Friday, January 2, 2015

New Urine Test Shows Promise for Bladder Cancer


The majority of the 300,000 bladder cancers detected in the US each year are non-invasive bladder cancers, and, in general, are not dangerous. However, most of these patients will have recurrences and some will develop muscle-invasive, potentially fatal bladder cancer. Predicting who will "progress" to invasive disease is almost impossible and surveillance involves invasive testing including cystoscopy and biopsies of the bladder. 

Trinity J. Bivalacqua. MD, PhD
Trinity J. Bivalacqua, MD, PhD, Director of Urologic Oncology at the Brady Urological Institute explains, "Because of the high rate of tumor recurrence, we have to perform frequent follow-up cystoscopy procedures, but this results in an unacceptable rate of invasive procedures and ballooning costs." A new urine test developed at Johns Hopkins may become part of the arsenal in detecting new and recurrent bladder cancer.

Mutations in the promoter of the telomerase reverse transcriptase (TERT) gene have been demonstrated in upwards of 66% of muscle-invasive urothelial cancers of the bladder and is the most frequently mutated gene in advanced bladder cancers.[1,2] George Netto, MD, a genitourinary pathologist at Johns Hopkins states, "These are the most common genetic alterations ever identified in early bladder cancer."

The TERT promoter gene.  From Kinde et al. [3].

George Netto, MD
Researchers from the Brady Urological Institute, including Drs. Bivalacqua and Netto with collaborators from the Ludwig Cancer Research team, investigated 76 patients with a variety of bladder cancers. The looked at TERT mutations in early tumors from these patients and in follow-up urine samples as they monitored these patients for progression. They found a high rate of TERT promoter mutations in most (approximately 75%) tumors, including both papillary and flat lesions; and tumors of low- and high-grade nature. More importantly, among patients whose tumors harbored TERT promoter mutations, the same mutations were present in follow-up urines in seven of eight patients that recurred but in none of the six patients that did not recur – indicating that TERT may be a strong indicator of patients likely to recur!

"These exciting results strongly support the potential future analysis of TERT promoter mutations as a urine test that can facilitate the early diagnosis of bladder cancer, before it spreads deep into the bladder wall, in patients at high risk for disease progression. The test will also give us a non-invasive alternative to the many follow-up procedures we currently need to monitor our patients for recurrence of bladder cancer. This test has great potential to save many lives."

This work was published in Cancer Research.[3]

The story was extracted from:

"Urine Test Detects New, Recurrent Bladder Cancer" in Johns Hopkins Urology: News for Physicians, Winter 2015 by Johns Hopkins Medicine.

"Can Urine Test Can Detect Bladder Cancer Early" in Discovery: Volume XI, Winter 2015 by the Patrick C. Walsh Prostate Cancer Research Fund.

 

[1] Horn S, Figl A, Rachakonda PS, Fischer C, Sucker A, Gast A, et al. TERT promoter mutations in familial and sporadic melanoma. Science 2013;339:959–61.
[2] Killela PJ, Reitman ZJ, Jiao Y, Bettegowda C, Agrawal N, Diaz LA Jr., et al. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci U S A 2013;110:6021–6.
[3] Kinde I, Munari E, Faraj SF, Hruban RH, Schoenberg M, Bivalacqua T, Allaf M, Springer S, Wang Y, Diaz LA Jr, Kinzler KW, Vogelstein B, Papadopoulos N, Netto GJ. TERT promoter mutations occur early in urothelial neoplasia and are biomarkers of early disease and disease recurrence in urine. Cancer Res. 2013 Dec 15;73(24):7162-7. doi: 10.1158/0008-5472.CAN-13-2498. Epub 2013 Oct 11.

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