Effect of lymph node dissection and adjuvant therapy in patients with sentinel node+ melanoma: An observational multicenter study.

Abstract

e21569 Background: Currently, lymph node dissection (LND) is not mandatory for patients with sentinel node (SN)+ melanoma. Anti-programmed cell death receptor-1 (PD-1) monotherapy and dabrafenib/trametinib combination (for BRAF mutations) are standard adjuvant treatments for patients who undergo definitive surgery for melanoma. However, the effects of this approach remain unclear in patients with stage III melanoma in real-world clinical settings. We investigated the effects of the aforementioned therapeutic approaches on the prognosis of stage III melanoma in a Japanese cohort. Methods: We retrospectively analyzed clinical data of patients with SN+ melanoma treated with or without anti-PD-1 monotherapy or combination dabrafenib/trametinib therapy obtained from 39 independent institutions in Japan between 2018 and 2021. Survival outcomes (recurrence-free survival [RFS] and overall survival [OS]) were compared with regard to LND, adjuvant therapy type, and clinical factors. Results: We investigated 357 patients; 35.9% (128/357) of patients underwent LND, of whom 70.3% (90/128) received adjuvant therapy. LND was not performed in 64.1% (229/357) of patients, of whom 74.7% (171/229) received adjuvant therapy. RFS and OS did not differ between patients with and without LND (2-year RFS 54.5% vs. 51.5%, p = 0.98; 2-year OS 84.1% vs. 86.5%, p = 0.39). RFS and OS did not differ between patients with and without adjuvant therapy (2-year RFS 54.5% vs. 50.4%, p = 0.90; 2-year OS 83.4% vs. 89.8%, p = 0.33). Multivariate analysis of RFS after adjustment for adjuvant therapy, clinical subtype, tumor thickness, ulceration, and BRAF status showed significant differences between patients with and without adjuvant therapy (hazard ratio 3.06 [95% confidence interval 1.39–6.76]). Data analysis in 261 patients who received adjuvant therapy showed no difference between patients with and without LND (2-year RFS 55.9% vs. 52.6%, p = 0.74; 2-year OS 83.4% vs. 83.6%, p = 0.73). Regarding adjuvant therapy type, RFS and OS were significantly longer in patients who received BRAF/MEK inhibitors than in those treated with PD-1 monotherapy (2-year RFS 75.0% vs. 42.2%, p < 0.01; 2-year OS 89.3% vs. 79.5%, p = 0.01). Conclusions: Our study revealed that LND did not affect prognosis and adjuvant therapy reduced the recurrence of stage III melanoma in a Japanese cohort. Although the follow-up period was short, with regard to drug selection, RFS and OS were significantly longer in patients treated with BRAF/MEK inhibitors than in those who received PD-1 monotherapy. Factors contributing to the lower effectiveness of PD-1 monotherapy remain unclear and warrant further investigation.