Scottish Intercollegiate Guidelines Network

72

Cutaneous Melanoma
A national clinical guideline

Introduction

Prevention, surveillance and genetics

Diagnosis and prognostic indicators

Surgical management and staging

16

Further investigations and non-surgical staging

21

Adjuvant treatment of stage II and III disease

22

Patient follow up in stage I, II and III disease

23

Management of stage IV disease

27

Melanoma in women

31

10

Information for patients

32

11

Implementation and audit

39

12

Development of the guideline

42

References

45

July 2003

KEY TO EVIDENCE STATEMENTS AND GRADES OF RECOMMENDATIONS

LEVELS OF EVIDENCE
1++

High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs),

or RCTs with a very low risk of bias

1+

Well conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low

risk of bias

1-

Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias

High quality systematic reviews of case control or cohort studies

High quality case control or cohort studies with a very low risk of confounding or bias
and a high probability that the relationship is causal

++

2+

Well conducted case control or cohort studies with a low risk of confounding or bias
and a moderate probability that the relationship is causal

2-

Case control or cohort studies with a high risk of confounding or bias

and a significant risk that the relationship is not causal

Non-analytic studies, e.g. case reports, case series

Expert opinion

GRADES OF RECOMMENDATION
Note: The grade of recommendation relates to the strength of the evidence on which the
recommendation is based. It does not reflect the clinical importance of the recommendation.
A

At least one meta-analysis, systematic review of RCTs, or RCT rated as 1++

and directly applicable to the target population; or
A body of evidence consisting principally of studies rated as 1+, directly applicable to
the target population, and demonstrating overall consistency of results

A body of evidence including studies rated as 2++, directly applicable to the target
population, and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+

A body of evidence including studies rated as 2+, directly applicable to the target
population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++

Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+

GOOD PRACTICE POINTS

Recommended best practice based on the clinical experience of the guideline

development group

Scottish Intercollegiate Guidelines Network

ISBN 1 899893 88 1
First published 2003

SIGN consents to the photocopying of this guideline for the

purpose of implementation in NHSScotland
Scottish Intercollegiate Guidelines Network
Royal College of Physicians
9 Queen Street
Edinburgh EH2 1JQ
www.sign.ac.uk

1 INTRODUCTION

Introduction

1.1

THE NEED FOR A GUIDELINE

Cutaneous melanoma, previously referred to as cutaneous malignant melanoma, is a malignant
tumour of cutaneous melanocytes. The incidence of melanoma has been increasing rapidly for
the last few decades in most parts of the world. The reasons for this are not clear although the
role of sunlight exposure is widely accepted.
The epidemiology of cutaneous melanoma in Scotland has been described in detail elsewhere.1
Currently, over 600 cases of invasive disease are diagnosed in Scotland every year. Between 1979
and 1998, age-standardised incidence rates increased from 3.5 to 10.6 per 100,000 in males, and
from 7.0 to 13.1 in females. After 1995, the rate of increase levelled out in females younger than
65 years at diagnosis. Between the years of diagnosis 1979 and 1993, five year survival increased
from 58% to 80% in males, and from 74% to 85% in females. Most of this improvement in
prognosis was attributable to a higher proportion of thinner tumours.
Although melanoma is the major cause of skin cancer mortality, it is usually curable, if recognised
and treated at an early stage. The visibility of the vast majority of melanomas makes them
accessible tumours. There is variation in approaches to all stages of melanoma management in
Scotland. Surgical management of the primary lesion has changed considerably over time.
Melanoma in its later stages remains relatively resistant to currently available treatments.
Considerable efforts have been made to encourage increased public and professional awareness
of melanoma in recent years.

1.2

REMIT OF THE GUIDELINE

Many specialties and professions are involved in the management of patients with melanoma.
This guideline provides advice at all stages of the patients pathway of care, from primary prevention
to early recognition, treatment and follow up. The guideline covers both established management
techniques and newer approaches such as sentinel node biopsy. It does not address melanomas
of non-cutaneous origin such as melanomas arising from mucosae, ocular melanomas and other
rare non-cutaneous sites.
The guideline should be of interest and relevance to primary care providers, dermatologists,
surgeons, pathologists, medical and clinical oncologists, public health physicians, nurses, health
promotion professionals and epidemiologists.

1.3

PATIENT AND CARER INFORMATION

i
1.4

Effective communication and appropriate information giving are integral components of

high quality patient care. The guideline highlights the points throughout the journey of
care when patients should routinely be given information about their care and the services
available to them.

STATEMENT OF INTENT
This guideline is not intended to be construed or to serve as a standard of medical care. Standards
of care are determined on the basis of all clinical data available for an individual case and are
subject to change as scientific knowledge and technology advance and patterns of care evolve.
These parameters of practice should be considered guidelines only. Adherence to them will not
ensure a successful outcome in every case, nor should they be construed as including all proper
methods of care or excluding other acceptable methods of care aimed at the same results. The
ultimate judgement regarding a particular clinical procedure or treatment plan must be made by
the doctor, following discussion of the options with the patient, in light of the diagnostic and
treatment choices available. It is advised however that significant departures from the national
guideline or any local guidelines derived from it should be fully documented in the patients
case notes at the time the relevant decision is taken.

CUTANEOUS MELANOMA

1.5

REVIEW AND UPDATING

This guideline was issued in 2003 and will be considered for review as new evidence becomes
available. Any updates to the guideline will be noted on the SIGN website: www.sign.ac.uk

2 PREVENTION, SURVEILLANCE AND GENETICS

Prevention, surveillance and genetics

2.1

INTRODUCTION
Melanoma, especially when diagnosed at an advanced stage, can cause serious morbidity and
may be fatal despite treatment. Prevention of the disease, or failing that, minimising its
consequences by early detection, are key goals.

2.2

CAUSATION
A comprehensive review of evidence by the International Agency for Research on Cancer (IARC)
has concluded that solar radiation is a cause of melanoma.2
Two more recent systematic reviews focussed on the relationship between patterns of sun exposure
and risk of melanoma. The first was a high quality review of case control studies which concluded
that intermittent unaccustomed exposure was more important than age at sunburn.3 The second
study was a review of ecological and case control studies and concluded that exposure to high
levels of sunlight in childhood is a strong determinant of risk, but that exposure in adulthood
also plays a part.4

2++

The contribution of specific wavelength bands and the action spectrum for melanoma induction
are unknown.3 Sunburn is mainly due to UVB (280 to 320 nm) radiation, implicating UVB as a
contributing factor to the pathogenesis of melanoma. There is accumulating evidence for the role
of UVA (and sunbeds) in the pathogenesis of melanoma.5

2.3

PRIMARY PREVENTION
Primary prevention is defined as prevention targeted towards the general population.
There is indirect evidence that sun avoidance and other sun-protective measures (eg clothing,
hats and opaque sunscreens) are likely to reduce the risk of melanoma. Sunscreen effectiveness is
difficult to demonstrate for a number of reasons. High risk individuals are more likely to use
sunscreen, although sunscreen use may be associated with greater sun exposure.6,7 It may be that
sunscreens offer a false sense of security and lead to increased time spent in the sun. 6,7 Most
sunscreens offer greater protection from UVB, reducing the risk of sunburn, but not of exposure
to UVA. 6,7 Some ingredients found in sunscreens may be carcinogenic.6,7 Case control studies and
clinical trials have shown no reduction or increase in melanoma incidence with broad spectrum
sunscreen use. Little is known about the potential long term effects of sunscreen use.6,7 Given
these potentially adverse effects of sunscreens in relation to risk of melanoma, physical protection
measures should be regarded as more important than sunscreen use.6,7

2++

There may be theoretical risks associated with sun avoidance,8 eg a lack of vitamin D, but the
balance of evidence in terms of risks and benefits favours a cautious approach to sun exposure. In
the absence of evidence to support recommendations about specific aspects of protection measures
in Scotland, the advice below is based on the Australian guidelines on melanoma, interpreted in
the light of the Scottish climate.9

Table 1 : Prevention of Melanoma

n
Use clothing as the primary means of protecting against the sun
n
People of fair complexion should be especially careful about sun exposure
n
Avoid using sunbeds, tanning booths, and tanning lamps as an increased risk has been reported
in some studies5
n
Use broad spectrum sunscreens with a minimum sun protection factor (SPF) of 15 as an
adjunct to sun avoidance and other sun protective measures, providing this does not lead to
increased time spent in the sun
n
Avoid exposure to direct, intense sunlight, especially around midday (eg seek out shade)
n
Provide children with appropriate sun protection for outdoor activities.

CUTANEOUS MELANOMA

2.3.1

PUBLIC EDUCATION TO PROMOTE PRIMARY PREVENTION

As melanoma is potentially preventable, educating the general public might be an important
preventive measure. Six randomised controlled trials (RCTs) of interventions aimed at a variety of
target groups including the general public, employees and school children were identified.1015
All interventions were in some part reliant on brochures and leaflets to deliver preventive
information. Leaflets significantly increased short term user-knowledge of sun awareness measures,
and assisted in the early detection of melanoma (see also section 2.4.4). The tone of a leaflet or
educational brochure is important when delivering health promotion messages relating to sun
awareness and should be non-alarmist.11
Two observational studies suggest that interactive computer-based educational packages may
result in higher short term knowledge gain (sun awareness) when compared to non-interactive
packages.16,17 A retrospective cohort study of French primary school children found that health
education programmes could improve the knowledge, attitude and behaviour of young children.
Children with a fair complexion (the target of this campaign) showed the best improvement in
their responses.18

1+

2+

Leaflets, brochures and educational packages can significantly influence increased short term
user-knowledge of sun awareness measures, and can assist in the early detection of melanoma
(see also section 2.4.4). Insufficient evidence was identified to enable recommendations to be
made about the style or content of leaflets and brochures.
D

Brochures and leaflets should be used to deliver preventive information on melanoma to

the general public.

Leaflets and brochures used in melanoma prevention work should be non-alarmist.

If computer-based learning programmes are used they should be interactive in nature.

2.4

SCREENING AND SURVEILLANCE

2.4.1

IDENTIFICATION OF INDIVIDUALS AT HIGHER RISK

2.4.2

A review of the literature on the reliability and usefulness of risk-assessment tools suggests that
patients can count the number of moles 5 mm or larger in reasonable agreement with physicians,
but that they cannot accurately distinguish atypical moles from others.19 No longitudinal studies
of the use of risk-assessment tools in primary care were identified.

2++

A cross-sectional study that sent postal questionnaires to a random sample of households from a
general practice population found that self assessment of risk was generally poor compared with
the assessment of a dermatologist, suggesting that it might be very difficult to identify systematically
a high risk population suitable for screening. 20

An RCT carried out in 11 communities in Western Australia showed that targeted advertising can
increase the yield of individuals with a higher prevalence of risk factors.21 This may not be
immediately transferable to Scotland, where disease prevalence is lower and baseline awareness
may be lower.

1+

RISK FACTORS
Risk factors for melanoma have been identified mainly from case control studies (see Table 2).
The strength of a risk factor is usually expressed in terms of an odds ratio (OR). In the context
of this guideline, the OR is the ratio of the odds in favour of exposure to a risk factor in people
with melanoma to the odds in favour of exposure to the same risk factor among people who have
not developed melanoma. For relatively rare diseases such as melanoma, the OR can be thought
of as being equivalent to the relative risk, that is, the ratio of the incidence rate of melanoma
among exposed individuals to the incidence rate among unexposed individuals. The higher the
OR (or relative risk), the stronger the association between the risk factor and melanoma. This is
important from the perspective of an individual, but from a public health perspective a lower OR
for a commonly occurring risk factor may be more important than a higher OR for a risk factor
which occurs rarely in the population.

2 PREVENTION, SURVEILLANCE AND GENETICS

Table 2: Established risk factors for cutaneous melanoma

Risk factor

OR*

Information

11-50 common moles >2mm

1.7-1.9

The risk of melanoma rises with the

number of common moles.19

51-100 common moles >2mm

3.2-3.7

>100 common moles >2mm

7.6-7.7

Family history of melanoma

1.8

Previous history of melanoma

Standardised incidence ratio range

4.5 - 25.622 (see section 7.8).

The presence of 1-4 atypical moles.

1.6-7.3

Red or light-coloured hair19

1.4-3.5

Presence of actinic lentigines

19

1.9-3.5

Atypical moles: ill-defined or irregular

border; irregular pigmentation; diameter
>5 mm; erythaema (blanchable in lesion or
at edge); accentuated skin markings.19
Actinic lentigines: flat, brown skin lesions
associated with acute and chronic sun
exposure. No direct malignant potential.
Relative risk range 239-1,224 for
extracutaneous as well as cutaneous
melanoma. 23,24

Giant congenital melanocytic

naevi 20 cm in diameter
Unusually high sun exposure19

2.6

Reported growth of a mole

2.3

19

Melanoma in a first degree family

member (parent, sibling or child of the
patient; see section 2.5).19

Skin that does not tan easily19

1.98

19

Light coloured eyes

1.55-1.60

Light coloured skin19

1.40-1.42

Affluence

Relative risk approximately 3.0 for people

residing in areas defined as Carstairs
deprivation category 1 (least deprived)
compared to Carstairs category 7 (most
deprived).25,26

Female sex

Female:male ratio of age-standardised

incidence rates is approximately 1.3:1.0.25

Age

Melanoma is rare in absolute terms in

childhood and adolescence but risk begins
to increase with age during adolescence, the
elderly being at highest risk.25 The validity of
some risk factors, such as hair colour and sun
exposure, is lower in the elderly.19

*OR = odds ratio. In some cases the range of ORs from more than a single study are given.
eg A person with skin that does not tan easily has an approximately twofold (1.98 times) risk of
developing melanoma compared to someone with skin that tans (after allowing for other risk
factors). This is modest in comparison, for example, to the approximately 10-fold or greater risk
of developing lung cancer in someone who smokes cigarettes compared to a person who has
never smoked.27

CUTANEOUS MELANOMA

2.4.3

SURVEILLANCE OF INDIVIDUALS AT HIGHER RISK

Results from a Scottish cohort study suggest that surveillance of individuals at higher risk, once
identified, can lead to early diagnosis of thin lesions. The cost effectiveness of this approach is
unclear.28

2.4.4

2+

PUBLIC EDUCATION TO PROMOTE EARLY DETECTION

A study in the west of Scotland suggested that a public education campaign and rapid referral
system to encourage earlier detection of melanoma could result in sustained decreases in the rate
of diagnosis of thick melanomas (>3.5mm) and mortality in females, but not in males.29 This
contrasts with the results of the Cancer Research Campaign Mole Watcher Study that did not
find lower cumulative mortality from melanoma in regions exposed to a health education
intervention compared to non-intervention regions.30

The available evidence is insufficient to recommend for or against the routine screening of
individuals at higher risk of melanoma. Interventions to promote the awareness of risk factors
and skin self awareness are probably warranted.

2.4.5

Healthcare professionals and members of the public should be aware of the risk factors
for melanoma.

Individuals identified as being at higher risk should be

n
advised about appropriate methods of sun protection
n
educated about the diagnostic features of cutaneous melanoma
n
encouraged to perform self examination of the skin.

MASS SCREENING
No randomised controlled trials on mass screening were identified. Two American systematic
reviews of screening for melanoma (and other skin cancers) have identified observational data to
suggest that screening in high risk groups might be effective. 19,31

2.5

2++

A formal programme of mass screening for melanoma in Scotland is not recommended.

GENETICS
A recent consensus document estimated that one to two percent of melanomas were attributable
to the inheritance of melanoma susceptibility genes.32 The document also estimates that a similar
percentage of melanoma patients come from melanoma prone families with three or more first
degree relatives with melanoma.
Members of such families are at significantly increased risk of developing melanomas. Many
more melanoma patients have only one relative who also has melanoma.33 An intensive search
for putative melanoma susceptibility genes has identified mutations in the CDKN2A gene in 2030% of melanoma prone families in Scotland, reflecting rates reported in other parts of the
world.34 -37 This mutation is less frequently found in families with only two affected members.
Mutations in the CDK4 gene have been found in only three families and it is likely that there are
as yet unidentified melanoma susceptibility genes. Current expert consensus recommends that
genetic testing in familial or sporadic melanoma is not appropriate in a routine clinical setting
and should only be undertaken in the context of appropriate research studies and when appropriate
counselling services are available.38
D

Genetic testing in familial or sporadic melanoma is not appropriate in a routine clinical

setting and should only be undertaken in the context of appropriate research studies.

3 DIAGNOSIS AND PROGNOSTIC INDICATORS

Diagnosis and Prognostic Indicators

The vast majority of melanomas are visible, if not to the patient, then at least to friends, family
or health professionals. Members of the general public and health professionals should be aware
of the signs suggestive of melanoma. In Scotland, melanomas occur more commonly in women
than men. The most frequent site is the leg for women and the trunk in men. A small number of
patients have occult primary lesions and present with metastatic disease. Up to ten percent of
melanomas can be amelanotic (non-pigmented), increasing diagnostic difficulty.

3.1

TYPES OF MELANOMA
Melanomas are subdivided into types on the basis of clinical features and pathology.

3.1.1

SUPERFICIAL SPREADING MELANOMA (SSM)

This is the most frequently encountered type of melanoma; characteristically an asymmetrical
pigmented lesion with irregular borders, irregular pigmentation and sometimes an irregular outline.
Patients may have noted growth, a change in sensation and/or colour, crusting, bleeding or
inflammation of the lesion. The duration of the symptoms varies from a few months to several
years.

3.1.2

NODULAR MELANOMA (NM)

The second most common type is nodular melanoma. This usually has a shorter presentation and
a greater tendency to bleed and/or ulcerate.

3.1.3

LENTIGO MALIGNA MELANOMA (LMM)

The next in frequency is the type that occurs most often in sun damaged skin on the head and
neck of older patients. This is the only variety that has a clearly recognised and often lengthy preinvasive (in situ) lesion termed Lentigo Maligna (LM) before progressing in some instances to an
invasive melanoma (LMM).

3.1.4

ACRAL LENTIGINOUS MELANOMA (ALM)

The least common type of melanoma in Scotland is the acral lentiginous melanoma. This occurs
on sites including the palms, soles and beneath the nails.

3.2

CLINICAL DIAGNOSIS
Suspicious pigmented lesions are best examined in a good light with or without magnification
and should be assessed using the 7 point checklist or ABCDE systems given below.39,40 The
presence of any major feature in the 7 point checklist, or any of the features in the ABCDE
system, is an indication for referral. The presence of minor features should increase suspicion. It
is accepted that some melanomas will have no major features.

Table 3: The 7 point checklist lesion system

Major features

Minor features

change in size of lesion

inflammation

irregular pigmentation

itch/altered sensation

irregular border

lesion larger than others

oozing/crusting of lesion

CUTANEOUS MELANOMA

Table 4: The ABCDE lesion system

A

Geometrical Asymmetry in two axes

Irregular Border

At least two different Colours in lesion

Maximum Diameter >6 mm

Elevation of lesion

Clinical diagnosis of melanoma is difficult and the accuracy of diagnosis may vary according to
a clinicians level of experience, with reports of considerable variation in sensitivity from 50 to
86% and an inverse relationship between sensitivity and experience. 41-43

High magnification dermatoscopy is more sensitive than non-dermatoscopic diagnosis when

used by clinicians with experience of the technique.44 High magnification requires more
sophisticated equipment than the current widely-used hand held dermatoscopy.

1+

Training clinicians to be experts in hand held dermatoscopy improves diagnostic accuracy but
it may diminish the sensitivity of the diagnosis of non-expert or untrained dermatologists.45-47
Observational studies have compared excision and pathological assessment to using other
preoperative assessment methods of diagnosis including magnetic resonance imaging (MRI),
high resolution ultrasound (US) and digital imaging of possible melanomas.48-51 These studies
failed to show significant benefit and require specialist equipment that is unlikely to be widely
available.
D

Clinicians should be familiar with the 7 point or the ABCDE checklist for assessing
lesions.

Clinicians using hand held dermatoscopy should be appropriately trained.

1+
3

A flow chart showing the suggested management of cutaneous melanoma is given at the end of
this chapter.
3.2.1

THE UNKNOWN PRIMARY

When melanoma presents as a metastasis and no primary melanoma site can be identified the
patient should be referred to the appropriate regional specialist (see section 8).

3.3

DELAY IN DIAGNOSIS
Nine observational studies exploring delay were identified.41,52-59 Significant delays (>three months)
in diagnosis of invasive melanoma are usually patient- rather than physician-related.41,52-59 Delay
was defined differently in each study, with some including both patient and physician components.

All of the studies identified show inconsistency between Breslow thickness (see section 3.8.4)
and delay, although melanomas diagnosed incidentally by health professionals were consistently
thinner than those noted by patients themselves.55
Several studies showed longer delays in older patients,42,57 in men, in rural versus urban dwellers
and in plantar melanomas.58,42

2+

There is inconsistency in findings regarding patients knowledge of melanoma and delay. Two
observational studies found that delay in presentation was shorter if the patient was aware of
possibility of malignancy.55,59 Conversely, another study found that delays were longer in those
with greater knowledge, perhaps due to false reassurance caused by greater knowledge42 (see
section 2.4.1).
Physician delay accounts for a very small part of the total delay in diagnosis.41 Medical delays
were shorter and the Breslow thickness was less when patients were seen by dermatologists as
opposed to general practitioners.41

3 DIAGNOSIS AND PROGNOSTIC INDICATORS

No studies were identified exploring the consequences of delays in diagnosis on patient outcomes.

3.4

Health professionals should be encouraged to examine patients skin during other clinical
examinations.

Patients with suspicious pigmented lesions should be seen at a specialist clinic in a time
commensurate with the level of concern indicated by the GP referral letter.

Emphasis should be given to the recognition of early melanoma by both patients and
health professionals.

EDUCATING HEALTH PROFESSIONALS ABOUT DIAGNOSIS

An Australian RCT demonstrated a decrease in the number of benign lesions excised by GPs after
being given algorithms and cameras as aids to diagnosis.60 In an American RCT, the use of a
booklet, magnifying and measuring tools and feedback sessions improved the ability of primary
care residents to triage suspicious lesions. 61

3.5

1+
1-

Targeted education can enhance health professionals ability to diagnose melanoma.

BIOPSY OF SUSPICIOUS LESIONS

Biopsy of highly suspicious lesions should be by fast-track referral to the appropriate specialty
according to local circumstances.
The optimal specimen for full histological evaluation of a suspected melanoma is a complete
excision with a 2 mm surround of normal skin and a cuff of fat.62 This enables assessment of the
entire lesion and allows direct wound closure with a relatively short scar that will not compromise
subsequent wider surgery (see section 4.1). Elliptical excisions should be performed along the
long axis in the line of a natural skin crease or longitudinally in limbs and transversely over
joints. The exact surgical margins of excision should be recorded on the operation note.

2+

Non-excisional biopsy may lead to inadequate histology.63-67 The least useful type of biopsy is
the superficial shave variety. Two large studies demonstrate that non-excisional biopsy of the
primary lesion has no effect on prognosis.64,68

3.6

A suspected melanoma should be excised with a 2 mm margin and a cuff of fat.

If complete excision cannot be performed as a primary procedure a full thickness incisional

or punch biopsy of the most suspicious area is advised.

A superficial shave biopsy is inappropriate for suspicious pigmented lesions.

GPs should refer urgently all patients in whom melanoma is a strong possibility rather
than carry out a biopsy in primary care.

The local availability of fast-track services for patients in whom melanoma is suspected
should be advertised widely to general practitioners.

Newly diagnosed patients should receive both verbal and written information about
melanoma including the treatment options and support services available to them.

LENTIGO MALIGNA MELANOMA

Biopsy of in situ lentigo maligna melanoma (LMM) and of invasive LMM should be approached
differently. The frequently facial site and large diameter of such lesions may render full excision
difficult or excessively destructive. In these instances incisional biopsy(s) of the most clinically
suspicious areas are appropriate. Lentigo maligna melanoma ideally should be surgically removed
as in other invasive types.69 Where the size, site or patient comorbidity prevents this, other

2+

CUTANEOUS MELANOMA

techniques can be considered. Cryotherapy and topical-5-fluorouracil have been used but there is
a risk of local recurrence and no reduction in the risk of developing invasive disease. 70 The
patient should be fully appraised of these risks. Several small studies also report the use of
radiotherapy in pre-malignant LM and LMM with good recurrence-free intervals and excellent
cosmesis.71-73

3.7

PATHOLOGICAL DIAGNOSIS

3.7.1

HANDLING A SUSPECTED MELANOMA

2+

The volume of evidence addressing the handling of suspected melanomas is small.

Recommendations on how to describe and select tissue blocks from a suspected melanoma are
available from standard surgical pathology textbooks.74
Accepted practice has been supplemented by best practice guidelines published in 2000.62

Appropriate treatment, follow up and prognostication for patients with melanoma are entirely
dependent on accurate pathological diagnosis and microscopic staging. The macroscopic
description of the specimen, together with adequate and appropriate methods of block selection,
is central to this process.
D

The macroscopic description of a suspected melanoma should:

n
state the biopsy type, whether excision, incision, or punch
n
describe and measure the biopsy (in mm)
n
state the size of the lesion in mm and describe the lesion in detail (shape, pattern of
pigment distribution, presence or absence of a nodular component and presence or
absence of ulceration)
n
state the clearance of the lesion (in mm) from the nearest lateral margin and the deep
margin.
Selection of tissue blocks:
the entire lesion should be submitted for histopathological examination
n
the lesion should be sectioned transversely at 3 mm intervals and the blocks loaded
into labelled cassettes
n
cruciate blocks should not be selected (they limit the assessment of low power
architectural features such as symmetry).
n

Note: a photograph of the macroscopic specimen may be of great value, especially if the precise
origins of labelled blocks are drawn onto the photograph to permit exact orientation.

3.8

PROGNOSTIC INDICATORS

3.8.1

HISTOGENETIC TYPE
Superficial spreading melanomas are less prone to recurrence when compared to nodular
melanomas, however both groups have similar survival figures when matched for tumour
thickness.75 Cochrans prognostic model (see section 3.8.11) uses an assessment of the histogenetic
type (SSM versus all others) to calculate the risk of tumour recurrence but this variable is not
required for the calculation to derive the probability of survival.75 Classifying melanomas into
different subtypes is reported to be of no prognostic relevance. Both desmoplastic and neurotropic
melanomas (long regarded as being particularly aggressive) have similar survival rates to other
subtypes although lesions with a neurotropic component are associated with a higher rate of
local recurrence.62,76-78
Although the majority of studies do not demonstrate a significant association between histogenetic
subtype and patient outcome, histogenetic type does appear to play a role in determining the
likelihood of recurrence. Histogenetic type also defines a group of well recognised
clinicopathological entities.

10

2++
2+
4

2++

3 DIAGNOSIS AND PROGNOSTIC INDICATORS

B
3.8 2

The histogenetic type should be included in the pathology report.

MELANOMA CELL TYPE

The relationship between cell type and outcome is unclear. Studies that examine melanomas of
all thicknesses tend to find either no evidence of a relationship or a weak association that is lost
on multivariate analysis.75,76,79-81,90,258 The effect of cell type on prognosis may only become apparent
in the specific subgroup of patients with thick tumours exhibiting paradoxical behaviour. Here,
the presence of a spindle cell or Spitz-like phenotype may confer a modest survival advantage.81

3.8.3

The predominant cell type in the vertical growth phase should be stated, especially for
thick tumours.

RADIAL VERSUS VERTICAL GROWTH PHASE

Tumour growth phase correlates strongly with clinical outcome.76,82 A study of 501 patients with
primary melanomas identified a subgroup of 122 as being in radial growth phase only. No
patients in this subgroup showed evidence of metastatic disease during a minimum follow up
period of 100 months. The OR for a patient with radial growth phase melanoma surviving for
eight years was given as 1.0.76 A second study evaluated 624 patients, of whom 161 had melanoma
displaying radial growth phase characteristics only. None of the patients developed metastatic
disease at long term follow up (median 13.7 years). 82
B

3.8.4

BRESLOW THICKNESS

2+
2++

An accurate (to within 0.1 mm) measurement of the Breslow thickness should be included
in the pathology report for any melanoma that has an invasive component.

CLARK LEVEL
In a study of 5,093 patients (minimum follow up seven years) the Clark level of invasion yielded
additional prognostic information in patients with a Breslow thickness of <1mm.86 This observation
has also been confirmed by the large study (based on 17,600 patients) used to derive the new
American Joint Committee on Cancer (AJCC) staging system (see section 4.1).110 A small study
of patients with metastasising lesions <1.5 mm noted significantly higher metastases of level IV
lesions compared to control groups.87 A detailed systematic review of the staging of melanoma
reports similar results.88
B

3.8.6

2++

The growth phase characteristics should be stated in the pathology report of all melanomas
except nodular melanomas which, by the time of diagnosis, show only vertical growth
phase characteristics.

A strong association between tumour thickness and prognosis was originally demonstrated by
Breslow83 and has since been verified in many large scale studies of melanoma.75,76,84 ,85,110 Breslow
thickness is the single most important prognostic variable in primary cutaneous melanoma.

3.8.5

2-

2++
2+
1+

The Clark level of invasion should be provided when the lesion has a Breslow
thickness <1 mm.

ULCERATION
A small study of 177 subjects with intermediate thickness melanomas (1.51 to 3.99 mm) identified
epidermal ulceration as one (of four) variables that predicted visceral and bony metastases.89
Ulceration has been shown to act as a prognostic variable after adjustment for other variables.76,84
A study of 1,042 patients identified epidermal ulceration as a significant prognostic variable and
this was incorporated into a mathematical model for predicting recurrence and survival at three,
five and ten years.75 Ulceration was confirmed as a strong prognostic variable in the recent large
scale study that validates the AJCC guidelines.110 Some studies also show that increasing breadth
of epidermal ulceration is associated with an increasingly unfavourable prognosis (see section
3.8.11).75

2+

11

CUTANEOUS MELANOMA

3.8.7

The presence or absence of histological evidence of epidermal ulceration should be noted

in the pathology report.

When Cochrans model is used to calculate the likelihood of recurrence or

death the breadth of ulceration should be stated in mm.

MITOTIC RATE
Although some studies have identified mitotic rate as a significant prognostic variable,76,90 with
survival probability decreasing in a linear relationship with increasing mitotic rate, the exact
strength of this parameter remains unclear. Mitotic rate appears to be a less useful predictor of
survival than variables such as tumour thickness and epidermal ulceration and it is not used as a
staging parameter in the revised AJCC guidelines.110 In some studies the prognostic significance
of mitotic index is either greatly weakened or entirely subsumed after multivariate analysis assesses
other histological and clinical variables.75,90

3.8.8

It is desirable to comment on the mitotic rate, expressed in terms of mitoses per

mm2, in the vertical growth phase component.

INFLAMMATORY REACTION
The association between survival advantage and the presence of tumour infiltrating lymphocytes
(TILs) within the vertical growth phase component is unclear. Although one study demonstrated
a strong correlation,76 the presence of an inflammatory response loses independent prognostic
strength on multivariate modelling.75

3.8.9

REGRESSION

2++
2+

If late regression is apparent it should be included in the pathology report.

LYMPHOVASCULAR INVASION AND SATELLITES

A systematic review found that the prognosis for patients with microsatellites is essentially
identical to that for patients with macrosatellites.88 There was no demonstrable difference in
survival for patients with satellites compared to those with in-transit metastases.

1+

A prospective cohort study of 258 patients with clinical stage I melanoma found that 13 out of
14 patients with histological evidence of lymphatic invasion developed in-transit metastases
after a median interval of 10 months and concluded that lymphatic invasion correlates strongly
with early locoregional cutaneous relapse.91

2++

A study of 140 patients with thick (>3 mm) stage I melanomas reported that the identification of
lymphatic invasion was associated with an increased risk of metastasis but not with overall
survival.90 However, in a series of 17,600 patients the presence of microsatellites had a profound
negative impact on prognosis and in the new AJCC staging system the presence of satellites
upstages the tumour from I or II to IIIb or IIIc.110
Identifying lymphovascular invasion and/or microscopic satellites confers considerable prognostic
value. The presence of lymphatic invasion accurately predicts early cutaneous relapse and should
be included as a stratification criterion for the selection of patients for adjuvant therapy.

12

2++

It is desirable to comment on the host inflammatory response using Clarks

classification system.76

There is an adverse association between histological evidence of regression and outcome, but the
strength of this relationship is disputed.75,76,87 One large study identified tumour regression in the
radial growth phase as a variable that retained predictive strength after multivariate analysis. 76 In
a subsequent study of 1,042 patients the significance of tumour regression was subsumed by the
other clinical and histological features studied.75 Extensive late regression might indicate that the
melanoma has, at some time, been significantly thicker than it now appears. Tumours with this
feature are liable to be understaged.87

3.8.10

2++

2+

3 DIAGNOSIS AND PROGNOSTIC INDICATORS

The histological identification of microsatellites also defines a subset of patients at much greater
risk of relapse. The presence of microsatellites correlates strongly with occult metastatic disease
in regional lymph nodes.
B

3.8.11

Identification of lymphatic space invasion and/or microscopic satellites should be included

in the pathology report.

DERIVING A PROGNOSTIC INDEX

Models attempting to predict accurate survival for patients with melanoma have become
increasingly complex in order to accommodate both the clinical and histopathological data
demonstrated to be of independent prognostic significance.75,76,92 The Cochran model predicts
survival at three, five and ten years, based on simple clinical data (age, sex and anatomic site) in
combination with the Breslow thickness and the breadth of epidermal ulceration.75 An
individualised risk score is derived that predicts the likelihood of survival for any patient with
invasive melanoma. The model can be modified to calculate risk of recurrence (at three, five and
ten years) by inclusion of histogenetic subtype. (Worked examples of how to use Cochrans
model are available on the SIGN website at www.sign.ac.uk).

3.9

If the likelihood of survival is calculated using the Cochran model, the breadth of any
epidermal ulcer should be measured by micrometer and stated in the pathology report.

The way in which the prognostic index is discussed with a patient should be tailored to
the needs of the individual patient.

SPECIALIST PATHOLOGY REPORTING

Significant discrepancy exists between general pathologists, dermatopathologists and between
experts in pigmented lesion pathology, in the reporting of melanocytic tumours.93-95 Both underand over-diagnosis of malignancy is recognised and, for melanoma, there is poor agreement on
the assessment of prognostic parameters.

3.10

2++

Pathologists responsible for reporting melanocytic lesions must be aware of the diagnostic
pitfalls in this area. Participation in appropriate continuing professional development
(CPD) activity is advisable.

Cases where significant diagnostic doubt exists should be referred for specialist opinion,
preferably to a panel of experts.

2++

MELANOMA PATHOLOGY REPORT

The table below outlines the important features of a melanoma pathology report.
Table 5: Features of a melanoma pathology report
Essential features

Desirable features

Breslow thickness

Histogenetic type

Clark level (if Breslow thickness <1 mm)

Cell type

Ulceration

Host inflammatory response

Growth phase characteristics

Mitotic rate

Regression
Lymphovascular space invasion
Microscopic satellites
Microscopic clearance (mm)

13

CUTANEOUS MELANOMA

3.11

PATHOLOGICAL EXAMINATION AND REPORTING OF THERAPEUTIC AND

SENTINEL LYMPH NODE DISSECTION SPECIMENS
Detailed protocols for dissection of therapeutic lymph node dissection specimens are available
in standard textbooks of surgical pathology.74,96
The surgical report should identify
n
n
n

the exact number of lymph nodes within the resection specimen

the total number of nodes containing metastatic disease
extracapsular spread (attributed with a significant reduction in disease free survival although
it does not impact on overall survival).97

When macroscopic examination reveals tumour within a node, a single block of tissue is sufficient
to confirm the observation. Nodes that appear tumour free should be serially sliced (if large) and
all of the tissue processed. Small nodes may be processed intact and levelled to ensure thorough
examination.
Sentinel lymph node biopsies (SNLB) are processed using either lymphoscintigraphy and/or blue
dye to trace the afferent lymphatic channels and node. Protocols giving further details are available.
96,98,99
Nodes identified by lymphoscintigraphy (usually technetium99) should be fixed in formalin
for 24 hours to allow for radioactive decay.
When dye has been used, the sentinel node should be examined macroscopically to determine
whether any staining has occurred. The node should then be bisected through its longest
circumference and both halves processed for the removal of ten serial sections. Sections one,
three, five and ten should be examined by routine haematoxylin and eosin staining. Sections two
and four should be stained immunohistochemically for S-100 protein and HMB-45. Sections six
and seven act as negative controls for immunohistochemistry (IHC) and sections eight and nine
can be used for additional studies or to repeat any unsatisfactory stains.99 If the appearances in
the first set of ten sections are deemed suspicious then additional sets of ten sections can be cut
and stained.
Although IHC facilitates the detection of melanoma in sentinel nodes, the possibility of false
positive results, for example, the misinterpretation of capsular naevus cells, remains. This can be
minimised by careful evaluation of the immunochemical preparations in the context of the
corresponding haematoxylin and eosin stained section.
Groups of sections at multiple levels throughout the sentinel node are sometimes examined, but
there is no evidence that such rigorous sampling increases the diagnostic yield. Detecting melanoma
cells in SNLB using polymerase chain reaction (PCR) techniques cannot be recommended at
present due to concerns regarding both sensitivity and specificity.100

14

3 DIAGNOSIS AND PROGNOSTIC INDICATORS

MELANOMA MANAGEMENT FLOW CHART

Patient / relative / carer notes change /
discharge / bleeding / altered sensation / new lesion

Opportunistic detection by health professional.

Irregular colour, margin, surface, asymmetry

Suspicious Pigmented
Lesion

Feedback to GP

Feedback to GP
Consult GP for
assessment

Benign - Reassure

i
i

Suspicious

Benign Reassure

Refer to appropriate
specialist for assessment
Benign - Reassure

Equivocal, arrange review

photograph within 2 months

Equivocal - Reassess +
photo within 2 months

Suspicious

Local excision if practical

Benign - Reassure
Pathology

Melanoma

Reassess for local lymph nodes and other suspicious pigmented lesions.
Arrange wide excision by locally appropriate specialty sentinel node biopsy

FNAC or
Biopsy

Pathology negative

Clinically suspicious
positive nodes

Evidence of lymph node

metastases

Follow up

Consider need for other treatment

according to clinical exam

Evidence of melanoma elsewhere

i
i

Removal of draining
lymph nodes

i
i

No involved nodes

Refer medical oncology for possible

clinical trial

Refer medical oncology or other

appropriate specialty

No obvious residual
metastatic disease

i
Feedback to GP

Follow up

i = Opportunity to give verbal and / or written information to patients and carers

15

CUTANEOUS MELANOMA

Surgical management and staging

4.1

SURGERY FOR PRIMARY MELANOMA

Historically very wide margins of excision were advocated in the management of melanoma.
Appreciation of Breslow thickness as a prognostic indicator (see section 3.8.4) supports the
concept of a conservative approach to surgery, with narrowing of the margins of excision.101-104
The safety of these narrower margins has been demonstrated in a series of studies.105-108

3
1+

A comparison of 1 cm and 3 cm margins for tumours up to 2 mm thick found no overall survival

difference between the two groups.105 A small number of patients with lesions thicker than 1mm
developed local recurrence.107-109 A 1cm margin should therefore be adequate for melanomas less
than 1mm thick. For lesions between 1-2 mm thickness a width excision of 1-2 cm should be
considered, in the context of a full clinical assessment.

1+
3

The following recommendations use the TNM staging classification recently updated by the
American Joint Committee on Cancer (AJCC; see section 4.2).110
D

In pTis (melanoma in situ) a surgical excision margin of 2 to 5 mm is

recommended to achieve complete histological excision.

In pT1 (melanoma 0 to 1 mm thickness) a surgical excision margin of 1 cm is

recommended.

In pT2 (melanoma 1 to 2 mm thickness) a surgical excision margin of 1 to 2 cm is

recommended.

In pT3 (melanoma 2 to 4 mm thickness) a surgical excision margin of 2 cm is

recommended.

In pT4 (melanoma > 4 mm thickness) a surgical excision margin of 2 cm is recommended.

p = pathological

T = tumour

The suggested width of excision at sites of aesthetic and functional importance requires clinical
consideration. The deep excision margin should incorporate adipose tissue down to, but not
including, the deep fascia.111,112 The majority of melanomas should be excised with direct wound
closure (see section 3.5). No evidence was identified on the role of optimal timing of wide
excision in melanoma.

4.1.1

Wider excision requires referral to a specialist centre to facilitate the use of reconstructive
and staging techniques.

The deep excision margin should incorporate adipose tissue down to, but not including,
the deep fascia.

SURGICAL CLEARANCE
Guidelines recommend that the microscopic distance of the lesion from the lateral and deep
margins should be measured in mm and the results stated in the pathology report,62
(see section 3.5).
Measurement of surgical clearance is standard practice in reporting other tumours (eg breast and
colorectal carcinoma) where the adequacy of surgical removal dictates the need for further
treatment. This is directly comparable to the management of melanoma where the requirement
for further surgical excision is dictated by a combination of the Breslow thickness and the distance
of the lesion from the surgical margins defined at the time of initial surgery.

16

4 SURGICAL MANAGEMENT AND STAGING

4.2

The microscopic clearance of the tumour from the nearest lateral margin and from the
deep margin should be stated (in mm) for all excision biopsies.

Surgical excision margins should be recorded by the surgeon.

STAGING MELANOMA
Melanoma should be staged using the TNM staging classification described by the American
Joint Committee on Cancer110 and outlined in Table 6.
Table 6: AJCC Staging Classification
Melanoma TNM Classification

T classification
Breslow thickness

Ulceration Status

Stage

5 year
survival rate (%)

T1

1 mm

a: without ulceration and level II/III

b: with ulceration or level IV or V

IA
IB

95.3
89-90.9

T2

1.01 2 mm

a: without ulceration
b: with ulceration

IB
IIA

89-90.9
77.4-78.7

T3

2.01 4 mm

a: without ulceration
b: with ulceration

IIA
IIB

77.4-78.7
63-67.4

T4

> 4 mm

a: without ulceration
b: with ulceration

IIB
IIC

63-67.4
45.1

N classification
No. of Metastatic Nodes

Nodal Metastatic Mass

N1

1 node

a: micrometastasis*
b: macrometastasis**

IIIA
IIIB

69.5
59

N2

2-3 nodes

a: micrometastasis*
b: macrometastasis**

IIIA/B
IIIB/C

63.3
59

c: in-transit met(s) / satellite(s) without

metastatic lymph nodes

IIIB

No data available

IIIC

26.7

N3

4 or more metastatic nodes,

or matted nodes, or
in-transit combination of
in-transit mets/satellites or
ulcerated melanoma and
metastatic lymph nodes

M classification
Site

LDH

M1a

Distant skin,
subcutaneous, or nodal
mets

Normal

IV

18.8 +/- 3

M1b

Lung mets

Normal

IV

6.7 +/- 2

M1c

All other visceral mets

Any distant mets

Normal
Raised

IV

9.5 +/- 1.1

Mets = metastases
LDH = Lactate Dehydrogenase
*Micrometastasis are diagnosed after elective or sentinel lymphadenectomy
** Macrometastasis are defined as clinically detectable nodal metastases confirmed by therapeutic
lymphadenectomy or when nodal metastasis exhibits gross extracapsular extension.

17

CUTANEOUS MELANOMA

4.3

MANAGEMENT OF REGIONAL LYMPH NODES

Examination of the regional lymph node basin is an essential component of the clinical evaluation
of melanomas (see section 3.7.1). The presence or absence of nodal metastasis is the most
significant predictor of outcome in melanomas.113

2++

The risk of developing nodal metastases increases with the thickness of the primary melanoma.114,115
Metastasis to lymph nodes is rare in melanomas less than 1 mm thick. At least 25% of melanomas
between 1.5 and 4 mm will have microscopic lymph node metastasis at the time of primary
diagnosis and this rises to over 60% incidence in melanomas more than 4 mm thick.116,117
Regional lymph node metastasis is associated with poor prognosis, survival being less than half
that of patients without nodal involvement. 118-120
4.3.1

MANAGEMENT OF PALPABLE LYMPH NODES

Melanoma patients who have palpable lymph node(s) either at their first presentation or at a
follow up visit should have a sample taken for fine needle aspiration cytology (FNAC). If the first
sample is unsatisfactory or negative with persistent suspicion, it should be repeated. If doubt
persists an open biopsy can be performed.9,121

4.3.2

2++

Palpable regional lymphadenopathy must be fully investigated in patients with primary

melanoma.

If there is palpable lymphadenopathy FNAC should be used to obtain cytological

confirmation of metastases.

If open biopsy is undertaken the incision must be placed in the same line as for a potential
radical lymphadenectomy.

THERAPEUTIC LYMPH NODE DISSECTION

Nodal involvement indicates an advanced stage of disease. Confirmation of metastatic melanoma
in one node is an indication for radical dissection of that lymph node basin. The number of
involved nodes is of prognostic significance. Ten year survival varies between 20 to 45% dependent
on the extent of nodal involvement.9,113,118,120
Therapeutic lymph node dissection is beneficial in controlling locoregional disease. The risk of
recurrence in the dissected node field remains, particularly with head and neck melanomas.122,123

2++

Groin nodes include a superficial group of inguinal nodes below the inguinal ligament and the
obturator and iliac group of nodes which lie deeper in the pelvis. Ilioinguinal dissection offers a
survival benefit in patients with palpable positive inguinal nodes compared with inguinal block
dissection of the femoral triangle node.124 ,125

2++

Head and neck melanomas have the most variable pattern of lymph node metastasis and require
a variety of types of neck dissection that may include the parotid or the posterior occipital chain
nodes.123

4.3.3

Radical lymph node dissection requires complete and radical removal of all draining
lymph nodes to allow full pathological examination.

Regional lymph node dissection carries a well defined and significant morbidity and
should be undertaken only by surgeons with appropriate expertise.

MANAGEMENT OF NON-PALPABLE NODES

The high incidence of occult metastasis in clinically impalpable nodes has prompted surgeons to
investigate regional lymph nodes. This is achieved either by elective lymph node dissection or by
sentinel lymph node biopsy.

18

4 SURGICAL MANAGEMENT AND STAGING

4.3.4

ELECTIVE LYMPH NODE DISSECTION

Although retrospective series126-128 suggest that resection of clinically non-involved lymph nodes
provides a survival advantage in melanomas of intermediate thickness, this has not been confirmed
in RCTs.129-131

2+

The Intergroup Surgical Melanoma Trial132 identified a small subgroup of patients with a possible
survival advantage following elective lymph node dissection. This subgroup consisted of patients
<60 years with non-ulcerated melanomas of 1 to 2 mm thickness situated on limbs. Sentinel
lymph node biopsy (see section 4.3.5) has replaced elective lymph node dissection as a method
of staging the regional lymph node basin.

1+

4.3.5

Elective lymph node dissection should not be routinely performed in patients with primary
melanoma.

SENTINEL LYMPH NODE BIOPSY (SLNB)

The sentinel lymph node is defined as the first node in the lymphatic basin that drains the lesion
and is the node at greatest risk for the development of metastasis.133 Biopsy of this node can assist
in staging patients at risk of metastatic disease. Current practice is for patients with a positive
sentinel node to proceed to radical node dissection.
The standard for sentinel node biopsy is a triple diagnostic approach of lymphoscintography;
blue dye dermal infiltration and localisation using a hand held gamma probe.133-138 Performing
SLNB requires appropriate surgical expertise,133 specialist nuclear medicine services and the
availability of serial sectioning and immunohistochemistry techniques (see section 3.5).

2+

Sentinel lymph node biopsy accurately determines the presence or absence of metastasis within
the regional lymph node basin139-141 and it is a useful staging tool in melanomas >1 mm.110 In
thick melanomas (>4 mm) it can identify a subset of good prognosis melanomas which are node
negative.141

2++
4

4.4

SLNB should be considered as a staging technique in patients with a primary melanoma

>1 mm thick or a primary melanoma <1 mm thick of Clark level 4 (see section 3.8.5).

ISOLATED LIMB PERFUSION

Isolated limb perfusion (ILP) is a surgical technique that allows localised delivery of a high dose
of chemotherapy (usually melphalan). Minimal systemic leakage occurs confining toxicity to the
limb. ILP has been used in two clinical situations:142,143
n
n

adjuvant treatment for high risk primary melanoma

therapeutic treatment for major limb recurrence of melanoma.

Isolated limb perfusion is a significant surgical undertaking and should only be made available
in centres where a significant number of such operations are performed each year. One centre
can provide this service for a population of approximately five million people.

4.4.1

ILP should be performed in regional centres.

ADJUVANT TREATMENT
A prospective multicentre RCT involving 832 patients showed that prophylactic ILP with melphalan
cannot be recommended in high risk primary limb melanoma.144

1+

ILP should not be used as an adjuvant treatment.

19

CUTANEOUS MELANOMA

4.4.2

THERAPEUTIC TREATMENT
A multicentre RCT145 and reviews146,147 suggest that hyperthermic ILP with melphalan alone or
melphalan plus Tissue Necrosis Factor-a can produce a complete though short lived response rate
ranging from 50 to 90% in patients with limb recurrence (in-transit metastases).

ILP is the treatment choice for bulky limb disease for patients fit to undergo the procedure.

4.5

OTHER METHODS FOR CONTROLLING LOCOREGIONAL CUTANEOUS

RECURRENCE

4.5.1

CARBON DIOXIDE LASER ABLATION

The carbon dioxide laser delivers short wave length energy in a focussed light beam to destroy
tumour nodules. It can be applied under local anaesthetic, can be repeated and provides effective
local disease control.148-150

4.5.2

Carbon dioxide laser ablation can be considered for multiple lesions of trunk or abdomen
and for limb disease when ILP is not appropriate.

OTHER METHODS
Techniques such as cryotherapy, intralesional bacille Calmette-Guerin (BCG) and radiotherapy
have been used in the past. Their use has not been based on published scientific evidence.

20

14

Patients with substantial cutaneous recurrence should be referred to an appropriate centre

where a range of treatment options can be considered.

5 FURTHER INVESTIGATIONS AND NON-SURGICAL STAGING

Further investigations and non-surgical staging

Further investigation to determine precisely the extent of the disease is important in terms of
prognosis, treatment, entry into clinical trials, research and audit.
Following pathological microstaging of a patients melanoma (see section 3.7) the presence of
metastatic spread can be determined using three techniques:
Surgical: assessment of the impalpable node by sentinel node biopsy and of the palpable
node (see section 4)
Imaging: conventional radiography, ultrasound scanning (US), computerised tomography (CT),
magnetic resonance imaging (MRI) and positron emission tomography (PET)
Blood Tests: routine haematology, tumour markers, liver function tests and lactic
dehydrogenase (LDH).

5.1

IMAGING TECHNIQUES

5.1.1

CHEST X-RAY
One large retrospective study was identified that examined the role of chest X-ray (CXR) in
staging melanoma in 876 asymptomatic patients with stage I or II melanoma.151 One hundred
and thirty patients (15%) had suspicious CXR findings necessitating further investigation but
only one patient (0.1%) was found to have a true pulmonary metastasis.

5.1.2

ULTRASOUND SCANNING
Two retrospective studies have examined the ability of lymph node ultrasound scanning (US) to
stage melanoma. One study of 87 patients found the sensitivity of US to be 86% and the
specificity 74%.152 Ultrasound examination of the regional lymph nodes is a less accurate means
of determining nodal status than sentinel node biopsy.153

5.1.3

COMPUTED TOMOGRAPHY
Two relatively small retrospective studies have shown that computerised tomography (CT) scanning
does not assist in staging and may be counterproductive by generating false positives.154,155
C

5.1.4

Chest X-ray, ultrasound scanning and computerised tomography scanning are not indicated
in the initial assessment of primary melanoma unless indicated for investigation of clinical
symptoms and signs.

MAGNETIC RESONANCE IMAGING

Magnetic Resonance Imaging (MRI) is unable to image the lungs in sufficient detail to exclude
parenchymal disease such as metastases, and is therefore unable to provide a comprehensive
assessment of disease status in melanoma patients. No studies were found that examined the
routine use of MRI to identify distant disease in stage I-III melanoma. There is insufficient
evidence to make a recommendation on the role of MRI scanning and melanoma staging.

5.2

LABORATORY INVESTIGATIONS
Investigations such as full blood counts (FBC) and liver function tests (LFT) are not helpful in
identifying asymptomatic patients with distant disease.156,157 Elevated lactate dehydrogenase (LDH)
in the absence of clinical symptoms or signs is the first indicator of stage IV disease in 12.5% of
patients. By the time other blood parameters are significantly deranged, the patient will have
other manifestations of metastasis.156,157 For patients with advanced disease, LDH is now included
in the AJCC classification system.110 The evidence and availability of tumour markers such as
S100 protein, Melanoma Inhibitory Activity (MIA) protein and tyrosinase mRNA are limited.
Investigating these markers is not routinely indicated.202
D

Routine blood tests are not indicated in staging asymptomatic melanoma patients.
21

CUTANEOUS MELANOMA

Adjuvant treatment of stage II and III disease

Pathological features of primary melanoma, particularly thickness and ulceration, make it possible
to identify patients with stage II disease who are at high risk of local or systemic recurrence (see
section 3.7). Once patients have had melanoma recurrence in the local regional lymph nodes
(stage III disease), over 50% will subsequently develop further metastatic spread. These observations
support attempts to identify adjuvant treatment such as chemotherapy, immunotherapy and
radiotherapy, given after complete clinical surgical clearance of melanoma.
An RCT of adjuvant chemotherapy and immunotherapy including the use of BCG and DTIC (see
section 8.2) reported negative results.158 A number of well designed trials of adjuvant therapy
open to new patients are ongoing.

6.1

1+

RADIOTHERAPY FOLLOWING LYMPH NODE DISSECTION

Three retrospective cohort studies,159-161 two studies using historical controls162,163 and an
observational study were identified.164 Studies in small numbers of patients have shown that
outcomes following lymph node dissection plus radiotherapy were not significantly different
from those following dissection alone.165
D

3
1-

The routine use of adjuvant radiotherapy is not recommended for patients who have had
therapeutic lymph node dissections.

6.2

IMMUNOTHERAPY

6.2.1

INTERFERON
The observation that a large number of primary melanomas undergo partial regression and a small
number of melanoma patients experience total regression of the whole melanoma has led to the
concept of using either specific or non-specific immune stimulation as therapy for melanoma.
Adjuvant interferon has been used in at least 10 large RCTs involving over 5,000 patients.166-175
Interferon dosage, frequency and route of administration and total duration of therapy all varied,
but no trial reported significant overall survival benefit for interferon-treated patients. Several of
the larger studies do report longer disease-free intervals after surgery169-171 but there is no evidence
of a dose or duration of treatment effect. Toxic effects of interferon include extreme lassitude,
muscle aches, headache, rigors, nausea, vomiting, and marrow toxicity, the latter being the
cause of death in two patients in the first reported high dose study.

1++

Final results are not yet available for some of these trials, and until these are published it would
be premature to offer interferon to patients with AJCC stage II or stage III melanoma.

6.2.2

Adjuvant interferon should not be used for AJCC stage II and III melanoma patients other
than in a trial setting.

Patients with AJCC stage II and III disease should be offered entry into RCTs to confirm
whether or not interferon therapy extends the disease-free interval after surgery.

VACCINES
Melanoma vaccines are still in the research phase. There are some Phase I and II studies that do not
have controls. The vaccinia melanoma oncolysate (VMO) RCT involved 217 patients but did not
show an advantage for the vaccine.176 An RCT including 700 patients compared vaccinia melanoma
cell lysates (VMCL) to no immunotherapy and found that VMCL did not significantly improve overall
survival or relapse-free survival.177 An RCT comparing interferon alfa-2b with a GM2 ganglioside
vaccine was closed early when the interferon showed evidence of increased relapse-free survival and
overall survival.178 Melanoma vaccines are not currently available commercially.

22

Patients should be entered into vaccine clinical trials as appropriate.

11++

7 PATIENT FOLLOW UP IN STAGE I, II AND III DISEASE

Patient follow up in stage I, II and III disease

7.1

INTRODUCTION
The purpose of the follow up clinic is to
provide reassurance and psychological counselling
provide comprehensive information about all aspects of the patients melanoma
detect recurrent disease
teach patients techniques of self examination for discovery of local and nodal recurrence
detect new primary melanomas.

n
n
n
n
n

Follow up is an opportunity to provide relevant information to patients, carers and family

members.

No RCTs on follow up methods were identified. Eight retrospective studies179-186 and one prospective
cohort study187 were identified which highlight the following issues:
who should be followed up?
how frequently should patients be followed up?
for how long should patients be followed up?
how are recurrences detected?

n
n
n
n

These questions are addressed in this section.

7.2

WHO SHOULD BE FOLLOWED UP?

Current practice is that all patients with an invasive melanoma who are at risk of recurrent
disease have a period of follow up and all patients with stage III disease have a prolonged follow
up, often for the rest of their life. Patients with melanoma in situ have no risk of recurrence.179
Patients with a pure radial growth phase tumour have a very low chance of recurrence.82

7.3

Patients who have had melanoma in situ do not require follow up.

Patients with an invasive melanoma should have a period of follow up; stage III patients
with lymph node metastases should have longer, possibly lifelong, follow up.

SITE OF INITIAL RECURRENCE

Large retrospective studies show that between 60 and 80% of first recurrences are local and/or
nodal.180-189,188

7.4

TIMING AND RATE OF RECURRENCE

The timing and rate of recurrence of melanoma is well recognised (see Figure 1 & Table 7).185,188

Table 7: Timing and rate of recurrence of melanoma

Tumour thickness

Recurrence rate

Median recurrence time

<1.5 mm

2-19%

25-32 months

>1.5 mm

47-66%

12-16 months

The annual risk of recurrence for tumours <1.5 mm thick remains <6% for the first five years
dropping to under 1% for the next five years. Tumours >1.5 mm thick have a higher risk of
recurrence in the first year, dropping to <2% after year five.179,184,185 Overall most studies indicate
that about 80% of recurrences occur within the first three years179,188,189 but up to 16% of first
recurrences have been reported to occur after five years185 and late recurrence (more than ten
years) is well recognised.190-193

23

CUTANEOUS MELANOMA

Figure1: Breslow thickness plotted against recurrence rates, years 1 to 10 following surgery
Graph compiled from data from McCarthy et al, 1988185

7.5

FREQUENCY AND DURATION OF FOLLOW UP: VARIATION IN CURRENT

PRACTICE
Many follow up frequencies and durations have been suggested but there is no overall consistency
in the recommendations made for either follow up frequency or duration. Examples of the variation
in recommendations are given below.

7.5.1

THIN TUMOURS
The variation in the management of tumours <0.75 thick mm is considerable. Three studies
recommend follow up at yearly intervals for between 15 years and life. 184-186 Two studies advocated
six-monthly reviews for five years or ten years,187,188 reducing to yearly for a further five years187 or
for life;188 and another suggested that tumours less than 0.6 mm needed no follow up but those
over 0.6 mm needed three-monthly reviews for eight years.181 Another study recommended threemonthly follow up for three years only.179

7.5.2

THICK TUMOURS
For thick tumours > 4 mm the recommendations are equally varied. Five papers propose an initial
three-monthly follow up for three,179,188 four,117 five187 or eight years.181 Two papers suggest onemonthly follow up for the first two years.185,186 One advocated six-monthly visits for the third
year and then yearly for life,185 whilst the other recommended two-monthly visits for the third
year, six-monthly visits for the fourth year and then yearly visits until year 15.186

A further study recommended two-monthly follow up for the first year, three-monthly for year
two, four-monthly for year three, five-monthly for year four, six-monthly for year five to ten and
then yearly for life.194
7.5.3

LIFELONG SURVEILLANCE
One aspect of follow up recommended by both Australian and North American authors is lifelong
surveillance of all patients with the aim of detecting late recurrences and picking up second
primaries.184,185 Similar follow up practice has been advocated by Italian authors.188 The risk of
recurrence after eight years was considered to be too low for French authors to recommend
follow up after this time.181 British authors, while acknowledging the benefits of a lifelong

24

7 PATIENT FOLLOW UP IN STAGE I, II AND III DISEASE

follow up, suggest limiting the follow up period to five years due to limited resources.179 Another
UK group suggests follow up for 15 years but accept that a five year period may be more
manageable.186

7.6

The specific frequency and duration of follow up should be determined from the timing
and rate of recurrence of the individual patients melanoma.

PSYCHOLOGICAL AND EMOTIONAL SUPPORT

None of the studies identified explored patients psychological and emotional needs when
determining the frequency or length of follow up.

7.8

Follow up frequency and duration should take account of patients psychological and
emotional needs.

SECOND PRIMARIES
Three retrospective studies found second primaries in 1.2%, 2% and 7% of their patients.179,185,195
The timing of discovery ranged from synchronous with the initial melanoma to more than 10
years later. The second primaries were usually thinner. One paper estimated that the Scottish
melanoma patients in their study had a 200-fold increase in risk of developing a second melanoma
compared to the general population,195 (see Table 2, section 2.4.2).

7.9

HOW ARE RECURRENCES DETECTED?

Large retrospective studies have shown that 90% of recurrent disease in patients with stage I and
II is detected solely by signs or symptoms noted either by the patient or the physician, with
imaging techniques (usually chest X-ray) detecting the remainder.180,181,183,196,199 Patients own
detection rates in between clinic visits are generally in the range of 33 - 72% 179,181,183,186,199,197 but
in one study where patients with stage I-III melanoma were meticulously educated in self
examination techniques the rate of self detection rose to 100%. 198 The rate of self detection in
one prospective trial was much lower at 17%.187 Three retrospective studies indicate that the
overall survival time is the same for patient-detected recurrences as for those detected in the
clinic.183,186,199

7.9.1

ROUTINE LABORATORY TESTS

Routine laboratory tests (full blood count and liver function tests) do not detect asymptomatic
recurrent disease in stages I-III.156,180,181,182,198
Lactate dehydrogenase (LDH) is a marker of liver metastases and tumour burden in patients with
stage IV disease that indicates a poor prognosis with a median survival of six months.199-201 Two
studies have looked at LDH as a first indicator of metastases. In stage III disease an elevated LDH
was the first indicator in 12.5% of patients (with a sensitivity of 73%) when tested for every
three months.157 In a prospective cohort study of stages I-IV disease an elevated LDH was the first
indicator in 2% of recurrences when patients were tested every 12 months (stages I and II
melanoma) or every six months (stages III and IV melanoma).187

7.9.2

TUMOUR MARKERS
A variety of new tumour marker blood tests have been developed:
n
n
n

S100B protein
Melanoma Inhibitory Activity (MIA) protein
Tyrosinase mRNA.

1+

None of these tests is currently sensitive or specific enough to be used in clinical practice.202

25

CUTANEOUS MELANOMA

7.9.3

IMAGING
Chest X-ray

In stages I and II, four retrospective18,183,198,203 and one prospective study187 have reported the
percentage of metastases detected by routine chest X-ray to be 0%198,203 (frequency of examination
six-monthly203 or 12-monthly198), 4.5%187 (frequency of examination 12-monthly), 5%181 (frequency
of examination six-monthly) and 11%183 (frequency of examination three-monthly in year one,
four-monthly in year two, six-monthly in years three to five and yearly thereafter). There is
evidence that the identification by chest X-ray of treatable asymptomatic pulmonary metastases
gives no overall survival advantage when compared to symptomatic pulmonary disease.134 In
stage II and III melanoma, one retrospective study detected 6% of recurrences by chest X-ray
(frequency of examination two-monthly for year one, four-monthly for year two, six-monthly for
year three and yearly thereafter).180 In stage III melanoma, one prospective study detected 4.4% of
recurrences by chest X-ray (frequency of examination six-monthly).187
Ultrasound (US)

In stage I and II melanoma, two retrospective studies were identified which used abdominal US
routinely during follow up in asymptomatic patients. One study found that 5% of metastases
were detected (frequency of examination six-monthly)181 and the other found that none were
detected using this modality (frequency of examination six-monthly).203 A single prospective trial
found a detection rate of 1.5% (frequency of examination 12-monthly).187
In stage III melanoma a single prospective trial found a detection rate of 4.4% of all detected
metastases using abdominal ultrasound (frequency of examination six-monthly).187 In this study
21% of all metastases in stages I and II; and 9.5% in stage III were detected by using ultrasound
to examine regional nodes.
Computed tomography (CT)

In stage I and II melanoma, two retrospective studies were identified that used CT routinely for
examination of brain, chest and abdomen during follow up in asymptomatic patients. 181,203 The
first study detected less than 1% of metastases using CT, the second reported a detection rate of
21% (frequency of examination in both studies six-monthly). In stage III, four retrospective
studies were identified which looked at the usefulness of CT as a staging exercise upon a patient
being diagnosed as stage III. One study found that CT offered a 2% chance of finding further
metastases.183 The other three studies found a true positive rate of detecting further metastatic
disease of 4% (false positive rate of 8%),204 7% (false positive rate of 22%)155 and 16% (false
positive rate of 12%).205
D

Routine full blood counts, liver function tests, tumour markers, chest X-rays, ultrasound
scans, computed tomography and lactate dehydrogenase are not recommended as part of
a follow up schedule in the asymptomatic patient.
n

26

Patients should be educated in self assessment techniques to detect local and nodal
recurrent disease and secondary lesions and appraised of the possibility of late recurrence
There should be an easy route into the clinic if problems occur between clinic visits or
after discharge.

8 MANAGEMENT OF STAGE IV DISEASE

Management of stage IV disease

The outlook for patients with distant and visceral metastatic melanoma is poor with survival
time ranging from six to nine months. Survival appears to be increased in women and in those
patients who have undergone surgery for metastases.206 Poorer survival is associated with initial
metastases to the skin and brain; poor Karnovsky status; involvement of more than two primary
sites;206 short durations of remission; visceral compared to non-visceral metastases;207 an ECOG
status of one or less, and metastases to the lungs, gastrointestinal tract or liver.208

8.1

SURGERY
Metastasectomy may be an option for patients with distant skin, node and visceral metastases. In
subcutaneous metastases prevention of ulceration of superficial lesions is best ensured by resection
when they are at a size where skin closure is possible. Surgery of single or localised metastases
has been shown to improve survival.208 The proportion of patients suitable for metastasectomy
ranges from 10 to 25%.206,209,210 Five year survival of 14-33% was described in one retrospective
review for those with distant subcutaneous and lung metastases respectively. This study showed
prognostic significance for Breslow thickness, number of metastases and prior disease-free
interval. 206

8.2

Metastasectomy should be considered in patients with stage IV disease.

CHEMOTHERAPY, CHEMOIMMUNOTHERAPY AND IMMUNOTHERAPY

No RCTs were identified comparing systemic therapy with placebo or best-supportive care in
metastatic cutaneous melanoma.211 The most commonly used agent is DTIC (dacarbazine), a
single agent with an overall response rate activity of approximately 20%.211

8.2.1

SINGLE AGENT OR COMBINATION THERAPY

A meta-analysis comparing the gold standard DTIC with combination chemotherapy, with or
without immunotherapy, found a response rate to treatment of 16.9% for single agent DTIC; no
statistically significant benefit for multiple drug regimens with or without DTIC compared to
single agent DTIC was identified.212 Interferon (IFN) combined with DTIC produced a 53%
greater response rate than DTIC alone though there was no increase in survival.
One of the most popular combination regimens, the Dartmouth regimen (DTIC, cisplatin,
carmustine and tamoxifen), was compared with single agent DTIC in a randomized Phase III
study.213 There was more toxicity with the combination regimen in that 21% versus 2% were
taken off treatment due to unacceptable side effects. The response rate was higher with the
combination therapy (18.5% versus 10.2%) but there were no complete responses and no survival
difference between the two treatments.

1++

The oral preparation of DTIC, temozolamide, has been shown to have equivalent efficacy and
better CNS penetration.214
Tamoxifen
Most published studies are Phase II non-randomised studies incorporating fewer than fifty patients.
One review of seven Phase II and nine RCTs concluded that tamoxifen does not improve patient
outcome.215 Two RCTs published since the review also conclude against any benefit for addition
of tamoxifen.216,217
Interferon a

1+

An overview of trials including six published and five unpublished melanoma trials of 1,164
patients evaluated regimens with or without IFN.218 The overall response rates for IFN containing
regimens was 24% compared with 17% without IFN. Analysis of five trials where the survival
data were reported demonstrated a pooled odds ratio for improved survival of 0.69 but heterogeneity
of patient groups may have led to the non-significant result.218

27

CUTANEOUS MELANOMA

Multiple drug regimens and DTIC-based chemoimmunotherapy combinations increase response

rates but improved rates do not correlate with better survival

1+

Interleukin 2
Interleukin 2 (IL2) has been given intravenously or subcutaneously as a single agent or in
combination with IFN and chemotherapy. Although durable responses are occasionally seen, the
data do not support its routine use outwith a clinical trial.219
A

Dacarbazine (DTIC) is the standard single agent of choice in stage IV melanoma.

Multiple drug regimens including those with tamoxifen and interferon a do not improve
survival compared to single agent DTIC and are not recommended outside of clinical
trials.

Patients should be evaluated before every cycle of chemotherapy and treatment discontinued
if there is poor tolerance or lack of benefit after three cycles.

Patients with metastatic melanoma should be treated within a clinical trial wherever
possible and be offered palliative care.

8.3

RADIOTHERAPY

8.3.1

RADIOSENSITIVITY
There is evidence that melanoma cells in vitro have a spectrum of radiosensitivity and that
melanoma should not be considered a uniformly radioresistant disease.220 Experimental studies
have suggested that atypical, large radiotherapy fraction sizes may be more efficacious than
standard treatments but at present there are no randomised trials to support the use of large
fraction sizes routinely.220,221

8.3.2

BONE METASTASES
Studies looking at the treatment of bone metastases usually include only a small percentage of
patients with melanoma. Recommendations have been extrapolated from the data available
from studies of bone metastases from various tumour types. When using single fractions to
palliate pain from bone metastases, an 8 Gy fraction is effective and provides superior pain relief
to lower doses.222 There does not appear to be an advantage to using 20 Gy in four fractions over
an 8 Gy single fraction.223 Some patients may benefit from higher dose, fractionated regimens,
although this has not been fully established. 224

8.3.3

Single dose radiotherapy of a least 8 Gy is an effective treatment for bone metastases.

All patients with painful bone metastases should be offered radiotherapy.

2+
2++
4

SPINAL CORD COMPRESSION

There is no clear evidence to support or refute the use of radiotherapy (in combination with other
treatments) to alleviate the pain and neurological deficit associated with spinal cord compression
caused by metastatic melanoma.225,226
The value of surgical intervention in such patients has been established.226 Patients with symptoms
of spinal cord compression should be referred urgently to an appropriate surgeon.227

28

4
3

All patients with spinal cord compression should be referred urgently for surgical
intervention and/or palliative radiotherapy.

3
4

8 MANAGEMENT OF STAGE IV DISEASE

8.3.4

BRAIN METASTASES
Although central nervous system (CNS) involvement by melanoma is a common finding at autopsy,
brain metastases are diagnosed in only approximately 10% of patients before death.228 For cerebral
metastases from all tumour types, good performance status, favourable response to corticosteroid
treatment, and the absence of systemic disease are statistically significant predictive factors for a
better survival. 229
Postoperative radiotherapy has been used as adjuvant treatment following the resection of CNS
disease. However, no survival benefit of postoperative radiotherapy has been demonstrated.230,228
Radiotherapy without surgery, combined with corticosteroids appears to palliate the symptoms
of some patients with inoperable cerebral metastases from melanoma but again there is no
evidence of a survival benefit.220,230,231 Radiosurgery (stereotactic radiotherapy) has been used to
treat inoperable patients who are fit enough to undergo this procedure, and the results may be
equivalent to radiotherapy alone.232 Radiosurgery remains an experimental technique in the
treatment of this disease.

8.4

Patients with good performance status, favourable response to corticosteroid treatment,

the absence of systemic disease and who harbour favourable CNS disease should be
considered for surgical resection of their CNS disease.

If surgery is not possible, whole brain radiotherapy combined with corticosteroids may
help palliate neurological symptoms.

4
2+

SPECIALIST PALLIATIVE CARE

The General Medical Council has stated that basic palliative care skills are required by every
member of the medical profession.233 The Clinical Standards Board for Scotland (CSBS) has
agreed standards for the provision of both basic and specialist palliative care.234 Specialist palliative
care is an integral component of the care of patients with advanced malignancy, required at
varying times during their illness. SIGN guideline no. 44 (Control of pain in patients with
cancer) covers the evidence base for pain control in all cancers.235
Patients who develop metastatic melanoma require input from a number of agencies both within
and outwith the health service. They may need rehabilitative, functional, social and/or financial
support services, most of which are available in specialist palliative care settings, as well as in
primary care and cancer centres. The evaluation of the effectiveness of specialist palliative care
involves assessment of the different dimensions of care provided, such as pain and other symptom
control, psychological care, care of the family and carers, rehabilitation and terminal care.
Three RCTs were identified that included all carcinomas, which, in the context of palliative care,
are reasonable to relate to patients with melanoma.236-238 The first two studies looked at the effect
of coordinating all services available within the NHS, local authorities and the voluntary sector
via the addition of nurse coordinators. A total of 203 cancer patients expected to live for less
than one year were randomly assigned to either the intervention or the routine services group.
Patients assigned to the intervention group spent fewer days in hospital, required fewer home
visits and their family were less likely to feel angry about their relatives death.236,237 The third
RCT used place of death as the outcome measure in a study of 434 patients with incurable
malignant disease.238 The intervention group had inpatient and outpatient hospital services provided
by the palliative medicine unit, the unit served as a link to community services, predefined
guidelines maintained communication between services and community staff took part in an
educational programme. Significantly more intervention group patients died at home and spent
less time in nursing homes in their last months of life.

1+

A systematic review of the effectiveness of specialist palliative care teams identified 18 studies,
including five randomised controlled trials.239 Specialist palliative care teams were associated
with more time spent at home by patients, satisfaction of patients and their carers, symptom
control, a reduction in the number of inpatient hospital days, a reduction in overall cost, and
with the patient dying where they wished.

29

CUTANEOUS MELANOMA

30

Patients with advanced melanoma require a coordinated multiprofessional approach with

input from a specialist palliative care team.

Patients with poorly controlled symptoms should be referred to specialist palliative care
at any point in the cancer journey.

9 MELANOMA IN WOMEN

Melanoma in women

9.1

PREGNANCY
Pregnancy is frequently associated with increased activity of benign melanocytes leading to
pigmentary changes. This has led to concern that pregnancy is deleterious for women with
melanoma.
The prognoses of women with thickness-matched melanomas who embarked on a pregnancy
after apparently successful surgical treatment of AJCC stage I or II melanoma have been
compared.240-243 No difference in disease-free or overall survival is found between women who
have, and women who have not, become pregnant after melanoma treatment. Prognosis is mainly
dependent on tumour thickness.240-243
There is no substantial evidence of an effect of pregnancy in women with stage III and IV
melanoma, but as the prognosis for these groups is already poor, the possibility of a maternal
death during pregnancy or when the child is an infant is high. Obstetricians and others managing
pregnant women with advancing stage IV melanoma should be aware that terminating the pregnancy
will have no effect on the outcome for the mother.

2++

The placenta of an infant born to a mother with stage III or IV melanoma should be examined for
the presence of melanoma metastases. If they are present there is a 20% risk of death of the baby
from transplacental melanoma.244-246

9.2

Women who develop melanoma during a pregnancy show a greater mean thickness of the primary
lesion at the time of excision than age-matched non-pregnant women.242,243 This suggests either
delayed diagnosis or accelerated growth due to the hormonal and immunological environment
of pregnancy. There is no evidence to support the suggestion that it is physiological for melanocytic
naevi to change during pregnancy.247

2++

There are no good data on prognosis for women who embark on a pregnancy having had a
melanoma diagnosed and treated during a previous pregnancy. One paper reports that patients
with stage I or II disease have no greater recurrence rate than non-pregnant age-matched controls
but that those with nodal disease have significantly higher recurrence rates.248

Women with a significant risk of recurrence (localised disease of >1mm thickness) who
wish to become pregnant after surgery for stage I or II melanoma should be advised to
delay pregnancy for two years postsurgery, as the likelihood of recurrence is highest during
this period.

Pregnant women who present with growing or changing pigmented lesions should be
treated as non-pregnant women.

ORAL CONTRACEPTION AFTER MELANOMA TREATMENT

Meta-analysis provides no evidence that use of the oral contraceptive is a risk factor for
melanoma.249 Five large studies indicate that oral contraceptive use by women after surgery for
stage I or II melanoma does not adversely affect their prognosis.248,250-254

9.3

2++

Women who have had a melanoma treated should select contraception in the same way
as women who have not had a melanoma.

HORMONE REPLACEMENT THERAPY (HRT) AFTER MELANOMA TREATMENT

Five case controlled studies show no effect of HRT as a risk factor for melanoma.251,252,255,256,257

2+

Women who have had stage I and II melanoma and who wish to take HRT should be
treated as women who have not had melanoma.

31

CUTANEOUS MELANOMA

10

Information for patients

Patients and their families need information to help them understand and cope with the diagnosis
of melanoma, the treatment options and possible outcomes.

10.1

FEEDBACK FROM PATIENTS

Twelve focus groups with melanoma patients in three different areas of Scotland were held in
July and August 2002. To protect patient confidentiality clinicians wrote to patients directly
asking them to contact SIGN if they were interested in taking part in a focus group. An external
consultant led each group and SIGN Executive staff took notes. All focus group participants
agreed to the discussions being recorded on audiotape for the purposes of analysis. A total of 75
people attended the groups, 27 men and 48 women.
The key messages from the focus group reports were fed back to the guideline development group
and guided both the good practice points in this section and The Notes For Discussion With
Patients and Example Patient Information Leaflet (sections 10.5 and 10.7).

10.2

KEY MESSAGES FROM PATIENT FOCUS GROUPS

Diagnosis
Most patients would prefer the diagnosis to be given face to face, with exceptions in the interest
of receiving the diagnosis in a speedy manner. Diagnoses given on answerphones, via letters that
arrived at the weekend, or by phone calls to the workplace were generally unacceptable.
Information giving at diagnosis
Many people reported that their minds went blank at diagnosis, and that some basic written
information to take away (including definitions of terms), and scheduling a follow up appointment
shortly afterwards to answer patients and/or families questions would be helpful.
Information giving throughout the journey of care
The best approach is a mix of verbal and written information. The level of detail required is
personal and varies from patient to patient. Information for family and friends is also required.
Patient anxiety
Most reported profound anxiety as a result of a cancer diagnosis, with no clear time limit when
this fades. Patients had many unanswered questions, such as: What caused my melanoma? What
is melanoma? How can I prevent it in the future? What changes should I make in my life? How
do I break this news to partners, families and friends?
Frequency of follow up
Every three months in the first year then every six months in or after the second year were
perceived to be adequate follow up schedules for most patients. After year two, most patients are
happy to be seen annually or to be discharged with open access back to see a specialist if
required: specialists should make it clear to patients to get in touch if they are worried.
Which clinician?
Patients in various locations reported seeing different clinicians: general practitioners, surgeons,
oncologists and dermatologists. Some patients reported having had no contact with a dermatologist.
Many patients reported feeling ill-equipped to check their own skin and felt confused and anxious
about this. Many patients felt that they had been rushed through appointments. The majority of
patients liked the idea of having access to a specialist nurse who could spend more time with
them and who could also have a psychological counselling role.

32

10 INFORMATION FOR PATIENTS

10.3

INFORMATION PROVISION
An RCT of stage I melanoma patients suggests that a structured information programme to
inform patients about melanoma progression and treatment options increased patients knowledge
of the disease, the risk factors involved and possible preventative measures.258 The study reported
no difference in psychological variables. A second RCT found that facilitated education programmes
for stage I and II melanoma patients, in which one element was an information programme in
relation to cancer recurrence, had a positive effect on coping behaviour and affective distress
values.259 A prospective cohort study with patients with metastatic disease found that patients
who understood the expected outcomes of their disease had higher quality of life scores and
longer survival periods.260
The provision of information to patients increases their knowledge of the disease, can enhance
coping behaviour and reduce levels of affective distress.

10.4

Patients should receive targeted information throughout their journey of care.

Healthcare professionals working with cancer patients should have training in

communication skills.

2+

PATIENT SUPPORT GROUPS

Patients benefit from psychoeducational interventions provided in a structured group, facilitated
by qualified personnel.258-261 The studies suggest that facilitated groups can help patients cope
better at all stages of the disease, increase knowledge levels and reduce affective distress.

10.5

11+
2

Health service patient support groups should be structured, facilitated by trained

professionals and incorporate health education.

Information on all patient support groups should be made easily available to patients.

1-

NOTES FOR DISCUSSION WITH PATIENTS

The following points were drawn up by the guideline development group using the feedback
from the focus groups held with patients (see section 10.1). These notes may be of use to health
professionals when discussing melanoma with patients and carers. They may also be useful in
guiding the production of local patient information materials. The advice is divided into sections
to highlight the issues that patients and carers might wish to discuss at each stage of care.
PREDIAGNOSIS
The information that I got was really very factual about what it is and what will happen now and I found that very
helpful cause I got it before the diagnosis and they told me that it couldve been malignant and so I was expecting
it and I knew what would come next and I was quite fine with that. (patient quote)
n
n
n
n
n
n
n

How long will it be before the results are back?

How will I receive my diagnosis?
If the results are negative, how likely is it that I may get skin cancer in the future?
How accurate are the test results?
How will I be given the results?
What happens next if it is cancer?
Where can I get more information in the meantime and who can I speak to?

33

CUTANEOUS MELANOMA

DIAGNOSIS
When I went out I said to the nurse whats a melanoma?.
I think a good simple leaflet wouldve been good at the time and then maybe a recommended website, Im always
kind of wary going into websites, you want something thats recommended by them, a good website.
I wanted to know how not to make it happen again. (patient quotes)
n
n
n
n
n
n
n
n
n
n
n
n

What is melanoma?
What does malignant mean?
What caused it?
Why did this happen to me Im not a sun worshipper and never have been?
Who can I talk to?
What are my treatment options?
Where can my family and I find more information?
Are my family and/or other relatives likely to get melanoma?
How will I tell my family? Can I get help to do this?
How long will treatment go on for?
Will it be painful treatment?
Am I going to die?

TREATMENT
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n

What is involved in the surgery?

What are the types of surgery and their success rates?
How long will I need to wait?
What happens after surgery?
Will the scarring be bad? Will I need skin grafts? Where will these be taken from?
Will I get all my treatment here, or will I have to go somewhere else? Where will that be?
How do I get to that hospital?
Will I have to see lots of different doctors, or will it be the same one?
Which specialists am I likely to see?
If I want to ask questions who should I phone? Whats the phone number?
How long will my treatment last?
Will I be able to drive to and from hospital?
Will I be able to carry on working? How much sick leave will I need?
Am I entitled to any benefits (if I have to stop work for a long time)? Who do I ask?
What are the side effects of chemotherapy?
When will I know if I am cured?

FOLLOW UP
I would like to be on top of the facts and to be in control of the situation so that I know what Im looking for and know
what to do to prevent it as far as is possible. (patient quote)
n
n
n
n
n
n
n
n
n
n
n
n
n

34

How often will I be followed up and for how long?

Who will I see in the clinic?
What should I do if I am worried in between hospital appointments?
How is my GP involved?
Can I phone someone in the clinic?
How do I check my skin in between visits? What am I looking for?
What is a body map?
Why do some patients have photographs taken?
How can I check my back if I live alone or if my partner feels uncomfortable helping me?
Can melanoma come back somewhere I cant see it?
Can I still go out in the sun?
Can I still holiday in sunny destinations? What precautions should I take?
Where can I get information and support for myself and my family?

10 INFORMATION FOR PATIENTS

PALLIATIVE CARE
n
n
n
n
n
n
n

n
n

10.6

How long have I got?

Will there be a lot of pain? How will the pain be controlled?
Can I stay at home? Who will care for me?
Which specialists am I likely to see?
Is there a local respite unit for day care?
Is there a hospice, or are there hospice beds in hospital? How are they accessed?
How do I access advice from occupational therapy on coping with practical problems and on
provision of equipment to help me cope at home?
Where can I get advice about or obtain a loan or provision of a wheelchair?
Where can I get advice or help with coping with symptoms like extreme tiredness or general
weakness?

SOURCES OF FURTHER INFORMATION FOR PATIENTS

Please note that the information from some organisations will be particularly focussed on advanced
stages of cancer and should be accessed with caution as the information may not be relevant and
could be upsetting to some patients and their carers. This information is correct at the time of
going to press.

10.6.1

NATIONAL ORGANISATION SPECIFIC TO CUTANEOUS MELANOMA/SKIN CANCER

Marcs Line Resources Centre
Dermatology Treatment Centre, Level 3, Salisbury District Hospital,
Salisbury, Wiltshire, SP2 8BJ
Tel: 01722 415071
Email: marcsline@wessexcancer.org
MARCS Line (Melanoma And Related Cancers of the Skin) is a national resource on matters
pertaining to skin cancer.

10.6.2

NATIONAL ORGANISATIONS RELATED TO CANCER

CancerBACUP Scotland
Suite 2, 3rd Floor, Cranston House, 104-114 Argyle Street, Glasgow G2 8BH
Tel: 0141 223 7676, Fax: 0141 248 8422, FREEPHONE: 0808 800 1234 Mon-Fri 9-7
www.cancerbacup.org.uk
Offers a free cancer information service staffed by qualified and experienced cancer nurses, a
growing number of CancerBACUP centres in hospitals up and down the country and a freephone
information service on all types of cancer, staffed by specialist cancer nurses. Produces over 60
booklets and CancerBACUP News three times a year.
Cancer Research UK
P.O. Box 123, Lincolns Inn Fields, London WC2A 3PX
Tel: 020 7009 8820, Fax: 020 7269 3100
www.cancerresearchuk.org/
A new charity that was formed in 2002 as a result of the merger between The Cancer Research
Campaign and Imperial Cancer Research Fund.
Macmillan Cancer Relief Scotland
Osbourne House, 1-5 Osbourne Terrace, Edinburgh, EH12 5HG
Tel: 0131 346 5346, Fax: 0131 346 5347, Helpline:0808 808 2020 Mon-Fri 9-6
www.macmillan.org.uk
A UK charity supporting people with cancer and their families with specialist information,
treatment and care.

35

CUTANEOUS MELANOMA

Maggies Centres Scotland

The Stables, Western General Hospital, Edinburgh, EH4 2XU
Tel: 0131 537 3131, Fax: 0131 537 3130
Maggies Centre Glasgow
The Gatehouse, Dumbarton Road, Glasgow, G11 6PA
Tel: 0141 330 3311, Fax: 0141 330 3363
Email: maggies.centre@ed.ac.uk, www.maggiescentres.org
The goal of Maggies is to keep people who have cancer as healthy in mind and body as is
possible, by enabling them to participate actively in the treatment of their disease. A Maggies
Centre is also opening in Dundee.
Marie Curie Cancer Care Scotland
29 Albany Street, Edinburgh, EH1 3QN
Tel: 0131 456 3700
www.mariecurie.org.uk
Dedicated to the cure of people affected by cancer and the enhancement of their quality of life
through its caring services, research and education.
Tak Tent Cancer Support Scotland
Flat 5, 30 Shelley Court, Gartnavel Complex, Glasgow, G12 0YN
Tel: 0141 211 0122, Fax: 0141 211 3988
Email: tak.tent@care4free.net, www.taktent.org.uk
Promotes the care of cancer patients, their families, friends and the staff involved professionally
in cancer care by providing practical and emotional support, information, counselling and therapies
as required. Network of local support groups throughout Scotland. The Youth Group, conTak,
provides support for 16 to 25 year olds affected by cancer.
10.6.2

NATIONAL HEALTH EDUCATION AND SUPPORT AGENCIES

NHS Health Scotland (formerly known as the Health Education Board for Scotland or HEBS)
Woodburn House, Canaan Lane, Edinburgh, EH10 4SG
Tel: 0131 536 5500, Textphone: 0131 536 5503, Fax: 0131 536 5501
www.hebs.scot.nhs.uk
Scotlands national agency for health education, promotion, advice and information.

10.6.3

OTHER USEFUL RESOURCES

The Skin Cancer Foundation
www.skincancer.org/melanoma
A North American website with some useful sections and resources.

10.7

EXAMPLE PATIENT INFORMATION SHEET

An example information sheet for patients who have had a level II or III melanoma <1 mm thick
removed is given on the next page. Healthcare professionals may wish to adapt this for use in
their own departments, remembering to insert the relevant local details.

36

10 INFORMATION FOR PATIENTS

INFORMATION FOR PATIENTS WHO HAVE HAD A PRIMARY

MELANOMA OF THE SKIN
You have recently had a small operation on your skin and examination of the sample under
the microscope showed that the problem was a malignant melanoma, a type of skin cancer.
You may have a lot of questions and worries, and the purpose of this leaflet is to help with
some of them but not to be a substitute for a good conversation with your specialist. It is a
good idea to:
n

write down all the questions you would like answered and bring them to your next
hospital visit
bring another family member or close friend so that you can both discuss the information
after your visit and be sure that you both have the same memory of what was said. This
will help your family understand what has happened which makes it in turn easier for you
to cope with a worrying situation.
HOW WILL I BE FOLLOWED UP?

Your melanoma was in the skin and has been removed by either one or two operations. After
these the majority of people who have had melanomas of a similar thickness as yours remain
well with no further problems, but because just over one in ten do develop signs of melanoma
spread, we plan to see you back at the clinic for check ups every (insert local details). At
these visits we will:
n
n
n

look at and feel your scar

check the lymph glands in your groin or armpit to be sure none are bigger than normal
give you a total body skin examination to be sure that you do not have another small early
treatable melanoma (once you have had one melanoma you are at increased risk of
developing a second so we aim to identify and treat this as soon as possible).

Some people with melanoma have a very large number of moles. If you are in this group we
may take photographs of some of these moles, and compare your skin with these photos at
your clinic visits. Not everyone however needs these photographs.
If you have any worries between visits we will always see you early so do not hesitate to
phone (insert relevant phone number) and ask for your pigmented lesion clinic appointment
to be brought forward.
WHY DID I GET A MELANOMA?
We also want to know the answer to this question so that we can try to prevent other people
developing melanoma in the future. In about two thirds of people with melanoma too much
sun exposure is important. This may be a childhood spent in a sunny country, or a history of
many sunny summer holidays, particularly if you remember severe sunburn with blistering or
peeling. People with melanoma are usually white skinned and have very pale skin which does
not tan easily but goes red in the sun. They are often fair or red haired, have blue eyes and
may have a lot of both moles and freckles. However, about one third of people with melanoma
do not fit in to the group described above and may have inherited genes which makes them
more likely to develop melanoma. Research in this area is ongoing.
ARE MY CHILDREN MORE LIKELY TO GET MELANOMA?
In Scotland, one melanoma patient in 50 has a history of melanoma in a close relative. If you
are in this group your children could be at increased risk. In these families we offer regular
skin examinations to all family members. If you do not have a close relative who has also had
melanoma your children are not at greater risk, but most families that have had a person with
melanoma become very careful and sensible about avoiding sun damage. If any of your family
members have moles on their skin, which you would like us to check, please ask. We will be
happy to help.

37

CUTANEOUS MELANOMA

WHAT DO I DO NOW?
Most people with melanoma do not tolerate sunbathing well and sunburn could increase your
risk of a second melanoma. We therefore suggest that you become very sensible over sun
exposure. This does not mean never having a holiday in a sunny country but it does mean
avoiding strong Mediterranean noonday sun. Comfortable cotton clothing is an excellent
sunscreen so plan your holiday wardrobe around long cotton trousers or skirts, long- sleeved
cotton tops and a hat.
Sunscreen creams, even those called total sunblock, have not yet been shown to protect
against melanoma. They do prevent sunburn, so use them as part of your skin protection
routine, but not in place of clothing. Remember that you can get sunburned in Scotland as
well as on a Spanish beach so do follow the safe sun routine during good weather in this
country as well as abroad.
FURTHER INFORMATION
Please ask us any other questions that are important to you. Women may want to ask about
future pregnancies, use of the oral contraceptive or hormone replacement therapy. Advice is
best tailored to you personally so do tell us your particular worries. Although there is a large
amount of information on the Internet, much of it is aimed at the minority of patients whose
melanoma has spread beyond their skin. It therefore does not apply to you, and you may find
it unnecessarily alarming.
CONTACT TELEPHONE NUMBER (insert relevant number)
Please try to have your clinic card with you when you telephone as it carries your hospital
number which will help us obtain your records as quickly as possible.

38

11 IMPLEMENTATION AND AUDIT

11

Implementation and audit

11.1

MANAGED CLINICAL NETWORKS

Managed Clinical Networks (MCNs) are defined as:
linked groups of health professionals and organisations from primary, secondary and tertiary
care, working in a coordinated manner, unconstrained by existing professional and Health Board
boundaries, to ensure equitable provision of high quality clinically effective services throughout
Scotland. 262
Managed Clinical Networks allow representatives from relevant specialties to discuss individual
treatment plans and be aware of those patients likely to progress from an early stage in their
disease. In the case of melanoma, the likely specialists who would be included in a MCN may
be GPs, dermatologists, pathologists, surgeons in subspecialties, medical and clinical oncologists
and palliative care specialists. Managed Clinical Networks are particularly beneficial for patients
being cared for by health professionals unfamiliar with melanoma and they should also ensure
that all eligible patients are offered the opportunity to enter into appropriate trials of new therapy.
They require an administrative infrastructure and specialist nurse support which means they may
have financial implications.

11.2

ECONOMIC IMPLICATIONS
The development process for this guideline has included explicit consideration of economic and
resource issues. This has been achieved through a review of the economics literature on specific
recommendations and through the use of the SIGN resource use implications checklist. The aim
of considering health economic aspects as an integral part of the guideline was to ensure the
efficient use of healthcare resources and to provide information to assist implementation.

11.2.1

COST-EFFECTIVENESS EVIDENCE
A systematic literature review was performed for a number of specific recommendations in the
guideline. Each study identified was reviewed according to a standard checklist used to critique
economic evaluations.

11.2.2

SCREENING FOR CUTANEOUS MELANOMAS

A well conducted cost-effectiveness analysis using a hypothetical cohort of 50 year old Australians
suggested that screening for melanoma by primary care physicians may be relatively cost effective.263
Comparing an organised programme of screening to the existing opportunistic regime, the model
predicted that the cost per life year saved for men was Aus$6,853 to $12,137 for five-yearly and
two-yearly screening respectively. The programme was less cost effective in women principally
due to lower mortality from melanoma. The cost effectiveness of screening in high-risk populations
has also been addressed in two American studies.264,265 The findings suggested that such programmes
were cost effective compared to other screening programmes used in the USA. The cost-effectiveness
ratios were however sensitive to changes in the cost of the screening test and the prevalence of
disease and hence the economic efficiency of screening high-risk individuals in Scotland may
differ. No economics evidence was found which would support mass screening programmes.

11.2.3

SENTINEL LYMPH NODE BIOPSY

The key interest here is how the information obtained from the SLNB changes patient management,
subsequent outcomes and associated costs. Only one study was identified, a cost analysis of 73
patients in the USA undergoing SLNB or an elective lymph node dissection (ELND).266 The results
indicate that significant cost savings could be made by using SLNB rather than ELND. The study
was non-randomised and hence subject to potential bias in the distribution of cost drivers between
the groups, making the conclusion unreliable. Information on final patient outcomes was also
lacking making it hard to be certain of the cost effectiveness of the intervention, particularly
when applied to the UK setting.

39

CUTANEOUS MELANOMA

11.2.4

ADJUVANT INTERFERON THERAPY

Five economic evaluations or cost studies relating to adjuvant interferon therapy were
reviewed.270-274 Three studies used the trial results from the E1684 trial and hence investigated the
cost effectiveness of adjuvant high-dose interferon therapy versus observation alone. 270-272 These
studies all found cost per life year gained and cost per QALY (Quality Adjusted Life Years)
figures that would be considered broadly acceptable by current conventions. The UK metaanalysis and economic analysis however found insufficient evidence of benefit and thus, given
its considerable incremental cost, concluded that it could not be recommended for routine use
in the UK.273 The remaining economic evaluation was a French study examining the cost
effectiveness and cost utility of low-dose interferon in patients with surgical resection of AJCC
stage II melanoma versus observation alone.274 The cost effectiveness ratios in this study represent
reasonable value for money. The majority of economic evaluations were based on the E1684 trial
however that had the most positive findings, therefore cost effectiveness will tend to have been
overstated. Further, if no significant difference exists in overall survival (as was found in the
E1684 and French studies), the use of life years gained as an outcome is not tenable (since
obviously no life years have been gained) rendering the cost-effectiveness results invalid. The
robustness of the findings of the economic evaluations must be questioned.

11.2.5

FOLLOW UP OF PATIENTS WITH STAGE I AND II DISEASE

A German study used retrospective case note review to examine the relative cost effectiveness of
various tests used in the follow up of patients with stage I-III disease.275 The study did not assess
the value of surveillance per se nor the cost effectiveness of various frequencies of contact. The
results indicated that at any stage of melanoma and follow up the most cost-effective test was
physical examination and that lymph node sonography was the best performing imaging procedure,
albeit less cost effective than physical examination. Similar conclusions were reached in a French
study of patients with stage I melanoma.181 Both studies suffered from methodological weaknesses
but they tend to support the recommendations made in section 7.

11.2.6

RESOURCE IMPLICATIONS CHECKLIST

n

Are resource implications of implementation of the guideline likely to be significant nationally

or locally such that they cannot be absorbed within existing resource allocations?
It is hard to ascertain whether the implementation of this guideline can be met within existing
resources. This is because the guideline contains both recommendations that may require
new funds for implementation and recommendations that may halt certain existing practices,
thereby freeing up resources. The net effect of this is hard to quantify and will depend on
current standards, practices and resources in each Health Board area.

Will the guideline affect outcomes or resource use in other areas of the NHS (such as primary
care, other clinical specialties, support departments)?
By recommending that all health professionals should be encouraged to examine patients for
potential melanomas, there is likely to be a potential impact on all areas of clinical practice
in NHSScotland. Resources for staff training and education may be required to implement
this recommendation. Many of the recommendations made in section 2 will have an impact
on pathology departments. Similarly, the need for appropriate palliation services recommended
in section 8.4 may require investment if adequate services are not already available.

Will guideline implementation affect outcomes or resource use in partner organisations (eg
social work or the voluntary sector)?
Palliative care services provided by charitable organisations may experience resource effects
through the implementation of the guideline. Such organisations may also be involved in the
provision of patient/carer information and support groups.

40

Will guideline implementation affect costs to patients, for example will they face additional
visits to hospital/GPs or have to spend longer in hospital?

11 IMPLEMENTATION AND AUDIT

The costs of appropriate primary preventative products recommended in the guideline

(sunscreens, hats and clothing) will result in costs to patients.
n

Impact on other groups?

Implementation of the guideline is unlikely to affect other groups.

11.3

IDEAS FOR RESEARCH

n

n
n
n
n
n

11.4

A quantitative questionnaire study exploring patients views of melanoma care in Scotland,

focussing on their views on diagnosis, follow up and education for self examination.
A long term follow up trial to evaluate the Cochran model of survival, using survival statistics
from the Scottish Melanoma Group database with reference to the following histological
prognostic parameters:
n
ulceration
n
the relationship between the presence of regression and follow up
n
the role of melanoma cell type
n
the plasma cell in the inflammatory infiltrate
n
sentinel node pathology.
A study of negative SNLB patients that correlates tumour thickness, negative SNLB status and
prognosis.
A prospective trial to define the role of CT, MRI and PET in staging patients with stage II and
III (in both gross- and micro-metastatic) disease.
The role of specialist melanoma nurses.
Health professionals communications skills in caring for patients with cancer.
Who uses sunbeds and why?
The role of PET scanning to identify distant disease.
Does psychological and emotional support from an early stage of diagnosis influence outcomes
for patients?

AUDIT
The Scottish Executive publication, Cancer in Scotland: Action for Change, highlighted the
importance of prospective clinical audit of cancer services.276 In Scotland, through the Scottish
Melanoma Group (SMG), there has been a long tradition of data collection relating to melanoma
of all sites other than the eye.277 The development of this guideline provides an opportunity to
review the content of the SMG dataset, taking account of the measurable recommendations, as
well as the needs of other stakeholders (in relation to clinical standards, waiting times etc). A
multidisciplinary group has been convened to review the SMG dataset, with a view to developing
a draft dataset and data definitions for consultation through the three cancer networks in Scotland,
prior to implementation. The dataset produced will be available from the SIGN website
www.sign.ac.uk

41

CUTANEOUS MELANOMA

12

Development of the guideline

12.1

INTRODUCTION
SIGN is a collaborative network of clinicians, other healthcare professionals, and patient
organisations, funded by NHS Quality Improvement Scotland. SIGN guidelines are developed by
multidisciplinary groups using a standard methodology based on a systematic review of the
evidence. Further details about SIGN and the guideline development methodology are contained
in SIGN 50: A Guideline Developers Handbook, available at www.sign.ac.uk

12.2

THE GUIDELINE DEVELOPMENT GROUP

Dr Valerie Doherty (Chairman)
Mr Taimur Shoaib (Secretary)
Ms Moira Black
Dr David Brewster
Dr Graham Duncan
Dr Alan T Evans
Dr Marie Fallon
Mrs Carol Horne
Professor Rona MacKie
Mrs Lesley Marley
Mr Alan J McKay
Dr Kathryn McLaren
Dr Iain McLellan
Dr Nigel McMillan
Mr Jack Miller
Dr Marianne Nicolson
Dr Jonathan Norris
Dr Gerry Robertson
Mr Duncan Service
Mrs Karen Smith
Mr David Soutar
Ms Joanne Topalian

Consultant Dermatologist, Royal Infirmary, Edinburgh

Specialist Registrar in Plastic Surgery,
Canniesburn Hospital, Glasgow
Health Visitor, Perth
Director of Cancer Registration in Scotland,
Information and Statistics Division, Edinburgh
General Practitioner, Kirkcaldy
Consultant Histopathologist,Ninewells Hospital, Dundee
Senior Lecturer in Palliative Medicine,
Western General Hospital, Edinburgh
Manager, TakTent Cancer Support, Glasgow
Consultant Dermatologist, Glasgow University
Senior Health Promotion Officer, NHS Tayside, Dundee
Consultant Vascular Surgeon,
Gartnavel General Hospital, Glasgow
Senior Lecturer, Pathology, University of Edinburgh
General Practitioner, Kilmalcolm, Renfrewshire
Consultant Radiologist, Western Infirmary, Glasgow
Consultant Surgeon, Dr Grays Hospital, Elgin
Consultant in Medical Oncology, Aberdeen Royal Infirmary
Consultant Dermatologist,
Dumfries and Galloway Royal Infirmary
Consultant Clinical Oncologist,
Beatson Oncology Centre, Glasgow
Information Services Officer, SIGN
Specialist Nurse, Plastic Surgery,
Ninewells Hospital,Dundee
Consultant Plastic Surgeon, Canniesburn Hospital, Glasgow
Programme Manager, SIGN

The membership of the guideline development group was confirmed following consultation
with the member organisations of SIGN. Declarations of interests were made by all members of
the guideline development group. Further details are available from the SIGN Executive.
The development group is also very thankful to the following people for their contributions to
the development of this guideline:
Dr Douglas Adamson
Ms Ailsa Brown

42

Consultant Clinical Oncologist,

Ninewells Hospital, Dundee
Health Economist, Greater Glasgow Health Board

12 DEVELOPMENT OF THE GUIDELINE

12.3

SYSTEMATIC LITERATURE REVIEW

Literature searches were initially conducted in Medline, Embase, Cinahl, Cancerlit, and the
Cochrane Library using the year range 1993-2001. The literature search was updated with new
material during the course of the guideline development process. A final update literature search
was performed in March 2003. Key websites on the Internet were also used, such as the National
Guidelines Clearinghouse. The searches were extended back to 1970 in areas where evidence
was scarce. These searches were supplemented by the reference lists of relevant papers and group
members own files. The Medline version of the main search strategies can be found on the SIGN
website.

12.4

CONSULTATION AND PEER REVIEW

12.4.1

NATIONAL OPEN MEETING

The national open meeting is the main consultative phase of SIGN guideline development, at
which the guideline development group presents its draft recommendations for the first time.
The national open meeting for this guideline was held in March 2002 and was attended by all of
the key specialties relevant to the guideline. The draft guideline was available on the SIGN
website for a limited period at this stage to allow those unable to attend the meeting to contribute
to the development of the guideline.

12.4.2

SPECIALIST REVIEW
The guideline was also reviewed in draft form by a panel of independent expert referees, who
were asked to comment primarily on the comprehensiveness and accuracy of interpretation of
the evidence base supporting the recommendations in the guideline. SIGN is very grateful to all
of these experts for their contribution to this guideline.
Dr Alan Begg
Dr Frederick Benton
Ms Elizabeth Boon
Professor Martin Cook
Dr Michael Cornbleet
Mr Neil Cox
Ms Ashley Duff
Dr Tim Eisen

General Practitioner, Montrose

Medical Director, St Columbas Hospice, Edinburgh
Lay reviewer, Annan, Dumfriesshire
Consultant Pathologist, Royal Surrey County Hospital, Guildford
Senior Medical Officer, Scottish Executive
Consultant Dermatologist, Cumberland Infirmary, Carlisle
Lay reviewer, Edinburgh
Consultant Medical Oncologist,
The Royal Marsden Hospital, London
Dr Jeffrey Evans
Consultant Oncologist, Beatson Oncology Centre, Glasgow
Professor Martin Gore
Consultant Medical Oncologist,
The Royal Marsden Hospital, London
Dr Dermot Gorman
Consultant in Public Health, Lothian NHS Board
Dr Robert Grant
General Practitioner, Markinch Medical Practice, Fife
Dr Iain Henderson
General Practitioner, Kingsway Medical Practice, Glasgow
Dr Richard Johnson
Consultant Radiologist, Christie Hospital, Manchester
Dr Hassan Kamel
Consultant Pathologist, Medical School, Edinburgh
Mr Peter Lapsley
Chief Executive, Skin Care Campaign, London
Professor Hugh MacDougall Consultant Clinical Oncologist,
Western General Hospital, Edinburgh
Dr Graham McKillop
Consultant Radiologist, Royal Infirmary, Edinburgh
Dr Allan Merry
General Practitioner, Ardrossan
Dr Wolter Mooi
Consultant Pathologist, Amsterdam
Dr Julia Newton Bishop
Dermatologist, St Jamess University Hospital, Leeds
Dr Pawlam Patel
Consultant Medical Oncologist,
St Jamess University Hospital, Leeds
Professor Bruce Ponder
Consultant Oncologist, Addenbrookes Hospital, Cambridge
Professor Roy Rampling
Consultant Oncologist, Beatson Oncology Centre, Glasgow
Dr Robin Russell Jones
Consultant Dermatologist, St Thomass Hospital, London

43

CUTANEOUS MELANOMA

Ms Jeanette Semple
BACP Accredited Counsellor, Glasgow
Professor Anthony Swerdlow Professor of Epidemiology,
The Institute for Cancer Research, London
Mr Meirion Thomas
Consultant Surgeon, The Royal Marsden Hospital, London
Ms Margaret Thomson
Senior Occupational Therapist, Scottish Occupational Therapy
Network in Oncology and Palliative Care,
North Glasgow Hospitals Trust
Professor John Thompson
Director, The Sydney Melanoma Unit, Professor of Surgery
(Melanoma and Surgical Oncology),
The University of Sydney, Australia
Ms Jennifer Whelan
Head of CancerBACUP Scotland, Glasgow
12.4.3

SIGN EDITORIAL GROUP

As a final quality control check, the guideline is reviewed by an Editorial Group comprising the
relevant specialty representatives on SIGN Council to ensure that the specialist reviewers comments
have been addressed adequately and that any risk of bias in the guideline development process as
a whole has been minimised. The Editorial Group for this guideline was as follows:
Professor Peter Donnelly
Mr Douglas Harper
Dr Grahame Howard
Professor Gordon Lowe
Dr Safia Qureshi
Dr Sara Twaddle
Dr Peter Wimpenny

Academy of Medicine
Royal College of Surgeons, Edinburgh
Royal College of Radiologists, Faculty of Oncology
Chairman of SIGN, Co-editor
SIGN Programme Director
Director of SIGN, Co-editor
School of Nursing and Midwifery

Each member of the guideline development group then approved the final guideline for publication.

44

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Update to printed guideline

20 Feb 2004
Section 10.6.2 Cancer Research UK
Changed from Cancer Research UK
P.O. Box 123, Lincoln's Inn Fields, London WC2A 3PX
Tel: 020 7269 3100
www.cancerresearchuk.org/
to
Cancer Research UK
P.O. Box 123, Lincoln's Inn Fields, London WC2A 3PX
Tel: 020 7009 8820, Fax: 020 7269 3100
www.cancerresearchuk.org/
Section 10.6.2 Maggie's Centres Scotland
Changed from Maggie's Centres Scotland
The Stables, Western General Hospital, Edinburgh, EH4 2XU
Tel: 0131 537 3131, Fax: 0131 537 3130
Maggie's Centre Glasgow
The Gatehouse, Dumbarton Road, Glasgow, G11 6PA
Tel: 0141 330 3311, Fax: 0141 330 3363
Email: maggies.centre@ed.ac.uk, www.maggies.ed.ac.uk
to
Maggie's Centres Scotland
The Stables, Western General Hospital, Edinburgh, EH4 2XU
Tel: 0131 537 3131, Fax: 0131 537 3130
Maggie's Centre Glasgow
The Gatehouse, Dumbarton Road, Glasgow, G11 6PA
Tel: 0141 330 3311, Fax: 0141 330 3363
Email: maggies.centre@ed.ac.uk, www.maggiescentres.org

15 Aug 2003
Amendments to quick reference guide and back page of guideline
Risk factors for cutaneous melanoma
Changed from Giant congenital melanocytic naevi 20 mm diameter
to
Giant congenital melanocytic naevi 20 cm diameter

ADJUVANT TREATMENT OF STAGE II & III DISEASE

D

The routine use of adjuvant radiotherapy is not recommended

for patients who have had therapeutic lymph node dissections

Adjuvant interferon should not be used for AJCC stage II & III
melanoma patients other than in a trial setting

Patients with AJCC stage II & III disease should be offered

entry into trials to confirm whether or not interferon
therapy extends the disease-free interval after surgery
Patients should be entered into vaccine clinical trials as
appropriate

PATIENT FOLLOW UP IN STAGE I, II & III DISEASE

D

Patients who have had melanoma in situ do not require follow up

Patients with an invasive melanoma should be followed up

The frequency and duration of follow up should be
determined from the timing and rate of recurrence of the
individual patients melanoma, taking into account the
patients psychological and emotional needs
Stage III patients with lymph node metastases may need
lifelong follow up

Routine full blood counts, liver function tests, tumour markers,

chest X-rays and lactate dehydrogenase are not recommended
as part of a follow up schedule in the asymptomatic patient
Patients should be educated in self assessment techniques to
detect local and nodal recurrent disease and secondary
lesions and appraised of the possibility of late recurrence
There should be an easy route into the clinic if problems
occur between clinic visits or after discharge

MANAGEMENT OF STAGE IV DISEASE

INFORMATION FOR PATIENTS

Dacarbazine (DTIC) is the standard single agent of choice

in stage IV melanoma
Multiple drug regimens (eg with tamoxifen and interferon )
do not improve survival compared to single agent DTIC
and are not recommended outside clinical trials

Metastasectomy should be considered in patients with stage

IV disease
All patients with painful bone metastases should be offered
radiotherapy

Single dose radiotherapy of at least 8 Gy is an effective treatment

for bone metastases

All patients with spinal cord compression should be referred

urgently for surgical intervention and/or palliative radiotherapy

Patients with favourable CNS disease, good performance

status, favourable response to corticosteroid treatment,
and without systemic disease should be considered for
surgical resection of their CNS disease
If surgery is not possible, whole brain radiotherapy
combined with corticosteroids may help palliate
neurological symptoms

Patients with metastatic melanoma should be treated within a

clinical trial wherever possible and be offered palliative care

Patients with advanced melanoma require a coordinated

multiprofessional approach with input from a specialist palliative
care team

Patients with poorly controlled symptoms should be referred to

specialist palliative care at any point in the cancer journey

MELANOMA IN WOMEN

Women with a significant risk of recurrence (localised

disease of >1mm) who wish to become pregnant after
surgery for stage I & II melanoma should be advised to
delay pregnancy for two years postsurgery, as the
likelihood of recurrence is highest during this period
Women who have had a melanoma treated should select
contraception in the same way as women who have not
had a melanoma
Women who have had stage I & II melanoma and who
wish to take HRT should be treated as women who have
not had melanoma

Patients should receive targeted information throughout their

journey of care

Marcs Line Resources Centre

MARCS Line (Melanoma And Related Cancers of the Skin)
Dermatology Treatment Centre, Level 3
Salisbury District Hospital, Salisbury, Wiltshire, SP2 8BJ
Tel: 01722 415071
Email: marcsline@wessexcancer.org
CancerBACUP Scotland
Suite 2, 3rd Floor, Cranston House, 104-114 Argyle Street,
Glasgow G2 8BH
Tel: 0141 223 7676, Fax: 0141 248 8422
FREEPHONE: 0808 800 1234
www.cancerbacup.org.uk
Tak Tent Cancer Support Scotland
Flat 5, 30 Shelley Court, Gartnavel Complex
Glasgow, G12 0YN
Tel: 0141 211 0122 Fax: 0141 211 3988
Email: tak.tent@care4free.net, www.taktent.org.uk
Maggies Centres Scotland
maggies.centre@ed.ac.uk, www.maggies.ed.ac.uk

72

CUTANEOUS MELANOMA

PREVENTION, SURVEILLANCE & GENETICS

B

Healthcare professionals and members of the public should be

aware of the risk factors for melanoma

Genetic testing should only be undertaken in the context of

appropriate research studies

RISK FACTORS FOR CUTANEOUS MELANOMA

INCREASING
RISK

Individuals identified as being at higher risk should be:

advised about appropriate methods of sun protection
educated about the diagnostic features of cutaneous
melanoma
encouraged to perform self examination of the skin

THE 7 POINT CHECKLIST

MAJOR FEATURES
Change in size of lesion
Irregular pigmentation
Irregular border
MINOR FEATURES
Inflammation
Itch/altered sensation
Lesion larger than others
Oozing/crusting of lesion

THE ABCDE SYSTEM

A. Geometrical Asymmetry
in 2 axes
B. Irregular Border
C. At least 2 different Colours
in lesion
D. Maximum Diameter >6mm
E. Elevation of lesion

SURGERY

Clinicians should be familiar with the 7 point or ABCDE

checklist for assessing lesions
Clinicians using hand held dermatoscopy should be
appropriately trained
Health professionals should be encouraged to examine
patients skin during other clinical examinations

RECOMMENDED EXCISION MARGINS

Emphasis should be given to the recognition of early

melanoma by both patients and health professionals
Patients with suspicious pigmented lesions should be seen
at a specialist clinic in a time commensurate with the level
of concern indicated by the GP referral letter
GPs should refer urgently all patients in whom melanoma is a
strong possibility rather than carry out a biopsy in primary

The deep excision margin should incorporate adipose tissue

down to but not including the deep fascia
Excision margins should be recorded by the surgeon
In open biopsy the incision must be placed in the same line
as for a potential radical lymphadenectomy

A suspected melanoma should be excised with a 2 mm margin

and a cuff of fat

If complete excision cannot be performed as a primary

procedure a full thickness incisional or punch biopsy of the
most suspicious area is advised
A superficial shave biopsy is inappropriate for suspicious
pigmented lesions

Radical lymph node dissection requires complete removal

of all draining lymph nodes for pathological examination
Elective lymph node dissection should not be performed
routinely in patients with primary melanoma
SLNB should be considered as a staging technique in
patients with a primary melanoma >1 mm or a primary
melanoma <1 mm of Clark level 4

ILP is the treatment choice for bulky limb disease for

patients fit to undergo the procedure
Carbon dioxide laser ablation can be considered for
multiple lesions of trunk or abdomen and for limb disease
when ILP is not appropriate

11-50 common moles >2mm

51-100 common moles >2mm
>100 common moles >2mm

Family history of melanoma

Previous history of melanoma
Presence of 1-4 atypical moles
Red or light coloured hair
Presence of actinic lentigines
Giant congenital melanocytic naevi 20 cm diameter
Unusually high sun exposure
Reported growth of a mole
Skin that does not tan easily
Light coloured eyes
Light coloured skin
Affluence
Female sex
Age
C

DIAGNOSIS & PROGNOSTIC INDICATORS

PATHOLOGY
D

The macroscopic description of a suspected melanoma should:

state the biopsy type (excision, incision, or punch)
describe and measure (in mm) the biopsy
describe and measure (in mm) the lesion

Submit the entire lesion for histopathological exam

Section the lesion transversely at 3 mm intervals
Do not select cruciate blocks

Features of a melanoma pathology report

Essential features
Desirable features
B Breslow thickness

B Histogenetic type

B Clark level (if Breslow Thickness

Cell type

B Ulceration

Host inflammatory

B Growth phase characteristics

Mitotic rate

<1mm)

C Regression
B Lymphovascular space invasion
B Microscopic satellites
D Microscopic clearance (mm)

response

STAGING

MARGINS

pT1 (melanoma 0 to 1 mm)

1 cm

pT2 (melanoma 1 to 2 mm)

1 to 2 cm

pT3 (melanoma 2 to 4 mm)

2 cm

pT4 (melanoma >4 mm)

2 cm

OTHER INVESTIGATIONS/NON-SURGICAL STAGING

C

Chest X-ray, ultrasound and computerised tomography scanning

are not indicated in the initial assessment of primary melanoma,
unless indicated for investigation of clinical symptoms and
signs

Routine blood tests should not be used to stage asymptomatic

melanoma patients