QWill gene expression profiling replace sentinel lymph node biopsy (SLNB)?

Aaron Farberg, MD

Aaron Farberg, MD

Dermatologist and Mohs Surgeon
Baylor University Medical Center
Dallas, TX

The results of the Multicenter Selective Lymphadenectomy Trials (MSLT-I and II) have caused an important discussion of the utility of SLNB.1,2 The results indicate that the SLNB procedure itself confers no survival benefit, and that SLNB should now be regarded solely as a staging procedure. Previously, SLNB has been the strongest predictor of disease-specific survival for patients with intermediate-thickness melanoma, however, there is no clear consensus.3,4 Although studies have shown the clinical utility of SLNB for melanoma, these analyses do not consider the potential risks or financial cost of the procedure.5

Bigby et al, has questioned the role of SLNB noting that the added prognostic value of SLNB status is unproven.6 Marchetti et al, further predicts a diminished role for SLBN if trials demonstrate adjuvant therapy is efficacious in patients with high-risk localized disease.7 Gershenwald in AJCC8 also notes that Stage IIb/IIc patients have a lower 5/10 year MSS compared to Stage IIIa patients.8

The future as predicted by Bigby and Marchetti is now. Recently, immunotherapy (permbrolizumab) was approved for cutaneous melanoma stage IIb/IIc. Although the primary endpoint of progression free survival was met in the recent interim analysis, due to its significant side effect profile, physicians will need to balance the potential risks of immunotherapy with its benefits. Fundamentally, the community of clinicians managing patients with CM need to ensure we are using immunotherapy in the patients who will benefit most. While we have previously used SLNBx as the primary entry criterion for clinical trials and systemic therapy in melanoma, the recent FDA approval mandates reconsideration of this paradigm. For example, a prognostic tool such as the 31-GEP (DecisionDx-Melanoma, Castle Biosciences) that provides individualized absolute risk estimates of disease recurrence may be more clinically useful – especially in patients who are being considered currently for SLNB and who obtain a negative SLN.

  1. Morton DL, Thompson JF, Cochran AJ, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370:599-609.
  2. Faries MB, Thompson JF, Cochran AJ, et al. Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med. 2017;376:2211-2222.
  3. Morton DL, Thompson JF, Cochran AJ, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355:1307-1317.
  4. Zagarella S, Lee S, Heenan P. Sentinel lymph node biopsy status is not the most powerful predictor of prognosis in cutaneous melanoma. Australas J Dermatol. 2017;58:256-358
  5. El Sharouni MA, Strodell MD, Ahmed T, et al. Sentinel node biopsy in patients with melanoma improves the accuracy of staging when added to clinicopathological features of the primary tumor. Ann Oncol. 2021;32(3):375-383.
  6. Bigby M, Zagarella S, Sladden M, Popescu CM. Time to reconsider the role of sentinel lymph node biopsy in melanoma. J Am Acad Dermatol. 2019;80(4):1168-1171.
  7. Marchetti MA, Bartlett EK. Sentinel lymph node biopsy in cutaneous melanoma – where do we stand? JAMA Dermatol. 2021;157(10):1159-1160.
  8. Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eight edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472-492.