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In this perspective, the authors review the role of sentinel lymph node biopsy (SLNB) staging for melanoma in the era of effective systemic therapies. Currently, SLNB may be useful in providing a more accurate representation of the risk–benefit balance of adjuvant therapy. However, given the significant morbidity and costs associated with SLNB staging, patients, especially those with stage IIB/C melanoma, might decline SLNB staging if it is discussed upfront that they will be offered adjuvant systemic therapy irrespective of the result.
The authors further suggest that, with the emergence of therapeutic options independent of SLNB status as well as validated biomarkers to predict risk, the need for SLNB staging will be lower in the upcoming decade.
This abstract is available on the publisher's site.
Sentinel lymph node biopsy (SLNB) has been introduced in the 1990s to identify patients who might benefit from completion lymph node dissection. Neither SLNB nor CLND improved survival, but SLNB staging did provide the best staging, above Breslow thickness and ulceration. The SLN status and SLN tumour burden were used in all trials until date looking at modern adjuvant systemic therapy with immune checkpoint inhibition (ICI) or targeted therapies (TT). Adjuvant ICI and TT are shifting towards stage II melanoma. The question is whether there is still role for SLNB in melanoma, in this day and age, and if so, how does the future look for SLNB staging? The SLN status and SLN tumour burden might be useful for a consultation to discuss the number needed to treat in a risk/benefit discussion. For stage IIB/C patients, it seems likely, however, that patients will forego a nuclear scan followed by the risk of surgical intervention and morbidity associated with SLNB if they opt to receive adjuvant therapy regardless of the SLNB result. For stage I/IIA, it is still required to detect high-risk patients who might benefit from adjuvant therapy. However, biomarkers are emerging, such as gene expression profilers (GEP), immunohistological signatures and liquid biopsies with ctDNA. There still is a role for SLNB staging in melanoma today, but we expect that the availability of therapeutic option independent of SLNB status as well as emergence of validated biomarkers to predict risk will reduce the need for SLNB staging in the upcoming decade to the point it will no longer be used.
Over the years, I have come to appreciate the insightful and often prescient works of these authors. Their publications seem bold, often contradicting mainstream tenets related to melanoma, or offering alternative assessment and perspectives regarding scientific investigations. This paper includes highlights of some of those contrarian perspectives that have, over time, proven true. With the many recent advances in immunotherapy and risk assessment, this paper discusses what the current value of sentinel lymph node biopsy (SLNB) is in the management of melanoma. The authors recount the historical diminution of the role SLNB plays in treatment, prognostication, and staging of melanoma patients. Initially, SLNB in combination with completion lymph node dissection (CLND) was believed to be therapeutic as well as prognostic. The procedure was also incorporated into the staging paradigms for melanoma, effectively mandating SLNB for accurate staging. The lack of therapeutic value of SLNB plus CLND, as anticipated by the authors, is now confirmed and their reasoning for having had this view is nicely illustrated in Figure 1.
This paper puts forth reasons to expect diminishing value of SLNB in prognosticating and in determining who may benefit from adjuvant therapy.The advent of immunotherapies as adjuvant therapy for both stage III and more recently stage II melanoma is nicely explained and summarized. The authors point out that these advances will "most probably lead to a reduction of SNLB…".
The paper segues into a candid review and discussion of the potential role of biomarkers in the future care of melanoma patients. It is noted that, while more study is needed, a genetic expression profile represents a potential non-interventional prognosticating tool to identify individuals who can safely forgo SLNB procedures for prognostication. Furthermore, liquid biopsies (ctDNA), which are already used in breast, colon, and other solid organ cancers, hold future promise for melanoma and may, in some cases, diminish the value of SLNB.
In the discussion, they pose the question, “Based on the data described above, why would we subject any patient with a clinical stage IIB/C melanoma to SLNB staging if we offer them adjuvant systemic therapy regardless of the result? Why would we subject them to the potential morbidity of such a staging procedure?" They also make a very good point that patients may decline SLNB staging options if it is discussed up-front with them that they will be eligible for adjuvant systemic therapy regardless of the result. But they also emphasize that these options must be properly validated and that clinical studies demonstrate the value of these alternatives in the decision-making process.
In my estimate, this paper presents bold yet defensible predictions for the future of SLNB. Based on the authors’ track record of accurately predicting changes in melanoma management, this paper merits attention and its predictions should be duly noted.