NATURE REVIEWS | UROLOGY VOLUME 11 | OCTOBER 2014 | 589
University of Southern
California,
1441 Eastlake Avenue,
Suite 7416,
Los Angeles, CA 90089,
USA (S.D., A.K.S.).
Memorial Sloan–
Kettering Cancer
Center, USA (B.H.B.).
University of Oklahoma
Medical Center, USA
(M.S.C.). University of
Wisconsin, USA
(T.M.D.). Thomas
Jefferson University
Philadelphia, USA
(L.G.G.). MD Anderson
Cancer Center, USA
(H.B.G., A.M.K.).
University of Minnesota,
USA (B.R.K.). University
of Michigan, USA
(C.T.L.). Ohio State
University, USA (K.S.P.).
University of North
Carolina, USA (R.S.P .).
Vanderbilt University,
USA (M.J.R.). University
of Chicago, USA (N.D.S.,
G.D.S.). Radboud
University Medical
Center, The Netherlands
(J.A.W.). Johns Hopkins
University, USA (M.P .S.).
Correspondence to: S.D.
daneshma@usc.edu
EXPERT CONSENSUS DOCUMENT
Hexaminolevulinate blue-light cystoscopy in non-muscle-
invasive bladder cancer: review of the clinical evidence
and consensus statement on appropriate use in the USA
Siamak Daneshmand, Anne K. Schuckman, Bernard H. Bochner, Michael S. Cookson, Tracy M. Downs,
Leonard G. Gomella, H. Barton Grossman, Ashish M. Kamat, Badrinath R. Konety, Cheryl T. Lee,
Kamal S. Pohar, Raj S. Pruthi, Matthew J. Resnick, Norm D. Smith, J. Alfred Witjes, Mark P. Schoenberg
and Gary D. Steinberg
Abstract | Hexaminolevulinate (HAL) is a tumour photosensitizer that is used in combination with blue-light
cystoscopy (BLC) as an adjunct to white-light cystoscopy (WLC) in the diagnosis and management of non-
muscle-invasive bladder cancer (NMIBC). Since being licensed in Europe in 2005, HAL has been used in
>200,000 procedures, with consistent evidence that it improves detection compared with WLC alone. Current
data support an additional role in the reduction of recurrence of NMIBC. Since the approval of HAL by the FDA
in 2010, experience of HAL–BLC in the USA continues to expand. To define areas of need and to identify the
benefits of HAL–BLC in clinical practice, a focus group of expert urologists specializing in the management
of patients with bladder cancer convened to review the clinical evidence, share their experiences and reach a
consensus regarding the optimal use of HAL–BLC in the USA. The focus group concluded that HAL–BLC should
be considered for initial assessment of NMIBC, surveillance for recurrent tumours, diagnosis in patients with
positive urine cytology but negative WLC findings, and for tumour staging.
Daneshmand, S. et al. Nat. Rev. Urol. 11, 589–596 (2014); published online 23 September 2014; doi:10.1038/nrurol.2014.245
Introduction
Bladder cancer is one of the most frequently diagnosed
tumours worldwide: an estimated 74,690 new diagnoses
were expected to be made and 15,580 deaths were esti-
mated in the USA in 2014.
1
Although most patients are
diagnosed at a relatively early stage, with non-muscle-
invasive bladder cancer (NMIBC), the risk of dying
from high-grade NMIBC remains substantial. Disease
prognosis is affected in part by the high risk of tumour
recurrence: depending on the grade at initial diagno-
sis, up to 61% of patients with NMIBC will experience
recurrence within the first year after initial resection,
and up to 78% will experience recurrence within
5 years.
2
Moreover, patients with NMIBC are also at
risk of progression to muscle-invasive bladder cancer
(MIBC), with approximately 17% risk at 1 year and 45%
risk at 5 years.
2
Owing to the high risk of both recur-
rence and progression, patients require regular follow-
up monitoring with cystoscopy after transurethral
resection of the bladder tumour (TURBT).
3,4
Both the
high prevalence of disease and the need for intensive
endoscopic surveillance make bladder cancer one of the
most costly cancers to treat.
5
Optimal management of bladder cancer begins with
urine cytology and thorough cystoscopic assessment of
the bladder. The current standard of care is white-light
cystoscopy (WLC), which enables the urologist to map
and resect all visible lesions. Tissue specimens are then
sent for pathological review to confirm the diagnosis
and define the pathological stage. Bladder tumours can
display numerous gross morphological features, ranging
from erythematous mucosa to papillary tumours or solid
masses.
6
However, not all cancerous areas are readily
visible using WLC. The current general recommenda-
tion, according to the guidelines of urological associ-
ations, is to biopsy any area of the urothelium with an
abnormal appearance, or if patients have positive urine
cytology but no evidence of bladder cancer on WLC, to
take random biopsies from normal-looking mucosa.
3
Competing interests
S.D. declares that he has been a meeting participant and lecturer
for Cubist and Endo. H.B.G. declares that he has served as a
consultant for Telormedix and as a scientific advisor for Abbott
Molecular and Heat Biologics. A.M.K. declares that he has
received grant or research support from Abbott, FKD and Cubist
and has served on membership, advisory committee or review
panels for Sanofi, Photocure, and Taris. B.R.K. declares that he
has served as a consultant for Dendreon, GTx and Photocure, is a
stockholder of Axogen and has worked on a clinical trial for
Dendreon. M.J.R. declares that he has served as a consultant
advisor for Dendreon and has been involved in a clinical trial for
Genomic Health. J.A.W. declares that he is an advisor for
Photocure and Ipsen. G.D.S. declares that he has served as a
consultant, scientific advisor and speaker for Photocure and KARL
STORZ. The authors were reimbursed by Photocure and KARL
STORZ Endoscopy-America for their attendance at the consensus
meeting. The other authors declare no competing interests.
CONSENSUS
STATEMENTS
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