Hexvix® (hexylaminolevulinate) - guided fluorescence cystoscopy: a teaching aid and reference source Back

Bernard Malavaud, MD, Professor of Urology, Hôpital Rangueil, Toulouse, France

The 2010 European Association of Urology (EAU) guidelines highlight three conditions for the optimal management of non-muscle-invasive bladder cancer (NMIBC):1

i) Complete and accurate transurethral resection of the bladder (TURB)

ii) Stratification for recurrence and progression in low, intermediate and high-risk groups, according to the Sylvester scoring system,2 and

iii) Risk-adapted use of adjuvant treatments and surveillance

Although the EAU guidelines are generally accepted by the urology community, wide variations in clinical practice and in recommendations made in local guidelines remain.3,4

Right from publication of the initial report by Jichlinski and colleagues,5photodynamic diagnosis (PDD) has raised high expectations in terms of improved detection of tumours and quality of resection in NMIBC. The first meta-analysis of prospective studies fully supported such expectations, the findings showing that Hexvix® (hexylaminolevulinate)-guided PDD improves the detection rate of papillary and flat cancer lesions by 20% and 39%, respectively. The research also showed markedly reduced rates of residual tumours and improved recurrence-free survival.6 The clinical implications in terms of management of both low-risk and high-risk NMIBC were addressed in a recent structured discussion.7 In the same article, Bordier and colleagues also discuss mechanisms for controlling the troublesome rate of false-positives in the detection of flat lesions. 

In light of and in line with these findings, five main indications for Hexvix-guided PDD have recently been proposed by a European expert panel.8 That panel notes that the technique should be used:

i) On initial suspicion of bladder cancer

ii) In patients with positive urine cytology, but negative white-light cystoscopy

iii) To aid assessment at time of tumour recurrence in patients not previously staged by PDD

iv) In the follow up of patients with multifocal tumours and carcinoma in situ (CIS)

v) As a teaching tool, given that it provides clear visualisation of tumours and their margins

The last indication is of crucial importance, since the current literature base for white-light cystoscopy and TURB suggests wide variations in success between surgeons and centres. A combined analysis of seven European Organisation for Research and Treatment of Cancer (EORTC) trials, for example, showed a greater than six-fold variability in the recurrence rate at first cystoscopy for single-site tumours, which persisted even after adjusting for T stage, grade and immediate postoperative intravesical chemotherapy.9 Similarly, in another study, 47 patients referred after a resection that was assumed to be complete underwent a second TURB in a reference tertiary centre. Residual tumour was found in 70% of the patients at the site of initial resection (10/47) or at a different site (23/47).10 With Hexvix-guided PDD reducing residual and recurrent tumour rates,6 one might safely assume that the technique will provide a turning point in the quality of care for NMIBC. That in mind, it is surprising that so little attention has been pain in the literature to how to define a positive finding, although PDD demands finesse and understanding of the biology of transitional urothelium to offer its full potential. Can the general appearance of PDD-positive papillary tumours give any clue as to the stage – and possibly the grade – of the lesion? In what respect can PDD refine our understanding of the morphological variants of CIS?11

From March 2007 to June 2009, we performed 542 TURB. 75 (13.8%) patients met the French Association of Urology criteria for examination using PDD (highgrade cytology, multifocal papillary lesions on ambulatory white-light  fibroscopy, size >3 cm). In all cases, suspicious lesions visible under white light and Hexvix-guided PDD were noted on a bladder chart with their corresponding characteristics and were harvested by bipolar resection in saline. 176 lesions were individually retrieved and sent in separate vials for pathological examination to establish any correlation between endoscopy and pathology. With the objective of providing a structured presentation of the endoscopic and microscopic aspects of NMIBC (1973 and 2004 World Health Organization [WHO] classifications), we selected typical cases identified through this process and organised them in the form of a poster (see below).

It is our hope that this work will provide a valuable teaching and reference aid.