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London Cancer
Guidelines for Cutaneous
Malignant Melanoma
Management
August 2013
Review:
Version:
Lead author:
August 2014
1.0
David Chao
Contents
1.
Introduction .............................................................................................................. 3
2.
Screening and surveillance ......................................................................................... 3
3.
Management in primary care ..................................................................................... 3
4.
Management in secondary care ................................................................................. 4
4.1. Management of adult patients ................................................................................... 4
4.2. Management of TYA patients ..................................................................................... 4
5.
Staging ...................................................................................................................... 6
6.
Surgical Management ................................................................................................ 9
6.1. Primary excision .......................................................................................................... 9
6.2. Sentinel lymph node biopsy ........................................................................................ 9
6.3. Lymphadenopathy ...................................................................................................... 9
6.4. Lymph Node Dissection (LND)................................................................................... 10
7.
Histopathology and molecular profiling ................................................................... 11
7.1. Minimum dataset ...................................................................................................... 11
7.2. Molecular Profiling .................................................................................................... 11
8.
Adjuvant Treatments ............................................................................................... 11
9.
Follow up management ........................................................................................... 13
9.1. Definition of patients at high risk of relapse ............................................................. 13
9.2. Follow up for In Situ disease ..................................................................................... 13
9.3. Follow up for Stages I & IIA ....................................................................................... 13
9.4. Follow up for Stages IIB, IIC, IIIA, IIIB & IIIC ............................................................... 14
9.5. Follow up for occult primary ..................................................................................... 14
9.6. PET scans ................................................................................................................... 14
9.7. Patient preference .................................................................................................... 14
10.
Imaging ................................................................................................................ 15
11.
Management of advanced or metastatic disease .................................................. 15
2
1. Introduction
The London Cancer guidelines for the management of malignant melanoma are the result of
the merger of the previous guidelines of the Skin Cancer Tumour Boards for North Central
and North East London. The guidelines have been updated to incorporate the
 2010 British Association of Dermatology guidelines
(http://www.bad.org.uk/Portals/_Bad/Guidelines/Clinical%20Guidelines/Melanoma
%20guidelines%202010.pdf), and the
 2010 NICE IOG for Skin Cancers (http://guidance.nice.org.uk/CSGSTIM).
2. Screening and surveillance
The system will adopt the 2010 BAD guidelines for both screening and surveillance.
3. Management in primary care
Patients may present to their general practitioner with a changing pigmented lesion. The
weighted 7-point checklist may be helpful in assessing pigmented lesions.
Major features
2 points
 Change in size
 Irregular shape
 Irregular colour
Minor features
1 point
 Largest diameter 7mm or more
 Inflammation
 Oozing
 Change in sensation
Suspicion is greater for lesions scoring 3 points. However, any one feature is adequate to
prompt an urgent referral if the concerns about cancer are strong. Biopsy or attempted
excision should not be carried out in primary care. Any melanoma excision in primary care is
a breach of the NICE IOG but the clinical governance arrangements are in transition
currently. In the past breaches were collated by the network who then reported these to
the PCTs for further action. Since the PCTs have been dissolved it is unclear who will accept
responsibility for such breaches and the Pathway Board is working with the Clinical
Commissioning Groups on an appropriate alert system.
At this stage, the GP can do one of the following:
 Reassure the patient and discharge
 Reassure the patient but point out signs to look for which may represent malignant
change and request the patient to return
 Reassure the patient but take a photograph. Once again advise if change is noted, to
return
3


Review the patient within 2 weeks in the event that the lesion is
infected/traumatised. The lesion must be covered by a dressing for the 2 week
period
Refer to local Plastic Surgery/Dermatology Unit via the urgent suspected cancer
route/two week rule (TWR). London Cancer has a Suspected Skin Cancer fax form
with all dermatology units listed.
4. Management in secondary care
4.1. Management of adult patients
Patients are referred in via the TWR and can be seen by Dermatologists or Plastic Surgeons.
In the clinic the following model is used,
 A full history is taken
 The patient is asked to undress and examined thoroughly in bright light with a
magnifying glass or dermatascope.
 The lesion may be photographed
 The lesion is documented and if deemed suspicious excised
 Where possible the clinic will offer immediate biopsy service. If not possible, the
biopsy will be preformed as soon as possible
 Biopsy is an excision biopsy (excising the lesion with a 2mm margin). If excision is not
possible, then incision biopsy is acceptable
 When biopsy is undertaken, care is given to orientation of scar with view to
future excisions
 The pathology request form will give the following details - name, age, gender, DOB,
hospital number, site, brief history, differential diagnosis and orientation stitch
if necessary.
 Patients are requested to return in 2-3 weeks for the results. Patients should be
encouraged to request their results if they do not hear within 4 weeks.
 If the pathology records melanoma, then patients are requested to return to the
appropriate clinic
If the patient may be managed by the LSMDT (in situ or stage IA melanoma) then definitive
treatment may be carried out at that hospital and surgical margins are given in section 5.1.
However, for patients under 18y or 18-24y additional guidance is available (see section 3.2).
For patients with stage IB melanoma or above the option of Sentinel Lymph Node Biopsy
should be considered. This staging procedure is offered by the two main SSMDT at the
Royal Free Hospital and the Royal London Hospital. It is stressed that co-morbidities and
informed patient choice are vital determinants for this procedure.
4.2. Management of TYA patients
UCLH is the designated Principal Treatment Centre for The North Thames Teenage and
Young Adult (TYA) Network, which includes organisations affiliated with London Cancer. The
4
Royal Free Hospital (RFH) has been awarded TYA Designated Hospital status for patients
with skin cancer acknowledging the specific expertise for managing skin cancer at this Trust.
There are 3 distinct groups of young patients with skin cancer to be considered under this
guidance.
1) All patients 18y and under: These patients must be referred to Adolescent
Dermatology at UCLH and discussed at the Skin Cancer SSMDT at the Royal Free
Hospital. If it is deemed appropriate then patients should undergo their further
surgical treatment at the RFH. Follow up should take place back at UCLH.
2) Patients aged 19 to 24y with melanoma under breslow thickness 1mm and no other
poor prognostic markers, such as ulceration or mitotic activity: There is a conflict
here between the TYA and Skin Cancer IOG. Under TYA IOG such patients should be
offered treatment at the Principal Treatment Centre (in this case UCLH) or the
designated TYA centre (in this case RFH) only, but it must be recognised that this is
generic guidance. Under Skin Cancer IOG such patients are dealt with locally by the
LSMDT and do not require referral onwards to the SSMDT. Discussion at the Skin
Cancer Pathway Board has highlighted that for this good prognosis group of patients
mandatory referral to the SSMDT would only lengthen treatment and travelling
times, potentially compromising outcome. Therefore the pragmatic compromise will
be that these patients will be offered the choice between further surgery at the site
of the LSMDT or to be referred to the SSMDT. Those patients who stay with the
LSMDT for further treatment will be provided with a TYA information pack detailing
appropriate support services for them and the LSMDT will be required to complete a
form on each patient which will be forwarded directly to the TYA MDT. Those
requiring further support will be contacted by the designated TYA CNS.
3) Patients aged 19 to 24y with melanoma of breslow thickness 1mm or greater, with or
without other poor prognostic markers: This patient group is currently obliged to be
referred to the SSMDT for further treatment under Skin Cancer IOG. These patients
will be provided with an information pack detailing appropriate support services for
them and the Skin Cancer CNS will dial into the TYA MDT on Wednesday afternoons
on alternate weeks to discuss these patients. Those requiring further support will be
contacted by the designated TYA CNS.
These guidelines have been ratified by the TYA Pathway Board.
5
5. Staging
Staging for melanoma is based on the AJCC and the current working version is the 7 th edition 2010.
a
Table 1. Primary Tumor (T)
Enlarge
TX
Primary tumor cannot be assessed (e.g., curettaged or severely regressed melanoma).
T0
No evidence of primary tumor.
Tis
Melanoma in situ.
T1
Melanomas ≤1.0 mm in thickness.
T2
Melanomas 1.01–2.0 mm.
T3
Melanomas 2.01–4.0 mm.
T4
Melanomas >4.0 mm.
2
Note: a and b subcategories of T are assigned based on ulceration and number of mitoses per mm as shown below:
T
Thickness (mm)
Ulceration Status/Mitoses
classification
2
T1
≤1.0
a: w/o ulceration and mitosis <1/mm .
2
b: with ulceration or mitoses ≥1/mm .
T2
1.01–2.0
a: w/o ulceration.
b: with ulceration.
T3
2.01–4.0
a: w/o ulceration.
b: with ulceration.
T4
>4.0
a: w/o ulceration.
b: with ulceration.
a
Reprinted with permission from AJCC: Melanoma of the skin. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer,
2010, pp 325-44.
Table 2. Regional Lymph Nodes (N)
a
Enlarge
NX
Patients in whom the regional nodes cannot be assessed (e.g., previously removed for another reason).
N0
No regional metastases detected.
N1–3
Regional metastases based upon the number of metastatic nodes and presence or absence of intralymphatic metastases (in transit or satellite metastases).
Note: N1–3 and a–c subcategories assigned as shown below:
N
No. of Metastatic Nodes
Nodal Metastatic Mass
Classification
b
N1
1
a: micrometastasis.
c
b: macrometastasis.
b
N2
2–3
a: micrometastasis.
c
b: macrometastasis.
c: in transit met(s)/satellites(s) without metastatic nodes.
N3
≥4 metastatic nodes, or matted nodes, or in transit
met(s)/satellite(s) with metastatic node(s).
No = number.
a
Reprinted with permission from AJCC: Melanoma of the skin. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer,
2010, pp 325-44.
b
Micrometastases are diagnosed after sentinel lymph node biopsy and completion lymphadenectomy (if performed).
c
Macrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or when nodal metastasis exhibits gross extracapsular
extension.
Table 3. Distant Metastasis (M)
a
Enlarge
M0
No detectable evidence of distant metastases.
M1a
Metastases to skin, subcutaneous, or distant lymph nodes.
M1b
Metastases to lung.
M1c
Metastases to all other visceral sites or distant metastases to any site combined with an elevated serum LDH.
Note: Serum LDH is incorporated into the M category as shown below:
M
Site
Serum LDH
Classification
M1a
Distant skin, subcutaneous, or nodal mets.
Normal.
M1b
Lung metastases.
Normal.
M1c
All other visceral metastases.
Normal.
Any distant metastasis.
Elevated.
LDH = lactate dehydrogenase.
a
Reprinted with permission from AJCC: Melanoma of the skin. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer,
2010, pp 325-44.
7
Table 4. Anatomic Stage/Prognostic Groups
a
Enlarge
Stage
0
IA
IB
IIA
IIB
IIC
III
T
Tis
T1a
T1b
T2a
T2b
T3a
T3b
T4a
T4b
Any T
N
b
Clinical Staging
N0
N0
N0
N0
N0
N0
N0
N0
N0
≥N1
M
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
Stage
0
IA
IB
IIA
IIB
IIC
IIIA
IIIB
IIIC
IV
Any T
Any N
M1
IV
a
T
Tis
T1a
T1b
T2a
T2b
T3a
T3b
T4a
T4b
T1–4a
T1–4a
T1–4b
T1–4b
T1–4a
T1–4a
T1–4a
T1–4b
T1–4b
T1–4b
Any T
Any T
N
c
Pathologic Staging
N0
N0
N0
N0
N0
N0
N0
N0
N0
N1a
N2a
N1a
N2a
N1b
N2b
N2c
N1b
N2b
N2c
N3
Any N
M
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M0
M1
Reprinted with permission from AJCC: Melanoma of the skin. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer,
2010, pp 325-44.
b
Clinical staging includes microstaging of the primary melanoma and clinical and/or radiologic evaluation for metastases. By convention, it should be used after complete
excision of the primary melanoma with clinical assessment for regional and distant metastases.
c
Pathologic staging includes microstaging of the primary melanoma and pathologic information about the regional lymph nodes after partial or complete lymphadenectomy.
Pathologic Stage 0 or Stage IA patients are the exception; they do not require pathologic evaluation of their lymph nodes.
8
6. Surgical Management
6.1. Primary excision
In situ
< 1.0mm
< 1.0mm + ulceration/mitoses
1.0 – 2.0mm
2.1-4.0mm
> 4mm
1
2
complete excision, >5mm margin
1cm margin
1cm margin 1
1cm minimum, up to 2cm if possible 1
≥ 2cm margin 1,2
> 3cm margin, where possible
refer for wide local excision and SLNB
results of the MSG/BAPS study of 1cm vs 3cm margins have been discussed by the Board
6.2. Sentinel lymph node biopsy

All tumours of ≥ 1.0mm should be referred or < 1.0mm with ulceration or mitotic
activity should be referred to the appropriate surgeons at the Royal Free Hospital or
Royal London Hospital.

SLNB cannot be carried once a wide local excision has already been completed and
therefore all dermatologists/surgeons who perform primary excisions must be aware
of the guidelines.

SLNB must only be carried out by experienced surgeons using a dual technique
(lymphoscintigraphy and blue dye), who are core members of the SSMDT and meet
NICE IOG criteria. There must be adequate dermatopathology support for this
service.

All patients with positive SLNB (stage III) must have CT head/neck if
appropriate/thorax/abdomen/pelvis or PET prior to completion lymphadenectomy.

SLNB gives valuable prognostic information and identifies patients who are at higher
risk of relapse to be considered for adjuvant treatment or clinical trial. It is accepted
that currently there is no evidence for survival benefit. It is the recommendation of
the Pathway Board that SLNB continues to be the standard of care for these reasons,
and that patients should be offered the option of having SLNB with proper
counselling. The 2010 BAD UK guidelines reflect current practice across London
Cancer.
6.3. Lymphadenopathy

Patients who present with suspicious lymphadenopathy should be investigated with
fine needle aspiration cytology (FNAC) or core biopsy, which is preferred, with or
without imaging guidance. If the FNAC is negative and clinical suspicion is high then
open biopsy should be considered but referral to the SSMDT is strongly
recommended at this point. It is vital that if open biopsy is performed then the
9
incision must be such as to allow subsequent complete block dissection of the
regional nodes without compromise.

All patients should have blood tests and CT head/neck if appropriate/
thorax/abdomen/pelvis or PET prior to lymphadenectomy.
6.4. Lymph Node Dissection (LND)
Radical lymph node dissections (LND) should only be performed by a designated core
member of the SSMDT at the Royal Free Hospital or Royal London Hospital. Pre-operative
staging investigations should be carried out as listed previously. The decision as to whether
or not surgery should proceed prior to scanning should be made after SSMDT discussion
with an informed patient. The block dissection specimen should be marked and orientated
for the pathologist.
Axilla
It is recommended that axillary LND should include all nodes in levels I – III, and this may
require either resection or division of pectoralis minor.
Inguinal
The management of inguinal lymph node metastases is controversial. A superficial inguinal
lymph node dissection should be considered in the presence of:
 A single clinically involved node in the femoral triangle
 Medical co-morbidities which would increase the risk associated with more
extensive surgery
 A positive superficial inguinal sentinel node
A pelvic lymph node dissection ileo-obturator should be considered:
 If there is >1 clinically palpable subinguinal node,
 If there is U/S and / or CT evidence of pelvic node involvement
 If pathological review of the superficial specimen shows multiple microscopically/
macroscopically involved nodes
Cervical
Cervical nodal disease should be reviewed and treated by either surgeons in the SSMDT
with expertise in head and neck skin cancer including melanoma, or by a Head and Neck
MDT with a special interest in melanoma. Some LSMDT have core members who are Head
and Neck surgeons and dissections may take place locally if in the best interests of the
patient and only after discussion with the SSMDT.
A comprehensive, and not a selective neck dissection should be performed. The term
comprehensive allows either:
 A radical dissection of levels 1-5
 Modified radical – the above, sparing spinal accessory nerve, internal jugular vein
and sternocleidomastoid muscle.
10

Extended radical – Radical dissection including parotid and/or posterior occipital
chain.
The risk of recurrence is high (up to 28%) despite comprehensive surgery and so surgery
may be combined with adjuvant radiotherapy. This is the only nodal group shown to have
improved local recurrence rate with post-operative radiotherapy [ Guadagno BA et al,
Lancet Oncol 2009; 10: 409–16]. If extra-capsular spread is noted, then the management
should be discussed at the SSMDT.
7. Histopathology and molecular profiling
7.1. Minimum dataset
All pathology departments should be reporting the minimum dataset as stipulated by the
Royal College of Pathologists. Staging should be according to the 7th edition AJCC staging
2010; the full text can be round on
http://jco.ascopubs.org/content/27/36/6199.full.pdf+html and there is an excellent
summary of the differences between the 6 & 7th versions on
http://www.cancerstaging.org/staging/PDFs/gershenwald-melanoma.pdf
7.2. Molecular Profiling
This will be of increasing importance in determining the treatment options for all cancers.
For melanoma the only target mutation with a licensed drug is in the BRaf oncogene as of
May 2013 but there is no doubt that this list will grow. It may be helpful to know other
target mutations for clinical trial purposes as well. For all melanomas stage IIB and above it
is proposed to test for the BRaf mutation at the time of initial diagnosis where there is
sufficient tissue. This will guide subsequent therapy, be it for clinical trials or standard
therapy. Currently all sites in London Cancer use the Roche-funded central laboratories for
this purpose.
8. Adjuvant Treatments
In the UK there are no formally recognised adjuvant therapies for any stage of malignant
melanoma. Clinical trials remain the most important consideration and all LSMDT should be
reviewing melanoma patients for their suitability for adjuvant clinical trials and referring
them on to the SSMDT in good time.
Radiotherapy remains a contentious adjuvant therapy. There is evidence for some benefit
in reducing local relapse following lymphadenectomy for Head and Neck melanomas but
there is as yet no evidence for an overall survival benefit [Guadagno BA et al, Lancet Oncol
2009; 10: 409–16]. Similarly following axillary or groin dissection adjuvant radiotherapy
may improve progression-free survival but not overall survival and there may be reduction
in quality of life due to lymphoedema [Henderson MA et al, J Clin Oncol 2013; 31 suppl;
abstr 9001]. Such patients should be discussed in the SSMDT on a case by case basis and
11
referred for radiotherapy as appropriate taking into account comorbidities, toxicity from the
radiotherapy and patient preference.
12
9. Follow up management
The purpose of follow up is to try to catch any relapse as early as possible. Arguably without
effective therapies for advanced melanoma close follow up would have had little impact on
survival. However, since 2011 with the introduction of the BRaf mutation inhibitors and
immunotherapy as effective new treatments for advanced melanoma the therapeutic
landscape has changed. Finding patients with minimal volume disease relapse, particularly
in the brain, and avoiding high dose steroid usage, makes clinical sense especially for
immunotherapeutic strategies which have a slower onset of action. Therefore there is now
a case for closer surveillance. The following guidelines have been based on a consensus
document signed by UK melanoma oncologists and due to be published on the Melanoma
Focus website in 2013.
9.1. Definition of patients at high risk of relapse
There is no precise definition of high risk but most adjuvant clinical trials have taken stage
IIC, IIIB & IIIC disease where the 5y survival is <60%. The Pathway Board feels that this may
be too restrictive and prefers to broaden the net. Since the highest risk period is within the
first 3y this should be the focus of the most intense surveillance.
9.2. Follow up for In Situ disease
Clinical Review
Patients may be discharged and GP alerted or Yearly follow up for 5y before discharge
Blood Tests
No blood tests are recommended
Imaging
No routine imaging is recommended
9.3. Follow up for Stages I & IIA
Clinical Review
Years 1-3, 3-4 monthly review
Years 4-5, 6 monthly review
Years 6-10, annual review or discharge depending upon patient preference with GP alerted
Blood Tests
No blood tests are recommended
Imaging
No routine surveillance CT scans are recommended
13
9.4. Follow up for Stages IIB, IIC, IIIA, IIIB & IIIC
Clinical Review
Years 1-3, 3-4 monthly review
Years 4-5, 4-6 monthly review
Years 6-10, annual review or discharge depending upon patient preference with GP alerted
Blood Tests
No blood tests are recommended but routine kidney function tests may be needed prior to
CT scanning
Imaging
CT Brain/Chest/Abdomen/Pelvis at baseline
CT Brain thereafter only if symptomatic or upon systemic relapse
CT Chest/Abdomen/Pelvis every 6 months for first 3 years only
9.5. Follow up for occult primary
This group of patients should be followed up as per Stages IIB, IIC, IIIA-B
9.6. PET scans
While CT imaging is considered the standard of care PET scans may be used instead
depending upon availability and physician preference. PET scans may also be used if there is
concern on CT imaging where the PET scan would influence clinical management and it may
also be considered for occult primaries.
9.7. Patient preference
CT scans remain the gold standard investigation, particularly for some areas of the body
such as the lungs, but entail ionizing radiation. While the additional risk to patients from
exposure to CT scans remains controversial this is at the very least a theoretical concern.
Patients should be counselled appropriately about the intention of CT scan follow up and
ultimately it is very much patient preference whether to have follow up scans.
14
10. Imaging
Imaging modality
Staging
Surveillance
Indications and notes
CT, MRI
Required
for surgical planning of locally
invasive lesion and/or clinical suspicion of
metastases
PET
May replace CT or MRI depending upon physician
preference
Ultrasonography +/FNA
For investigation of local lymph node basin or other
masses if clinically suspicious
Bone scans
For suspected bony metastases
CT,MRI, PET
Detection of asymptomatic disease according to
risk profile.
11. Management of advanced or metastatic disease
The treatment algorithms for advanced melanoma are evolving at a tremendous pace. The
algorithms presented below are for licensed and/or NICE approved therapies but in most
cases clinical trials afford the best prospects for patients by offering them the possibility of
cutting edge therapies.
All such patients must be discussed with the appropriate SSMDT and both SSMDTs
operating in London Cancer must be fully aware of the clinical trial portfolio available within
London Cancer which should include Phase I trials. Where there is a gap in the portfolio the
Lead for Research will see if there are relevant trials available at other institutions in and
around London. The clinical trial portfolio will be updated regularly and will be available on
the London Cancer website.
Stage
Off study
Skin metastases
Excision
Isolated limb perfusion 1
Laser ablation
Radiotherapy
ECT 2
Visceral disease
Metastectomy for solitary disease if stable
Single agent Dacarbazine
15
Single agent alpha-interferon
BRaf mutation inhibitor 3
Ipilimumab 4
CNS disease
Metastectomy for solitary disease
Stereotactic Radiotherapy
Whole brain Radiotherapy
Bone metastases
Pamidronate
Radiotherapy
1
Patients need to be referred to the Royal Marsden Hospital for this procedure
2
Electro-Chemo Therapy is NICE approved (IPG446) and available at the Royal London
Hospital and the Royal Free Hospital
3
Vemurafenib is the only licensed and NICE approved BRaf mutation inhibitor currently
(TA269)
4
Ipilimumab is the only licensed and NICE approved immunotherapy currently and is for
second line therapy and beyond (TA268)
16