Prognosis of deep margin excisions within or beyond subcutaneous fat for invasive acral melanoma of the sole: A multi-institutional retrospective study.
Authors: Koizumi Shigeru , Ichigozaki Yuki , Kitagawa Hiroshi , Kiniwa Yukiko , Sato Sayuri , Takai Toshihiro , Doi Reiichi , Ito Takamichi , Kuwatsuka Yutaka , Maekawa Takeo , Asai Jun , Miyagawa Takuya , Matsushita Shigeto , Funakoshi Takeru , Yamamoto Yosuke , Kishi Akiko , Takenouchi Tatsuya , Kokubu Hiraku , Ito Shusaku , Nakamura Yasuhiro 
Published: July 2024

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Background: There is scant evidence concerning the optimal deep margins for wide excision (WE) of primary tumors in melanoma surgery. Despite the importance of preserving plantar subcutaneous fat in the sole for cushioning function, no study data exists on the optimal depth margins for acral melanoma of the sole (sole AM). Thus, we aimed to compare the prognosis associated with different deep margin excisions for sole AM. Methods: We conducted a retrospective review of clinical records from patients with invasive resectable sole AM who underwent WE of the primary tumor across 41 Japanese institutions. The prognosis was compared between two groups based on different deep margin excisions: those with tumors excised within (S-group) or beyond (D-group) the subcutaneous fat. Kaplan—Meier analysis and multivariable Cox proportional hazard models were used to estimate the survival probabilities. Propensity-score matching (PSM) was used to adjust for numerical differences in baseline characteristics. Results: This study included a total of 425 patients (median age 73 years) with invasive sole AM, who underwent WE based on the peripheral surgical margins recommended in the National Comprehensive Cancer Network guidelines. The median follow-up period was 48 months. The S-group included 263 patients and the D-group 162 patients. The baseline characteristics significantly differed between the two groups in terms of Breslow thickness ( P < 0.01), presence of ulcer ( P < 0.01), and presence of in-transit, satellite, and regional lymph node metastasis ( P < 0.01). The other baseline characteristics were similar. Although local recurrence-free survival (LRFS) did not significantly differ between groups, the S-group showed significantly longer disease-free (DFS) and overall survival (OS) than the D-group (5-year LRFS, 96% vs. 90%; P = 0.08; 5-year DFS, 70% vs. 41%; P < 0.01; 5-year OS, 84% vs. 69%; P < 0.01). In contrast, multivariable Cox proportional hazard models showed no significant differences in LRFS, DFS, and OS between the two groups (LRFS, hazard ratio [HR], 1.87, P = 0.18; DFS, HR, 1.05, P = 0.77; OS, HR, 1.08, P = 0.72). After PSM, the groups were balanced at a 1:1 ratio (128 patients in each group) and no statistical significance was found in LRFS, DFS, or OS between the adjusted groups (5-year LRFS, 97 % vs. 91 %; P = 0.40; 5-year DFS, 65 % vs. 48 %; P = 0.053; 5-year OS, 80 % vs. 73%; P = 0.18). Subgroup analysis of stage I, II, and III also indicated no statistical significance in LRFS, DFS, and OS between the two groups (stage I: LRFS, P = 0.11; DFS, P = 0.65; OS, P = 0.26; stage II: LRFS, P = 0.37; DFS, P = 0.06; OS, P = 0.85; stage III: LRFS, P = 0.29; DFS, P = 0.67; OS, P = 0.85). Conclusions: In sole AM, WE with excessive deep margins beyond the subcutaneous fat did not improve prognosis. Excision of the primary tumor within the subcutaneous fat may be an optimal deep margin for sole AM.