Survival of Patients With Primary Cutaneous Melanoma (Stages 0-IIА and IIB-IIC), Depending on the Presence of the <i>BRAF</i> Mutation in the Tumor and Surgical Treatment Option

Abstract

Background: Cutaneous melanoma is an extremely aggressive disease with an unpredictable prognosis. Even among patients with similar tumor parameters and extent of surgical treatment, survival may vary. The extent of surgical resection of primary cutaneous melanoma is well-established, and a BRAF mutation in the tumor is an unfavorable prognostic factor for patient survival. The mutation presence is mainly used as a marker for prescribing targeted therapy. The impact of the extent of surgery and the method for restoring a tissue defect on survival of patients with similar stages remains unexplored. The impact of the BRAF mutation in the tumor on survival of patients with cutaneous melanoma depending on the surgery method has also not been studied. We analyzed the surgical treatment outcomes of 221 patients with primary cutaneous melanoma (stages 0-IIA and IIB-IIC) who were found to have the BRAF mutation and underwent different extents of tumor excision with closure of the surgical tissue defect.Objective: To analyze the impact of the BRAF mutation in the tumor on 5-year survival of patients with primary cutaneous melanoma (stages 0-IIA and IIB-IIC), depending on the extent of surgery and the method of replacing the tissue defect.Materials and methods: We used data from 221 patients with primary cutaneous melanoma (stages 0-IIA and IIB-IIC) and assessed their BRAF mutation status, extent of tumor excision, and method of closing the tissue defect. The patients were divided into 2 groups: the main group (wide excision of the tumor and plastic replacement of the tissue defect) and the comparison group (standard margin and linear closure of the tissue defect). After surgery, all the patients underwent tumor analysis for the BRAF p.V600E/K mutation using real-time PCR. DNA was isolated using the cobas® DNA Sample Preparation Kit on a cobas® z 480 analyzer. We used the following statistical methods: frequency analysis, z test to check the equality, and Kaplan-Meier survival analysis and such software as MedCalc 12.5 (1993-2013, MedCalc Software) and SPSS 26 (IBM Corp, 2019, IBM SPSS Statistics for Windows, Armonk, NY, USA). Results: Wide excision of primary cutaneous melanoma (stages 0-IIA and IIB-IIC) was found to increase 5-year progression-free survival in patients with subsequent plastic replacement of the tissue defect compared with patients with standard margin and linear closure of the tissue defect and 5-year overall survival in patients with stage 0-IIA melanoma. In patients with 0-IIA stage melanoma and positive BRAF mutation test results, wide excision with reconstructive and plastic defect closure improved the 5-year progression-free survival. Conclusions: The 5-year progression-free survival and 5-year overall survival increased by 20.9% (P = .005) and 13.0% (P = .031), respectively, in patients who underwent wide excision of primary cutaneous melanoma followed by plastic replacement of the tissue defect compared with patients with standard excision of primary tumors and linear closure of the tissue defect. The 5-year progression-free survival increased by 23.7% (P = .017) in patients with stage IIB-IIC melanoma, regardless of the BRAF mutation. In patients with 0-IIa stage melanoma and positive BRAF mutation test results who underwent wide excision, the 5-year progression-free survival increased by 20.7% (P = .047) compared with patients who underwent tumor excision with a standard margin.

Keywords

• cutaneous melanoma
• braf mutation
• surgical treatment
• progression-free survival
• overall survival