Continue
NCCN Clinical Practice Guidelines in Oncology™
Melanoma
V.1.2010
www.nccn.org
Version 1.2010, 10/19/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
Practice Guidelines
in Oncology – v.1.2010 Melanoma
Guidelines Index
Melanoma Table of Contents
Staging, Discussion, ReferencesNCCN
®
Continue
NCCN Melanoma Panel Members
Daniel G. Coit, MD/Chair
Memorial Sloan-Kettering Cancer Center
William E. Carson, III, MD
The Ohio State University
Comprehensive Cancer Center -
James Cancer Hospital and
Solove Research Institute
Raza A. Dilawari, MD
St. Jude Children’s Research Hospital/
University of Tennessee Cancer Institute
Dominick DiMaio, MD
Allan C. Halpern, MD
Memorial Sloan-Kettering Cancer Center
¶
¶
¶
¶
¥
Þ
Robert Andtbacka, MD
Huntsman Cancer Institute
at the University of Utah
Christopher K. Bichakjian, MD
University of Michigan
Comprehensive Cancer Center
UNMC Eppley Cancer Center
at The Nebraska Medical Center
Valerie Guild
Aim at Melanoma
�
�
�
Merrick I. Ross, MD
The University of Texas
M. D. Anderson Cancer Center
Susan M. Swetter, MD
Stanford Comprehensive Cancer
Center
Kenneth K. Tanabe, MD
Massachusetts General Hospital
Cancer Center
John A. Thompson, MD
Fred Hutchinson Cancer Research
Center/Seattle Cancer Care Alliance
Vijay Trisal, MD
City of Hope
Comprehensive Cancer Center
Marshall M. Urist, MD
University of Alabama at Birmingham
Comprehensive Cancer Center
Jeffrey Weber, MD, PhD
H. Lee Moffitt Cancer Center &
Research Institute
Michael K. Wong, MD, PhD
Roswell Park Cancer Institute
¶
¶
‡
¶
¶
†
†
�
†
¶
, ¶
†
¶
F. Stephen Hodi, Jr. MD
Dana-Farber/Brigham and Women’s
Cancer Center
Mohammed Kashani-Sabet, MD
UCSF Helen Diller Family
Comprehensive Cancer Center
Mark C. Kelley, MD
Vanderbilt-Ingram Cancer Center
Julie R. Lange, MD ScM
The Sidney Kimmel Comprehensive
Cancer Center at Johns Hopkins
Anne Lind, MD
Siteman Cancer Center at Barnes-Jewish
Hospital and Washington University
School of Medicine
Lainie Martin, MD
Fox Chase Cancer Center
Mary C. Martini, MD
Robert H. Lurie Comprehensive Cancer
Center of Northwestern University
Scott K. Pruitt, MD, PhD
Duke Comprehensive Cancer Center
�
�
�
† Medical oncology
Þ Internal medicine
¶ Surgery/Surgical oncology
‡ Hematology/Hematology oncology
* Writing Committee member
�
�
Dermatology
Pathology
¥ Patient Advocacy
*
*
NCCN Guidelines Panel Disclosures
Version 1.2010, 10/19/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
Practice Guidelines
in Oncology – v.1.2010 Melanoma
Guidelines Index
Melanoma Table of Contents
Staging, Discussion, ReferencesNCCN
®
This manuscript is being
updated to correspond
with the newly updated
algorithm.
Table of Contents
NCCN Melanoma Panel Members
Clinical Presentation and Preliminary Workup (ME-1)
Stage 0 (in situ), Stage I-II (ME-2)
Stage III (ME-3)
Stage IV (ME-4)
Follow-up (ME-5)
Persistent disease or True local scar recurrence, In-transit recurrence (ME-6)
Nodal recurrence (ME-7)
Distant metastatic disease (ME-8)
Principles of Biopsy (ME-A)
(ME-B)
Principles of Complete Lymph Node Dissection (ME-C)
Systemic Therapy Options for Advanced or Metastatic Melanoma (ME-D)
Guidelines Index
Print the Melanoma Guideline
Summary of Guidelines Updates
Principles of Surgical Margins for Wide Excision of Primary Melanoma
These guidelines are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment.
Any clinician seeking to apply or consult these guidelines is expected to use independent medical judgment in the context of individual clinical
circumstances to determine any patient's care or treatment. The National Comprehensive Cancer Network makes no representations nor warranties
of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. These
guidelines are copyrighted by National Comprehensive Cancer Network. All rights reserved. These guidelines and the illustrations herein may not
be reproduced in any form without the express written permission of NCCN. ©2009.
Clinical Trials:
Categories of Evidence and
Consensus:
NCCN
The
believes that the best management
for any cancer patient is in a clinical
trial. Participation in clinical trials is
especially encouraged.
To find clinical trials online at NCCN
member institutions,
All recommendations
are Category 2A unless otherwise
specified.
See
NCCN
click here:
nccn.org/clinical_trials/physician.html
NCCN Categories of Evidence
and Consensus
For help using these
documents, please click here
Staging
Discussion
References
Version 1.2010, 10/19/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
Practice Guidelines
in Oncology – v.1.2010 Melanoma
Guidelines Index
Melanoma Table of Contents
Staging, Discussion, ReferencesNCCN
®
Summary of changes in the 1.2010 version of the Melanoma guidelines from the 2.2009 version include:
Summary of the Guidelines Updates
UPDATES
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
( )
( )
( )
( ):
ME-1
ME-2
ME-3
ME-B
( )
( )
( )
( ):
( ):
ME-4
ME-5
ME-8
ME-A
ME-D
�
�
�
�
�
�
�
�
�
�
�
�
Pathology Report: “Mitotic rate” changed from category 2B to category 2A.
Stage IB, Stage II, N0 pathway:
Workup: The recommendations were revised for clarity.
“Encourage sentinel node biopsy” changed to “ sentinel node biopsy”.
Stage III in-transit pathway; Primary Treatment: “Consider sentinel node biopsy” changed to “Consider sentinel node biopsy
.”
Principles of Surgical Margins for Wide Excision of Primary Melanoma
Footnote 2: The panel revised the footnote to read, “Clinical margins do not need to correlate with final histologic margins.”
�
� Discuss and offer
for
resectable in-transit disease
Stage IV Metastatic; Workup: “Chest x-ray and/or chest CT” was removed.
The Workup recommendations for all stages were revised extensively.
Distant metastatic disease; Workup: “Chest x-ray, and/or chest CT” was removed.
Disseminated; Without brain metastases: The pathways for First/Second line therapy and performance scores were removed (this
information is now on page ME-D) and replaced with “Systemic therapy”.
“With brain metastases” pathway: “Clinical trial” was removed.
Principles of Biopsy
Sixth Bullet: “Satellitosis, if present....” changed to “Microsatellitosis, if present...”
Systemic Therapy Options for Advanced or Metastatic Melanoma
Dacarbazine, Temozolomide, and High-dose interleukin-2 changed from “category 2B” to “category 2A”.
Footnotes “1” and “3” are new to the page.
Version 1.2010, 10/19/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
Practice Guidelines
in Oncology – v.1.2010 Melanoma
Guidelines Index
Melanoma Table of Contents
Staging, Discussion, ReferencesNCCN
®
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Breslow
thickness
+
Ulceration status
+
Assess deep and
peripheral
margin status
+
Satellitosis, if
present, should
be reported
+
Mitotic rate
+
Clark level (for
lesions 1 mm)�
Suspicious
pigmented
lesion
Biopsya
Inadequateb
Melanoma
confirmedb
Rebiopsy �
�
�
H&P with
attention to
locoregional
area, draining
lymph nodes
Complete skin
exam
Assessment of
melanoma
related risk
factorsc
a .
If diagnostic biopsy is inadequate for treatment decisions, rebiopsy may be appropriate.
Risk factors for melanoma include family history of melanoma, prior primary melanoma, and other factors such as atypical
moles/dysplastic nevi.
b
c
dAdverse features include positive deep margins, lymphovascular invasion (LVI) or mitotic rate 1 per mm .� 2
See Principles of Biopsy (ME-A)
Stage IB, Stage II
( 1 mm thick with
ulceration or Clark level
IV, V or > 1 mm thick,
any characteristic), N0
(ME-2)
�
Stage IV
Metastatic (ME-4)
ME-1
CLINICAL
PRESENTATION
PATHOLOGY
REPORT
PRELIMINARY
WORKUP
Stage III
(ME-3)
CLINICAL STAGE
Stage 0 in situ
or
Stage IA ( 1 mm thick,
Clark level II or III) with
no adverse features
(ME-2)
�
d
Stage IA ( 1 mm thick,
Clark level II or III) with
adverse features
(ME-2)
�
d
Version 1.2010, 10/19/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
Practice Guidelines
in Oncology – v.1.2010 Melanoma
Guidelines Index
Melanoma Table of Contents
Staging, Discussion, ReferencesNCCN
®
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
d
e
i
Adverse features include positive deep margins, lymphovascular invasion (LVI) or mitotic rate 1 per mm .
Decision not to perform SLNB may be based on significant patient comorbidities, patient preference or
other factors.
.
Sentinel lymph nodes should be evaluated with multiple sectioning and immunohistochemistry.
IFN has been associated with improved DFS, however, its impact on overall survival is unclear.
� 2
g
h
fSentinel node biopsy is an important staging tool, but the impact of SLNB on overall survival is unclear.
See Principles of Surgical Margins for Wide Excision of Primary Melanoma (ME-B)
ME-2
Wide excision
(category 1)
with sentinel
node biopsy
g
h
Sentinel
node
negative
Sentinel
node
positive
See Stage III Workup and
Primary Treatment (ME-3)
Wide excisiong
Wide excision
(category 1)
g
Wide excision
(category 1)
with sentinel
node biopsy
g
h
WORKUP PRIMARY TREATMENT
�
�
�
H&P
Stage IB, IIA:
No further workup
required
Stage IIB-IIC:
Chest x-ray
(optional); routine
imaging not
recommended
Further imaging
as clinically
indicated
�
�
�
(CT scan, PET,
MRI)
See Stage III Workup and
Primary Treatment (ME-3)
Sentinel
node
negative
Sentinel
node
positive
ADJUVANT TREATMENT
Discuss and
offer sentinel
node
biopsye,f
See
Follow-Up
(ME-5)
Stage 0 in situ
or
Stage IA 1 mm thick,
Clark level II or III) with
no adverse features
��
d
If Stage IB, IIA:
Clinical trial
or
Observation
If Stage IIB, IIC:
Clinical trial
or
Interferon alfa
(category 2B)
Observation
or
i
CLINICAL STAGE
Stage IB, Stage II
( 1 mm thick with
ulceration or Clark
level IV, V or
> 1 mm thick, any
characteristic), N0
�
H&P
Imaging only
(CT scan, PET, MRI)
to
evaluate specific
signs or symptoms
Consider
sentinel node
biopsye
See
Follow-Up
(ME-5)
Wide excision
(category 1)
g
Stage IA ( 1 mm
thick, Clark level II
or III) with adverse
features
�
d
Version 1.2010, 10/19/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
Practice Guidelines
in Oncology – v.1.2010 Melanoma
Guidelines Index
Melanoma Table of Contents
Staging, Discussion, ReferencesNCCN
®
Complete surgical excision to clear
margins, if feasible
(category 2B)
Consider sentinel node biopsy for
resectable in-transit disease
preferred,
(category 2B)
or
h
Hyperthermic perfusion/infusion
with melphalan (category 2B)
or
Clinical trial
or
Intralesional injection
(BCG, IFN) (category 2B)
or
Local ablation therapy (category 2B)
or
RT (category 2B)
or
Systemic therapy
or
Topical imiquimod (category 2B)
l
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Stage III
(Clinically positive
node(s))
Clinical trial
or
or
Observation
( )
Interferon alfa
category 2B
i
Clinical trial
or
and/or
Consider RT to nodal basin
if Stage IIIC (category 2B)
with multiple nodes involved
or extranodal extension
or
Observation
( )Interferon alfa category 2Bi
Stage III
in-transit
If free of
disease
(See
Follow-up
ME-5)
g
i
k
l
hSentinel lymph nodes should be evaluated with multiple
sectioning and immunohistochemistry.
IFN has been associated with improved DFS, however, its impact
on overall survival is unclear.
Clinical trials assessing alternatives to complete lymph node
dissection, such as careful observation.
j
See Principles of Surgical Margins for Wide Excision of
Primary Melanoma (ME-B)
See Systemic Therapy Options for Advanced or Metastatic Melanoma (ME-D)
.
.
.
See Principles of Complete Lymph Node Dissection (ME-C)
�
�
�
FNA preferred, if feasible, or
lymph node biopsy
Consider baseline imaging
for staging and to evaluate
specific signs or symptoms
(category 2B)
(Chest x-ray, CT ± PET, MRI)
Pelvic CT if inguinofemoral
nodes positive
�
�
FNA preferred, if feasible,
or biopsy
Consider baseline imaging
for staging and to evaluate
specific signs or symptoms
(category 2B)
(Chest x-ray, CT ± PET, MRI)
ME-3
CLINICAL/
PATHOLOGIC STAGE
WORKUP PRIMARY TREATMENT ADJUVANT TREATMENT
Stage III
(Sentinel node
positive)
Consider baseline imaging
for staging and to evaluate
specific signs or symptoms
(category 2B)
(Chest x-ray, CT ± PET, MRI)
Lymph node dissection
or
Clinical trial
j
k
Clinical trial
or
Observation
or
Interferon alfa ( )i category 2B
Wide excision of primary tumor
(category 1)
+ complete lymph node dissection
g
j
Version 1.2010, 10/19/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
Practice Guidelines
in Oncology – v.1.2010 Melanoma
Guidelines Index
Melanoma Table of Contents
Staging, Discussion, ReferencesNCCN
®
Stage IV
Metastatic
See Treatment for Limited (Resectable)
or Disseminated Disease (Unresectable)
ME-8)
�
�
�
FNA preferred, if feasible or biopsy
LDH
Encourage chest/abdominal/pelvic CT, MRI
brain, and/or PET as clinically indicated
(category 2B)
CLINICAL/
PATHOLOGIC
STAGE
WORKUP
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
ME-4
Version 1.2010, 10/19/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
Practice Guidelines
in Oncology – v.1.2010 Melanoma
Guidelines Index
Melanoma Table of Contents
Staging, Discussion, ReferencesNCCN
®
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
RECURRENCEo
Stage IIB - IV NED
FOLLOW-UPm
Distant
recurrencep
Persistent
disease or true
local scar
recurrencen,o,p
Local, satellitosis,
and/or in-transit
recurrenceo,p
Nodal
recurrencep
(See ME-6)
(See ME-6)
(See ME-7)
(See ME-8)
nPersistent disease or true local scar recurrence is defined by presence of in situ
and/or radial growth phase.
o
p
Local recurrence without in situ or radial growth phase, with deep dermal or
subcutaneous fat recurrence within the melanoma scar or satellite metastasis
adjacent to the melanoma scar.
Initial clinical recurrence should be confirmed pathologically whenever possible.
Stage 0
in situ
�
�
H&P (with emphasis on nodes and skin)
every 3-12 mo for 5 y, then
annually as clinically indicated
Routine lab testing/radiologic imaging to screen for
asymptomatic recurrent/metastatic disease is not
recommended
�
�
�
�
�
H&P (with emphasis on nodes and skin)
every 3-6 mo for 2 y, then
every 3-12 mo for 3 y, then
annually as clinically indicated
Consider chest x-ray, CT and/or PET-CT scans to
screen for recurrent/metastatic disease (category 2B)
Consider brain MRI annually (category 2B)
Routine lab testing/radiologic imaging to screen for
asymptomatic recurrent/metastatic disease is not
recommended after 5 y
�
�
�
�
CLINICAL/
PATHOLOGIC
STAGE
Stage IA - IIA NED
ME-5
mCommon Follow-up Recommendations For All Patients:
Follow-up schedule influenced by risk of recurrence, prior primary
melanoma, and family history of melanoma, and includes other
factors, such as atypical moles/dysplastic nevi, and patient anxiety.
�
�
�
At least annual skin exam for life
Educate patient in monthly self skin exam
(and monthly self lymph node exam for Stage IA - IV NED)
Lab tests and/or imaging are indicated to investigate for specific
signs and symptoms
See Common Follow-up Recommendations
For All Patients. (Below)
Version 1.2010, 10/19/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
Practice Guidelines
in Oncology – v.1.2010 Melanoma
Guidelines Index
Melanoma Table of Contents
Staging, Discussion, ReferencesNCCN
®
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
TREATMENT OF RECURRENCEp
Local, satellitosis,
and/or
in-transit
recurrenceo,p
Re-excise tumor site to appropriate
margins. (See ME-B)
Consider lymphatic mapping/SLNB
according to thickness
Clinical trial,
or
Observation
or
( )
Interferon alfa
category 2B
i
�
�
Biopsy to confirm
Workup appropriate
to stage
a,p
( )See ME-2
�
�
FNA (preferred) or biopsy
Consider baseline imaging
for staging and to evaluate
specific signs or symptoms
(category 2B)
(Chest x-ray, CT ± PET, MRI)
p
a
i
l
n
o
p
IFN has been associated with improved DFS, however, its impact on overall survival is unclear.
Persistent disease or true local scar recurrence is defined by presence of in situ and/or radial growth phase.
Local recurrence without in situ or radial growth phase, with deep dermal or subcutaneous fat recurrence within the melanoma
scar or satellite metastasis adjacent to the melanoma scar.
Initial clinical recurrence should be confirmed pathologically by biopsy whenever possible.
See Principles of Biopsy (ME-A).
See Systemic Therapy Options for Advanced or Metastatic Melanoma (ME-D).
ME-6
WORKUP
Excise lesion(s) to clear margin, if
feasible; consider sentinel node biopsy
preferred,
or
Hyperthermic perfusion/infusion with melphalan
(category 2B)
or
Clinical trial
or
Intralesional injection (BCG, IFN) (category 2B)
or
Local ablation therapy (category 2B)
or
RT (category 2B)
or
Systemic therapy
or
Topical imiquimod (category 2B)
l
Recommendations
should be based
on stage o