Imagine this scenario. You’re going in for surgery for a malignant tumor found in your bladder. After the operation, you’re told that they “got it all”, but then you learn that you still have a greater than 50% chance of the cancer coming back within a year!
That’s the situation with non–muscle-invasive bladder cancer (NMIBC), the most common type of bladder cancer. Although NMIBC is unlikely to prove fatal, the relapse rate seems absurdly high, with an 80% risk off recurring within five years.
Given these odds, you might feel fairly motivated to consider a non-toxic light-based strategy that could not only expunge the tumor but also lower your risk of recurrence. Such an approach exists in the form of photodynamic diagnosis (PDD).
In PDD, a photosensitizing agent is injected into the body and becomes selectively concentrated in the tumor tissue. Exposure to light then causes the malignant tissues to fluoresce or glow a certain color, thus enabling the surgeon to discern hard-to-see spots of cancer. The lesion or tumor can then be removed “on the spot” with either surgery or photodynamic therapy.
Coupling Photodiagnosis with Surgery
One reason for the high risk of NMIBC recurrence is the persistence of cancer following surgical removal of the tumor using transurethral resection of bladder tumor or TURBT. The difficulty here is that multiple lesions (spots of cancer) may exist at the time of surgery. Many of these lesions may be flat and inconspicuous, thus easily missed with the standard diagnostic approach, called white-light cystoscopy. (Note: A cystoscope, which has lenses like a telescope or microscope, can be passed through the urethra, the tube leading into the bladder.)
Without the added benefit of fluorescence, standard white-light cystoscopy often misses the lesions on the bladder’s internal lining. This could help explain the high risk of bladder cancer recurrence after the TURBT procedure. The use of a photosensitizing agent during cystoscopy is also known as fluorescence cystoscopy, and it’s among the more powerful applications of PDD, allowing for greatly improved detection and visualization of cancer within the bladder.
In the context of bladder cancer, the PDD approach is closely coupled with treatment and uses a photosensitizer known as Hexvix (generic name: Hexaminolevulinate). Produced by a Norwegian company called Photocure ASA, this optical imaging agent begins to fluoresce upon exposure to blue light, and it can be used to identify cancerous tissue that the surgeon can then remove. Hexvix has been commercially available in Europe since 2006 and is now considered an established tool in the detection of NMIBC.
Edinburgh Clinical Trial Offers Proof Positive
A study by the Edinburgh Urological Cancer Group at Western General Hospital in Edinburgh, Scotland, recently sought to compare the efficacy of Hexvix-PDD-guided surgery for bladder cancer to the standard white-light approach. In this controlled clinical trial, only bladder cancer patients who had undergone the standard TURBT procedure (mentioned above) were enrolled in the study. Recurrences were assessed at the first follow-up cystoscopy.
The findings leave little doubt that the photodynamic way is the smart way to approach bladder cancer. Of the 808 patients in this study, those who underwent the standard white-light method at the time of surgery were three times more likely to have recurrence than patients who had undergone surgery coupled with the blue-light PDD strategy. These findings showed a high level of statistical significance, as reported in the August 2015 issue of Urology.
A modified version of the Hexvix-PDD intervention was studied at the Institute of Clinical Medicine at Aarhus University in Aarhus, Denmark. In this study, a total of 190 cases were managed with the PDD blue light strategy; these patients were compared to a control group of 216 patients receiving the standard white-light strategy. In this study, however, the researchers added chemotherapy with mitomycin C immediately after surgery in an attempt to provide additional protection.
Once again, the Hexvix-PDD strategy offered a superior advantage. As with the previous study, the risk of recurrence was three times higher in patients receiving standard white light cystoscopy than in those patients receiving PDD-guided surgery. A key finding was that surgery was completely avoided at every third follow-up visit. Also, patients with recurrent disease (which tends to be harder to treat) benefited from this strategy of blending PDD-guided surgery with mitomycin-C chemo immediately after the operation, as reported in the June 2015 Scandinavian Journal of Urology.
Most research on PDD-assisted surgery for bladder cancer has confirmed a significant benefit for blue-light cystoscopy at the time of surgery. This applies to all NMIBC tumor types (Ta, T1, and CIS), regardless of the risk of recurrence, according to an expert review of the evidence published in the November 2014 issue of European Urology. The experts concluded that PDD-assisted surgery can improve the quality and completeness of the procedure, reduce the risk of recurrence, and finally delaying the time to recurrence. Such outcomes can reduce the need for costly hospitalization and treatments for recurrent tumors—two reasons bladder cancer is still the most expensive cancer in the world.
Mariappan P, Rai B, El-Mokadem I, Anderson CH, Lee H, Stewart S, Donat R. Real-life Experience: Early Recurrence With Hexvix Photodynamic Diagnosis-assisted Transurethral Resection of Bladder Tumour vs Good-quality White Light TURBT in New Non-muscle-invasive Bladder Cancer. Urology. 2015 Aug;86(2):327-31.
Lykke MR, Nielsen TK, Ebbensgaard NA, Zieger K. Reducing recurrence in non-muscle-invasive bladder cancer using photodynamic diagnosis and immediate post-transurethral resection of the bladder chemoprophylaxis. Scand J Urol. 2015 Jun;49(3):230-6.
Witjes JA, Babjuk M, Gontero P, Jacqmin D, Karl A, Kruck S, Mariappan P, Palou Redorta J, Stenzl A, van Velthoven R, Zaak D. Clinical and cost effectiveness of hexaminolevulinate-guided blue-light cystoscopy: evidence review and updated expert recommendations. Eur Urol. 2014 Nov;66(5):863-71
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