When used alone, urinary biomarkers miss a substantial proportion of patients with bladder cancer and are subject to false-positive results in others, and the accuracy is poor for low-stage and low-grade tumors, according to a study published online in Annals of Internal Medicine.
The diagnostic accuracy of biomarkers may be slightly higher for the initial diagnosis of bladder cancer in patients who present with signs and symptoms, rather than just for surveillance.
Dr. Roger Chou
“Urinary biomarkers in combination with cytologic evaluation are more accurate than biomarkers alone; research is needed to understand how the use of urinary biomarkers with other diagnostic tests affects the use of cystoscopy and clinical outcomes,” wrote Dr. Roger Chou of Oregon Health and Science University, Portland, and his colleagues. (Ann Intern Med. 2015 Oct 26. doi:10.7326/M15-0997).
At the current time, six urinary biomarkers have been approved by the Food and Drug Administration for the diagnosis or surveillance of bladder cancer. These include quantitative nuclear matrix protein 22 (NMP22) (Alere NMP22 [Alere]), qualitative NMP22 (BladderChek [Alere]), qualitative bladder tumor antigen (BTA) (BTA stat [Polymedco]), quantitative BTA (BTA TRAK [Polymedco]), fluorescent in situ hybridization (FISH) (UroVysion [Abbott Molecular]), and fluorescent immunohistochemistry (ImmunoCyt [Scimedx]).
Dr. Chou and his team systematically reviewed the evidence on the accuracy of urinary biomarkers for diagnosing bladder cancer in adults who are experiencing signs or symptoms suggestive of the disease or who are undergoing surveillance for recurrent disease.
Their review was conducted as part of a larger analysis for the evaluation and treatment of non–muscle-invasive bladder cancer, which was nominated by the American Urological Association to the Agency for Healthcare Research and Quality, to be used for updating its guidelines.
The authors identified 57 studies that met their inclusion criteria and evaluated the diagnostic accuracy of the urinary biomarkers. They found that across all 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, while negative ones ranged from 0.21 to 0.48.
Overall, evidence was strongest for quantitative NMP22, qualitative BTA, FISH, and ImmunoCyt (moderate strength of evidence) but relatively sparse for other biomarkers (low strength of evidence). For all of the biomarkers, sensitivity was greater for higher-stage and higher-grade tumors (high strength of evidence).
In addition, only a few of the studies looked at the effects of patient characteristics on the diagnostic accuracy of urinary biomarkers. But the diagnostic accuracy clearly did not differ according to factors such as age, gender, smoking status, or receipt of prior intravesical therapy. Also, eight of the studies also did not find any consistent differences in specificity according to factors that included other types of urological cancers, renal calculi, prostatitis, benign prostatic hypertrophy, urinary tract infection, or hematuria. However, specificity was higher in some of the studies in the absence of other urological conditions.