NMP-22 for Bladder Cancer Screening and Surveillance
In 2004, more than 56,000 Americans will be diagnosed with bladder cancer (American Cancer Society, 2004). Urethrocystoscopy is considered the gold standard for bladder cancer diagnosis, but it is not a screening test. Researchers have been challenged to develop a noninvasive urine test that reliably differentiates hematuria associated with bladder cancer from that associated with nonmalignant etiologies. Several well-established and some novel tests for bladder cancer screening diagnosis and surveillance, including urinalysis, voided cytology, and the Nuclear Matrix Protein 22 (NMP-22) assay, one of a growing number of assays developed as a specific, sensitive nonnvasive test for bladder cancer, are reviewed. Until the sensitivity of the NMP-22 is improved, or another urine assay emerges that provides significantly greater sensitivity while maintaining adequate specificity, urethrocystoscopy will remain the reference test for detecting and diagnosing bladder cancer and its recurrence.
In 2004, more than 56,000 Americans will be diagnosed with bladder cancer (American Cancer Society [ACS], 2004). The majority of these tumors will be superficial, and a small but important minority will be invasive. Superficial tumors respond favorably to localized treatment, but the recurrence rate varies from 30% to 70% and the risk of progression to an invasive malignancy is 10% to 30% (Messing, 2002). In contrast to superficial malignancies, invasive tumors are locally aggressive and prone to distant metastases, associated morbidity, and death. More than 12,000 Americans will die of bladder cancer in 2004 (ACS, 2004) and the anticipated prognosis for persons with an advanced stage tumor is less than 1 year (Dreicer, 2001). The overall risk of bladder cancer rises with aging, but young adults and African Americans are more prone to clinically aggressive tumors (Messing, 2002; Yossepowitch & Dalbagni, 2002). Finally, even though overall mortality rates have declined over the past decade, women continue to have relatively low 5-year survival rates for (as yet) unknown reasons (Wai & Miller, 2002; Yossepowitch & Dalbagni, 2002).
Since bladder cancers arise from the urothelium and shed cells and other debris into the urine, urologic clinicians continue to seek for a noninvasive tumor marker that is detectable in the urine; reliably identifies the presence, recurrence, or progression of a urothelial cancer; and differentiates a malignancy from nonmalignant conditions known to cause similar signs and symptoms. These studies principally rely on three common measures of validity: sensitivity, specificity, and predictive value. Sensitivity is defined as the percentage of positive cases identified by the assay (true positives); specificity is the percentage of negative cases with a negative test result (true negatives); and predictive value is the result of either negative or positive values indicating the percentage of true-negative and true-positive cases in all negative and positive test cases (Van der Poel & Debruyne, 2001). Each of these outcomes must be measured against a reference test for predicting the presence or absence of a disease. In the case of bladder cancer, this test is urethrocystoscopy, which allows direct visualization of tumors and confirmation by biopsy and pathologic analysis. While direct visualization of the urothelium is considered the "gold standard" for bladder cancer diagnosis, it is not a screening test. Instead, urethrocystoscopy is an invasive procedure that carries some risk of infection and urethral injury (Messing, 2002).
The challenge, then, is to develop a noninvasive urine test that reliably differentiates hematuria associated with bladder cancer from that associated with nonmalignant etiologies. Several well-established and some novel tests for bladder cancer screening diagnosis and surveillance, including urinalysis, voided cytology, and the Nuclear Matrix Protein 22 (NMP-22) assay (one of a growing number of assays developed as a specific, sensitive noninvasive test for bladder cancer) will be reviewed.
In 2004, more than 56,000 Americans will be diagnosed with bladder cancer (American Cancer Society, 2004). Urethrocystoscopy is considered the gold standard for bladder cancer diagnosis, but it is not a screening test. Researchers have been challenged to develop a noninvasive urine test that reliably differentiates hematuria associated with bladder cancer from that associated with nonmalignant etiologies. Several well-established and some novel tests for bladder cancer screening diagnosis and surveillance, including urinalysis, voided cytology, and the Nuclear Matrix Protein 22 (NMP-22) assay, one of a growing number of assays developed as a specific, sensitive nonnvasive test for bladder cancer, are reviewed. Until the sensitivity of the NMP-22 is improved, or another urine assay emerges that provides significantly greater sensitivity while maintaining adequate specificity, urethrocystoscopy will remain the reference test for detecting and diagnosing bladder cancer and its recurrence.
In 2004, more than 56,000 Americans will be diagnosed with bladder cancer (American Cancer Society [ACS], 2004). The majority of these tumors will be superficial, and a small but important minority will be invasive. Superficial tumors respond favorably to localized treatment, but the recurrence rate varies from 30% to 70% and the risk of progression to an invasive malignancy is 10% to 30% (Messing, 2002). In contrast to superficial malignancies, invasive tumors are locally aggressive and prone to distant metastases, associated morbidity, and death. More than 12,000 Americans will die of bladder cancer in 2004 (ACS, 2004) and the anticipated prognosis for persons with an advanced stage tumor is less than 1 year (Dreicer, 2001). The overall risk of bladder cancer rises with aging, but young adults and African Americans are more prone to clinically aggressive tumors (Messing, 2002; Yossepowitch & Dalbagni, 2002). Finally, even though overall mortality rates have declined over the past decade, women continue to have relatively low 5-year survival rates for (as yet) unknown reasons (Wai & Miller, 2002; Yossepowitch & Dalbagni, 2002).
Since bladder cancers arise from the urothelium and shed cells and other debris into the urine, urologic clinicians continue to seek for a noninvasive tumor marker that is detectable in the urine; reliably identifies the presence, recurrence, or progression of a urothelial cancer; and differentiates a malignancy from nonmalignant conditions known to cause similar signs and symptoms. These studies principally rely on three common measures of validity: sensitivity, specificity, and predictive value. Sensitivity is defined as the percentage of positive cases identified by the assay (true positives); specificity is the percentage of negative cases with a negative test result (true negatives); and predictive value is the result of either negative or positive values indicating the percentage of true-negative and true-positive cases in all negative and positive test cases (Van der Poel & Debruyne, 2001). Each of these outcomes must be measured against a reference test for predicting the presence or absence of a disease. In the case of bladder cancer, this test is urethrocystoscopy, which allows direct visualization of tumors and confirmation by biopsy and pathologic analysis. While direct visualization of the urothelium is considered the "gold standard" for bladder cancer diagnosis, it is not a screening test. Instead, urethrocystoscopy is an invasive procedure that carries some risk of infection and urethral injury (Messing, 2002).
The challenge, then, is to develop a noninvasive urine test that reliably differentiates hematuria associated with bladder cancer from that associated with nonmalignant etiologies. Several well-established and some novel tests for bladder cancer screening diagnosis and surveillance, including urinalysis, voided cytology, and the Nuclear Matrix Protein 22 (NMP-22) assay (one of a growing number of assays developed as a specific, sensitive noninvasive test for bladder cancer) will be reviewed.
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