18F-FDG PET/CT: a useful imaging modality that goes beyond tumor staging in the rapidly advancing era of immune checkpoint inhibitors and targeted agents in cutaneous melanoma

Introduction: Cutaneous melanoma, deriving from the malignant transformation of melanocytes, has the highest mortality rate among skin cancers. Its incidence continues to increase annually, and survival odds are significantly worsened if metastasis to distant sites occurs. Combined positron emission tomography/computed tomography (PET/CT) using the radioactively labeled glucose analogue [¹⁸F]fluorodeoxyglucose (¹⁸F-FDG)plays an important role in the staging of melanoma patients, however, ¹⁸F-FDG PET/CT imaging potential goes beyond diagnosis and staging. Recent studies have suggested that ¹⁸F-FDG PET/CT could play a vital role in monitoring melanoma progression and evaluating responses to novel, highly specific targeted therapeutic approaches.

The purpose of this educational exhibit is to review the most recent literature pertaining to the vast utility of ¹⁸F-FDG PET/CT in clinical management of melanoma with a focus on the more recent novel cancer therapeutics and highlighting instances of ¹⁸F-FDG PET-derived parameters that may be of significant clinical use when traditional prognostic biomarkers for melanoma cannot be properly evaluated.

Methods: The PubMed, Web of Science, and Google Scholar databases were searched to accumulate articles relating to the clinical PET practices in imaging malignant melanoma using the terms "melanoma", "fluorodeoxyglucose" and "FDG". Review articles and scientific studies were compiled from the databases to accumulate a comprehensive body of literature. The articles encompassed today’s knowledge of melanoma as derived from PET studies and reflected the most recent innovations in molecular imaging with PET of metastatic melanoma.

Results: ¹⁸F-FDG PET/CT is increasingly used in patients with advanced cutaneous melanoma. Combined with cerebral magnetic resonance imaging, ¹⁸F-FDG PET/CT is the preferred imaging strategy for staging metastatic melanoma with high overall accuracy for detection of distant metastases. However, strong evidence is still required to support the standard use of this modality for predicting and monitoring therapy response and toxicity. Novel therapeutic approaches, including immune checkpoint inhibitors (ICIs) (directed towards cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death protein-1 (PD-1), or the ligand of PD-1 (PDL-1)) and targeted therapy with small molecule inhibitors specifically targeting BRAF and MEK signaling pathways, have markedly changed the clinical management of advanced melanoma. Although these therapeutic approaches have significantly improved the prognosis of metastatic melanoma, only 30–40% of these cases respond to ICIs. As more of these novel therapeutics are employed in the battle against melanoma, there is a greater need for imaging biomarkers suitable for pre-therapeutic stratification and response assessment. Distinct baseline and follow-up PET-derived parameters, such as total lesion glycolysis (TLG), metabolic tumor volume (MTV), and maximum standardized uptake value (SUV_max), have been shown to be particularly impactful for the prognostic evaluation of patients submitted to ICIs and targeted therapy. Such imaging metrics can provide promising prognostic information for clinical decision making and may serve as new tools for better stratification and selection of patients with advanced melanoma, who would benefit most from these treatment strategies.

Conclusions: This educational exhibit reviews evidence for the rational use of ¹⁸F-FDG PET/CT scans in staging, clinical decision making, monitoring response to treatment and follow-up in advanced melanoma. As ¹⁸F-FDG PET continues to gain traction as a tool to clinically manage melanoma, and the medical community gravitates towards using newer highly specific treatments, clinicians will need to establish standardized protocols and guidelines to determine optimal thresholds to evaluate patient prognosis before and after treatment with these novel therapeutic regimens.