Melanoma: summary of NICE guidance

thebmj | 1 August 2015 31

EDUCATION PRACTICE

Communication and support

•

To help people make decisions about their care,

follow the recommendations on communication,

information provision, and support in the NICE

guideline on improving outcomes for people with

skin tumours including melanoma.

Assessing melanoma

•

Assess all pigmented skin lesions that are referred

for assessment or identied during follow-up using

dermoscopy carried out by healthcare professionals

trained in this technique. Do not routinely use

confocal microscopy or computer assisted diagnostic

tools.

Photography

•

For a clinically atypical melanocytic lesion that does

not need excision at rst presentation use baseline

photography (preferably dermoscopic). Also use this

technique to review the clinical appearance of the

lesion three months aer rst presentation to identify

early signs of melanoma.

EDUCATION PRACTICE

Wales Cancer Trials Unit, Cardiff

CF14 4YS, UK

University of Leeds, Leeds, UK

National Collaborating Centre for

Cancer, Cardiff, UK

Correspondence to

: F Macbeth

[email protected]om

Cite this as: BMJ 2015;351:h3708

doi: 10.1136/bmj.h3708

This is one of a series of BMJ

summaries of new guidelines

based on the best available

evidence; they highlight important

recommendations for clinical

practice, especially where

uncertainty or controversy exists.

Further information about the

guidance, a list of members of the

guideline development group,

and the supporting evidence

statements are in the full version

on thebmj.com.

Melanoma is the h most common cancer in the United

Kingdom, with more than 13 000 cases diagnosed in 2011

and its incidence is rising rapidly.

Clinical practice seems

to vary in the UK, especially with regard to the use of der-

moscopy and photography, access to sentinel lymph node

biopsy, vitamin D measurement and advice, follow-up

policies, and the use of routine follow-up imaging. Patient

groups have reported inadequate information on manage

ment options.

This article summarises the most important recent rec-

ommendations from the National Institute for Health and

Care Excellence (NICE) on the diagnosis and care of people

with melanoma.

Recommendations

NICE recommendations are based on systematic reviews

of the best available evidence and explicit consideration

of cost eectiveness. When minimal evidence is available,

recommendations are based on the guideline development

group’s experience and opinion of what constitutes good

practice. Evidence levels for the recommendations are in the

full version of this article on bmj.com. The recommendations

specically apply to secondary and tertiary care locations,

where these patients should all be managed by specialist

multidisciplinary teams (MDTs), but they will also aect the

management of patients with melanoma in primary care.

The staging of melanoma is detailed and complex and

the full staging system is available online.

The brief expla-

nations of stage given may not be precise and are there

to help make the context of the recommendation clearer.

GUIDELINES

Melanoma: summary of NICE guidance

Fergus Macbeth,

Julia Newton-Bishop,

Susan O’Connell,

James E Hawkins,

on behalf of the

Guideline Development Group

THE BOTTOM LINE

•

Use dermoscopy to examine all pigmented lesions referred for assessment

and ensure that all staff are adequately trained in its use

•

Consider sentinel node biopsy as a staging tool for patients with stage II

melanoma and stage 1B melanoma thicker than 1 mm. Use box 1 or the

options grid being developed to discuss the potential advantages and

disadvantages of the procedure with patients

•

If a sentinel node biopsy is positive for melanoma, discuss the potential

advantages and disadvantages of completion lymphadenectomy with the

patient using box 2 or the options grid being developed

•

Consider regular imaging in patients at greater risk of progression to stage

IV (metastatic) melanoma. Use box 3 or the options grid being developed to

discuss potential advantages and disadvantages of this with the patient

HOW PATIENTS WERE INVOLVED IN THE CREATION OF THIS ARTICLE

Committee members involved in this guideline update included lay members who contributed

to the formulation of the recommendations summarised here. Patient and carer organisations

were among the stakeholders who commented on the draft guideline.

AMELIEBENOIST/SPL

32 1 August 2015 | thebmj

EDUCATION PRACTICE

Taking tumour samples for genetic testing

With the advent of eective treatments for people with

metastatic disease, genetic testing of tumour samples for

driver mutations (such as BRAF), which determine the like-

lihood of response to therapy, is becoming more important.

For those who are being considered for systemic therapy:

•

Oer genetic testing using a secondary (metastatic)

melanoma tissue sample or a primary melanoma

tissue sample if a secondary sample is not available or

is of inadequate cellularity.

However:

•

Do not oer genetic testing of stages IA-IIB primary

melanoma (≤4 mm thick with ulceration or >4 mm

thick with no ulceration, no spread) at presentation

except as part of a clinical trial.

•

For stage IIC primary melanoma (>4 mm thick, no

spread, ulcerated), consider genetic testing.

•

For stage III melanoma (spread to lymph nodes or

the cutaneous or subcutaneous lymphatics proximal

to those nodes—“in transit” metastases), consider

testing metastatic tissue; if insucient material is

available, genetic testing of the primary tumour may

be necessary.

Managing suboptimal vitamin D levels

Many people with melanoma have suboptimal levels of

vitamin D at diagnosis but are usually advised to avoid sun

exposure to reduce the risk of further melanomas. Vita-

min D is important for bone health and possibly for other

aspects of health, so further reduction in levels should be

avoided. The guideline also suggests avoiding high levels

as a result of unnecessary supplementation.

•

Measure vitamin D levels at diagnosis in all people

with melanoma.

•

For people whose vitamin D levels are thought to be

suboptimal, provide advice on supplementation and

monitoring in line with local policies and the NICE

guideline on vitamin D.

Staging investigations

The role of sentinel lymph node biopsy (SLNB) is contro-

versial, with its routine use varying greatly across E ngland

and Wales. Not all people routinely need imaging at

d iagnosis:

•

Do not oer imaging or SLNB to people who have stage

I melanoma with a Breslow thickness of 1 mm or less.

•

Consider SLNB as a staging rather than a therapeutic

procedure for people with stages IB-IIC melanoma

with a Breslow thickness of more than 1 mm, and give

these people detailed verbal and written information

about the possible advantages and disadvantages (see

box 1).

•

Oer computed tomography staging to people with

stage IIC melanoma who have not had SLNB and to

people with stage III (lymph nodes or in transit spread)

or suspected stage IV melanoma (distant metastases).

Include imaging of the brain for people with suspected

stage IV melanoma.

•

Consider whole body magnetic resonance imaging for

children and young people (from birth to 24 years)

with stage III or suspected stage IV melanoma.

Advantages

SLNB helps to find out whether the cancer

has spread to the lymph nodes and is

better than ultrasound scans at finding

very small cancers in the lymph nodes

It can help predict what might happen in

the future. For example, in people with a

1-4 mm thick primary melanoma, about

one in 10 dies within 10 years if SLNB is

negative; about three in 10 die if SLNB is

positive

People who have had SLNB may be

able to take part in clinical trials of new

treatments for melanoma. These trials

often cannot accept people who haven’t

had this operation

Disadvantages

The purpose of SLNB is not to cure the

cancer. There is no good evidence that

people who have the operation live longer

than those who do not have it

The result needs to be interpreted with

caution. For every 100 people with a

negative SLNB result, about three will

develop a recurrence in the same group of

lymph nodes

The operation requires a general

anaesthetic

The procedure results in complications

such as deep venous thrombosis,

seromas, or wound infections in 4-10 of

every 100 people

Box 1

Possible advantages and disadvantages of sentinel lymph node biopsy (SLNB)

Advantages

Removing the rest of the lymph nodes

before cancer develops in them reduces

the chance of the cancer returning in the

same part of the body

The operation is less complicated and

safer than waiting until cancer develops

in the remaining lymph nodes and then

removing them

People who have had the operation may

be able to take part in clinical trials of new

treatments to prevent future melanoma.

These trials often cannot accept people

who have not had this operation

Disadvantages

Lymphoedema (long term swelling) may

develop; it is more likely if the operation

is in the groin and least likely in the head

and neck

In four out of five people, cancer will not

develop in the remaining lymph nodes, so

there is a chance that the operation will

have been done unnecessarily

There is no evidence that people who have

this operation live longer than those who

do not have it

Having any operation can cause

complications

Box 2

Possible advantages and disadvantages of completion lymphadenectomy

Advantages

Early detection of recurrence may allow

people to receive treatment with drugs

such as immunotherapeutic agents earlier

than they would otherwise, which might

lead to better outcomes

Some patients find it reassuring to have

regular scans

Disadvantages

There is currently no evidence that treating

recurrent melanoma earlier increases the

probability of a better outcome

Having regular scans may increase some

people’s anxiety, even though for many,

no recurrence will ever occur

Regular scans increase the body’s

exposure to radiation, which itself

increases the risk of second cancers later

in life. For example, imaging of the chest

results in a very small increase in the risk

of thyroid cancer

Imaging of the brain and neck results in

a small increase in the risk of developing

cataracts

Incidental abnormalities of no clinical

significance that require further

investigations might be identified, and

this may cause anxiety until the situation

is resolved

Box 3

Possible advantages and disadvantages of follow-up imaging

thebmj | 1 August 2015 33

EDUCATION PRACTICE

Follow-up after treatment for melanoma

•

All local follow-up policies should include

reinforcing advice about self examination as well

as health promotion for people with melanoma

and their families, including sun awareness while

avoiding vitamin D depletion (in line with local

policies and the NICE guideline on vitamin D),

and

smoking cessation.

•

Discharge people who have had stage 0 melanoma

aer completing treatment.

•

For those with stage IA melanoma (≤1 mm thick,

no spread, no ulceration, no mitoses), consider

follow-up two to four times during the rst year

aer completing treatment and discharge at the

end of that year. Do not routinely oer screening

investigations (including imaging and blood tests) as

part of follow-up.

•

For those with stages IB-IIB melanoma (any

thickness if not ulcerated, up to 4 mm thick if

ulcerated, no spread) or stage IIC melanoma

(>4 mm thick, ulcerated, no spread) with a

negative SLNB, consider follow-up every three

months for the rst three years aer completing

treatment, then every six months for the next two

years and discharge at the end of ve years.

Do not routinely oer screening investigations

(including imaging and blood tests) as part of

follow-up.

•

For people who have had stage IIC melanoma but no

SLNB or stage III (involved lymph nodes) melanoma,

consider follow-up every three months for the rst

three years aer completion of treatment, then every

six months for the next two years, and discharge at

the end of ve years.

•

For people who have had stage IIC melanoma, but

no SLNB, or stage III melanoma, and who would

become eligible for systemic therapy as a result

of early detection of metastatic disease, consider

surveillance imaging as part of follow-up if there

is a clinical trial of the value of regular imaging or

if the specialist skin cancer MDT agrees to a local

policy and specic funding for imaging six monthly

for three years is identied. Discuss the possible

advantages and disadvantages of surveillance

imaging (box 3) with the person.

•

For people who have had stage IV (distant

metastases) melanoma, oer personalised

follow-up.

Overcoming barriers

Dermoscopy is not routinely used in all clinics where

pigmented lesions are assessed, so equipment will need

to be purchased and sta trained. Vitamin D is rarely

measured and there is uncertainty about how best to

manage suboptimal levels. New guidance from the Sci-

entic Advisory Committee on Nutrition (SACN) expected

in 2015 will be helpful. Not all MDTs oer SLNB and some

that do reportedly do not always oer the choice of not

having it. Change is needed both in how this is discussed

with patients and in its provision where it is currently

unavailable.

Managing stages 0-II melanoma

With regard to excision margins:

•

Consider a clinical margin of at least 0.5 cm when

excising stage 0 melanoma (in situ), but if excision

does not achieve an adequate histological margin,

discuss further management with the MDT.

•

Oer excision with a clinical margin of at least 1 cm

to people with stage I (≤2 mm thick) and of at least

2 cm to people with stage II melanoma (1.01-2 mm

thick if ulcerated or >2 mm thick).

Managing stage III melanoma (lymph nodes or in transit

spread)

There is controversy and practice variation about the

management of involved lymph nodes found at SLNB,

by imaging, or at clinical examination.

•

Consider completion lymphadenectomy (removing

residual local lymph nodes) for people whose SLNB

shows micrometastases and give them detailed

verbal and written information about the possible

advantages and disadvantages (see box 2).

•

Oer therapeutic lymph node dissection to people

with palpable stages IIIB-IIIC nodal melanoma or

nodal disease detected by imaging.

•

Do not oer adjuvant radiotherapy to people with

stage IIIA disease or to those with stage IIIB or IIIC

melanoma unless a reduction in the risk of local

recurrence is estimated to outweigh the risk of

serious adverse eects.

Managing stage IV melanoma (distant metastases)

Many patients with metastases will be treated with tar-

geted therapy in line with NICE guidance on dabrafenib,

ipilimumab and vemurafenib.

6-9

However, some situa-

tions require separate advice:

•

Refer the care of people with oligometastases

(metastases of limited extent, for which ablation

or surgery may be feasible) to the specialist skin

cancer MDT for recommendations about staging and

management.

•

Consider surgery or other ablative treatments

(including stereotactic radiotherapy or

radioembolisation) to prevent and control symptoms

in consultation with site specic MDTs (such as MDTs

for the brain or bones).

•

Discuss the care of people with melanoma and brain

metastases with the specialist skin cancer MDT.

•

Refer people with melanoma and brain metastases

that might be suitable for surgery or stereotactic

radiotherapy to the brain and other central nervous

system tumours MDT for a recommendation about

treatment.

Cytotoxic chemotherapy may be indicated for patients

who are unsuitable for targeted systemic therapies:

•

Consider dacarbazine for people with stage IV

metastatic melanoma if immunotherapy or targeted

therapy is not suitable.

•

Do not routinely oer further cytotoxic chemotherapy

for stage IV metastatic melanoma to people

previously treated with dacarbazine except in the

context of a clinical trial.

thebmj.com

Previous articles in this

series

Ж Suspected cancer (part

1—children and young

adults)

(BMJ 2015;350:h3036)

Ж Suspected cancer (part

2—adults)

(BMJ 2015;350:h3044)

Ж Management of

anaemia in chronic

kidney disease

(BMJ 2015;350:h2258)

Ж Bronchiolitis in

children

(BMJ 2015;350:h2305)

Ж Challenging behaviour

and learning disabilities

(BMJ 2015;350:h2652)

34 1 August 2015 | thebmj

EDUCATION PRACTICE

Key findings: efficacy of interventions

The table lists the evidence for the eects of methods to

remove ear wax.

Clinical guide to treatments

•

For such a commonly occurring condition, there

is little high quality evidence available to guide

practice.

•

All procedures for removing wax should be

essentially pain-free.

•

Ear irrigation (syringing): This is generally

considered to be eective, but evidence is limited.

Irrigation is usually performed using a motorised

pump with a governable pressure. Syringing with

unregulated manual syringes should no longer be

used.

•

Ear irrigation may be associated with vertigo and

tympanic membrane perforation in some people.

Pain, damage to the skin of the ear canal, and otitis

externa are other possible adverse eects.

Ear

irrigation may rarely cause permanent deafness;

therefore, people with hearing in only one ear should

not have this ear irrigated.

A history of ear disease or

ear surgery is also a contraindication.

•

Manual removal (other than ear irrigation), including

other mechanical methods of removing ear wax by

sta trained in the use of specic instruments such

as microsuction, is probably eective, although the

evidence is limited.

Mechanical removal of wax with

suction, probes, or forceps is considered eective, but

it can cause trauma to the ear canal, depending on

the experience and training of the operator and the

ease of view.

•

Wax soeners: Overall, we found limited high quality

evidence on the eects of proprietary wax soeners.

–

With regard to the use of wax soeners before

irrigation, we found very weak evidence that

wax soeners may be better than no treatment.

However, we found no good evidence that wax

soeners improved wax clearance aer irrigation

compared with saline.

We found no good evidence

that any one type of wax soener was better than

any other for use before irrigation.

–

With regard to the use of wax soeners alone,

we found very weak evidence that wax soeners

may be better than no treatment.

We found no

consistent evidence that wax soeners alone

improved wax clearance compared with sterile

water or normal saline. We found no good evidence

that any one type of wax soener alone was better

than any other.

•

Overall, many of the included randomised controlled

trials had weak methods, which limited the

robustness of any conclusions that could be drawn.

SUMMARIES OF BMJ CLINICAL EVIDENCE

Ear wax

Tony Wright

University College London Ear

Institute, London, UK

Correspondence to

: T Wright

anthony[email protected]

Cite this as: BMJ 2015;351:h3601

doi: 10.1136/bmj.h3601

This series comprises summaries

of BMJ Clinical Evidence, a

database of systematic overviews

of the best available evidence on

the effectiveness of commonly

used interventions (available at

http://clinicalevidence.bmj.com/).

Ж Linktothisarticleonline

forCPD/CMEcredits

Ear wax only becomes a problem if it causes a hearing

impairment or other ear related symptoms. The accumu-

lation of wax occurs for many dierent reasons, includ

ing overproduction or underproduction of its constituent

components, a failure to self clear because of slow skin

migration, or mechanical issues such as the use of cot-

ton buds or hearing aids. Wax may obscure the view of

the tympanic membrane and may need to be removed for

diagnostic reasons or for taking impressions before tting

a hearing aid or making ear plugs.

If wax needs to be removed, there are various options

available. These include: irrigation (syringing); the use of

wax soeners or solvents alone; the use of wax soeners

before irrigation; and the manual removal of wax by use

of an oto-endoscope and small instruments or a binocular

microscope with suction and micro instruments. Irriga-

tion relies on getting water past the wax in the ear canal,

so that it builds up deep to the wax and then pushes it

outwards. Thus, if the wax is completely occluding the

canal, this technique can easily make matters worse by

impacting the wax against the tympanic membrane. If

there are pre-existing changes to the tympanic mem

brane, damage can occur; so there are many contraindica-

tions to irrigation. Oto-endoscopes give only a monocular

view of the ear canal, and practice is needed with instru-

mentation to become competent at wax removal without

trauma. Binocular microscopes give a stereoscopic view

and are probably the safest way of dewaxing an ear, espe-

cially when suction is used, but they are expensive and

users need training.

THE BOTTOM LINE

•

Ear wax only needs to be removed if it causes hearing impairment, other

symptoms, or if view of the tympanic membrane is required for diagnostic

reasons or for taking impressions for hearing aids or ear plugs

•

Ear irrigation (syringing) is generally considered to be effective, but evidence

is limited and it may be associated with adverse effects

•

There are insufficient data on other mechanical methods of wax removal or on

use of wax softeners to draw robust conclusions on their effectiveness

Evidence for the effects of methods to remove ear wax

Effects Treatment

Trade-off between benefits and harms

Clinicians and patients should weigh

up beneficial and harmful effects

according to individual circumstances

and priorities

Ear irrigation (syringing)—

considered to be effective, but

may be associated with adverse

effects*

Unknown effectiveness

Data are currently insufficient or of

inadequate quality

Manual removal (other than ear

irrigation)

Wax softeners before irrigation

Wax softeners alone

*Although we found no randomised controlled trials, there is consensus that

irrigation is effective at removing ear wax.