Commentary on Impact of National Comprehensive Cancer Network Guidelines on Case Selection and Outcomes for Sentinel Lymph Node Biopsy in Thin Melanoma

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The value of the sentinel lymph node biopsy (SLNB) lies in its prognostic information. Indeed, the status of the sentinel lymph node is the most important prognostic feature in melanomas of intermediate thickness (hazard ratio = 1.23 for tumor thickness and 6.53 for a positive sentinel lymph node).1 The ability to identify patients with an increased risk of regional recurrence or metastasis has taken on new significance in the era of checkpoint inhibitors, one of which, ipilimumab, is now approved by the FDA in the adjuvant setting. It is probable that in the near future, other checkpoint inhibitors with fewer side effects, such as pembrolizumab and nivolumab, may also be approved in the adjuvant setting for patients with Stage III disease. However, the value of the SLNB may be limited by its morbidity and cost when the expected rate of positivity is very low. The National Comprehensive Cancer Network (NCCN) currently recommends that SLNB be offered to patients with melanomas ≥1.00 mm in depth with exceptions made for thin melanomas <1.00 mm when one of the 2 histologic features are present: ulceration or ≥1 mitotic figure for tumors >0.75 mm.2 Ulceration and mitotic figures are associated with an increased likelihood of sentinel lymph node metastasis.3,4 Notably, the presence of mitotic figures was removed from the staging of thin melanomas in the recently released 8th edition of the AJCC staging system for melanoma,5 but the presence of mitotic figures are still included in NCCN recommendations for SLNB in thin melanomas as long as they are >0.75 mm in depth.2
In this issue, Nguyen and colleagues6 examined a dataset of 859 thin melanomas with a median follow-up of 79 months with attention focused on SLNB outcomes in 2 clinical scenarios: NCCN 2010 guidelines (recommending SLNB for tumors <1.00 mm with a mitotic rate of 1 or more/mm) versus 2016 guidelines (recommending SLNB in tumors <1.00 mm only when the depth was >0.75 mm with a mitotic rate of 1 or more/mm). They report that 11% fewer tumors qualified for SLNB under the 2016 versus 2010 NCCN guidelines and that 2016-qualifying cases also had lower 10-year nodal recurrence–free survival and disease-free survival. The authors have very clearly demonstrated that expanding the indication for SLNB to thin melanomas <0.75 mm with the only criterion being a mitotic rate of ≥1, very few patients will have a positive node. However, requiring a depth >0.75 mm and ≥1 mitotic figures reduced the number of thin melanomas qualifying for SLNB and more accurately selected cases with higher risk of SLN positivity.
In their recent publication entitled, “Is mitotic rate still useful in the management of patients with thin melanoma?” Tejera-Vaquerizo and colleagues7 reported on 203 melanomas <1.0 mm and found that 14.3% had a positive SLNB if the mitotic count was >1 while only 3.2% had a positive node if the mitotic count was 1 or 0. Five-year melanoma-specific survival was 98.7% in node-negative patients versus 75% in node-positive patients, and the estimated 5-year melanoma-specific survival was 100% for patients with ≤1 mitotic figure versus 91.4% for tumors with mitotic count >1. The question now remains as to what the NCCN Guidelines Committee for Melanoma will do with the 2018 guidelines, given these data and the fact that the mitotic rate has been dropped from the latest AJCC staging system. It may be that the simple tweaking of the threshold for mitotic figures from the presence of a single mitotic figure to >1 mitotic figure will have predictive value on both the status of the sentinel node and overall melanoma-specific survival.

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