Merseyside and Cheshire Network
Skin Clinical Network Group
Network Guidelines for the Management of Patients with
Malignant Melanoma
Melanoma Guidelines – Final Oct 09 Page 1 of 29
Contents
Page
Foreword
4
Introduction
4
Current configuration of services in Merseyside and Cheshire
Multi-disciplinary team (MDT)
5
Diagnosis and management of malignant melanoma
 Clinical diagnosis
 Who to refer to secondary care
 Who to refer to Cancer Centre Plastic Surgery Team
 Who to refer for oncology opinion
6-7
Staging of patients
 Who should be staged
 Staging patients with stage IIb-III disease
8
Surgical management of malignant melanoma
 Surgery for malignant melanoma
 Management of primary lesion
 Subungal melanoma
 Isolated limb perfusion
 Management of lymph node disease
 Management of satellites and in-transit metastasis
 Surgery for metastatic disease
9-11
Histopathology
12
Follow-up of patients
 Low risk patients
 Intermediate/high risk patients
 Patients with advanced disease
 Shared care follow-up
13-15
Systemic therapy
16
Radiotherapy
 Adjuvant
 Palliative
17
Palliative Care
18-21
Melanoma Guidelines – Final Oct 09 Page 2 of 29
Contents
(Cont.)
Page
Rare sub-types
22
Mucosal melanoma
22
Research
22
References
23-26
Contributors
27
Appendix 1
Staging systems
Appendix 2
Algorithm of clinical trials
Appendix 3
Local contact information
Melanoma Guidelines – Final Oct 09 Page 3 of 29
28
Foreword
The following guidelines are based on the recently published Melanoma Study Group,
British Association of Dermatologists and Manchester and North Cheshire Melanoma
guidelines, expanded and adapted to reflect local practice and new information available
since their publication. They have been discussed and agreed at a Network meeting held
on (see front page). They are guidelines for patient management and are seen to represent
a minimum standard of care. As with all guidelines, they are subject to interpretation. At
present, they focus primarily on cancer centre referral and management. However, it
would be hoped that these can be expanded to include instruction on how to access the
service at a local level.
Introduction
The incidence of melanoma continues to rise on a world-wide basis. Recent data from
the UK show that the incidence and mortality continues to rise in males whilst in females
the incidence and mortality rates were static or declining over the last 5 years.
The Calman-Hine model for the provision of cancer services is based on a hub and spoke
model, with high impact-low tech treatments being delivered close to the patient’s home,
and complex treatments or management of rare tumours being managed in cancer centres.
The NHS Cancer Plan set down guidance for management of cancer, with a specific
focus on maximum waiting times for diagnosis and treatment.
Most cancer centres will also function as a cancer unit for their local population. Cancer
centres are not defined by physical criteria such as buildings or geographical location;
rather they are usually a “virtual” centre which delivers comprehensive cancer services to
the network. However, a certain amount of co-localisation is advantageous to facilitate a
joined up service.
The management of malignant melanoma is multi-disciplinary, involving dermatologists,
plastic surgeons, oncologists, pathologists, radiologists, palliative care and specialist
nurses. National accreditation standards for cancer units and cancer centres are
imminent. These will set down the professional, administrative and procedural
frameworks that must be in place for a MDT, cancer unit or cancer centre to be
accredited. Central to this are agreed network guidelines for the management of patients
with specific tumour types.
The recently revised AJCC staging system for malignant melanoma is a comprehensive
review of prognostic factors in malignant melanoma and a pragmatic staging system for
these patients. Based on this system, melanoma should no longer be considered
“unpredictable” and patient management can be decided in a risk-adjusted manner.
Melanoma Guidelines – Final Oct 09 Page 4 of 29
Configuration of melanoma services in Merseyside and Cheshire
Cancer Network
Dermatology services are provided on site at each of 6 designated cancer units.
Plastic Surgery services are centred on 2 sites: Whiston Hospital and Countess of Chester
Hospital. Specialist services (new and follow-up clinics) are outreached to each cancer
unit.
Oncology services are provided solely at the Clatterbridge Centre for Oncology. Skin
Oncology services are outreached with the future plans of a single regional SSMDT
linking Arrowe Park Hospital, Clatterbridge Centre for Oncology and Whiston Hospital.
Palliative care services are provided at each cancer unit, Clatterbridge Centre for
Oncology and a linked network of hospice services.
The majority of histopathology services for melanoma are provided at the cancer unit
level. Specialist dermatopathology services are provided at The Royal Liverpool
Hospital and Whiston Hospital.
There is free movement of patients between GPs, units and centres. Whilst patterns of
movement can be predicted with a certain degree of reliability, a large number of factors
influence this including the mobility of the population, historic patterns of referral, and
real and/or perceived differences in resources across the network etc.
The cancer centre is a virtual centre comprising specialist dermatology services, plastic
surgery, oncology, specialist histopathology and palliative care.
The cancer unit comprises non-specialist dermatology, non-specialist surgery and nonspecialist histopathology.
The cancer centre provides a cancer unit service for its local population.
Multi-disciplinary team (MDT)
MDT working is a central component of Cancer Accreditation. Configuration of the
MDT is evolving with a model of local MDT’s linked to a single SSMDT.
Melanoma Guidelines – Final Oct 09 Page 5 of 29
Diagnosis and management of malignant melanoma
Clinical diagnosis of malignant melanoma
The seven-point checklist emphasizing a history of change in size, shape, colour of a preexisting pigmented lesion is recommended for use in both patient and primary care
education.
Major features are
 Change in size
 Irregular shape
 Irregular colour
Minor features are
 Largest diameter 7mm or more
 Inflammation
 Oozing
 Change in sensation
All lesions with one major or three minor features are suspicious of malignant melanoma
and should be referred to a clinician that sees a large number of patients with pigmented
lesions. In the majority of cases, this will be a dermatologist.
Who to refer for surgery
The following patients should be referred urgently to a dermatologist or plastic surgeon
with experience in malignant melanoma
 Patients with a lesion suspicious of malignant melanoma (see above)
 All patients that had a lesion removed by their family doctor that is
subsequently reported as melanoma should be referred to a dermatologist
experienced in performing wide local excisions or a plastic surgeon.
Patients to refer for cancer centre plastic surgery opinion




Patients requiring a further wide local excision (where there is likely to be
technical difficulty achieving a good repair)
Patients with local recurrence
Patients requiring a lymph node dissection (where local surgical expertise
does not exist)
Patients with head and neck melanoma (in conjunction with ENT surgeons)
Melanoma Guidelines – Final Oct 09 Page 6 of 29
Patients to refer for oncology opinion
This will depend on a number of factors including trials available, patients wishes etc. It
will change on a year-by-year basis, as new treatments evolve and clinical trials open and
close. In general, the following patients should be referred:







Stage IIa-c if trial available
Stage III disease
Stage IV disease
Family of 3 or more close relatives with malignant melanoma
One or more previous melanomas
Any patient that wishes to see an oncologist and discuss management options
Any patient that a colleague feels may benefit from an oncology opinion
Melanoma Guidelines – Final Oct 09 Page 7 of 29
Staging
There is no consensus on which patients should be staged and how this should be done
(see section on follow-up). Up-staging from stage II to stage III will be relatively
common if sentinel node biopsy is used, but the clinical implications of this stage
migration are poorly understood. The incidence of upstaging to stage IV is low; several
publications have identified a high false positive rate with routine CT staging.
We have attempted to adopt a pragmatic, risk adjusted strategy for staging and this is set
out below.
Who should be staged?
The following patients should have staging investigations
 Stage IIb primary > 2mm with ulceration
 Stage IIc primary > 4mm
 Stage III disease
 Stage IV disease
Staging investigations for patients with stage IIb-IIIa disease
The following staging investigations should be carried out
 Full blood count
 Biochemistry including LFTs and LDH.
 U/S + CXR
 Sentinel Lymph node mapping (Stage II disease  2mm Breslow)
 Other investigations as appropriate on an individual basis.
Staging investigations for patients with stage IIIb-IV disease
The following staging investigations should be carried out




Full blood count
Biochemistry including LFTs and LDH.
CT chest/abdomen (+pelvis for lower limb primaries)
Other investigations as appropriate on an individual basis.
PET scanning in Melanoma
The place of PET scanning in melanoma remains in discussion. Presently, PET scanning
may have an important role in select cases where metastatectomy is considered or where
clarification of CT staging for suspected stage IV patients.
Melanoma Guidelines – Final Oct 09 Page 8 of 29
Surgical management of cutaneous melanoma
Surgery for malignant melanoma
Surgery for malignant melanoma should be carried out by appropriately trained and
experienced clinicians. In the majority of cases, this will be by dermatologists and plastic
surgeons. Stage IIA is a major cut off point but needs clear recognition of thickness i.e.
1-2 mm with ulceration or 2-4mm without ulceration. Hence up to 4 mm thick MM with
no ulceration may not benefit from routine staging investigation.
Management of primary lesion
In any skin lesion suspected of being melanoma, a narrow margin excision biopsy with 1
to 2 mm margin should be done. Excision biopsy allows accurate assessment of tumour
thickness and other prognostic features. For this reason, incision biopsy or punch biopsy
are not recommended in general, although they may be appropriate in a few
circumstances – this decision should be made by an appropriately experienced cancer
centre dermatologist or plastic surgeon. If it is not possible to do an excision biopsy,
then the patient should be referred to a cancer centre plastic surgeon or
dermatologist for further management. Depending on the histology following
excision, the following approach is recommended:
Benign lesions
Non melanoma malignant lesions
no further treatment
treat as appropriate
Melanoma lesions
further wider excision
Further wide excision should be carried out within 4 weeks of the primary surgery. The
planned margins of excision depend on histological features.
Target margins are set out below. They are based on the recently published UK
guidelines. Of note, the recently presented BAPS study of 1 versus 3 cm margin showed
an improved relapse free survival but not overall survival for the wider margin.
Melanoma Guidelines – Final Oct 09 Page 9 of 29
Lesion
Stage 0
Stage IA
Stage IB
Stage IIa
Stage IIb
> Stage IIb
In-situ
< 1mm, no
ulceration, Clark’s
level II-III
< 1mm and
ulceration/Clark’s
level IV/V
1.01-2mm, no
ulceration
1.01-2mm +
ulceration
> 2mm +
ulceration
Tis
T1a
Lateral margin
2-5mm
5mm
Depth
2-5mm
5mm
T1b
10mm
10 mm or up to
deep fascia
T2a
10mm
up to deep fascia
T2b
20mm
up to deep fascia
T3a – T4b
20mm
up to deep fascia,
excise
fascia/muscle if
involved
Subungual melanoma
Melanoma of the nail apparatus always arise from germinal matrix of nail, which lies
beneath proximal nail fold and lunula, this area should be included in biopsy.
Adjuvant isolated limb perfusion
There is no role for isolated limb perfusion as adjuvant therapy
Management of regional lymph nodes
Elective lymph node dissection
There is no benefit to elective lymph node dissection and it should not be undertaken
Sentinel node biopsy
The role of sentinel node biopsy remains uncertain. It undoubtedly gives very useful
prognostic information for individual patients and is increasingly a pre-requisite for
clinical trial entry. It remains unclear how best to manage a patient with a positive
sentinel lymph node and in the absence of a clinical trial, most clinicians would advise
Melanoma Guidelines – Final Oct 09 Page 10 of 29
proceeding to completion lymphadenectomy. The network currently supports sentinel
Lymph node mapping in patients with Melanoma of  2mm with the clinical service is
underpinned by a commitment to clinical trial participation. The service is currently
based at the Whiston site.
Therapeutic regional lymphadenectomy
Therapeutic regional lymphadenectomy confers a survival advantage in patients with
involved regional nodes. Management of clinically enlarged nodes or nodes detected on
imaging may include an FNA, trucut biopsy or excision biopsy prior to
lymphadenectomy.
It is preferable, although not mandatory, to re-stage patients with a CT scan of the chest,
abdomen (and pelvis in lower limb primaries) prior to lymphadenectomy if this may
change surgical management.
Management of satellites and in-transit metastasis
Complete surgical excision should be done. Wider margins are not advocated.
In multiple small lesions Co2 laser ablation is helpful.
In younger patients isolated limb perfusion may be indicated to control local and regional
recurrences and to salvage the limb from amputation. The network currently refers
patients to the ILP service at Gartnavel Hospital, Glasgow. Wherever possible, this
service should be streamlined through one referral process following joint surgical and
medical oncology assessment.
Surgery for metastatic disease
Development of metastatic disease is an ominous sign and median survival is short.
However a small number of patients may benefit from metastatectomy, both in terms of
quality of life and possibly overall survival. These include patients with isolated brain
metastasis, solitary or anatomically resectable liver metastases and solitary or a small
number of lung metastases. Patients most likely to benefit are those with (i) a long
disease-free interval (at least 12 months and preferably significantly longer) and (ii)
evidence of stable metastatic disease with no new metastasis (usually determined by a
repeat scan 6-8 weeks later). Management of these patients is highly individualised and
early discussion with the appropriate specialist surgeon is advised.
Melanoma Guidelines – Final Oct 09 Page 11 of 29
Histopathology
Expert histopathology is a cornerstone of a specialist clinical service. Many of the
important prognostic factors in melanoma remain histological and future improvements
in our understanding of this condition are likely to occur with improvements in
histopathology and molecular diagnostics.
Pathology request forms should be accurately completed and contain appropriate clinical
details. These should include
 Age of patient
 Site of lesion
 Appearance of lesion
 History of trauma
 Any relevant history
 Whether pregnant/on OCP
The pathologists report should give the following minimum data
 Site of tumour
 Type of surgical procedure
 Description of macroscopic appearance and dimensions
 Where possible, a statement on whether the lesion is primary, recurrent or
metastatic.
 Whether there is significant ulceration present
 Breslow thickness
 Clark’s level for tumours < 1 mm (where possible to assess accurately)
 Presence of radial growth and/or vertical growth phase
 Frequency of mitotic figures in mm-2
 Presence or absence of tumour regression
 Presence (and degree) or absence of lymphocytic infiltrate
 Presence of obvious lymphatic, vascular or perineural infiltrate
 Histological type of melanoma
 Presence of micro-satellites
 Whether excision is complete, and the minimum margin of excision to
peripheral and deep surgical margin
 Pathological staging
Histology specimens sent for expert specialised review may include only a small amount
of tissue or part of the specimens and information on margins etc. may not be available.
Melanoma Guidelines – Final Oct 09 Page 12 of 29
Follow up
The risk of recurrence is related closely to stage at presentation. For patients with stage I
disease (< 2 mm), the risk of recurrence is low but the rate of recurrence remains constant
over at least 15 years. For intermediate and high risk disease the risk of recurrence is
highest in the first 5 years and reduces significantly thereafter, but patients continue to
relapse up to at least 15 years after surgery.
Follow-up guidelines should be based on a number of factors including the actual risk of
recurrence, evidence that routine follow-up leads to earlier detection of recurrence and
that earlier detection of recurrence leads to improved outcomes, emotional needs of the
patient, the availability of resources etc.
The data on the role of routine review and investigations are confusing. The strongest
data are presented by groups that have strict review policies, these support routine clinical
review but not routine investigations. In one large series, the majority of relapses in
patients with stage I or II disease were detected either by history and examination. 2.3%
of 2003 patients being observed for 2 years developed a second malignant melanoma.
The UK guidelines recommend that patients be reviewed 3-monthly for 3 years. They
state that the evidence for this is poor, level C, and that for stage 1 patients, decisions
may be made on an individual basis.
What is urgently needed is a randomised trial comparing routine follow-up with
expectant follow-up. In the absence of this, it is entirely reasonable to identify a group of
patients with very low risk of recurrence, educate them about the risk of recurrence and
the risk of second mole, and manage them expectantly.
Guidance on follow-up has been issued by the MSG/BAD group and is adapted here for
local use (see over). This guidance is considered a minimum standard and individual
clinicians may choose to see patients more often.
Shared care follow-up
This should be arranged wherever practical, on a schedule as set out below. Routine
investigations (where indicated) should be co-ordinated by the unit/centre but can be
done locally. Good communication is the key to successful shared care.
Melanoma Guidelines – Final Oct 09 Page 13 of 29
Follow-up of patients with stage I-IV disease
Thickness
Stage 5 year
survival
IA
95.3 +/0.8%
Location
< 1 mm with
ulceration or
Clarke’s level
4-5 or 1.012mm, no
ulceration
IB
GP or Cancer
Unit
1.01-2 mm
with
ulceration
or 2.01-4 mm
no ulceration
IIA
2.01-4 mm
with
ulceration to
all stage III
Metastatic
disease-on
treatment
IIB
to
IIIC
Metastatic
disease-no
treatment/
treatment
completed
IV
< 1 mm, no
ulceration,
Clarke’s level
1-3
90.9+/-2%
Follow-up
Investigations
Follow-up
optional but
patients must
be educated
about self
exam, risk of
second
melanoma etc.
3 monthly for
1 year, then 4
monthly for 1
year, then 6
monthly for 3
years, then
discharge
3 monthly for
1 year, then 4
monthly for 1
year, then 6
monthly for 3
years, then
yearly for 5
years, then
discharge
none
as above
as for IIA
none
as above
see below
see below
as above
see below
see below
89.0 +/1.4%
74.7 +/3.4%
Cancer Centre
or shared care
by agreement
26.7 +/- 5%
63.0 +/- 3%
to
27% +/- 5%
Melanoma Guidelines – Final Oct 09 Page 14 of 29
none
Follow up of patients with advanced disease
Patients on observation
 As appropriate
Patients receiving treatment
 Imaging
 before treatment i.e. either CXR + ultrasound abdomen or CT chest +
abdomen
 repeat every 2-3 cycles of treatment
 repeat after completion treatment (usually 6 cycles)
 repeat 6 monthly or when clinical suspicion of disease progression
(whichever shorter)
Melanoma Guidelines – Final Oct 09 Page 15 of 29
Systemic therapy
The systemic treatment of malignant melanoma is a specialist area, best accommodated in
a research-based practice. Current standard therapies are less than perfect and every
effort should be made to provide access for patients to appropriate clinical trials.
National and international organisations involved in melanoma clinical trials include the
NCRI melanoma clinical studies group and the EORTC melanoma group, these are
supplemented by the pharmaceutical industry, local charities and investigator led
research.
Adjuvant therapy
The recently revised AJCC staging and prognostic system for malignant melanoma
allows us to accurately predict likelihood of relapse in for any patient. Unfortunately, we
have not yet identified an effective adjuvant therapy that can be applied to the majority of
patients.
There is no proven adjuvant therapy to improve survival in low and intermediate risk
melanoma.
Interferon–2b (Intron) is licensed for the adjuvant treatment of high risk melanoma. The
actual benefits of this treatment are marginal and still debated. The most recent metaanalysis identified a 2-3% 5 yr absolute survival advantage. Patients at high risk of
recurrence (see guidance above) should be referred for an oncology opinion and, where
possible, offered the opportunity to take part in a clinical trial.
Advanced disease
The majority of patients with metastatic melanoma have a very poor prognosis. Whilst
there are there are occasional long term survivors, for the majority of patients treatment is
given with palliative intent.
Response rates with standard chemotherapy are approximately 10% although many more
patients will get stable disease, a useful outcome in melanoma. There is no proven
survival advantage to chemotherapy for advanced melanoma, partly because this has
never been done. Similarly, there is no proven advantage to earlier treatment of
metastatic disease in melanoma. Where possible, patients should be offered the
opportunity to take part in a clinical trial.
Melanoma Guidelines – Final Oct 09 Page 16 of 29
Radiotherapy indications for cutaneous melanoma
Adjuvant Local Radiotherapy
To be considered if:


Post-operative irradiation can be considered in order to maximise local control
when either inadequate margins or macroscopic disease remain in situ and further
surgery is not feasible for medical reasons, for unacceptable morbidity, or for
cosmetic limitations.
Mucosal melanoma appear to have a different biological response to radiotherapy
and there is an inherent difficulty in obtaining wide surgical margins. Adjuvant
radiotherapy should be considered to the primary site +/- lymph node areas.
Radiotherapy should be discussed between ENT, maxillofacial, neurosurgeons
and clinical oncologists. The high incidence of metastatic spread makes it
desirable to avoid surgical morbidity.
Adjuvant Nodal Radiotherapy
This is controversial and potential improvements in local control need to be balanced
with treatment related morbidity. International trials are ongoing (TROG). Retrospective
series suggest improved local control when radiotherapy is used after lymph node
dissection in high-risk patients. It should therefore be considered if:




Extra-capsular extension
Known residual disease
N2a disease or greater in the neck
More than 5 nodes, or more than 50% of nodes sampled involved
Dose 50 gy/25# or equivalent; technique dependent on site.
Palliative Radiotherapy
Painful/bleeding or troublesome lesions in bone and soft tissue may be palliated with
short courses of conventionally fractionated radiotherapy. Cranial radiotherapy may
benefit patients with brain metastases who are able to maintain reasonable performance
status with or without steroids.
Dose depends on patient performance status, site and volume of treatment.
Melanoma Guidelines – Final Oct 09 Page 17 of 29
Clinical Guidelines for Palliative Care for Patients with Malignant
Melanoma
Patients and families should have supportive care from diagnosis onwards. This includes:

Access to information about their disease, aspects of management, available
services, and how to access them. This may for example include local and
national patient support networks.

Advice on practical and financial help.

Emotional and spiritual support, with specialist help for those with difficulties in
adjustment and coping.

An active and rehabilitative approach to maximise functional recovery and
adaptation to the consequences of the cancer and its treatment.

A meticulous approach to the relief of pain, and other distressing symptoms at any
stage. This should lead to early referral to specialist services if management of
problems should prove difficult.
Palliative care describes the multidisciplinary approach to the needs of the individual
with progressing or advanced cancer and their family, with the aim of maintaining best
quality of life and support through the terminal stages and into bereavement. Palliative
care is an integral part of the care provided by all primary and hospital teams. Specialist
palliative care is provided by those with training and who work exclusively within this
area across community, hospital, and hospice settings.
Specialist Services
There are a range of specialist services which might provide relatively short term input in
response to need at any stage of the cancer journey. Referrals may be made through
hospital or community teams, but early identification of potential or developing
problems, and prompt referral, is essential. Specialist services in relation to melanoma
may include:






Psychological support
Lymphoedema management
Pain specialists
Palliative care
Complementary therapies
Cancer information services
Melanoma Guidelines – Final Oct 09 Page 18 of 29
Specialist psychological support may be indicated in patients or their relatives with
difficulties in psychological adjustment leading to disabling anxiety and depression and
much less commonly, psychiatric illness co-existing with cancer. Such problems may
also extend to the carers and include complicated grief leading to abnormal bereavement.
The future for psycho-oncology services for the cancer network is under consideration,
Lymphoedema Management – this is led by nurses and physiotherapists with specialist
training. It is important to recognise the need for early referral of patients at high risk of
lymphoedema development, as well as those showing early signs of the problem.
Cancer Information Services:
Pain Specialist Teams are hospital based and provide out-patient clinic services. Often
pain associated with active, progressing cancer is managed by palliative care specialists
as there are often multiple co-existent problems; however pain specialists provide
valuable advice and help for those with intractable pain. Referral to a chronic pain service
may be appropriate for those who are cured of their cancer but live with difficult pain as a
result of treatment or the disease.
Specialist Palliative Care Teams are multidisciplinary and have specialist palliative care
nurses and doctors as core members. In general, specialist palliative care professionals
aim to work alongside the oncology or primary care team and would not take over care of
the patient except when in an in-patient hospice setting. They network closely with
colleagues across hospital, community (particularly community Macmillan nurses) and
hospice settings. They should be seen as a resource, particularly in difficult and
distressing situations and those where considerable on-going support to patient and
family is required.
Hospices are funded from charitable donations and the NHS. Currently the NHS funds
approximately 50% of Hospice running costs in most areas. They provide a range of
services which include in-patient care for symptom control, brief (1-2 weeks) respite for
families and terminal care. They are unable to make commitments for indefinite
intermediate/continuing care, where nursing home may be more appropriate. Hospice
services include counselling, family support, management of breathlessness and
lymphoedema. Day care at hospices provides access to a range of multiprofessional
services including medical assessment, as well as support for those who are socially
isolated as a result of malignant disease.
Melanoma Guidelines – Final Oct 09 Page 19 of 29
Some specific palliative care problems in melanoma
Lymphoedema
In melanoma, limb swelling may occur due to lymphatic obstruction. This may be a
consequence of treatment, or lymph node involvement with tumour. Patients should be
referred to specialist lymphoedema services for assessment and management. Proactive
treatment can significantly reduce lymphoedema and control swelling even in the
presence of progressive disease. Acute infective episodes may present as florid cellulites,
but frequently may be a case of mild erythema and general malaise. These should always
be treated actively with antibiotics.
Pain
Pain associated with advanced disease requires thorough assessment to identify the type
and cause of pain e.g. soft tissue, visceral, bony, neuropathic. Individual pains must be
dealt with appropriately.
If it is proving difficult to relieve pain, or there are problems with side effects of drugs, it
is important to seek advice as early as possible. Uncontrolled cancer pain should be
viewed as an oncological emergency and warrants admission to hospital or hospice.
Pain due to liver metastases may be a feature of metastatic melanoma. Non-steroidal antiinflammatory drugs are often effective with or without opiates. In the case of severe
pains, steroids (dexamethasone 4-16 mg daily) can be helpful in bringing pain under
control. In resistant cases, coeliac axis nerve block can be considered.
Cerebral Metastases
Symptoms due to brain metastases may be improved with dexamethasone (16mg daily).
In patients with good performance status, who are not expected to deteriorate quickly
with extracranial disease, referral should be considered for cranial irradiation, which can
enable a proportion of patients to subsequently discontinue steroid therapy.
Fungating Tumours
Cutaneous and subcutaneous melanoma deposits may ulcerate leading to several potential
problems: pain, pruritis, exudate / superadded infection, malodour (which may induce
Melanoma Guidelines – Final Oct 09 Page 20 of 29
nausea) and surface bleeding as melanomas tend to be vascular tumours. This is
frequently a very distressing complication for the patient.
Malodour is caused by necrotic tumour and anaerobic infection. The following measures
may be considered: metronidazole (topical or systemic), topical live yoghurt, and
occlusive dressings eg opsite, granuflex. Oxidising agents such as hydrogen peroxide, or
benzoyl peroxide may be considered in severe cases.
Superficial bleeding from fungating tumours may be controlled by physical measures i.e.
pressure dressings with or without topical haemostatic agents (adrenalin, tranexamic
acid). Other topical agents which may be considered include sucralfate, and alum
solution. Silver nitrate applied to bleeding points, or diathermy may be helpful.
Oral haemostatic agents may be helpful e.g. tranexamic acid ( 0.5-1.5 mg qds), or
etamsylate 500mg qds.
Referral for radiotherapy should be considered
Melanoma Guidelines – Final Oct 09 Page 21 of 29
Rare Subtypes
A number of rare melanoma subtypes exist. These include uveal tract melanoma, mucosal
melanoma and melanoma of soft parts (which is managed as a sarcoma). It is
recommended that management of all rare melanoma subtypes is discussed with the
cancer centre/MDT team.
Mucosal Melanoma
Management of mucosal melanomas should involve the appropriate site specialised team
but should be discussed with an oncologist. Extensive surgery for anal melanoma is not
indicated and patients should have wide local excision and radiotherapy.
Research
The involvement of cancer patients in clinical trials is a key tenet of the NHS Cancer
Plan. This is to be facilitated by the National Cancer Research Network and led by the
NCRI CSGs.
Melanoma Guidelines – Final Oct 09 Page 22 of 29
References
Final Version of the American Joint Committee on Cancer Staging System for Cutaneous
Melanoma. Balch C, Buzaid A, Soong S et al. Journal of Clinical Oncology 2110, 19
(16); 3635-48.
UK guidelines for the management of cutaneous melanoma
Roberts D, Anstey A, Barlow R et al.
British Journal of Dermatology 2002, 146; 7-17.
Primary staging and follow-up in melanoma patients – monocentre evaluation of
methods, costs and patient survival.
Hofmann U, Szedlak M, Jung E and Schadendorf.
British Journal of Cancer 2002, 87; 151-157
Narayan D. Ariyan S. Surgical management of primary melanoma. Clin. Plast Surg.
2000; 27: 409-419
Surgical margin excision width in high risk (minimum 2 mm) cutaneous melanoma; a
randomised trial of 1cm versus 3 cm excision margins in 900 patients.
Thomas M et al
Proc ASCO 2002, 21 (1), 1358.
Prospective evaluation of a follow-up schedule in cutaneous melanoma patients:
recommendations for an effective follow-up strategy.
Garbe et al
JCO 2003, 21 (3) 520-529
Radiotherapy References
Surgery and radiotherapy in the treatment of cutaneous melanoma.
Testori A, Rutkowski P, Marsden J, Bastholt L, Chiarion-Sileni V, Hauschild A,
Eggermont AM.
Ann Oncol. 2009 Aug;20 Suppl 6:vi22-9
Adequate surgical management of primary melanoma and regional lymph node
metastasis, and rarely distant metastasis, is the only established curative treatment.
Surgical management of primary melanomas consists of excisions with 1-2 cm margins
and primary closure. The recommended method of biopsy is excisional biopsy with a 2
mm margin and a small amount of subcutaneous fat. In specific situations (very large
lesions or certain anatomical areas), full-thickness incisional or punch biopsy may be
Melanoma Guidelines – Final Oct 09 Page 23 of 29
acceptable. Sentinel lymph node biopsy provides accurate staging information for
patients with clinically unaffected regional nodes and without distant metastases,
although survival benefit has not been proved. In cases of positive sentinel node biopsy or
clinically detected regional nodal metastases (palpable, positive cytology or
histopathology), radical removal of lymph nodes of the involved basin is indicated. For
resectable local/in-transit recurrences, excision with a clear margin is recommended. For
numerous or unresectable in-transit metastases of the extremities, isolated limb perfusion
or infusion with melphalan should be considered. Decisions about surgery of distant
metastases should be based on individual circumstances. Radiotherapy is indicated as a
treatment option in select patients with lentigo maligna melanoma and as an adjuvant in
select patients with regional metastatic disease. Radiotherapy is also indicated for
palliation, especially in bone and brain metastases.
Role of radiation therapy in the treatment of melanoma.
Schild SE.
Expert Rev Anticancer Ther. 2009 May;9(5):583-6
Melanoma has been widely described as radioresistant but this should not be construed as
meaning that melanoma is radioincurable. Many melanoma cell lines are as radiosensitive
as other tumors commonly treated successfully with radiotherapy (RT). The use of RT
requires careful planning resulting in the administration of a tumoricidal dose to the
tumor cells with adequate sparing of normal tissues. RT has been used for primary
therapy, postresection adjuvant therapy and palliation of symptomatic melanoma.
Curative RT has been given for uveal melanoma yielding patient survival equivalent to
enucleation. RT has been administered to patients with unresectable disease yielding
relatively favorable results. As an adjuvant therapy postoperatively, RT has been used
selectively to improve local disease control. Finally, RT is used successfully as a
palliative maneuver for symptoms related to distant metastatic melanoma in patients with
incurable disease.
A higher radiotherapy dose is associated with more durable palliation and longer survival
in patients with metastatic melanoma.
Olivier KR, Schild SE, Morris CG, Brown PD, Markovic SN.
Cancer. 2007 Oct 15;110(8):1791-5.
BACKGROUND: Oncologists are often reluctant to recommend radiotherapy (RT) to
palliate metastatic melanoma due to a perception that this tumor is "radioresistant." The
Mayo Clinic experience was analyzed to determine the efficacy of palliative RT.
METHODS: Eighty-four consecutive patients with 114 lesions that were not metastatic to
Melanoma Guidelines – Final Oct 09 Page 24 of 29
the central nervous system (CNS) were evaluated for the response of the presenting
symptom, the duration of response, and survival after RT. The median dose delivered was
30 grays (Gy) and the median biologic effective dose (BED) was 39.0 Gy(10).
Performance status was not uniformly available for all patients. RESULTS: Complete
resolution of the presenting symptom occurred in 10 lesions (9%). Of the lesions treated,
there was partial improvement in 86 (75%), no change in 12 (11%), and worsening in 6
(5%) lesions. The median survival was 3.8 months and freedom from disease progression
(FFP) for individual lesions was 6 months. Patients treated with >30 Gy had significantly
longer FFP compared with patients given </=30 Gy (P = .01). In addition, patients treated
with >30 Gy had a significantly longer survival than those given a lesser dose (median of
2 months vs 8 months; P < .0001). Similarly, patients receiving a BED >39.0 Gy(10) also
were found to have longer FFP (P = .03) and survival (median of 2 months vs 8 months;
P < .0001) compared with those receiving a BED </=39.0 Gy(10). The dose per fraction,
number of previous therapies, and location of the lesions did not appear to impact the
effectiveness of RT. CONCLUSIONS: RT was found to provide effective palliation of
non-CNS metastasis from malignant melanoma and should be considered for
symptomatic patients. RT doses >30 Gy and a BED >39.0 Gy(10) were found to be
associated with longer palliation.
Palliative radiotherapy for recurrent and metastatic malignant melanoma: prognostic
factors for tumor response and long-term outcome: a 20-year experience.
Seegenschmiedt MH, Keilholz L, Altendorf-Hofmann A, Urban A, Schell H,
Hohenberger W, Sauer R.
Int J Radiat Oncol Biol Phys. 1999 Jun 1;44(3):607-18.
PURPOSE: Radiotherapy is used as a "last resort" for patients with advanced cutaneous
malignant melanoma. We have analyzed our 20-year clinical experience with respect to
different endpoints and prognostic factors in patients with locally advanced, recurrent, or
metastatic malignant melanoma. METHODS: From 1977 to 1995, 2,917 consecutive
patients were entered in the melanoma registry of our hospital. Radiotherapy was
indicated in 121 patients (56 females, 65 males) for palliative reasons in advanced
malignant melanoma stages UICC IIB/III/IV. The histology of the primary lesion was
nodular in 51 patients, superficial spreading in 35, acral-lentiginous in 8, and lentigo
maligna melanoma in 4 patients. Eleven patients had primary or recurrent lesions which
were either not eligible for surgery or had residual disease (R2) after resection of a
primary or recurrent lesion (UICC IIB); 57 patients had lymph node (n = 33) or in-transit
metastases (n = 24) (UICC III), and 53 had distant organ metastases (7 M1a; 46 M1b)
(UICC IV). Time from first diagnosis to on-study radiotherapy averaged 19 (median: 18;
range: 3-186) months. In most cases, conventional RT was applied with 2-6 Gy single
fractions up to a median total radiation dose of 48 (mean: 45; range: 20-66) Gy.
RESULTS: At 3 months follow-up, complete response (CR) was achieved in 7 (64%) and
Melanoma Guidelines – Final Oct 09 Page 25 of 29
overall response [complete (CR) and partial response (PR)] in all (100%) UICC IIB
patients, in 25 (44%) and 44 (77%) of 57 UICC III patients, and in 9 (17%) and 26 (49%)
of 53 UICC IV patients. Tumor progression during radiotherapy occurred in 25 (21%)
patients. Patients with CR survived longer (median: 40 months) than those without CR
(median 10 months) (p < 0.01). At last follow-up (Dec 31, 1996), 26 patients were still
alive: 6 (55%) UICC IIB, 17 (30%) UICC III, and 3 (6%) UICC IV patients (p < 0.01).
Univariate analysis revealed the following prognostic factors for complete response and
long-term survival: UICC stage (p < 0.001), primary location in the head and neck
region, total radiation dose above 40 Gy (all p < 0.05), while age, gender, and histology
had no impact. In multivariate analysis, UICC stage was the only independent prognostic
factor (p < 0.001). CONCLUSION: External beam radiotherapy can provide long-term
local control and effective palliation in malignant melanoma UICC stages IIB-IV. The
current UICC staging system is an excellent prognostic factor for initial and long-term
tumor response in metastatic melanoma. Therefore, prospective randomized trials using
external radiotherapy with or without adjuvant therapy for advanced malignant melanoma
are justified.
Melanoma Guidelines – Final Oct 09 Page 26 of 29
Contributors
Consultant Histopathologist: Dr Niamh Leonard
Consultant Plastic Surgeon: Mr Azhar Iqbal
Consultant Radiologist: Dr John Herbert
Consultant Dermatologist: MCCN MDT Lead Cancer Dermatologists
Consultant Medical Oncologist: Dr E Marshall
Consultant Clinical Oncologists: Dr I Syndikus
Consultant in Palliative Care: Dr Claire Littlewood
Primary Care Cancer Lead: Dr Murray Freeman
Melanoma Guidelines – Final Oct 09 Page 27 of 29
Appendix 1
Staging of Malignant Melanoma
Clark staging:

level I: all tumour cells above basement membrane (in situ)

level II: tumour extends to papillary dermis

level III: tumour extends to interface between papillary and reticular dermis

level IV: tumour extends between bundles of collagen of reticular dermis

level V: tumour invasion of subcutaneous tissue
Breslow Thickness: from the granular layer to the area of deepest penetration
AJCC Staging (2001)
Stage
Primary tumour pT
Lymph node N
0
in situ (Tis)
no nodes
Distant
metastases M
none
IA
< 1 mm no ulceration /
Clark’s II & III (T1a)
< 1 mm + ulceration /
Clark’s IV & V (T1b)
1.01-2 mm no ulceration (T2a)
no nodes
none
no nodes
none
no nodes
none
IIA
1.01-2 mm + ulceration (T2b)
2.01-4 mm no ulceration (T3a)
no nodes
no nodes
none
none
IIB
2.01-4 mm + ulceration (T3b)
> 4.0 mm no ulceration
no node
no nodes
none
none
IIC
> 4.0 mm + ulceration (T4b)
no nodes
none
IIIA
any thickness, no ulceration
1 node micrometastases (N1a)
none
IIIB
any thickness, with ulceration
any thickness, no ulceration
any thickness, +/- ulceration
1 node micrometastases (N1a)
up to 3 nodes micrometastasis (N2a)
in-transit met/satellites + node nodes (N2c)
none
none
none
IIIC
any thickness, with ulceration
any thickness, +/- ulceration
up to 3 nodes macrometastasis (N2b)
≥ metastatic nodes/matted nodes/
in-transit with nodes (N3)
none
any nodes
present
IB
IV
Note:
any thickness
M1a metastases in skin, subcutaneous tissue or distant lymph nodes
M1b metastases in lung
M1c all other sites or any site with raised lactate dehydrogenage
Melanoma Guidelines – Final Oct 09 Page 28 of 29
none
Melanoma Guidelines – Final Oct 09 Page 29 of 29