Survival in Patients With Sentinel Node–Positive Melanoma With Extranodal Extension

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  • 1 Melanoma and Sarcoma Surgical Unit,
  • | 2 Clinical Epidemiology and Trial Organization Unit,
  • | 3 Department of Pathology,
  • | 4 Plastic and Reconstructive Surgical Unit, and
  • | 5 Melanoma Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.

Background: Prognostic parameters in sentinel node (SN)–positive melanoma are important indicators to identify patients at high risk of recurrence who should be candidates for adjuvant therapy. We aimed to evaluate the presence of melanoma cells beyond the SN capsule—extranodal extension (ENE)—as a prognostic factor in patients with positive SNs. Methods: Data from 1,047 patients with melanoma and positive SNs treated from 2001 to 2020 at the Istituto Nazionale dei Tumori in Milano, Italy, were retrospectively investigated. Kaplan-Meier survival and crude cumulative incidence of recurrence curves were estimated. A multivariable logistic model was used to investigate the association between ENE and selected predictive factors. Cox models estimated the effect of the selected predictors on survival endpoints. Results: Median follow-up was 69 months. The 5-year overall survival rate was 62.5% and 71.7% for patients with positive SNs with and without ENE, respectively. The 5-year disease-free survival rate was 54.0% and 64.0% for patients with positive SNs with and without ENE, respectively. The multivariable logistic model showed that age, size of the main metastatic focus in the SN, and numbers of metastatic non-SNs were associated with ENE (all P<.0001). The multivariable Cox regression models showed the estimated prognostic effects of ENE associated with age, ulceration, size of the main metastatic focus in the SN, and number of metastatic non-SNs (all P<.0001) on disease-free survival and overall survival. Conclusions: ENE was a significant prognostic factor in patients with positive-SN melanoma. This parameter may be useful in clinical practice as a selection criterion for adjuvant treatment in patients with stage IIIA disease with a tumor burden <1 mm in the SN. We recommend its inclusion as an independent prognostic determinant in future updates of melanoma guidelines.

Submitted July 9, 2020; final revision received November 5, 2020; accepted for publication November 30, 2020. Published online July 26, 2021.

Author contributions: Study concept: Maurichi, Barretta, Miceli, Santinami. Data acquisition: Patuzzo, Gallino, Mattavelli, Barbieri, Leva, Spadola, Cortinovis, Sala. Data analysis and interpretation: Maurichi, Cossa, Nesa, Cimminiello, Di Guardo, Valeri, Santinami. Statistical analysis: Barretta, Miceli. Manuscript preparation: Maurichi, Barretta, Miceli, Angi, Lanza, Del Vecchio. Manuscript review and editing: All authors.

Disclosures: The authors have disclosed that they have not received any financial considerations from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Andrea Maurichi, MD, Melanoma and Sarcoma Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Giacomo Venezian 1, 20133 Milan, Italy. Email: andrea.maurichi@istitutotumori.mi.it

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