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Photodynamic Diagnosis – Fluorescence-assisted Cystoscopy in
Non-muscle-invasive Bladder Cancer
a report by
and Bernard Malavaud
1. Department of Pathology; 2. Department of Urology, Centre Hospitalier Universitaire Rangueil, Toulouse
In the EU, 119,200 cases of bladder cancer and 37,400 deaths were given in lieu. Recurrence was documented six months later and a full course
expected in 2004.
Bladder cancer has the unique characteristic of of BCG (six plus three instillations) was given with no adverse events, in line
encompassing a wide spectrum of clinical entities whose patterns of care with the reported safety of BCG in immunocompromised patients.
and aggressiveness range from a mildly disturbing medical condition to a Cytology remained positive and from 2000 to 2006 five sessions of random
life-threatening disease, aptly referred to as the ‘cat or tiger’ paradox. biopsies were performed, including sampling of the prostatic urethra. Upper
Muscle-invasive bladder cancer, which is readily seen at cystoscopy, tract imaging was unevocative and upper tract cytology remained negative.
requires transurethral resection for staging confirmation before
immediate cystectomy or non-surgical alternatives; treatment of non- PDD was recommended and performed as soon as hexyl aminolevulinate
muscle-invasive bladder cancer (NMIBC) is infinitely more complex as it (Hexvix
) gained approval from the French health authorities (February
must find a balance between conservation of the bladder reservoir and 2007). While WLC was unevocative, PDD showed three discrete areas of
the risk of recurrence or progression to a more aggressive stage of intense fluorescence (see Figures 1A and 1B). The limits were sharp and
cancer. Because of long-term survival and lifelong follow-up and care, per the fluorescent urothelial layer was easily detached by gentle strokes
patient NMIBC is the most expensive cancer to treat.
with the loop. Resection of all fluorescent lesions was achieved. Post-
resection, PDD did not show any suspicious margin, and further
Current diagnosis of NMIBC is based on white-light cystoscopy (WLC). In fulguration of the margins was performed.
a classic signal–receptor situation, the brain has to recognise the minute
changes in volume or surface appearance that are induced by local Histology revealed carcinoma in situ in all three areas. Interestingly,
tumour growth in order to create a coherent rendering from disparate haematoxylin and eosin (H&E) showed little differences in nucleus size or
The current literature on NMIBC suggests that there is a lot of orientation in the urothelium (no pleiomorphism; see Figure 1C [x400]),
room for improvement in this setting. Even after adjusting for T stage, with conserved differentiation of the superficial layer, as shown by
grade, multifocality and adjuvant intravesical chemotherapy, Brausi et al. retained anti-CK20 immune reactivity (see Figure 1D [x100]). The
reported manifold variations in the recurrence rate at first cystoscopy,
proliferative index was high (~35%; see Figure 1E [MIB-1 staining, x100])
suggesting large differences among the performances of expert tertiary and p53 immune reactivity was intense (<80%; see Figure 1F [x100]),
centres in the identification and resection of bladder cancer. with a final diagnosis of carcinoma in situ.
The introduction of photodynamic diagnosis cystoscopy (PDD) confirmed Comments
that up to 20% of lesions were not detected by conventional WLC
and Detection of carcinoma in situ is the most striking achievement of PDD.
that improved detection was found mainly for flat lesions, such as a prospective series of 298 patients who were sequentially explored by WLC
carcinoma in situ. The downside of such improvement was the high rate and PDD, 113 carcinoma in situ lesions were identified in 58 patients. PDD
of false-positive lesions, that is fluorescent lesions that did not meet all of detected more lesions than WLC (92 versus 68%), while a minority of lesions
the requisites of a bona fide cancer, such as dysplasia or hyperplasia. (five of 58) were found solely by WLC. High sensitivity in the detection of
carcinoma in situ combined with a low proportion of false-negative findings
By highlighting the minute metabolic abnormalities associated with was in line with the preliminary report by Jichlinski
cancer development, irrespective of visual alterations of the mucosa and observed in all reports to date.
The discrete delineation of the lesion is often
stroma, PDD is changing our understanding of NMIBC. The aim of this striking, in line with the sharp borders observed in the specimens.
article is to illustrate through three representative clinical case studies
how the development of fluorescent cystoscopy may influence some Detecting carcinoma in situ has significant prognostic implications as it is
aspects of NMIBC, such as the diagnosis of carcinoma in situ, the a strong predictor of recurrence and progression independent of the five
understanding of fluorescent non-cancer lesions and the management of other factors reported by Sylvester: number of tumours, tumour size,
high-grade lamina propria invasive tumours. previous recurrence rate, T category and grade.
In general, it is estimated
that such improved detection, by driving more extensive intraoperative
Case Study 1 – Carcinoma In Situ treatments or additional post-operative procedures, may result in 20% of
Mr L, 70 years of age, presented in 1999 with a single lesion of the right patients receiving more appropriate treatment.
bladder wall. Cytology was positive and resection showed a pT1G3 (World
Health Organization [WHO] 1973 classification) lesion. Adjuvant treatment Case Study 2 – ‘False-positive’ Papillary Hyperplasia
with bacillus Calmette-Guérin (BCG) was not implemented due to Mr D, 65 years of age, was diagnosed with two pTaG1 (WHO 1973
concomitant treatment with steroids; eight instillations of mitomycin C were classification) lesions in 2002 that required no adjuvant treatment. His
© TOUCH BRIEFINGS 2008 41