limitation: Restricted to English-language studies; no search for studies published only as abstracts; statistical heterogeneity present in most analyses; few studies for qualitative NMP22, quantitative BTA, and Cxbladder; and methodological shortcomings in almost all studies. Conclusion: Urinary biomarkers miss a substantial proportion of patients with bladder cancer and are subject to false-positive results in others. Accuracy is poor for low-stage and low-grade tumors. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO registration number: CRD42014013284)",
author = "Roger Chou and Gore, {John L.} and David Buckley and Fu, {Rongwei (Rochelle)} and Gustafson, {Kate (Katie)} and Griffin, {Jessica C.} and Sara Grusing and Shelley Selph",
year = "2015",
month = "12",
day = "15",
doi = "10.7326/M15-0997",
language = "English (US)",
volume = "163",
pages = "922--931",
journal = "Annals of Internal Medicine",
issn = "0003-4819",
publisher = "American College of Physicians",
number = "12",

}

TY - JOUR

T1 - Urinary biomarkers for diagnosis of bladder cancer

T2 - A systematic review and meta-analysis

AU - Chou, Roger

AU - Gore, John L.

AU - Buckley, David

AU - Fu, Rongwei (Rochelle)

AU - Gustafson, Kate (Katie)

AU - Griffin, Jessica C.

AU - Grusing, Sara

AU - Selph, Shelley

PY - 2015/12/15

Y1 - 2015/12/15

N2 - Background: Urinary biomarkers may be a useful alternative or adjunct to cystoscopy for diagnosis of bladder cancer. Purpose: To systematically review the evidence on the accuracy of urinary biomarkers for diagnosis of bladder cancer in adults who have signs or symptoms of the disease or are undergoing surveillance for recurrent disease. Data Sources: Ovid MEDLINE (January 1990 through June 2015), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and reference lists. Study Selection: 57 studies that evaluated the diagnostic accuracy of quantitative or qualitative nuclear matrix protein 22(NMP22), qualitative or quantitative bladder tumor antigen (BTA), fluorescence in situ hybridization (FISH), fluorescent immunohistochemistry (ImmunoCyt [Scimedx]), and Cxbladder (Pacific Edge Diagnostics USA) using cystoscopy and histopathology as the reference standard met inclusion criteria. Case-control studies were excluded. Data Extraction: Dual extraction and quality assessment of individual studies. Overall strength of evidence (SOE) was also assessed. Data Synthesis: Across biomarkers, sensitivities ranged from 0.57 to 0.82 and specificities ranged from 0.74 to 0.88. Positive likelihood ratios ranged from 2.52 to 5.53, and negative likelihood ratios ranged from 0.21 to 0.48 (moderate SOE for quantitative NMP22, qualitative BTA, FISH, and ImmunoCyt; low SOE for others). For some biomarkers, sensitivity was higher for initial diagnosis of bladder cancer than for diagnosis of recurrence. Sensitivity increased with higher tumor stage or grade. Studies that directly compared the accuracy of quantitative NMP22 and qualitative BTA found no differences in diagnostic accuracy (moderate SOE); head-to-head studies of other biomarkers were limited. Urinary biomarkers plus cytologic evaluation were more sensitive than biomarkers alone but missed about 10% of bladder cancer cases. Limitation: Restricted to English-language studies; no search for studies published only as abstracts; statistical heterogeneity present in most analyses; few studies for qualitative NMP22, quantitative BTA, and Cxbladder; and methodological shortcomings in almost all studies. Conclusion: Urinary biomarkers miss a substantial proportion of patients with bladder cancer and are subject to false-positive results in others. Accuracy is poor for low-stage and low-grade tumors. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO registration number: CRD42014013284)

AB - Background: Urinary biomarkers may be a useful alternative or adjunct to cystoscopy for diagnosis of bladder cancer. Purpose: To systematically review the evidence on the accuracy of urinary biomarkers for diagnosis of bladder cancer in adults who have signs or symptoms of the disease or are undergoing surveillance for recurrent disease. Data Sources: Ovid MEDLINE (January 1990 through June 2015), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and reference lists. Study Selection: 57 studies that evaluated the diagnostic accuracy of quantitative or qualitative nuclear matrix protein 22(NMP22), qualitative or quantitative bladder tumor antigen (BTA), fluorescence in situ hybridization (FISH), fluorescent immunohistochemistry (ImmunoCyt [Scimedx]), and Cxbladder (Pacific Edge Diagnostics USA) using cystoscopy and histopathology as the reference standard met inclusion criteria. Case-control studies were excluded. Data Extraction: Dual extraction and quality assessment of individual studies. Overall strength of evidence (SOE) was also assessed. Data Synthesis: Across biomarkers, sensitivities ranged from 0.57 to 0.82 and specificities ranged from 0.74 to 0.88. Positive likelihood ratios ranged from 2.52 to 5.53, and negative likelihood ratios ranged from 0.21 to 0.48 (moderate SOE for quantitative NMP22, qualitative BTA, FISH, and ImmunoCyt; low SOE for others). For some biomarkers, sensitivity was higher for initial diagnosis of bladder cancer than for diagnosis of recurrence. Sensitivity increased with higher tumor stage or grade. Studies that directly compared the accuracy of quantitative NMP22 and qualitative BTA found no differences in diagnostic accuracy (moderate SOE); head-to-head studies of other biomarkers were limited. Urinary biomarkers plus cytologic evaluation were more sensitive than biomarkers alone but missed about 10% of bladder cancer cases. Limitation: Restricted to English-language studies; no search for studies published only as abstracts; statistical heterogeneity present in most analyses; few studies for qualitative NMP22, quantitative BTA, and Cxbladder; and methodological shortcomings in almost all studies. Conclusion: Urinary biomarkers miss a substantial proportion of patients with bladder cancer and are subject to false-positive results in others. Accuracy is poor for low-stage and low-grade tumors. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO registration number: CRD42014013284)

UR - http://www.scopus.com/inward/record.url?scp=84950318200&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84950318200&partnerID=8YFLogxK

U2 - 10.7326/M15-0997

DO - 10.7326/M15-0997

M3 - Article

C2 - 26501851

AN - SCOPUS:84950318200

VL - 163

SP - 922

EP - 931

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

SN - 0003-4819

IS - 12

ER -