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Breslow thickness, Clark level, ulceration predict sentinel lymph node metastasis in thin melanomas
Ulceration, Breslow thickness and Clark level significantly predicted sentinel lymph node disease in patients with thin melanomas, according to results of a retrospective review.
Researchers used the Sentinel Lymph Node Working Group database to evaluate 1,250 patients with thin melanoma in an effort to determine the factors that predict sentinel lymph node (SNL) metastasis.
During median follow-up of 2.6 years, 65 patients (5.2%) developed sentinel lymph node metastases.
Univariable analysis showed Breslow thickness ≥0.75 mm, Clark level ≥IV, ulceration and absence of regression varied significantly between positive and negative SLN groups (P<.05 for all).
Researchers used those four variables, as well as mitotic rate, in a multivariable analysis.
Results indicated ulceration (OR=2.51; 95% CI, 1.25-5.06), Breslow thickness ≥.75 mm (OR-2.21; 1.06-4.61) and Clark level ≥IV (OR-1.8; 95% CI, 1.01-3.23) were significant predictors of sentinel lymph node metastasis.
Researchers reported 6.3% of patients with Breslow thickness ≥0.75 mm, 7% with Clark level ≥IV and 11.6% of patients with ulceration had SLN disease.
The rate of SLN disease in melanomas <0.75 mm was less than 5% regardless of Clark level and ulceration status.
“By using a 5% metastasis risk threshold, sentinel lymph node biopsy is indicated for melanomas ≥0.75 mm, but further study is needed to define indications for sentinel lymph node biopsy in melanomas <0.75 mm,” the researchers wrote.
Patients with positive SLN demonstrated significantly worse melanoma-specific survival than patients with negative SLN (P=.001). Five-year melanoma-specific survival was 97.8% among patients with negative SLN compared with 90.8% among those with positive SLN. Five-year RFS was 90.6% among patients with negative SLN vs. 85.8% among those with positive SLN.
“[Han and colleagues] confirmed that status of the sentinel node is a significant and important prognostic variable, even in patients with melanomas less than 1 mm in thickness,” James S. Goydos, MD, of Robert Wood Johnson Medical School at Rutgers University, wrote in an accompanying editorial. “Given that the morbidity that is associated with sentinel node biopsy remains low in experienced hands, and the finding of a negative sentinel node can save patients the anxiety and expense of intense clinical follow-up, the recommendation by these authors of performing a sentinel node biopsy in patients with melanomas of 0.75mm or greater in thickness seems reasonable and appropriate.”
For more information:
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Goydos JS. J Clin Oncol.2013;doi:10.1200/JCO.2013.50.1114.
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Han D. J Clin Oncol.2013;doi:10.1200/JCO.2013.51.8423.
Disclosure: The researchers report consultant or advisory roles with, as well as honoraria or other remuneration from, GlaxoSmithKline, Merck and Navidea Biopharmaceuticals. Goydos reports no relevant financial disclosures.
Perspective
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The status of the sentinel lymph node is one of the most important prognostic factors in patients with cutaneous melanoma. Its role as a prognostic indicator is generally accepted but, for multiple reasons, national guidelines do not recommend routine sentinel lymph node sampling.
In this study, Han and colleagues carried out an 18-year retrospective analysis of the Sentinel Lymph Node Working Group’s international database to determine predictors of sentinel lymph node metastases. They exclusively studied melanomas ≤1 mm in Breslow thickness — known as “thin” melanomas — because these are routinely not sampled yet carry an actuarial recurrence risk in the range of 10%, which can result in mortality. Thin melanomas comprised 24.4% of their entire database, and of these, only 5.2% (n=65) had metastases. Note, however, that this study was not based on all thin melanomas, but only those that had undergone sentinel lymph node sampling.
The study confirmed the involvement of the usual suspects in lymph node metastases. Ulceration and depth of invasion (Breslow thickness and Clark’s level) significantly predicted lymph node metastases. No new prognostic markers were discovered. The authors conclude that “Breslow thickness ≥ 0.75 mm should be the primary indication for [sentinel lymph node biopsy] in thin melanomas.”
This is the largest review of thin melanomas, and what it does is provide credence to what many have advocated in the past, namely that the threshold for action should be set at 0.75 mm, and that the perfect trifecta of ulceration, Breslow thickness ≥0.75 mm and Clark level ≥4 significantly increases risk. Importantly, if Breslow thickness is <0.75 mm, the risk of metastases is less than 5%, regardless of Clark level or even ulceration.
The morphologic criteria used to make these clinical decisions are the manifestation of behaviors encoded by genes that mark for aggressive tumor biology. In the future, uncovering these genes will allow for a higher precision in risk assessment above what we currently see by eye and will open the door for novel therapeutic intervention.