Cutaneous melanoma accounts for approximately 5% of all malignant skin cancers. It is, however, one of the cancers whose incidence has increased most in white populations around the world in recent years.1 Although it is an uncommon tumor, melanoma is considered to be very aggressive because of its ability to metastasize in early stages of the disease. Diagnosis is thus essential for adequate management. Survival is influenced by disease extent, which in turn influences both prognosis and treatment. In 2009, the American Joint Committee on Cancer (AJCC) proposed a 4-stage grouping system for cutaneous melanoma based on different risk groups (Table 1).2

Positron emission tomography (PET) is a nuclear medicine technique that uses molecules labeled with positron-emitting isotopes to capture images. Although there are theoretically no limits on the metabolic substrates that can be used to produce radioisotopes, the most widely used radioactive tracer is fluor-18-fluorodeoxyglucose (FDG). FDG is a glucose analog that is transported into the cell in the same way as its unlabeled analog. It is not, however, a substrate for isomerase and therefore does not enter the Krebs cycle. As a consequence, it undergoes what is known as metabolic trapping. Increased intracellular uptake and trapping of FDG by tumor cells—favored by higher levels of glycolysis and an increase in specific receptors and enzymes, such as hexokinase, together with a reduction in glucose-6-phosphate (which catalyzes hexokinase)—enables external detection of this radioactive tracer.

The accumulation of FDG in tumor cells is a reflection of the increase in glucose metabolism required to sustain a high rate of growth and/or proliferation. The detection of increased FDG uptake does not necessarily indicate cancer, as accumulation of FDG is not specific to tumor tissue. Increased FDG uptake on PET scans can also indicate the presence of inflammation or infection and is probably due to the accumulation of the tracer in macrophages and granulation tissue. Such findings can give rise to false positives. False negatives, however, are also a possibility, as not all tumors are FDG-avid. Malignant lesions may not show increased FDG uptake for numerous reasons, including the presence of high levels of endogenous glucose competing with FDG for uptake, tumors that are too small to be detected (below the resolution capacity of the scanner), tumors with a mucinous, necrotic, or cystic component, well-differentiated or slow-growing tumors, and tumors in certain anatomic locations (peripheral lesions may go undetected because of the partial-volume effect and cortical lesions may display similar activity to cortical gray matter). In PET, FDG metabolism can be evaluated visually or measured semiquantitatively using the standardized uptake value, which is the ratio between the concentration of FDG (in mCi/g) in the tumor and the injected dose of radioactivity (also in mCi) divided by the patient's body weight in grams.

Most PET scanners nowadays are multimodal PET-computed tomography (CT) scanners, as by combining anatomic and functional images, they provide more detailed information. They also offer shorter scan times, which, by reducing motion due to patient discomfort, result in higher-quality, easier-to-interpret images.

The usefulness of PET-CT in melanoma is still questioned. In this review of the literature, we will look at some of the issues that remain unresolved, such as when the scan should be performed, whether PET-CT has advantages over conventional diagnostic methods, and whether it provides a real benefit to patients.

Detection of recurrence is one of the most widely studied and accepted applications of PET in melanoma, with sensitivity, specificity, and diagnostic accuracy rates of between 70% and 100% reported by different studies and meta-analyses. Compared with conventional diagnostic methods, PET performs better in pinpointing the location of both locoregional and distant metastases.11,12 Most lesions that go undetected by PET are, as we have already mentioned, small or located in the liver, lungs, or brain. PET thus is an essential staging tool in recurrent melanoma and should be used in combination with MRI in the case of brain metastases.

The incidental detection of second tumors (benign or malignant) during a PET study can lead to changes in treatment plans, such as cancellation of surgery or modification of surgical procedures or systemic therapy.

PET findings can lead to treatment changes in between 8% and 61% of such cases.

PET is a highly effective tool for assessing response to chemotherapy or immunotherapy. It has been known for some years that the changes in glucose metabolism that occur after one or more treatment cycles precede changes that can be detected by conventional imaging techniques, such as CT and MRI. Few studies have analyzed the use of PET to assess response to chemotherapy in metastatic melanoma due to the poor response rates, but most of those that have agree that PET could be useful and is clearly superior to the use of the biomarker S-100B.

One of the first studies to investigate the value of PET in the assessment of treatment response in melanoma patients was that by Mercier et al., 13 who studied patients with locally advanced melanoma who underwent PET before and after hyperthermic isolated limb perfusion with melphalan and/or tumor necrosis factor. Pretreatment scans were performed to establish the true extent of disease and to confirm the suitability of patients for the scheduled treatment. The authors reported that PET was more sensitive than the standard protocol used at the center (88% vs 65%). In another study, Beasley et al.14 reported that while PET identified few cases of complete response after treatment, it had important prognostic value in terms of predicting survival and duration of complete response. Furthermore, protocol-based PET scanning can detect localized disease outside the limb in which surgical resection is indicated (Fig. 2).

Figure 2.

PET/CT image showing PET images (A) and superimposed PET/CT images (B). Note the multiple hypermetabolic foci indicating lymph node involvement and multiple subcutaneous metastases. PET indicates positron emission tomography; CT, computed tomography.

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In the case of assessing response to chemotherapy, the metabolic image captured by PET can identify nonresponders and therefore avoid unnecessary treatments and toxic effects. There also appears to be a relationship between survival and metabolic response as assessed by PET.15 Chemotherapy response by PET imaging has been found to be associated with longer overall survival, particularly in the first year, and longer disease-free survival. This association was not detected using S-100B.16

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  Lymph node status is the most important prognostic factor in patients with cutaneous melanoma. SLNB permits the microscopic detection of lymph node involvement, enabling accurate staging and appropriate treatment. FDG-PET is not a substitute for SLNB in such cases due to its lower sensitivity in the detection of microscopic disease.

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  FDG-PET may be a useful initial staging tool in melanoma patients with risk factors for distant metastases.

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  The main indication of FDG-PET in cutaneous melanoma is to detect recurrence or to restage disease following the detection of recurrence, particularly in patients who are candidates for resection with curative intent.

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  PET is a highly effective technique for assessing response to chemotherapy or immunotherapy, as metabolic changes precede morphologic changes detected by conventional techniques such as CT and MRI. It also helps to identify nonresponders and therefore avoids unnecessary, toxic treatments.

The authors declare that they have no conflicts of interest.