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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.
“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.
Up to 30% of patients with newly diagnosed bladder cancer will have muscle-invasive disease at the time of their initial diagnosis, suggesting an opportunity for screening tests to identify disease in earlier stages before the onset of hematuria. But screening requires the availability of a highly sensitive and specific test to properly identify patients who need further work-up while avoiding unnecessary testing and costs of evaluating true-negative results. Therefore, an unmet need exists for better noninvasive screening techniques, such as urine-based biomarkers.
In addition, patients with superficial bladder cancer tend to have recurrent but not progressive disease, necessitating life-long surveillance, and surveillance would be another setting in which urinary biomarkers would be valuable.
Are urinary biomarkers, with or without cytologic evaluation, adequate to avoid cystoscopy in patients with low-grade or low-stage disease? Also, what is the cost of missing a low-grade or low-stage tumor if a cytologic result is negative in the absence of cystoscopy? Few data exist to answer these questions decisively. To evaluate cost-effectiveness, studies need to evaluate presymptomatic patients or those with early-onset hematuria with one or all of the tests, or a combination, in addition to cystoscopy, cytologic evaluation, and imaging.
Biomarkers would provide value only if they circumvented the need for invasive evaluation or the need for more costly management if diagnoses were made earlier. Cost-effectiveness analyses would also need to incorporate estimated costs of missed diagnoses and overdiagnoses.
Thus, until urinary biomarkers become available that are sufficiently accurate to supplant the current recommended detection algorithms in biomarker-negative patients, they will not be a cost-effective addition to strategies to detect bladder cancer.
Dr. Phillip H. Abbosh and Dr. Elizabeth R. Plimack are with the Fox Chase Cancer Center in Philadelphia. These remarks were taken from their editorial accompanying Dr. Chou’s report (Ann Intern Med. 2015 Oct 26. doi:10.7326/M15-2445).
Up to 30% of patients with newly diagnosed bladder cancer will have muscle-invasive disease at the time of their initial diagnosis, suggesting an opportunity for screening tests to identify disease in earlier stages before the onset of hematuria. But screening requires the availability of a highly sensitive and specific test to properly identify patients who need further work-up while avoiding unnecessary testing and costs of evaluating true-negative results. Therefore, an unmet need exists for better noninvasive screening techniques, such as urine-based biomarkers.
In addition, patients with superficial bladder cancer tend to have recurrent but not progressive disease, necessitating life-long surveillance, and surveillance would be another setting in which urinary biomarkers would be valuable.
Are urinary biomarkers, with or without cytologic evaluation, adequate to avoid cystoscopy in patients with low-grade or low-stage disease? Also, what is the cost of missing a low-grade or low-stage tumor if a cytologic result is negative in the absence of cystoscopy? Few data exist to answer these questions decisively. To evaluate cost-effectiveness, studies need to evaluate presymptomatic patients or those with early-onset hematuria with one or all of the tests, or a combination, in addition to cystoscopy, cytologic evaluation, and imaging.
Biomarkers would provide value only if they circumvented the need for invasive evaluation or the need for more costly management if diagnoses were made earlier. Cost-effectiveness analyses would also need to incorporate estimated costs of missed diagnoses and overdiagnoses.
Thus, until urinary biomarkers become available that are sufficiently accurate to supplant the current recommended detection algorithms in biomarker-negative patients, they will not be a cost-effective addition to strategies to detect bladder cancer.
Dr. Phillip H. Abbosh and Dr. Elizabeth R. Plimack are with the Fox Chase Cancer Center in Philadelphia. These remarks were taken from their editorial accompanying Dr. Chou’s report (Ann Intern Med. 2015 Oct 26. doi:10.7326/M15-2445).
Up to 30% of patients with newly diagnosed bladder cancer will have muscle-invasive disease at the time of their initial diagnosis, suggesting an opportunity for screening tests to identify disease in earlier stages before the onset of hematuria. But screening requires the availability of a highly sensitive and specific test to properly identify patients who need further work-up while avoiding unnecessary testing and costs of evaluating true-negative results. Therefore, an unmet need exists for better noninvasive screening techniques, such as urine-based biomarkers.
In addition, patients with superficial bladder cancer tend to have recurrent but not progressive disease, necessitating life-long surveillance, and surveillance would be another setting in which urinary biomarkers would be valuable.
Are urinary biomarkers, with or without cytologic evaluation, adequate to avoid cystoscopy in patients with low-grade or low-stage disease? Also, what is the cost of missing a low-grade or low-stage tumor if a cytologic result is negative in the absence of cystoscopy? Few data exist to answer these questions decisively. To evaluate cost-effectiveness, studies need to evaluate presymptomatic patients or those with early-onset hematuria with one or all of the tests, or a combination, in addition to cystoscopy, cytologic evaluation, and imaging.
Biomarkers would provide value only if they circumvented the need for invasive evaluation or the need for more costly management if diagnoses were made earlier. Cost-effectiveness analyses would also need to incorporate estimated costs of missed diagnoses and overdiagnoses.
Thus, until urinary biomarkers become available that are sufficiently accurate to supplant the current recommended detection algorithms in biomarker-negative patients, they will not be a cost-effective addition to strategies to detect bladder cancer.
Dr. Phillip H. Abbosh and Dr. Elizabeth R. Plimack are with the Fox Chase Cancer Center in Philadelphia. These remarks were taken from their editorial accompanying Dr. Chou’s report (Ann Intern Med. 2015 Oct 26. doi:10.7326/M15-2445).
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.
“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.
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.
“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.
FROM ANNALS OF INTERNAL MEDICINE
Key clinical point:Urinary biomarkers used alone miss a substantial proportion of patients with bladder cancer and are subject to false-positive results in others.
Major finding: Urinary biomarkers were associated with sensitivities for bladder cancer that ranged from 0.57 to 0.82 and specificities that ranged from 0.74 to 0.88.
Data source: Systematic review of 57 studies of the comparative accuracy of urinary biomarkers for diagnosis of bladder cancer.
Disclosures: The Agency for Healthcare Research and Quality supported the study. Dr. Chou, Dr. Gore, and Dr. Fu reported receiving grants from the AHRQ during the study.
