What are the benefits of photodynamic diagnosis (PDD) during the performance of transurethral resection of bladder tumor (TURBT)?

Updated: Aug 03, 2019
  • Author: Gary David Steinberg, MD, FACS; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
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Answer

Photodynamic diagnosis (PDD) has emerged as a viable adjunct to white-light (WL) cystoscopy to assist in the performance of a complete TURBT. [15]  Lesions can be missed using WL cystoscopy, and PDD has been developed to assist in the detection of these lesions, reduce the rate of recurrence, and improve the completeness of resection. PDD exploits the photodynamic properties of several compounds, including hexaminolevulinate (HAL) (Hexvix, Cysview, Photocure; Oslo, Norway) and 5-aminolevulinic acid (5-ALA).

Approximately 1 hour prior to planned TURBT, 50 mL of reconstituted solution of HAL is instilled into the emptied bladder via an intravesical catheter. Following instillation, protoporphyrin IX accumulates preferentially in neoplastic tissue, producing a clearly demarcated red fluorescence with illumination with blue-violet light (380-440 nm). Cysview (HAL hydrochloride) was approved by the United States Food and Drug Administration in 2010 for use with the Karl Storz D-Light C PDD system with the blue-light (BL) setting as an adjunct to the WL setting in the detection of nonmuscle invasive papillary cancer of the bladder in patients suspected or known to have lesions on the basis of a prior cystoscopy.

A recent meta-analysis reviewed the raw data from prospective studies on 1,345 patients with known or suspected nonmuscle invasive bladder cancer on whom HAL and BL as an adjunct to WL cystoscopy. [16] HAL BL cystoscopy detected significantly more Ta tumors (14.7%; P< .001) and CIS lesions (40.8%; P< .001) than WL cystoscopy. Furthermore, recurrence rates up to 12 months were significantly lower overall with BL HAL versus WL cystoscopy (34.5% vs 45.4%; P =.006).

The European Association of Urology 2013 guidelines on nonmuscle invasive bladder cancer recommend PDD in patients who are suspected of harboring a high-grade tumor for guidance of TURBT. It is possible that BL HAL–assisted TURBT improves completeness and quality of resection and might obviate the need for perioperative intravesical instillation of chemotherapy or a second TURBT, but further study is needed in this area to test this hypothesis.

While 5-ALA is not currently approved for routine clinical use for the detection of bladder cancer in Europe or the United States, it has been extensively studied in numerous clinical trials. Furthermore, orally applied 5-ALA has been approved in Europe to enhance intraoperative detection of malignant glioma. Inoue et al evaluated the clinical value of PDD with intravesical (n=75) and oral (n=135) instillation of 5-ALA and PDD-guided TURBT for nonmuscle invasive bladder cancer in a multi-institutional retrospective study in 210 patients. [17] Rates of recurrence were compared with historical controls subjects who underwent TURBT with WL cystoscopy. 5-ALA–guided TURBT improved detection of CIS, as 72.1% of flat lesions (including dysplasia and CIS) could only be detected with BL 5-ALA–assisted TURBT. The route of administration of 5-ALA (oral vs intravesical) did not affect diagnostic accuracy or recurrence-free survival.

The management of nonmuscle invasive bladder cancer is expensive, stemming from high recurrence rates necessitating repeat TURBT and frequent surveillance cystoscopies. As HAL and 5-ALA have been shown to help increase the detection and reduce the recurrence of nonmuscle invasive bladder cancer, this technology may reduce the cost of bladder cancer management. Garfield et al assessed the cost effectiveness of BL HAL–assisted cystoscopy as an adjunct to WL cystoscopy versus WL cystoscopy alone at the time of initial TURBT and noted a cost savings of nearly $5,000 in the PDD group in their model over a 5-year projected period. [18, 19]


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