Primary staging and follow-up of high risk melanoma patients with whole-body18F-fluorodeoxyglucose positron emission tomography

We read with interest the article by Rinne et al.,1 who prospectively evaluated 100 consecutive high risk melanoma patients with whole-body positron emission tomography (PET) and conventional diagnostics. In 52 cases (Group A), PET was performed for primary staging. In 48 cases (Group B), there was clinical suspicion of progression, and therefore PET was performed for restaging during the follow-up. The authors concluded that PET “is a highly sensitive and specific technique for melanoma staging, with exception of the brain.” This study is particularly important because it is the first large prospective study to apply PET in the primary staging of melanoma patients. The authors define “high risk melanoma” as a tumor thickness of at least 1.5 mm and Clark Level IV. However, the mean Breslow thickness of the primary lesions is not mentioned, nor is the range. What is “high risk”? This discussion dates from the 1970s, when the term “high risk” was introduced.2 An elective lymph node dissection, performed on melanoma patients with Breslow thickness 1.5–4.0 mm, has shown to confer little, if any, survival advantage. The risk of metastases varies strongly according to thickness, and we think the term “high risk” is relative and needs reevaluation based on current knowledge, particularly regarding lymphatic dissemination. We agree with the authors that the earliest possible detection of metastases at a potentially curable stage is a major objective. PET appears to be very useful in Group B. However, in Group A, PET detected lymph node metastases in only 8% of patients, whereas no systemic metastases were found. With this percentage taken into account, we wonder if PET is sensitive enough for accurate regional staging. Biopsy of the first tumor-draining, sentinel lymph node (SN) is the most recent developed method for the detection of early micrometastases in the regional lymph nodes.3 SN biopsy, which was not mentioned in the article by Rinne et al., has the potential to become the procedure of choice in the regional staging of melanoma patients. With the SN biopsy, we found lymph node metastases in 28% and 67% of Stage I melanoma patients with Breslow thickness 1.51–4.0 and >4.0 mm, respectively,4 and this finding was confirmed by many others. It is not imaginary that a significant number of small metastases were missed by PET. Unfortunately, the sizes of the nine lymph node metastases detected by PET were not reported in the article. Borgstein et al. studied the size and distribution of tumor metastases within 50 tumor positive SN.5 They discovered that with an SN biopsy, micrometastases as small as 0.0005 mm2 could be detected. From subsequent lymph node dissections it became clear that in 75% of cases the SN was the only tumor positive lymph node, with a median metastasis area of 0.15 mm2. It is unclear, but very unlikely, that micrometastases smaller than 1 mm2 can be detected by 18F-fluorodeoxyglucose PET. Practical support for this is found in a recent study by Macfarlane et al.6 In summary, we think that SN biopsy is to be preferable for initial regional staging of Stage I melanoma. The SN biopsy has a lower detection limit (theoretically, one cell) and no risk of false-positivity, and it is obtainable in more hospitals than PET. In our opinion, the diagnostic accuracy of both SN biopsy and PET imaging needs to be prospectively studied in a large group of (unselected) patients with a higher prevalence of lymphatic metastases at presentation (Breslow thickness >3.0 or 4.0 mm). In a broader sense, the still-unknown prognostic relevance of detection of micrometastatic lymph node involvement could affect the place of either technique in the clinical management algorithm. G. Sophie Mijnhout M.D.*, Rik Pijpers M.D.*, Otto S. Hoekstra M.D., PhD.*, G. Jaap J. Teule M.D., PhD.*, Paul J. Borgstein M.D. , Sybren Meijer M.D., PhD. , * Department of Nuclear Medicine, Academisch Ziekenhuis van de Vrije Universiteit, Amsterdam, The Netherlands, Department of Surgical Oncology, Academisch Ziekenhuis van de Vrije Universiteit, Amsterdam, The Netherlands