COMMENTARY

Is Age a Risk Factor for Lymph Node Positivity in Thin Melanoma?

Graeme M. Lipper, MD

Disclosures

October 04, 2017

Who Gets Sentinel Lymph Node Biopsy?

In 2014 (the most recent year with available data), 76,665 new primary cutaneous malignant melanomas (MMs) were diagnosed in the United States, and 9324 people died from MM,[1] making this the most lethal form of skin cancer. Fortunately, 70% of newly diagnosed cutaneous MMs in the United States are thin (T1; Breslow thickness 1.0 mm or thinner) and carry an excellent prognosis,[2] but some of these "early" MMs still metastasize and prove lethal.

With current technology, sentinel lymph node biopsy (SLNB) is the most accurate and popular method for assessing occult metastatic disease in primary cutaneous MM, with prognostic and therapeutic implications. This procedure carries a 5% false-negative rate,[3] which is roughly equivalent to the percentage of postsurgical complications (eg, seroma, hematoma, lymphedema) following SLNB.[4]

Current guidelines published by the National Comprehensive Cancer Network (NCCN) support performing an SLNB if the probability of detecting occult nodal disease is 5% or greater—the so-called "5% threshold." Hence, the NCCN recommends offering SLNB to patients with primary cutaneous MM with Breslow thickness >0.75 mm, especially if other established risk factors are present,[5] including a Clark level IV/V, ulceration, and high mitotic rate.[6]

Risk Factors for Lymph Node Positivity

But younger patient age also carries an increased risk for occult nodal disease—at least according to a compelling new study by Sinnamon and colleagues.[7] Using a large oncology database (the National Cancer Database, >1500 US hospitals), Sinnamon and colleagues gathered a cohort of 8772 patients with thin (Breslow thickness 0.5-1.0 mm) melanoma who underwent wide excision and surgical evaluation of regional lymph nodes between 2010 and 2013. In this low-risk group, 333 patients (3.8%) still had nodal metastasis. Multivariable analysis showed the following risk factors:

  • Presence of mitoses was the strongest predictor of nodal disease, followed by Breslow thickness of 0.76 mm or greater.

  • Intriguingly, the third strongest risk factor was patient age, especially for patients younger than 40 years.

  • By NCCN criteria, SLNB would not be recommended for patients younger than 40 years with melanomas with a thickness of 0.50-0.75 mm, but this group had a lymph node positive rate of 5.6%.

  • Conversely, SLNB would be recommended for patients aged 65 years or older with melanomas with a thickness of 0.76 to 1.0 mm, despite the fact that only 3.9% of these patients had nodal metastasis.

Viewpoint

This pivotal study has the statistical power to be taken seriously, with immediate clinical ramifications. Of 8772 patients with thin primary cutaneous MM (T1, Breslow 0.5-1.0 mm), 3.8% had nodal disease, with a disproportionate number of these metastases occurring in patients aged 40 years or younger. Based on these findings, Sinnamon and colleagues concluded that current NCCN guidelines for SLNB "may be overly restrictive in younger patients and overly permissive in older patients."

In this context, oncologists should consider offering SLNB to younger patients with thin MM who wouldn't be offered SLNB on the basis of Breslow thickness alone. Conversely, the work-up for patients aged 65 years or older with borderline lesions (T1b, thickness 0.76-1.0 mm) may be "downgraded" to monitoring without SLNB, especially in cases where the procedure carries a higher risk for postsurgical complications.[8]

The one question this study doesn't address is whether SLNB improves clinical outcomes and long-term survival. Put another way: For patients with positive SLNB, what comes next? Complete lymphadenectomy? Chemotherapy? Immunotherapy? Until these options—alone or in combination—are shown to improve long-term survival, the practical utility of SLNB in patients with thin MM remains open to debate. To that point, current data only show improved 10-year disease-free survival for patients with intermediate (1.20-3.50 mm) or thick (>3.50 mm) melanomas who received more aggressive treatment based on positive sentinel lymph node status.[4]

Finally, with the advent of biological markers to predict tumor behavior, SLNB may become an obsolete procedure in the future. If we reach the point where a tumor's genetic fingerprint tells us more about how it will behave and what targeted therapies to try, then why put a patient through an unnecessary surgical procedure?

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