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From OncoLog, March 2012, Vol. 57, No. 3

Photos: Bladder cystoscopy
The same section of a patient’s bladder wall as viewed by standard (left) and fluorescence cystoscopy. In fluorescence cystoscopy, normal tissue appears blue and the tumor cells appear red.

Fluorescence Cystoscopy Detects Hard-to-Find Bladder Tumors

By Sarah Bronson

Fluorescence cystoscopy, although not yet widely used in the United States, has been shown to be effective for detecting tumors in the bladder that might not be visible with standard cystoscopy.

Because patients who have been treated for bladder cancer require routine monitoring over the course of long survival times and because bladder cancer recurs at a higher rate than many other cancers, this cancer is the most expensive cancer per patient from diagnosis to death. More accurate diagnostic techniques could substantially reduce this expense and improve disease management.

“Fluorescence cystoscopy has the potential to increase the number of tumors we can detect and to improve our resection of these tumors at the first go,” said Ashish Kamat, M.D., an associate professor in the Department of Urology at The University of Texas MD Anderson Cancer Center. “It has the potential to decrease the number of recurrences, thus reducing the number of interventions, the number of follow-up visits, and the economic impact on society of bladder cancer.”

What is fluorescence cystoscopy?

Fluorescence cystoscopy, also called blue light cystoscopy, is indicated as an adjunct to standard, white light cystoscopy for the detection of bladder tumors in patients known or suspected to have at least one bladder tumor. Using the blue light modality increases the detection rate for small or indistinct lesions that can go unseen under cystoscopy with white light alone. At MD Anderson, Dr. Kamat and H. Barton Grossman, M.D., a professor in the Department of Urology, have been using fluorescence cystoscopy since 2007, when they began doing clinical studies of the modality.

“Fluorescence cystoscopy has the potential to increase the number of tumors we can detect and to improve our resection of these tumors at the first go.”
– Dr. Ashish Kamat
Before fluorescence cystoscopy, a urethral catheter is inserted and the bladder emptied, and hexaminolevulinate (Cysview), an inert imaging agent, is slowly instilled through the catheter and retained for at least 1 hour. The hexaminolevulinate causes photoactive porphyrins to accumulate in rapidly proliferating cells, such as neoplastic cells. The bladder is then emptied, and the patient undergoes cystoscopy, in which the bladder is filled with water or saline through the cystoscope so that the bladder wall can be clearly viewed. The bladder wall is first examined for papillary tumors using standard white light cystoscopy. Next, a photodynamic diagnostic system that is attached to the cystoscope is activated, and the wall is examined again. Illuminated by blue light with a wavelength of 360–450 nm, normal tissue appears blue while the porphyrins that have accumulated in rapidly dividing cells appear red.

Thus, potentially malignant cells that do not visibly protrude from or contrast with the bladder wall—including any that are flattened when the bladder is filled and the wall distended—can become visible with blue light. Also, rapidly dividing cells can be detected at earlier stages, and larger areas of invasion can be revealed; consequently, malignant lesions can be resected sooner and more completely. Although sites of infection or recent biopsies also may fluoresce red, the percentage of false-positive diagnoses is comparable to that of white light cystoscopy alone.

Clinical studies

Fluorescence cystoscopy has been shown to be more sensitive than white light cystoscopy. A recent prospective, randomized study showed that blue light cystoscopy was significantly more likely to detect bladder carcinomas in situ and Ta/T1 tumors than was white light cystoscopy in patients known to have at least one such lesion, and the two modalities had similarly low false-positive rates and were similarly safe. Likewise, a phase III study showed that blue light detected more carcinomas in situ than did white light in patients with suspected or confirmed bladder cancer. Fluorescence cystoscopy was also well tolerated in this study, with hematuria as the most common adverse event.

In another study, patients examined with fluorescence cystoscopy had fewer recurrences of bladder cancer within 9 months of cystoscopy and longer disease-free intervals than did patients examined using white light only. Furthermore, some tumors classified as recurrences may actually be incipient but not observed at the time of the initial diagnosis; therefore, the more sensitive diagnostic technique may reduce the number of tumors overlooked at early stages that may remain after larger tumors have been treated.

Approval and use

Fluorescence cystoscopy is widely used in Europe, and hexaminolevulinate was approved by the U.S. Food and Drug Administration in May 2010 for use in the detection of non–muscle-invasive papillary bladder cancer. To date, only seven centers in the United States, including MD Anderson, use fluorescence cystoscopy, but Dr. Kamat expressed the hope that urologists throughout the United States will learn the technique so it can be offered to the appropriate patient populations.

FURTHER READING
Stenzl A, Burger M, Fradet Y, et al. Hexaminolevulinate guided fluorescence cystoscopy reduces recurrence in patients with non-muscle invasive bladder cancer. J Urol 2010;184:1907-1913.
Fradet Y, Grossman HB, Gomella L, et al. A comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of carcinoma in situ in patients with bladder cancer: a phase III, multicenter study. J Urol 2007;178:68-73.

For more information, contact Dr. Ashish Kamat at 713-792-3250.

Other articles in OncoLog, March 2012 issue:

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