Skip to main content

Advertisement

SpringerLink
Log in

Management of melanoma: can we use gene expression profiling to help guide treatment and surveillance?

  • Review
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Although the incidence of cutaneous melanoma (CM) has been increasing annually, the mortality rate has been decreasing, likely due to better prevention, earlier detection, improved surveillance, and the development of new therapies. Current clinical management guidelines by the National Comprehensive Cancer Network (NCCN) are based on patient risk assignment using staging criteria established by the American Joint Committee on Cancer (AJCC). However, some patients with localized disease (stage I–II), generally considered to have a good prognosis, will develop metastatic disease and die, whereas some patients with later stage disease (stage III–IV) will be cured by surgery, adjuvant therapy, and/or systemic therapy. These results emphasize the importance of identifying patients whose risk may be over or underestimated with standard staging. Gene expression profile (GEP) tests are noninvasive molecular tests that assess the expression levels of a panel of validated genes, providing information about tumor prognosis, including the risk of recurrence, metastasis, and cancer-specific death. GEP tests can provide prognostic information beyond standard staging that may aid clinicians and patients in treatment and surveillance management decisions. This review describes how combining clinicopathologic staging with a robust assessment of tumor biology may provide information that will allow more refined intervention and long-term management.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Miller KD et al (2022) Cancer treatment and survivorship statistics, 2022. CA Cancer J Clin. https://doi.org/10.3322/caac.21731

    Article  PubMed  Google Scholar 

  2. Berk-Krauss J, Stein JA, Weber J, Polsky D, Geller AC (2020) New systematic therapies and trends in cutaneous melanoma deaths among US Whites, 1986–2016. Am J Public Health 110:731–733

    Article  PubMed  PubMed Central  Google Scholar 

  3. NCCN Clinical Practice Guidelines in Oncology: Melanoma: Cutaneous Version 1.2023. https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf

  4. Gershenwald JE et al (2017) AJCC cancer staging manual. In: 8th edition AJCC melanoma staging system. Springer, New York, pp 563–589

  5. Gershenwald JE et al (2017) Melanoma staging: evidence-based changes in the American Joint Committee on cancer eighth edition staging manual. CA Cancer J Clin 67:472–492

    Article  PubMed  PubMed Central  Google Scholar 

  6. Gershenwald JE, Scolyer RA (2018) Melanoma Staging: American Joint Committee on Cancer (AJCC) 8th edition and Beyond. Ann Surg Oncol 25:2105–2110

    Article  PubMed  Google Scholar 

  7. Baade PD et al (2020) Long-term deaths from melanoma according to tumor thickness at diagnosis. Int J Cancer 147:1391–1396

    Article  CAS  PubMed  Google Scholar 

  8. Morton DL et al (2014) Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med 370:599–609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wong SL et al (2018) Sentinel lymph node biopsy and management of regional lymph nodes in melanoma: American Society of Clinical Oncology and Society of Surgical Oncology clinical practice guideline update. Ann Surg Oncol 25:356–377

    Article  PubMed  Google Scholar 

  10. Yamamoto M et al (2015) Sentinel lymph node biopsy is indicated for patients with thick clinically lymph node-negative melanoma. Cancer 121:1628–1636

    Article  PubMed  Google Scholar 

  11. Moody JA, Ali RF, Carbone AC, Singh S, Hardwicke JT (2017) Complications of sentinel lymph node biopsy for melanoma—a systematic review of the literature. Eur J Surg Oncol 43:270–277

    Article  CAS  PubMed  Google Scholar 

  12. Han D et al (2012) Sentinel node biopsy is indicated for thin melanomas ≥ 0.76 mm. Ann Surg Oncol 19:3335–3342

    Article  PubMed  PubMed Central  Google Scholar 

  13. Han D et al (2013) Clinicopathologic predictors of sentinel lymph node metastasis in thin melanoma. J Clin Oncol 31:4387–4393

    Article  PubMed  Google Scholar 

  14. Multicenter Selective Lymphadenectomy Trials Study Group et al (2022) Therapeutic value of sentinel lymph node biopsy in patients with melanoma: a randomized clinical trial. JAMA Surg. https://doi.org/10.1001/jamasurg.2022.2055

  15. Faries MB et al (2017) Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med 376:2211–2222

    Article  PubMed  PubMed Central  Google Scholar 

  16. Broman KK et al (2021) Surveillance of sentinel node-positive melanoma patients with reasons for exclusion from MSLT-II: multi-institutional propensity score matched analysis. J Am Coll Surg 232:424–431

    Article  PubMed  Google Scholar 

  17. Broman KK et al (2021) Active surveillance of patients who have sentinel node positive melanoma: an international, multi-institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy Trial II (MSLT-2). Cancer 127:2251–2261

    Article  CAS  PubMed  Google Scholar 

  18. Curti BD, Faries MB (2021) Recent advances in the treatment of melanoma. N Engl J Med 384:2229–2240

    Article  CAS  PubMed  Google Scholar 

  19. Dummer R et al (2020) Five-year analysis of adjuvant Dabrafenib plus Trametinib in stage III melanoma. N Engl J Med 383:1139–1148

    Article  CAS  PubMed  Google Scholar 

  20. Eggermont AMM et al (2020) Longer follow-up confirms recurrence-free survival benefit of adjuvant pembrolizumab in high-risk stage III melanoma: updated results from the EORTC 1325-MG/KEYNOTE-054 trial. JCO 38:3925–3936

    Article  CAS  Google Scholar 

  21. Luke JJ et al (2023) Pembrolizumab versus placebo as adjuvant therapy in stage IIB or IIC melanoma: final analysis of distant metastasis-free survival in the phase 3 KEYNOTE-716 study. JCO 41:LBA9505

    Article  Google Scholar 

  22. Luke JJ et al (2022) Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial. The Lancet 399:1718–1729

    Article  CAS  Google Scholar 

  23. Eggermont AMM et al (2021) Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol 22:643–654

    Article  CAS  PubMed  Google Scholar 

  24. Testori AAE, Chiellino S, van Akkooi ACJ (2020) Adjuvant therapy for melanoma: past, current, and future developments. Cancers 12:1994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chatziioannou E et al (2023) Features and long-term outcomes of stage IV melanoma patients achieving complete response under anti-PD-1-based immunotherapy. Am J Clin Dermatol. https://doi.org/10.1007/s40257-023-00775-7

    Article  PubMed  PubMed Central  Google Scholar 

  26. Sharon CE et al (2023) Long-term outcomes to neoadjuvant pembrolizumab based on pathological response for patients with resectable stage III/IV cutaneous melanoma. Ann Oncol S0923–7534(23):00734–00742. https://doi.org/10.1016/j.annonc.2023.06.006

    Article  CAS  Google Scholar 

  27. Poklepovic A, Carvajal R (2018) Prognostic value of low tumor burden in patients with melanoma. Oncology 32:e90–e96

    PubMed  Google Scholar 

  28. Conroy M, Naidoo J (2022) Immune-related adverse events and the balancing act of immunotherapy. Nat Commun 13:392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Papageorge MV et al (2023) The role of imaging and sentinel lymph node biopsy in patients with T3b–T4b melanoma with clinically negative disease. Front Oncol 13:1143354

    Article  PubMed  PubMed Central  Google Scholar 

  30. Wagner JD et al (2005) Inefficacy of F-18 fluorodeoxy-D-glucose-positron emission tomography scans for initial evaluation in early-stage cutaneous melanoma. Cancer 104:570–579

    Article  PubMed  Google Scholar 

  31. Helvind NM et al (2023) Earlier recurrence detection using routine FDG PET-CT scans in surveillance of stage IIB to IIID melanoma: a national cohort study of 1480 patients. Ann Surg Oncol 30:2377–2388

    Article  PubMed  Google Scholar 

  32. Dancheva Z et al (2022) Diagnostic and clinical value of [18F]FDG PET/CT in the follow-up regimen in IIA-IIID stage cutaneous malignant melanoma after first regional recurrence. Nucl Med Rev Cent East Eur. https://doi.org/10.5603/NMR.a2022.0039

    Article  PubMed  Google Scholar 

  33. Cohen PR, Kurzrock R (2022) Dermatologic Disease-Directed Targeted Therapy (D3T2): the application of biomarker-based precision medicine for the personalized treatment of skin conditions-precision dermatology. Dermatol Ther. https://doi.org/10.1007/s13555-022-00801-2

    Article  PubMed  Google Scholar 

  34. National Comprehensive Cancer Network. (2023) Breast Cancer, Version 4.2023. Breast Cancer, Version 4.2023. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf

  35. National Comprehensive Cancer Network: Melanoma: Uveal, NCCN Guidelines Version 1.2022, in NCCN Clinical Practice Guidelines in Oncology. https://www.nccn.org/professionals/physician_gls/pdf/uveal.pdf

  36. Gerami P et al (2015) Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. Clin Cancer Res 21:175–183

    Article  CAS  PubMed  Google Scholar 

  37. Greenhaw BN et al (2020) Molecular risk prediction in cutaneous melanoma: a meta-analysis of the 31-gene expression profile prognostic test in 1479 patients. J Am Acad Dermatol 83:745–753

    Article  PubMed  Google Scholar 

  38. Hsueh EC et al (2021) Long-term outcomes in a multicenter, prospective cohort evaluating the prognostic 31-gene expression profile for cutaneous melanoma. JCO Precis Oncol 5:589–601

    Article  Google Scholar 

  39. Arnot SP et al (2021) Utility of a 31-gene expression profile for predicting outcomes in patients with primary cutaneous melanoma referred for sentinel node biopsy. Am J Surg 221:1195–1199

    Article  PubMed  Google Scholar 

  40. Zager JS et al (2018) Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. BMC Cancer 18:130

    Article  PubMed  PubMed Central  Google Scholar 

  41. Thorpe RB et al (2021) Development and validation of a nomogram incorporating gene expression profiling and clinical factors for accurate prediction of metastasis in patients with cutaneous melanoma following Mohs micrographic surgery. J Am Acad Dermatol. https://doi.org/10.1016/j.jaad.2021.10.062

    Article  PubMed  Google Scholar 

  42. Keller J et al (2019) Prospective validation of the prognostic 31-gene expression profiling test in primary cutaneous melanoma. Cancer Med 8:2205–2212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Greenhaw BN, Zitelli JA, Brodland DG (2018) Estimation of prognosis in invasive cutaneous melanoma: an independent study of the accuracy of a gene expression profile test. Dermatol Surg 44:1494–1500

    Article  CAS  PubMed  Google Scholar 

  44. Dillon LD et al (2022) Expanded evidence that the 31-gene expression profile test provides clinical utility for melanoma management in a multicenter study. Curr Med Res Opin 38:1267–1274

    Article  CAS  PubMed  Google Scholar 

  45. Williams A, Hamilton O, Likar C, Thomay A, Garland-Kledzik M (2022) The benefit of positron emission tomography/computed tomography in stage I and stage II melanomas with high-risk decisiondx-melanoma scores. Am Surg. https://doi.org/10.1177/00031348221081760

    Article  PubMed  PubMed Central  Google Scholar 

  46. Scott AM, Dale PS, Conforti A, Gibbs JN (2020) Integration of a 31-gene expression profile into clinical decision-making in the treatment of cutaneous melanoma. Am Surg 86:1561–1564

    Article  PubMed  Google Scholar 

  47. Egger ME et al (2019) Should sentinel lymph node biopsy be performed for all T1b melanomas in the new 8th edition American Joint Cancer Staging System? J Am Coll Surg 228:466–472

    Article  PubMed  Google Scholar 

  48. Hanna AN et al (2019) Relationship between age and likelihood of lymph node metastases in patients with intermediate thickness melanoma (1.01–4.00 mm): a National Cancer Database study. J Am Acad Dermatol 80:433–440

    Article  PubMed  Google Scholar 

  49. Egger ME et al (2019) Age and lymphovascular invasion accurately predict sentinel lymph node metastasis in T2 melanoma patients. Ann Surg Oncol 26:3955–3961

    Article  PubMed  Google Scholar 

  50. Vetto JT et al (2019) Guidance of sentinel lymph node biopsy decisions in patients with T1–T2 melanoma using gene expression profiling. Future Oncol 15:1207–1217

    Article  CAS  PubMed  Google Scholar 

  51. Gastman BR et al (2019) Identification of patients at risk of metastasis using a prognostic 31-gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria. J Am Acad Dermatol 80:149–157

    Article  CAS  PubMed  Google Scholar 

  52. Whitman ED et al (2021) Integrating 31-gene expression profiling with clinicopathologic features to optimize cutaneous melanoma sentinel lymph node metastasis prediction. JCO Precis Oncol. https://doi.org/10.1200/PO.21.00162

    Article  PubMed  PubMed Central  Google Scholar 

  53. Jarell A et al (2022) Optimizing treatment approaches for patients with cutaneous melanoma by integrating clinical and pathologic features with the 31-gene expression profile test. J Am Acad Dermatol 87:1312–1320

    Article  CAS  PubMed  Google Scholar 

  54. Yamamoto M et al (2023) The 31-gene expression profile test informs sentinel lymph node biopsy decisions in patients with cutaneous melanoma: results of a prospective, multicenter study. Curr Med Res Opin 39:417–423

    Article  CAS  PubMed  Google Scholar 

  55. Dhillon S et al (2023) Routine imaging guided by a 31-gene expression profile assay results in earlier detection of melanoma with decreased metastatic tumor burden compared to patients without surveillance imaging studies. Arch Dermatol Res. https://doi.org/10.1007/s00403-023-02613-6

    Article  PubMed  PubMed Central  Google Scholar 

  56. Gerami P et al (2015) Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy. J Am Acad Dermatol 72:780–785

    Article  CAS  PubMed  Google Scholar 

  57. Podlipnik S et al (2022) Using a 31-gene expression profile test to stratify patients with stage I-II cutaneous melanoma according to recurrence risk: update to a prospective, multicenter study. Cancers 14:1060

    Article  PubMed  PubMed Central  Google Scholar 

  58. Huang AC et al (2017) T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature 545:60–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ribas A et al (2016) Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA 315:1600–1609

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Writing assistance was provided by Sonia K. Morgan-Linnell at Castle Biosciences, Inc.

Author information

Authors and Affiliations

  1. Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA

    Jonathan S. Zager

  2. Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, 10920 McKinley Dr., Tampa, FL, 33612, USA

    Jonathan S. Zager

  3. Desert Surgical Oncology, Eisenhower Medical Center, Rancho Mirage, CA, USA

    David M. Hyams

Authors
  1. Jonathan S. Zager
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David M. Hyams
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JSZ and DMH developed the content and provided writing assistance and reviewed the manuscript. Writing assistance was provided by Sonia K. Morgan-Linnell at Castle Biosciences, Inc. All authors approved on the final manuscript.

Corresponding author

Correspondence to Jonathan S. Zager.

Ethics declarations

Competing interests

JSZ receives personal fees from Castle Biosciences, Inc, JSZ is a co-investigator for ongoing Skyline Dx clinical trial. DMH receives honoraria from and is a consultant and speaker for Exact Sciences and Castle Biosciences, Inc. DMH receives research funding from Castle Biosciences, Inc.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Presented at the 9th International Congress on Cancer Metastasis through the Lymphovascular System, May 4–6, 2023, in San Francisco, CA. To be published in a Special Issue of Clinical and Experimental Metastasis: Molecular Mechanisms of Cancer Metastasis.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zager, J.S., Hyams, D.M. Management of melanoma: can we use gene expression profiling to help guide treatment and surveillance?. Clin Exp Metastasis (2023). https://doi.org/10.1007/s10585-023-10241-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10585-023-10241-7

Keywords

Search

Navigation