Improved detection of bladder tumours reduces cancer recurrence

Making tumours inside the bladder fluoresce red under blue light allows physicians to more easily find and remove them, substantially reducing the rate at which these cancers come back, says a Mayo Clinic physician who presented results of a large, multicentre international clinical trial.

The findings, which were reported at the annual meeting of the American Urological Association, show that this new diagnostic technique found more of the most common bladder tumours than the traditional white-light detection method in almost 17 percent of the patients, and demonstrated a 22 percent relative reduction in the recurrence rate within nine months of the procedure.

"This is the first demonstration that photodynamic diagnosis (PDD) cystoscopy along with the study drug (hexaminolevulinate) improves immediate detection, but more importantly reduces tumour recurrence rates of papillary bladder tumours; this is a significant improvement in treatment for our patients," says urologist Lance Mynderse, MD, who practices at Mayo Clinic’s campus in Rochester, Minnesota. The 766-patient phase III study was conducted in 28 US and European centres, and its principal investigator is Barton Grossman, MD, of the University of Texas M.D. Anderson Cancer Center. Dr Mynderse presented study results as spokesman for the lead enrolling site in North America.

Bladder cancer is a dangerous, very time-consuming and expensive cancer to treat, primarily because non-muscle invasive bladder tumours recur in up to 70 percent of patients, Dr Mynderse says. "Once a cancer develops anywhere in the bladder, it can come back in another place, rather like skin cancer recurrences," he says.

As a result, patients need to be re-examined every three to six months, and that means physicians need to examine the bladder from within, using a thin tube known as a cystoscope that has a lens and uses white light to illuminate the area. Additional testing is commonly performed and includes urine tests and radiographic studies. Once a tumour is detected, it is removed and then analysed by histopathology.

The study compared use of the traditional white-light cystoscopy with photodynamic diagnosis using a special light source and lenses that can switch from white to blue light. The blue light is designed for use with the study drug (hexaminolevulinate), which is instilled into a patient’s bladder prior to the therapeutic procedure. This acts as a prodrug that initiates a series of biochemical reactions in malignant cells which result in significant, preferential accumulation of photoactive porphryins. When the blue light is turned on, the tumours emit a red fluorescence. "The cancers appear bright red compared to normal tissue, which is a lighter blue-green," Dr Mynderse says. "It is quite dramatic. One sees bladder tumours in a whole new light."

This study enrolled patients with higher risk of tumour recurrence who had either multiple papillary non-invasive bladder cancers or papillary tumours that had recurred within a year of being treated. All patients received an examination with white-light cystoscopy, and half were randomised to receive the agent and blue-light examination. Investigators found that this new technology detected at least one additional Ta/T1 tumour in 16.9 percent of the 278 patients randomised to blue light.

There was also a 46 percent increase in detection of high-risk bladder cancers known as carcinoma in situ (CIS), using the blue-light technique, Dr Mynderse says.

The researchers then looked at 402 patients with Ta/T1 tumours who completed the study, and found a significant reduction in tumour recurrence in patients diagnosed with fluorescence cystoscopy (36 percent), compared with patients in the white-light group (46 percent).

"Using the blue light, it is much easier to tell when we have removed all the tumour in the bladder," Dr Mynderse says. "When no fluorescence remains, we really have improved our effectiveness in ridding the patient of the cancer."

(Source: Mayo Clinic: Annual Meeting of the American Urological Association: May 2009)