Predictors of subclinical metastasis to non-sentinel lymph nodes for patients having clinically localized cutaneous melanoma

Introduction. The use of modern adjuvant drug therapy in cases of cutaneous melanoma with sentinel lymph node (LN) (SLN) metastases reduced frequency of performance of completing lymphadenectomy. However, until now, domestic and foreign clinical recommendations indicate possibility of using this procedure in patients with an unfavorable prognosis while criteria are not provided for assessing the risk of non-sentinel LN (NSLN) damage and the need to perform lymphadenectomy.

Aim. To identify predictors of high risk of metastasis in NSLN in patients with cutaneous melanoma with subclinical metastases in SLN.

Materials and methods. The study included 92 patients with clinically localized cutaneous melanoma (cT1–4N0M0), who showed subclinical lesions as a result of SLN biopsy, and therefore underwent a final lymphadenectomy.

Results. In the examined group, 26 (28.3 %) patients, along with SLN lesions, showed metastases in NSLN. Recognition of several active LNs during radionuclide mapping of SLNs is associated with a significantly higher risk of NSLN damage – in 42.3 % vs 15.2 % in the group with radiopharmaceutical activity only in SLNs (p = 0.018). Tumors thickness of >2 mm is also associated with a high frequency of NSLN metastasis (100 % of cases). No metastasis to other LNs was observed in tumor thickness of <2 mm. In ulcerated melanomas, the incidence of NSLN lesions was 92.3 % (p = 0.02). Only subcapsular localization of SLN metastases is associated with a relatively low incidence of NSLN metastasis (13.3 % of cases) as compared with parenchymal, mixed localization, and multifocal lesion (42.9 % of cases) (p = 0.002). For SLN metastases > 4 mm in size, a incidence of NSLN damage was higher than for metastases of <4 mm in size (43.3% vs 19.3%; p <0.05), as that for invasion of LN structures of > 2 mm in size versus invasion of <2 mm in size (44.4% vs 15.7 %; p = 0,003). The identified predictors of NSLN involvement in practice are often combined forming a pattern of predictors. The number of prognostic parameters in the pattern has a significant effect on the incidence of NSLN lesions (<0.001). In particular, the presence of 2 or less predictors is associated with low risk of metastasis in NSLN (0–12.5 % of cases), 3-5 predictors - with a relatively high risk (37.5–44.4 % of cases), 6 predictors – with a very high risk (80 % of cases).

Conclusion. Recognition of predictors of metastasis in NSLN and their number allows us to decide on the need to perform final lymphadenectomy in patients with cutaneous melanoma with subclinical metastases in SLN. Conducting the final lymphadenectomy in patients with a high risk of multiple lesions of regional LNs will provide better locoregional control over stage III cutaneous melanoma and will create optimal conditions for adjuvant drug therapy.

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