Fujisawa Yasuhiro, Yoshikawa Shusuke, Takenouchi Tatsuya, Mori Shoichiro, Asai Jun, Uhara Hisashi, Ichigosaki Yuki, Fujimura Taku, Nakamura Yoshiyuki, Nakamura Yasuhiro, Ohno Fumitaka, Fukumoto Takeshi, Ozawa Toshiyuki, Namikawa Kenjiro, Sugihara Satoru, Hoashi Toshihiko, Shimauchi Takatoshi, Sawada Yu, Iwata Hiroaki, Maeda Taku, Miyagawa Takuya, Shibayama Yoshitsugu, Hatta Naohito, Kishi Akiko, Ishikawa Masashi, Kawahira Hisao, Katoh Norito, Okuyama Ryuhei
Department of Dermatology, Ehime University, 454 Shizugawa, Toon, Ehime, 791-0204, Japan.
Department of Dermatology, Shizuoka Cancer Center, Nagaizumi, Japan.
Int J Clin Oncol. 2025 May;30(5):844-855. doi: 10.1007/s10147-025-02747-9. Epub 2025 Apr 7.
Malignant melanoma (MM) is a rare but aggressive cutaneous cancer, accounting for only 2% of skin cancers in Japan but nearly half of skin cancer-related deaths. While the global incidence of MM is rising, its epidemiology varies significantly by ethnicity and geographic region. In Japan, melanoma incidence remains lower than in Western countries, with acral lentiginous melanoma (ALM) being the most prevalent subtype. However, comprehensive epidemiological and clinical data remain limited.
We analyzed data from 7442 Japanese melanoma patients collected between 2005 and 2022 through the Japanese Melanoma Study (JMS). Demographic, clinical, and survival data were evaluated, including subtype distribution, TNM staging, and treatment outcomes.
ALM was the most common subtype (40.8%), followed by superficial spreading melanoma (20.2%). Lymph node metastasis was observed in 28.6% of cases, and distant metastasis in 10.9%. The BRAF mutation rate was 27.2%, with significantly lower frequencies in ALM (8.5%) and mucosal melanoma (4.8%). Among Stage IV patients, those treated with both immune checkpoint inhibitors (ICIs) and BRAF(+ MEK) inhibitors demonstrated significantly improved survival compared to chemotherapy alone (P < 0.05). Adjuvant BRAF(+ MEK) inhibitor therapy also resulted in superior relapse-free survival compared to those who did not receive adjuvant therapy (P < 0.005).
This study provides the largest dataset of Japanese melanoma patients to date, highlighting distinct epidemiological and clinical characteristics. Given their lower BRAF mutation rates and the limited efficacy of current ICI treatments, these findings emphasize the urgent need for optimize immunotherapy strategies in Japanese melanoma patients.
恶性黑色素瘤（MM）是一种罕见但侵袭性强的皮肤癌，在日本仅占皮肤癌的2%，但却占皮肤癌相关死亡的近一半。虽然MM的全球发病率在上升，但其流行病学因种族和地理区域而异。在日本，黑色素瘤发病率仍低于西方国家，肢端雀斑样痣黑色素瘤（ALM）是最常见的亚型。然而，全面的流行病学和临床数据仍然有限。
我们分析了通过日本黑色素瘤研究（JMS）在2005年至2022年期间收集的7442例日本黑色素瘤患者的数据。评估了人口统计学、临床和生存数据，包括亚型分布、TNM分期和治疗结果。
ALM是最常见的亚型（40.8%），其次是浅表扩散性黑色素瘤（20.2%）。28.6%的病例观察到淋巴结转移，10.9%有远处转移。BRAF突变率为27.2%，在ALM（8.5%）和黏膜黑色素瘤（4.8%）中的频率显著较低。在IV期患者中，与单纯化疗相比，接受免疫检查点抑制剂（ICI）和BRAF（+MEK）抑制剂联合治疗的患者生存率显著提高（P<0.05）。与未接受辅助治疗的患者相比，辅助BRAF（+MEK）抑制剂治疗也导致无复发生存期更长（P<0.005）。
本研究提供了迄今为止最大的日本黑色素瘤患者数据集，突出了独特的流行病学和临床特征。鉴于其较低的BRAF突变率和当前ICI治疗效果有限，这些发现强调了迫切需要优化日本黑色素瘤患者的免疫治疗策略。
