Metastatic Evaluation of the Melanoma Patient

Educational Objectives

The goal of this program is to improve the metastatic evaluation in melanoma. After hearing and assimilating this program, the clinicians will be better able to:

1. Select appropriate imaging modalities for patients with metastatic melanoma.
2. Avoid unnecessary testing in patients with melanoma who are at low risk for metastasis.

Summary

Metastatic evaluation of melanoma: new patients receive a detailed history and full skin examination, including inspection of the primary site for satellite or in-transit metastases and palpation of regional and distant lymph nodes; they should follow up with an ophthalmologist, pigmented lesions in the genital tract should be identified on gynecologic examination, and a dentist can evaluate for mucosal lesions; constitutional and neurologic systems, and any system the patient is experiencing symptoms from, should be reviewed; lower-risk patients should not undergo more extensive workup as routine imaging has low yield and frequent false-positive findings; this category includes patients who are asymptomatic and have no palpable nodes, with disease that is clinical stage 0 (in situ) or clinical stage 1A (Breslow depth <0.8 mm without ulceration)

Sentinel lymph node biopsy (SLNB): the most sensitive and specific staging test for detecting micrometastatic melanoma in regional lymph nodes; in clinical stage 1A, SLNB is not recommended by the National Comprehensive Cancer Network (NCCN); SLNB can be considered in clinical stage 1B or T1a lesions with Breslow depth ≥0.5 mm and age ≤42 yr, location in the head or neck, mitotic index >2 mm², or lymphovascular invasion; in stage 1B or 2 disease (ie, Breslow depth >1 mm with any feature or nodal status), SLNB should be performed; positive SLNB may upstage a patient to stage 3 disease, for which adjuvant therapies are needed; SLNB is not recommended for pure desmoplastic melanomas due to low yield, but it is recommended for mixed desmoplastic melanomas; the decision to not perform SLNB also depends on patient comorbidities, preference, and tumor burden

Ultrasonography (USG): in patients with equivocal or palpable lymphadenopathy, any abnormal or suspicious lesion should be biopsied; USG is the best imaging modality, and adding fine needle aspiration (FNA) increases specificity to ≈100%; baseline testing is not recommended for patients with stage 1 and 2 disease except for surgical planning or if specific signs or symptoms are present; USG can be used if a patient meets criteria for SLNB but does not undergo it or if SLNB is unsuccessful; can be considered for patients with negative regional lymph node examination before SLNB; in patients at low risk for lymph node metastasis, USG is a justifiable choice for imaging surveillance; positron emission tomography-computed tomography (PET-CT) plays a role in detecting distant metastases in patients at intermediate and high risk for metastasis; in stage 3 disease with positive SLNB, USG surveillance can be an alternative to complete lymph node dissection; in stage 3 disease with clinically positive lymph nodes, USG is used to confirm the suspicion, preferably with FNA or core biopsy under USG guidance

Imaging in advanced disease: in patients with stage 3 disease, cross-sectional imaging should be done at baseline for staging; for stage 4 disease, a baseline chest, abdomen, and pelvic CT should be done with or without a PET-CT; magnetic resonance imaging (MRI) or CT of the brain with contrast is done at baseline and if the patient exhibits new signs or symptoms concerning for central nervous system (CNS) involvement; CT is more sensitive than chest x-ray and helps to visualize lymph nodes and bony structures; tumor imaging requires contrast; while noninvasive, it exposes patients to ionizing radiation; one study found that, in patients with T1B to T3B primary lesions who were clinically N0 and asymptomatic, baseline imaging did not upstage or change initial surgical management, and total cost was significant; given the low yield and high false-positive rates, imaging at diagnosis is not warranted in these patients

CT and MRI: a study found that USG was superior to CT in detecting locoregional lymph node metastases, and MRI and PET-CT were superior to CT for assessing systemic tumor spread; PET-CT is preferred for distant metastatic evaluation as it can detect hypermetabolic lesions and characterize intermediate lesions seen on CT with structural and functional data; it can image areas of the body not studied on routine CT and can detect lesions between 3 and 5 mm in size, but cannot detect cerebral metastases; PET-CT is more sensitive than CT alone; MRI is superior to CT for examining soft tissue diseases (no ionizing radiation is involved, but contrast is needed); MRI is particularly helpful for identifying brain metastases; it is important to detect and treat subclinical CNS metastases early, since symptomatic metastases have significant morbidity and poor survival; PET-CT is more accurate for staging and detecting long or soft tissue metastases, while MRI is more accurate for liver, bone, and brain metastases

Fludeoxyglucose (FDG) imaging and x-rays: FDG PET-MRI is better than FDG PET-CT at detecting cerebral metastases, while FDG PET-CT is better for pleural and lung metastases; FDG-based imaging cannot replace SLNB as it cannot reliably differentiate node-positive from node-negative patients; for patients with low-stage melanoma, chest x-ray is cost-inefficient, with low true-positive and high false-positive rates for baseline staging; however, it is appropriate as a surveillance method for patients with known lung metastasis from melanoma if used at 3- to 12-mo intervals

Laboratory testing: advances in precision medicine include gene expression profiling (GEP), assessment of key mutations in tumor genetics, and use of specific biomarkers; DecisionDx-Melanoma — a GEP that uses the tumor biology of individual patients to predict risk for metastasis, recurrence, and sentinel node positivity independent of traditional staging factors; MelaGenix — a quantitative, real-time polymerase chain reaction assay based on expression of 11 genes; it is used for American Joint Committee on Cancer (AJCC) stage 2 cutaneous melanoma and divides patients into groups with lower or higher chances of recurrence; BRAF — the most common mutation in melanoma; the NCCN recommends considering BRAF testing in stage 3A and completing testing in stage 3B and above to assess candidacy for BRAF inhibitor therapy; other tests — melanoma is particularly immunosensitive, and checkpoint inhibitors have a role to play; knowing the programmed death ligand-1 status may have value, but this is used only on a case-by-case basis; lactate dehydrogenase is utilized in patients with stage 4 disease as an independent predictor of poor outcome and nonspecific surrogate marker for tumor burden, and to upstage M categories

Readings

Keung EZ, Gershenwald JE. The eighth edition American Joint Committee on Cancer (AJCC) melanoma staging system: implications for melanoma treatment and care. Expert Rev Anticancer Ther. 2018;18(8):775-784. doi:10.1080/14737140.2018.1489246; Papageorgiou C, Apalla Z, Manoli SM, et al. Melanoma: Staging and Follow-Up. Dermatol Pract Concept. 2021;11(Suppl 1):e2021162S. Published 2021 Jul 1. doi:10.5826/dpc.11S1a162S; Swetter SM, Johnson D, Albertini MR, et al. NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2024. J Natl Compr Canc Netw. 2024;22(5):290-298. doi:10.6004/jnccn.2024.0036; Swetter SM, Thompson JA, Albertini MR, et al. NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2021. J Natl Compr Canc Netw. 2021;19(4):364-376. Published 2021 Apr 1. doi:10.6004/jnccn.2021.0018; Switzer B, Puzanov I, Skitzki JJ, et al. Managing Metastatic Melanoma in 2022: A Clinical Review. JCO Oncol Pract. 2022;18(5):335-351. doi:10.1200/OP.21.00686; Tutic-Sorrentino L, Cazzaniga S, Feldmeyer L, et al. PET-CT vs brain MRI for the detection of cerebral metastases of melanoma, a 5-year retrospective study. Clin Exp Dermatol. Published online April 16, 2024. doi:10.1093/ced/llae129.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Fronek was recorded at the 34th Annual Cutaneous Malignancy Update, held on January 27, 2024, in San Diego, CA, and presented by Scripps Health. For information about upcoming CME activities from this presenter, please visit scripps.org/for-health-care-professionals/continuing-medical-education-cme. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.75 CE contact hours.

Lecture ID:

ON151903

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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