American Society of Clinical Oncology Clinical Practice
Guideline for the Use of Larynx-Preservation Strategies in
the Treatment of Laryngeal Cancer
David G. Pfister, Scott A. Laurie, Gregory S. Weinstein, William M. Mendenhall, David J. Adelstein,
K. Kian Ang, Gary L. Clayman, Susan G. Fisher, Arlene A. Forastiere, Louis B. Harrison, Jean-Louis Lefebvre,
Nancy Leupold, Marcy A. List, Bernard O. O’Malley, Snehal Patel, Marshall R. Posner, Michael A. Schwartz,
and Gregory T. Wolf
A B S T R A C T
Purpose
To develop a clinical practice guideline for treatment of laryngeal cancer with the intent of
preserving the larynx (either the organ itself or its function). This guideline is intended for use by
oncologists in the care of patients outside of clinical trials.
Methods
A multidisciplinary Expert Panel determined the clinical management questions to be addressed
and reviewed the literature available through November 2005, with emphasis given to randomized
controlled trials of site-specific disease. Survival, rate of larynx preservation, and toxicities were
the principal outcomes assessed. The guideline underwent internal review and approval by the
Panel, as well as external review by additional experts, members of the American Society of
Clinical Oncology (ASCO) Health Services Committee, and the ASCO Board of Directors.
Results
Evidence supports the use of larynx-preservation approaches for appropriately selected patients
without a compromise in survival; however, no larynx-preservation approach offers a survival
advantage compared with total laryngectomy and adjuvant therapy with rehabilitation as indicated.
Recommendations
All patients with T1 or T2 laryngeal cancer, with rare exception, should be treated initially with
intent to preserve the larynx. For most patients with T3 or T4 disease without tumor invasion
through cartilage into soft tissues, a larynx-preservation approach is an appropriate, standard
treatment option, and concurrent chemoradiotherapy therapy is the most widely applicable
approach. To ensure an optimum outcome, special expertise and a multidisciplinary team are
necessary, and the team should fully discuss with the patient the advantages and disadvantages
of larynx-preservation options compared with treatments that include total laryngectomy.
J Clin Oncol 24. © 2006 by American Society of Clinical Oncology
INTRODUCTION
In 2005, an estimated 9,880 new cases of laryngeal
cancer will be diagnosed in the United States, ac-
counting for 3,770 deaths.1 Squamous cell carci-
noma is the predominant histologic type, and
approximately 40% of patients will have stage III or
IVdiseasewhenfirst evaluated.2Most casesof laryn-
geal cancer are associated with a history of tobacco
and/or alcohol use, so the treatment of patients is
complicated bymedical comorbidity and the devel-
opment of second primary cancers.3-5 Given the
fundamental role the larynx plays in human speech
and communication, determining the optimal
management of laryngeal cancers must involve
consideration of both survival and the functional
consequences of a given treatment approach. The
potentialmorbidity of curative treatment is a special
consideration when total laryngectomy, either for
primary therapy or as salvage treatment, is the rec-
ommendation. Total laryngectomy is widely recog-
nized as one of the surgical procedures most feared
by patients. Social isolation, job loss, and depression
are common sequelae.6,7 Pioneering work on pa-
tient preferences showed that approximately 25%of
healthy individuals interviewedwerewilling to trade
a 20% absolute difference in survival for the oppor-
tunity to save their voice.8Different voice rehabilita-
tions exist,9 but many patients are dissatisfied with
the results and report associated restrictions in their
The unabridged version of this arti-
cle can be found at www.asco.org/
guidelines/larynx/unabridged.
From the American Society of Clinical
Oncology, Alexandria, VA.
Submitted May 15, 2006; accepted
May 19, 2006; published online ahead of
print at www.jco.org on July 10, 2006.
Adopted on February 28, 2006, by the
American Society of Clinical Oncology
Authors’ disclosures of potential
conflicts of interest and author contribu-
tions are found at the end of this
article.
Address reprint requests to American
Society of Clinical Oncology, Cancer
Policy and Clinical Affairs, 1900 Duke
Street, Suite 200, Alexandria, Virginia
22314; e-mail: guidelines@asco.org.
© 2006 by American Society of Clinical
Oncology
0732-183X/06/2422-1/$20.00
DOI: 10.1200/JCO.2006.07.4559
JOURNAL OF CLINICAL ONCOLOGY A S C O S P E C I A L A R T I C L E
VOLUME 24 � NUMBER 22 � AUGUST 1 2006
1
http://www.jco.org/cgi/doi/10.1200/JCO.2006.07.4559The latest version is at
Published Ahead of Print on July 10, 2006 as 10.1200/JCO.2006.07.4559
Copyright 2006 by American Society of Clinical Oncology
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daily lives. Although the impact of the procedure on voice often
receives thegreatest attention, thepresenceof the stomamayadversely
affect quality of life as much, if not more.10 Accordingly, there has
been keen interest in the development and refinement of organ-
preservation therapies, such as radiation therapy alone, the combina-
tion of chemotherapy and radiation therapy (chemoradiotherapy
therapy), and function-preserving partial laryngectomy procedures.
With all three of these approaches, total laryngectomy is reserved for
tumor recurrence.
The American Society of Clinical Oncology (ASCO) fully appre-
ciates the controversy about how to best achieve the dual goals of cure
and preservation of function for patients with laryngeal cancer. As a
service to patients, to its members, and to practicing physicians gen-
erally, ASCO convened an Expert Panel under the auspices of the
Health Services Committee to develop recommendations regarding
the appropriate application of larynx-preservation therapies.
Accordingly, ASCO considers adherence to this guideline to be
voluntary, with the ultimate determination regarding its application
to be made by the physician in light of each patient’s individual
circumstances. In addition, the guideline describes administration of
therapies in clinical practice; it cannot be assumed to apply to inter-
ventions performed in the context of clinical trials, given that clinical
studies are designed to test innovative and novel therapies in a disease
and setting for which better therapy is needed. Because guideline
development involves a review and synthesis of the latest literature, a
practice guideline also serves to identify important questions for fur-
ther research and those settings in which investigational therapy
should be considered.
QUESTIONS
The following questions about squamous cell laryngeal cancer were
addressed by the Panel:
(1)What are the larynx-preservation treatment options for lim-
ited stage (T1, T2) primary site disease that do not compromise sur-
vival?What are the considerations in selecting among them?
(2) What are the larynx-preservation treatment options for ad-
vanced stage (T3, T4) primary site disease that do not compromise
survival?What are the considerations in selecting among them?
(3) What is the appropriate treatment of the regional cervical
nodes for patients with laryngeal cancer who are treated with an
organ-preservation approach?
(4) Are there methods for prospectively selecting patients
with laryngeal cancer to increase the likelihood of success of
larynx preservation?
METHODS
The members of the Expert Panel were selected for their expertise in
clinical medicine; medical, radiation, and surgical oncology; diagnos-
tic imaging; clinical research; outcomes/health services research; and
related disciplines (biostatistics, quality of life) with a focus on exper-
tise in head and neck and laryngeal cancer (Appendix A). To enhance
the focus of the published guideline on the implications for clinical
practice, the methodology of the guideline development is available
online, at both www.jco.org and www.asco.org.
GUIDELINE FOR LARYNX-PRESERVATION TREATMENT
We have summarized the recommended treatment strategies by T
stage, alongwith the basis for the recommendations and the quality of
the supporting evidence (Table 1). A complete review of the literature
and discussion of study results are available online.
What are the larynx-preservation treatment options
for limited stage (T1, T2) primary site disease that do
not compromise survival? What are the
considerations in selecting treatment options in
this setting?
Evidence base. There are no randomized studies in which radi-
ation therapywas comparedwith conservation surgerywith respect to
local control or survival for patients with limited-stage laryngeal can-
cer. Similarly, therearenorandomizedcontrolleddataoncomparison
of functional outcomes, specifically the quality of voice and swallow-
ingability, after surgeryor radiation therapy forpatientswith this stage
of disease.
The recommendations to address these questions are based
on evidence from prospective and retrospective cohort studies.11-75
The recommendations for T2 N� disease are based on data from
randomized controlled trials of chemoradiotherapy therapy (with
either induction or concurrent chemotherapy compared with radia-
tion therapy alone or surgery followed by adjuvant radiation thera-
py).77,78 The outcomes assessed included overall survival, disease-free
survival, rates of laryngeal preservation, local-regional control, toxic-
ity of therapy, and cost.
Limited-stagedisease represents a spectrum.Treatment selection
can be challenging, as the evidence base for most decisions is derived
from nonrandomized studies and various factors need to be consid-
ered when choosing therapy. Selected examples for glottic cancer are
illustrative. If voice outcome is predicted to be good after endoscopic
laser resection for aT1glottic cancer (eg, a superficial tumor located in
themiddle thirdof the cord, especiallyon its free edge), thenuseof this
modality is more efficient and thus preferred. However, lesions that
are indistinct, especially those arising in the context of widespread,
abnormal-appearingmucosa, are more suitable for radiation therapy
than for surgery. Radiation therapy is preferred bymany clinicians for
treatment of T2 glottic carcinoma characterized as superficial on ra-
diographic imaging, with preserved cord mobility, as local control
rates arehighandanticipated functionaloutcomesaregood.But some
investigators have noted compromised survival after the failure of
radiation therapy inT2glottic carcinoma indicating the importanceof
obtaining initial local control.56,59 As such, supracricoid partial laryn-
gectomy with cricohyoidoepliglottopexy remains a reasonable alter-
native for patientswith aT2 glottic carcinomawho after pretreatment
counseling would be willing to sacrifice voice quality in an effort to
improve local control. Induction chemotherapy has been investigated
as treatment for patients with limited-stage laryngeal cancer. How-
ever, insufficient data are currently available to recommend such an
approach outside the context of a clinical trial.
Recommendations
• All patients with T1-T2 laryngeal cancer should be treated,
at least initially, with intent to preserve the larynx.
• T1-T2 laryngeal cancer can be treated with radiation or
larynx-preservation surgery with similar survival outcomes. Se-
lection of treatment depends on patient factors, local expertise,
Pfister et al
2 JOURNAL OF CLINICAL ONCOLOGY
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and the availability of appropriate support and rehabilitative services.
Every effort should be made to avoid combining surgery with radia-
tion therapy because functional outcomes may be compromised by
combined-modality therapy; single-modality treatment is effective for
limited-stage, invasive cancer of the larynx.
• Surgical excision of the primary tumor with intent to
preserve the larynx should be undertaken with the aim of
achieving tumor-free margins; so-called narrow-margin exci-
sion followed by postoperative radiation therapy is not an ac-
ceptable treatment approach.
Table 1. Summary of Recommended Strategies for Treatment of the Primary Site for Larynx Preservation
Type of Cancer
Organ-Preservation Strategy
Basis for Recommendation Quality of EvidenceRecommended Other Options
T1 cancer of the glottis:
T1—tumor limited to the vocal cord(s)
(may involve anterior or posterior
commissure) with normal mobility
T1a—tumor limited to one vocal cord
T1b—tumor involves both vocal cords
Endoscopic resection
(selected patients) OR
radiation therapy
Open organ-
preservation
surgery
High local control rates and quality
of voice after endoscopic
resection compared with
radiation therapy; possible cost
savings; ability to reserve
radiation for possible second
primary cancers of the upper
aerodigestive tract; however,
not suitable for all patients
Comparison of outcomes
from case series/
prospective single-arm
studies
T2 cancer of the glottis,
favorable�:T2—tumor
extends to supraglottis
and/or subglottis, or with
impaired vocal cord mobility
Open organ-preservation
surgery OR radiation
therapy
Endoscopic resection
(selected patients)
Open organ-preservation surgery is
associated with highest local
control rates; however, leads to
permanent hoarseness; local
control rates after radiation therapy
are also high, and functional
outcomes may be better
Comparison of outcomes
from case series/
prospective single-arm
studies
T2 cancer of the glottis, unfavorable� Open organ-preservation
surgery OR concurrent
chemoradiation therapy
(selected patients with
node-positive disease)
Radiation therapy
Endoscopic
resection (selected
patients)
Higher local control rates after
surgery compared with radiation
therapy alone; quality of voice
after therapy of less concern if
vocal cord function is
irreversibly compromised by
tumor invasion; endoscopic
surgery requires careful patient
selection
For patients with T2 N�
disease, evidence from
randomized trials supports
concurrent chemoradiation
therapy as an organ-
preservation option
Comparison of outcomes
from case series/
prospective single-arm
studies; randomized
controlled clinical trials
comparing concurrent
chemoradiation therapy,
and/or induction
chemotherapy followed
by radiation, and/or
radiation therapy alone,
and/or surgery followed
by radiation
T1-T2 cancer of the supraglottis,
favorable�:T1—tumor
limited to one subsite of supraglottis
with normal vocal cord mobility
T2—tumor invades mucosa of more
than one adjacent subsite of supraglottis
or glottis or region outside the
supraglottis (eg, mucosa of base of
tongue, vallecula, medial wall of pyriform
sinus) without fixation of the larynx
Open organ-preservation
surgery OR radiation
therapy
Endoscopic resection
(selected patients)
Open organ-preservation surgery
associated with highest local
control rates; however, requires
temporary tracheostomy and
may lead to increased risk of
aspiration after therapy; local
control rates after radiation
therapy are also high, and
functional outcomes may be
better
Comparison of outcomes
from case series/
prospective single-arm
studies
T2 cancer of the supraglottis,
unfavorable�
Open organ-preservation
surgery OR concurrent
chemoradiation therapy
(selected patients with
node-positive disease)
Radiation therapy
Endoscopic
resection (selected
patients)
Open organ-preservation surgery
is more likely to yield higher
local control rates than radiation
therapy; for patients with T2
N� disease, evidence from
randomized trials supports
concurrent chemoradiation
therapy as an organ-
preservation option
Comparison of outcomes
from case series/
prospective single-arm
studies; randomized
controlled clinical trials
comparing concurrent
chemoradiation therapy,
and/or induction chemo-
therapy followed by
radiation, and/or radiation
therapy alone, and/or
surgery followed by
radiation
T3-T4 cancers of the glottis or supraglottis:
T3 glottis—tumor limited to the larynx
with vocal cord fixation, and/or invades
paraglottic space, and/or minor thyroid
cartilage erosion (eg, inner cortex)
T3 supraglottis—tumor limited to larynx
with vocal cord fixation and/or invades
any of the following: postcricoid area,
pre-epiglottic tissues, paraglottic space,
and/or minor thyroid cartilage erosion
(eg, inner cortex)
T4a glottis or supraglottis—tumor
invades through the thyroid cartilage
and/or invades tissues beyond the larynx
(eg, trachea, soft tissues of neck
including deep extrinsic muscle of the
tongue, strap muscles, thyroid, or
esophagus)
T4b glottis or supraglottis—tumor
invades prevertebral space, encases
carotid artery, or invades mediastinal
structures
Concurrent chemoradiation
therapy OR open organ-
preservation surgery (in
highly selected patients)
Radiation therapy Highest rate of larynx preservation
is associated with concurrent
chemoradiation therapy
compared with other radiation-
based approaches, at the cost
of higher acute toxicities but
without more long-term
difficulties in speech and
swallowing; when salvage total
laryngectomy incorporated, no
difference in overall survival;
organ preservation surgery is an
option in highly selected
patietns (eg, there are patients
with T3 supraglottic cancers
that have minimal or moderate
pre-epiglottic invasion and are
candidates for organ preserving
surgery)
Randomized controlled
clinical trials comparing
concurrent chemoradia-
tion therapy, and/or
induction chemotherapy
followed by radiation,
and/or radiation therapy
alone; and/or surgery
followed by radiation;
comparison of outcomes
from case
series/prospective single-
arm studies
�A favorable T2 glottic lesion is defined as a superficial tumor, on radiographic imaging, with normal cord mobility. An unfavorable T2 glottic lesion is defined as
a deeply invasive tumor on radiographic imaging, with or without subglottic extension, with impaired cord mobility (indicating deeper invasion). A favorable
supraglottic lesion is defined as a T1 or T2 tumor with superficial invasion on radiographic imaging and preserved cord mobility, and/or tumor of the aryepiglottic fold
with minimal involvement of the medial wall of the pyriform sinus. More locally advanced and invasive T2 suproglottic lesions are considered unfavorable.
Larynx Guideline
www.jco.org 3
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• Local tumor recurrence after radiation therapy may be
amenable to salvage by organ-preservation surgery, but total lar-
yngectomy will be necessary for a substantial proportion of pa-
tients, especially those with index T2 tumors.
• Concurrent chemoradiotherapy therapy may be used for
larynx preservation for selected patients with stage III, T2 N�
cancers when total laryngectomy is the only surgical option, when
the functional outcome after larynx-preservation surgery is ex-
pected to be unsatisfactory, or when surgical expertise in such
procedures is not available.
• Limited-stage laryngeal cancer constitutes a wide spec-
trum of disease. The clinician must exercise judgment when
recommending treatment in this category. For a given patient,
factors that may influence the selection of treatment modality
include extent and volume of tumor; involvement of the ante-
rior commissure; lymph node metastasis; the patient’s age,
occupation, preference, and compliance; availability of exper-
tise in radiation therapy or surgery; and history of