Treatment of primary melanoma

Following a histological examination of the suspicious lesion, the treatment for primary cutaneous melanoma is wide local excision under local or general anaesthetic (Roberts et al., 2002). The purpose of this treatment is to minimise the risk of local recurrence. The excision margins specified in the UK Guidelines (Roberts et al., 2002) are determined by the Breslow thickness of the lesion, as described and depicted earlier (Figure 11.6).

At the same time, a sentinel lymph node biopsy (SLNB) may be performed in patients with thick tumours in order to discover if the melanoma has spread from the skin to the lymph nodes. The sentinel lymph node(s), the first lymph node to which cancer may have metastasised, is identified by injecting a blue dye or a radioactive material, or both, into the skin at the site of the primary melanoma. The surgeon then uses a scanner to find the lymph node(s) containing the radioactive substance or looks for the lymph node(s) stained with dye. The lymph nodes are surgically removed and examined histologically. If the sentinel lymph node contains metastatic melanoma, then the surrounding lymph nodes are often removed during a subsequent procedure known as a lymphadenectomy. Whilst there is no proof to date that SLNB leads to an overall survival benefit for all patients, it is an accepted staging procedure. Its availability to patients is not standardised across the UK.

Adjuvant treatments
Adjuvant treatment can be defined as any treatment in addition to surgery which may reduce the risk of recurrence. There is currently none of proven benefit (Roberts et al., 2002) but patients should be referred for entry into clinical trials, examples of which include bevacizumab (AVAST-M).

Follow-up
It is recommended that patients are followed up ‘to reduce morbidity and mortality through the detection of metastatic disease and other primary melanomas’ (Sober et al., 2001, p. 6). It is estimated that 4–8% of patients diagnosed with a primary melanoma may develop a further primary melanoma within the first 3–5 years following diagnosis (Levi et al., 2005). It is suggested that ‘all patients with invasive melanoma should be followed up at three monthly intervals, for three years. Thereafter patients with melanomas less than 1.0 mm thick may be discharged but others should be reviewed 6 monthly for a further two years’ (Roberts et al., 2002).

Physical examination, by a health professional, is the mainstay of follow-up interventions. The site of the primary tumour and the adjacent skin should be examined for local recurrences and local metastatic disease; the draining lymph node basins should be examined for lymphadenopathy; and the remaining skin should be examined for other suspicious lesions such as other primary melanoma (Roberts et al., 2002). Routine investigations, such as blood tests and X-rays, contribute little to recurrence detection (Kersey et al., 1995), as most melanoma recurrences produce symptoms or can be found by physical examination.

Metastatic melanoma
Melanoma can spread to virtually any organ or tissue such as the skin, subcutaneous tissue, lymph nodes, lung, gastrointestinal tract, liver, bone and brain (Essner, 2001). The majority occurs in the first 3 years after diagnosis (Shumate et al., 1995; Poo-Hwu et al., 1999). Many of the first metastases, after treatment of the primary tumour, develop in the regional lymph nodes or in the skin close to or at the site of the primary tumour (McCarthy et al., 1988; Dickers et al., 1999).

Skin metastases often present as nodules but they may be inflammatory, cicatrical or bullous lesions (Lookingbill et al., 1993). They are normally flesh coloured, although they may be red, purple, brown or black and about a third are pigmented or ulcerated (Evans et al., 2003). Often round or oval in appearance, they can be non-tender, non-painful, solid, firm or rubbery in texture (Strohl, 1998). They can be moveable or fixed and vary in size and may present as single or multiple nodules in the skin (Strohl, 1998). Skin metastases can be found by palpation and visual examination, and diagnosis is most commonly confirmed by histological analysis following a biopsy: needle, incisional or excisional (Balch et al., 1994).

Lymph nodes are oval- or bean-shaped structures, found scattered throughout the body in groups, located along the length of the lymphatic system (Tortora and Derrickson, 2005). Lymph nodes containing metastatic melanoma are generally more firm and rubbery, and are non-tender compared with inflammatory nodes, which are usually softer, more resilient and tender (Balch et al., 1994). Lymph nodes can therefore be found by palpation but diagnosis is confirmed by histological analysis following a biopsy: needle, incisional or excisional (Balch et al., 1994).

The signs and symptoms of distant metastases to the lungs, liver, bone or brain depend on the site of relapse and on whether they are at single or multiple sites. Metastatic disease remains relatively resistant to current treatments with dacarbazine (an alkylating agent) being the current single chemotherapy agent of choice (Roberts and Crosby 2008).

Survival
To allow the health professional to identify those patients most at risk of developing metastases, offer prognostic information to patients and their families and to compare treatment results, the American Joint Committee on Cancer (AJCC) melanoma staging system classifies patients’ disease into tumour (T), regional lymph nodes (N) and distant metastases (M) (Kim et al., 2002). From this classification, melanomas are grouped into four stages, stages I–IV.

In Stage I and II, patients have a primary tumour but there is no evidence that the cancer has spread to the lymph nodes or distantly. Patients have favourable overall survival outcomes of up to 95% (Kim et al., 2002) (AJCC). Although patient age, site of the primary melanoma, level of invasion of the tumour and gender have been identified as prognostic factors, tumour thickness and the presence of ulceration of the lesion are the most powerful predictors of survival in patients in Stage I and II (Balsh et al., 2001). The 7th edition of the AJCC melanoma staging system will be published in the spring of 2009 and it is likely that the number of mitoses per square millimetre will also be included as an independent prognostic predictor.

The strongest indicator of survival is tumour thickness: the thinner the Breslow thickness, the better the prognosis (Table 11.4). Most patients diagnosed with melanoma have thin tumours. A total of 57.8% of patients in the South Australian Cancer registry from 1994 to 2000 had tumours ≤0.75 mm in thickness (Luke et al., 2003). Ulceration of the primary tumour carries a worse prognosis compared to non-ulcerated lesions.

Table 11.4 Illustration of a 5-year survival rates for patients diagnosed with cutaneous melanoma at each stage.     IA IB IIA IIB IIC IIIA IIIB IIIC   Ta: Non-ulcerated melanoma T1a 95% T2a 92% T3a 79% T4a 67%   N1a N2a 67% N1b N2b 54% N3 28%   Tb: Ulcerated melanoma   T1b 91% T2b 77% T3b 63% T4b 45%   N1a N2a 52% N1b N2b N3 24%     Source: Kim et al. (2002) and American Joint Committee on Cancer (2002).

In Stage III, patients have developed a lymph node metastasis or intransit/satellite lesion but have no distant metastases. The number of metastatic nodes, tumour burden and the presence and absence of melanoma ulceration are the most powerful predictors of survival in Stage III disease patients. In Stage IV disease, patients have developed distant metastases with the anatomic site of these metastases being the most significant predictor of survival (Kim et al., 2002). Patients with metastases in visceral sites have a poorer prognosis compared with those with metastases at non-visceral sites (i.e. skin, subcutaneous and distant lymph nodes) (Kim et al., 2002).