Update on urine-based markers for bladder cancer. How sensitive and specific are the new noninvasive tests?

Urine cytology is still the most commonly used noninvasive test to diagnose bladder cancer. However, cytology's ability to detect low-grade bladder tumors is limited, and its results require interpretation by a pathologist, are not available immediately, and are subjective. Several noninvasive urine-based tests are now available for detection and follow-up of bladder cancer. At least two of these new tests (BTA stat and AuraTek FDP) can easily be performed in the office, and the results are available in about 10 minutes. When choosing a test, physicians should keep in mind that none of the currently available tests is 100% accurate. However, the new urine-based tests are more sensitive than urine cytology and hence more reliable in detecting low-grade bladder cancer. They are useful tools in patients with urinary symptoms or microscopic hematuria or as office-based adjuncts to diagnostic procedures. Some of the markers that are being developed could significantly improve and simplify workup, diagnosis, and follow-up, and they may allow for detection of disease at an earlier stage, thus improving the chances of curative therapy.

Use of urine-based markers for detection and monitoring of bladder cancer.

Diagnosis and monitoring of bladder cancer present a difficult clinical problem. Urine cytology with confirmatory cystoscopy form the cornerstone of diagnosis at the present time. The subjectivity and low sensitivity of cytology led to the development of numerous tests as adjuncts to cystoscopy for the diagnosis and follow-up of bladder cancer patients. These tests usually are objective, quantitative (NMP-22, BTA TRAK, BLCA-4, telomerase activity, etc.), or qualitative (BTA Stat and FDP) and have higher sensitivity than cytology, but some have lower specificity. We review the different, new urine-based tests that were developed recently for the diagnosis and monitoring of patients with bladder cancer. The advantages and disadvantages of these tests are discussed, as well as their possible future role in the management of patients with bladder cancer.

Effects of vitamin D (calcitriol) on transitional cell carcinoma of the bladder in vitro and in vivo.

PURPOSE: Vitamin D (calcitriol) has significant antiproliferative effects on various tumor cells in vitro and in vivo. In the clinical situation a major impediment to systemic administration of calcitriol is the side effect of hypercalcemia. To test the potential usefulness of calcitriol for bladder cancer treatment, we studied the antiproliferative effect of vitamin D on 2 human bladder cancer cell lines, 253j and T-24, in vitro. We also examined the in vivo effects of calcitriol in an animal model of bladder cancer using intravesical administration to avoid the toxicity of systemic calcitriol therapy. MATERIALS AND METHODS: The presence of vitamin D receptors in normal and neoplastic human bladder tissue, and tumor cells T-24 and 253j was determined by immunoblot analysis. Tumor cell proliferation in the presence or absence of calcitriol was determined using a crystal violet assay. Calcitriol induced apoptosis was determined by morphology, polyadenosine diphosphate ribose polymerase cleavage and annexin V binding. In vivo studies were performed by weekly intravesical instillation of calcitriol in female Fischer 344 rats after induction of tumors by N-methyl nitrosourea. Calcitriol administration was started 3 weeks after tumor induction for 7 doses at weekly intervals. RESULTS: Normal and neoplastic human bladder tissue, and the cell lines expressed vitamin D receptors. In the 253j and T-24 cell lines proliferation was significantly inhibited by calcitriol. Progressive cleavage of full length polyadenosine diphosphate ribose polymerase was observed in calcitriol treated cells starting as early as 4 hours after exposure. Similar changes were not observed in the control cells treated with vehicle (ethanol) alone. After 24 hours of treatment with calcitriol 45.8% of 253j cells bound annexin compared to 16.5% of control cells (chi-square p <0.001). Of the control animals 66% developed bladder tumors and 55% of the animals treated with calcitriol early (3 weeks) after tumor induction developed bladder tumors. Almost all of the tumors that developed in the calcitriol group were unifocal, and only 20% were invasive compared to 50% of those in the control animals. CONCLUSIONS: These results demonstrate that calcitriol inhibits proliferation and induces apoptosis in human bladder tumor cells in vitro, and may have therapeutic potential in bladder cancer. In vivo studies using an N-methylnitrosourea induced model of bladder cancer demonstrate that early institution of intravesical calcitriol therapy after carcinogen exposure results in fewer tumors, which are also less likely to be multifocal, high grade or invasive. With our protocol a short course of intravesical calcitriol administration did not result in any significant toxicity.