Cxbladder- pro
The diagnosis of bladder cancer is generally made by cystoscopy and biopsy. Moreover, bladder cancer has a very high frequency of recurrence and therefore follow-up cystoscopy, along with urine cytology, is done periodically to identify recurrence early. Urine biomarkers that can reliably supplement or supplant these tests would be a major advance.
For patients with hematuria, American Urological Association (AUA) guidelines recommend cystoscopic evaluation of all adults older than 40 years with microscopic hematuria and for those younger than 40 years with risk factors for developing bladder cancer. Confirmatory diagnosis of bladder cancer is made by cystoscopic examination, considered to be the criterion standard, and biopsy. At initial diagnosis, about 70 percent of patients have cancers confined to the epithelium or subepithelial connective tissue. Non-muscle invasive disease is usually treated with transurethral resection, with or without intravesical therapy, depending on depth of invasion and tumor grade. However, a 50-75 percent incidence of recurrence has been noted in these patients with 10-15 percent progressing to muscle invasion over a five year period. Current follow-up protocols include flexible cystoscopy and urine cytology every three months for one to three years, every six months for an additional two to three years, and then annually, assuming no recurrence. A number of such tests have been developed, including the one under review here.
CxBladder (PacificEdge, Dunedin, New Zealand) is a recently released urine-based assay consisting of 5 mRNA markers, CDC2, HOXA13, MDK, IGFBP5, and CXCR5.The addition of CXCR5, or a mediator of neutrophil migration to sites of inflammation, allows the reduction of false positives secondary to the presence of acute or chronic inflammation. The sensitivity of this assay is superior to that of NMP-22 and cytology, at 83%, with a specificity of 85%. Interestingly, the specificity for high-grade tumors was 97% while the specificity for low-grade tumors was 69%. This offers a potential adjunct to cystoscopy for the diagnosis of urothelial carcinoma.
Several reviews have been performed to assess the myriad urine markers proposed for bladder cancer surveillance. They note that none of the markers has been proven sensitive and specific enough to replace cystoscopy.
References:
O’Sullivan P, Sharples K, Dalphin M, Davidson P, Gilling P, Cambridge L. A multigene urine test for the detection and stratification of bladder cancer in patients presenting with hematuria. J Urol. 2012 Sep. 188(3):741-7.
Shariat SF, Marberger MJ, Lotan Y, Sanchez-Carbayo M, Zippe C, Lüdecke G, et al. Variability in the performance of nuclear matrix protein 22 for the detection of bladder cancer. J Urol. 2006 Sep. 176(3):919-26; discussion 926.
Horstmann M, Patschan O, Hennenlotter J, Senger E, Feil G, Stenzl A. Combinations of urine-based tumour markers in bladder cancer surveillance. Scand J Urol Nephrol. 2009. 43(6):461-6.