4.1Surgery 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, 102, 103, 104} The safety of these narrower margins has been demonstrated in a series of studies.^{105, 106, 107, 108} Evidence level 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, 108, 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. Evidence level 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

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.

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.

4.1.1 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). Evidence level 4

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.

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.

4.2 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

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 Evidence level 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, 119, 120} Evidence level 2++

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} Evidence level 4

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.

4.3.2 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} Evidence level 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} Evidence level 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

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.

4.3.3 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.

4.3.4 ELECTIVE LYMPH NODE DISSECTION

Although retrospective series^{126, 127, 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, 130, 131} Evidence level 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. Evidence level 1+

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

4.3.5 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, 134, 135, 136, 137, 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). Evidence level 2+

Sentinel lymph node biopsy accurately determines the presence or absence of metastasis within the regional lymph node basin^{139, 140, 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 Evidence level 2++,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).

4.4 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}

• 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.

ILP should be performed in regional centres.

4.4.1 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 Evidence level 1+

ILP should not be used as an adjuvant treatment.

4.4.2 THERAPEUTIC TREATMENT

A multicentre RCT¹⁴⁵ and reviews^{146, 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). Evidence level 1-,4

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, 149, 150} Evidence level 4

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

4.5.2 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.

Patients with substantial cutaneous recurrence should be referred to an appropriate centre where a range of treatment options can be considered.