Meta-analysis of the performance of (18)F-FDG PET in cutaneous melanoma.

INTRODUCTION: The aim of this study was to perform a systematic review of the literature to evaluate the accuracy of FDG-PET in staging and restaging of cutaneous melanoma.
METHODS: Systematic methods were used to identify, select, and evaluate the methodologic quality of the studies as well as to summarize the overall findings of sensitivity and specificity. The search strategy consisted of identifying studies published between 2000 and 2006. Inclusion criteria were studies that evaluated the diagnostic performance of FDG-PET in staging/restaging of cutaneous melanoma. The results were compared and pooled with a meta-analysis published previously that included studies published until 1999. The meta-analysis included 95% confidence intervals (CI) of sensitivity, specificity, likelihood-ratio (LR), and diagnostic-odds-ratio (DOR).
RESULTS: The quantitative meta-analysis included 24 studies that were analysed in two groups: eight studies were included only in the regional staging analysis (group I), 13 studies were included only in the detection of distant metastases analysis (group II), and three studies were included in both analyses. Compliance with the methodologic-quality criteria was acceptable. We analysed the results of data presented in patients, lesions, basins, lymph-nodes, areas, and scans. Regarding the performance of FDG-PET in the detection of metastases, the pooled studies presented homogeneity for the negative-LR (0.15; 95% CI, 0.10-0.22) when analyzing lesions. When analyzing scans, there was global homogeneity for specificity (0.86; 95% CI, 0.77-0.92), positive-LR (5.86; 95% CI, 3.64-9.43), and DOR (37.89; 95% CI, 15.80-90.86). The pooled studies presented heterogeneity for the other items analysed. Regarding the detection of regional metastases, when analyzing lymph-nodes there was global homogeneity for specificity (0.99; 95% CI, 0.97-0.99; P = 0.101). The meta-regression evidenced that the variable that most influenced the DOR of the different studies and that can explain the heterogeneity was the year of publication; this may be related to the evolution of PET technology and an improvement of sensitivity/specificity.
CONCLUSION: FDG-PET is not useful in the evaluation of regional metastases, as it does not detect microscopic disease. However, FDG-PET could be useful in the detection of distant metastases, and could suggest its utility in the management of patients with cutaneous melanoma.

Dear Sir,

Following the publication of our study entitled “Meta-analysis of the performance of 18F-FDG PET in cutaneous melanoma” in the February 2010 issue [1], we reply to the comments presented in the above letter to the editor.

First, as described in the “Materials and methods” section, we performed a systematic search of the literature to identify relevant studies published between January 2000 and January 2006. Then, the meta-analysis was performed and the manuscript was prepared for publication. Finally, it was accepted for publication in 2009. Because of this 3-year delay between the literature search and publication, studies published after January 2006 were not included. The delay between the presentation of results as abstracts and full publication of results has been previously studied in the meta-analysis published by Scherer et al. [2]. In this meta-analysis, most studies were published in full within 2 years of their appearance as abstracts, although some studies presented a delay of up to 3 years. However, the results of our meta-analysis may be updated to include the most recent studies.

Second, the methodological quality criteria applied in our meta-analysis had been developed and applied in previous meta-analyses by Huebner et al. [3], Gould et al. [4], Delgado-Bolton et al. [5] and Schwimmer et al. [6]. These methodological quality criteria were developed to systematically analyse studies focusing on the performance of 18F-FDG PET. They apply 7 guidelines which include 38 items, in order to extensively evaluate the methodological quality of the studies and, also, establish guidelines for carrying out methodologically rigorous studies. These criteria are based on evidence-based medicine criteria and, to the best of our knowledge, are not biased. Regarding the quality assessment of studies of diagnostic accuracy included in systematic reviews (QUADAS) criteria [7, 8], which is a 14-item instrument, it can be useful for the assessment of diagnostic accuracy studies and, if used extensively, it will facilitate comparison among meta-analyses. However, the QUADAS tool has not been designed specifically for 18F-FDG PET. As evidenced in the meta-analysis by Kwee et al. [9], the QUADAS criteria present certain limitations when analysing 18F-FDG PET diagnostic accuracy studies. These authors eliminated 3 of the 14 criteria and added another different one. This indicates that the QUADAS criteria may not be the optimal tool for evaluating the methodological quality in 18F-FDG PET studies. Furthermore, the methodological quality criteria applied in our meta-analysis include certain guidelines and items not analysed or incomplete in the QUADAS criteria, such as: description of study design and patient selection criteria, characteristics of patient population finally studied, sensitivity and specificity data, and change in management information. These additional aspects not included in the QUADAS criteria can be of relevance when assessing the methodological quality and establishing guidelines for performing methodologically rigorous studies on 18F-FDG PET.

Third, regarding the end-points chosen for our meta-analysis, it would have been very interesting to analyse the diagnostic performance of 18F-FDG PET depending on the American Joint Committee on Cancer (AJCC) stage. Unfortunately, most of the original papers did not supply enough information on the AJCC stage of the patients included. Many studies included heterogeneous populations regarding the AJCC stage and the results of the 18F-FDG PET were not presented independently for each AJCC stage. Therefore, it was not possible to study this end-point. If future studies include enough details of population characteristics and present the results of sensitivity and specificity for each subgroup of patients, it will be possible to analyse this end-point in a meta-analysis.

Fourth, in our meta-analysis the quantitative analysis evaluated subgroups of studies that presented the same method of counting findings (patients, lesions, basins, etc.). We separately analysed like data (patients, lesions, basins, lymph nodes, areas or scans), because we considered the results of studies that referred to different data (patients, lesions, basins, etc.) not comparable. Because of this, the pooled data were reduced. However, we considered it methodologically more rigorous than pooling together different data.

Finally, we agree with the comment regarding the need for standardization in the reporting of studies to improve the information provided by each individual study, which will allow future meta-analyses and cost-effectiveness analyses to establish the role of 18F-FDG PET.