Risk Stratification and Treatment Implications for Patients With Early-Stage Melanoma and Sentinel Node Metastasis

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In a study reported in the Journal of Clinical Oncology, Moncrieff et al found that patients with stage IIIA melanoma (per American Joint Committee on Cancer [AJCC], 8th edition) with sentinel node metastatic tumor deposits ≥ 0.3 mm are at higher risk of disease progression vs those with smaller deposits—and that these patients may benefit from adjuvant systemic therapy. Risk in patients with smaller sentinel node deposits did not differ from that with stage IB (N0) disease.

Study Details

The study involved 3,607 adult patients from a consortium of nine high-volume cancer centers in Australia, Europe, and North America who had pathologic stage pT1b/pT2a primary cutaneous melanomas and who underwent sentinel node biopsy between 2005 and 2020. A total of 3,199 patients had stage IB (N0) disease and 406 had stage IIIA disease. Median follow-up was 34 months.

Key Findings

Survival analysis identified a sentinel node tumor deposit maximum dimension of 0.3 mm as the optimal cutpoint for stratifying survival. Among the 406 patients with stage IIIA disease, 267 (66%) had deposits ≥ 0.3 mm and were classified as a new high-risk group within stage IIIA; those with deposits < 0.3 mm were classified as a low-risk group. On multivariate analysis, ≥ 0.3 mm nodal metastases were significantly associated with mitotic rates of > 1/mm2.

Disease-specific survival at 5 years was 80.3% in the high-risk group vs 94.7% in the low-risk group (hazard ratio [HR] = 1.26, 95% confidence interval [CI] = 1.11­–1.44, P <.0001). Similar findings were observed for disease-free survival and distant metastasis–free survival (72.4% vs 92.1%, HR = 1.27, 95% CI = 1.14–1.41, P < .0001).

On multivariate analysis, compared with stage IB (N0) disease, hazard ratios for the low-risk vs high-risk stage IIIA patients were: 0.82 (P = .650) vs 3.71 (P < .001) for disease-specific survival; 1.05 (P = .841) vs 3.28 (P < .001) for disease-free survival; and 0.94 (P = .837) vs 3.12 (P < .001) for distant metastasis–free survival.

The investigators concluded, “Patients with AJCC IIIA melanoma with sentinel node tumor deposits ≥ 0.3mm in maximum dimension are at higher risk of disease progression and may benefit from adjuvant systemic therapy or enrollment into a clinical trial. Patients with sentinel node deposits < 0.3 mm in maximum dimension can be managed similar to their sentinel node–negative, AJCC IB counterparts, thereby avoiding regular radiological surveillance and more intensive follow-up.”

Marc D. Moncrieff, MD, of the Department of Plastic and Reconstructive Surgery, Norfolk and Norwich University Hospital NHS Trust, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported in part by the Australian National Health and Medical Research Council. For full disclosures of the study authors, visit

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