Moncrieff et al1 recently reported on results of sentinel node (SN) biopsy in a retrospective study of 3,607 patients with pT1b or pT2a melanoma, who underwent SN biopsy between 2005 and 2020 at nine cancer centers while also assessing the prognostic value of tumor deposit maximum dimension in patients with SN micrometastases. SN biopsy was positive in 408 patients (11.3%). These patients would be classified with stage IIIA disease according to the eighth edition of American Joint Committee on Cancer (AJCC).2 Survival analysis among SN-positive patients identified a SN tumor deposit maximum dimension of 0.3 mm as the optimal cut point for stratifying survival. Five-year disease-specific survival rates were 80.3% and 94.1% for patients with SN metastatic tumor deposits ≥ 0.3 mm and < 0.3 mm, respectively (hazard ratio, 1.26 [1.11 to 1.44]; P < .0001). The authors propose that indications for offering adjuvant systemic therapy in patients with AJCC IIIA melanoma should use this cutoff rather than the > 1 mm cutoff currently suggested in many guidelines.1 The newly identified high-risk (≥ 0.3 mm) subgroup comprised 271 (66.4%) patients of the stage IIIA cohort, whereas only 142 (34.8%) patients had SN tumor deposits > 1 mm in maximum dimension.1

However, there is a risk of overuse of SN biopsy in patients with T1b melanoma and overuse of adjuvant therapy in stage IIIA patients. In addition, it would be appreciated if the authors could elaborate on some specific aspects.

In the reported cohort of pT1b/pT2a melanomas, 27.7% (1,000 of 3,607) of the patients had pT1b thin melanoma (Table 1), of whom 7.5% (n = 75) had positive SN biopsy.1 However, the definition of pT1b disease has changed to also now include a large subset of patients with melanoma 0.8 to 1.0 mm Breslow thickness without ulceration.2 In a recent series (2017-2021) from Naples-Italy, where patients were offered SN biopsy taking largely into account the new definition of T1b melanomas (0.8 to 1.0 mm without or with ulceration or < 0.8 mm with ulceration), there were as many patients receiving SN biopsy for T1b melanoma than for a T2a melanoma, and the SN biopsy positivity rate was as low as 2.3% in patients with T1b melanoma.3 SN biopsy adds potential morbidity, more extensive surgery and anesthesia, and significant cost compared with a simple wide local excision. Thus, more elective use of SN biopsy in the population of T1b melanoma is warranted.3-5

The percentage of SN-positive patients with tumor deposit > 1 mm in maximum dimension (34.8%) also looks high. In a large series by Maurichi et al,6 only 19.4% of patients with thin melanomas and positive SN biopsy had a tumor deposit > 1 mm in maximum dimension.

From the AJCC database, the five-year disease-specific survival rate of the new stage IIIA cohort was 93%.2 Comparatively, the five-year disease-specific survival rate of 80.3% for patients with SN metastatic tumor deposits ≥ 0.3 mm (66.4% of the IIIA cohort) in the reported series is rather low and probably does not integrate advances in systemic therapy for relapsed/metastatic patients.1

Finally, the authors propose that indications for offering adjuvant systemic therapy in patients with AJCC IIIA melanoma should use the new cutoff of SN tumor deposits ≥ 0.3 mm in maximum dimension rather than the traditional > 1 mm cutoff.1 However, inclusion in adjuvant trials of AJCC IIIA patients with nonulcerated melanoma required that SN metastasis exceeds 1 mm.7,8 So, novel trials would be needed on the basis of the proposed new cutoff of ≥ 0.3 mm. Moreover, even for patients with AJCC eighth edition IIIA melanoma and tumor deposit > 1 mm, the benefit from adjuvant therapy was low compared with the other AJCC III subgroups.7,8 The benefit-to-toxicity ratio is not yet fully established and expanding the group further might not be desirable at present time.9

© 2022 by American Society of Clinical Oncology
Risk of Overusing Sentinel Node Biopsy in Patients With Thin Melanoma

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1. Moncrieff MD, Lo SN, Scolyer RA, et al: Clinical outcomes and risk stratification of early-stage melanoma micrometastases from an international multicenter study: Implications for the management of American Joint Committee on Cancer IIIA disease. J Clin Oncol 10.1200/JCO.21.02488 [epub ahead of print on July 18, 2022] Google Scholar
2. Gershenwald JE, Scolyer RA, Hess KR, et al: Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 67:472-492, 2017 Crossref, MedlineGoogle Scholar
3. Brancaccio G, Pellerone S, Scharf C, et al: Sentinel node biopsy in thin melanoma: A retrospective descriptive cohort study. J Eur Acad Dermatol Venereol 2022;36:e795-e796 Crossref, MedlineGoogle Scholar
4. Weitemeyer MB, Helvind NM, Brinck AM, et al: More sentinel lymph node biopsies for thin melanomas after transition to AJCC 8th edition do not increase positivity rate: A Danish population-based study of 7148 patients. J Surg Oncol 125:498-508, 2022 Crossref, MedlineGoogle Scholar
5. Herb JN, Ollila DW, Stitzenberg KB, et al: Use and costs of sentinel lymph node biopsy in non-ulcerated T1b melanoma: Analysis of a population-based registry. Ann Surg Oncol 28:3470-3478, 2021 Crossref, MedlineGoogle Scholar
6. Maurichi A, Miceli R, Eriksson H, et al: Reply to E. Hindié. J Clin Oncol 38:3238-3240, 2020 LinkGoogle Scholar
7. Hauschild A, Dummer R, Schadendorf D, et al: Longer follow-up confirms relapse-free survival benefit with adjuvant dabrafenib plus trametinib in patients with resected BRAF V600-mutant stage III melanoma. J Clin Oncol 36:3441-3449, 2018 LinkGoogle Scholar
8. Eggermont AMM, Blank CU, Mandalà M, et al: Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): Distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol 22:643-654, 2021 Crossref, MedlineGoogle Scholar
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DOI: 10.1200/JCO.22.01963 Journal of Clinical Oncology

Published online December 01, 2022.

PMID: 36455165

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