Screening for Transitional Cell Carcinoma

Jaclyn Smith, DVM (Medical Oncology)

Urinary bladder malignancies are overall rare, accounting for less than 2% of all reported cancers in dogs. However, transitional cell carcinoma (TCC) is by far the most common primary tumor found in the urinary bladder. Due to its highly invasive and metastatic nature, successful treatment with long-term survivals is uncommon. A study by Knapp et al (Urol Oncol 2000) showed that at the time of diagnosis, nodal and distant metastasis were found in 16% and 14% of dogs, respectively. However, they also found that at the time of death, 50% of dogs had distant metastasis. Since surgical removal does not typically extend median survival times, treatment is aimed at medical therapy. While overall response rates are often low (about 30%), greater than 70% of patients can experience stable disease and improved quality of life with progression free intervals around 6 months.

While some cancers can easily be detected early in the course of disease (e.g. a growing external mass or some leukemias), other tumor types may not cause overt clinical signs until they are more advanced. It is for these tumor types that screening tests may be most useful. They may lead earlier detection, and therefore enhance the treatment outcome in these patients.

Within the past decade, a screening test for dogs with TCC of the lower urinary tract has been developed. The veterinary bladder tumor antigen (V-BTA) test is a rapid latex agglutination dipstick test that detects tumor analytes in urine. These tumor analytes are glycoprotein fragments (e.g., laminin, fibronectin, type-IV collagen and proteoglycans), formed by invasive tumors degrading the basement membrane, which are released into the urine. A study by Henry et al (AJVR 2003) showed the overall sensitivity of the V-BTA test to be 88% (true positives); however, the specificity was very low (41%) for dogs with other urinary tract diseases other than TCC. The high number of false positives in this study was due to glucosuria, proteinuria, pyuria, and hematuria, all of which can be seen with both neoplastic and non-neoplastic urinary tract diseases.

Because of this, the V-BTA test may better be used as a screening test and NOT a confirmatory diagnostic tool. So, how should we interpret this test? A positive test in a dog with lower urinary tract signs is not particularly helpful due to the low specificity (both TCC and other urinary tract diseases present with similar signs: pollakiuria, stranguria, hematuria, and dysuria). Therefore, this is a poor test to rule in a diagnosis of TCC. However, a negative test result may be much more believable due to the high sensitivity of this test. Therefore, this test better utilized for ruling out TCC. A review article about biomarkers in veterinary cancer screening by Carolyn Henry (Vet Journal 2010) discusses the terms “SpPIn” and “SnNOut” as they relate to the V-BTA test. The V-BTA test is a highly sensitive test (Sn), where a negative result (N) can rule ‘out’ a diagnosis. It is NOT a specific test (Sp) because a positive result (P) does not rule ‘in’ a diagnosis.

This test historically has been deemed to have no clinical value by many veterinarians due to the low specificity. However, when applied in the strictest sense of the word ‘screening’, the V-BTA test may be useful to evaluate at-risk patients. For example, including such a screening test in routine geriatric evaluations for breeds predisposed to developing TCC (Scottish terriers, Shetland sheepdogs, Beagles, West Highland White Terriers, etc). A positive test result would then prompt further diagnostic testing (imaging) to rule in/out TCC vs. other lower urinary tract diseases. Thus, this may lead to an earlier diagnosis and therefore, possibly better outcomes.

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