Swiss Recommendations for Systemic Therapies in Locally Advanced and Metastatic Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent type of non-melanoma skin cancer. Its incidence has been rising in recent years, with the highest rate reported in Switzerland compared to other countries in Europe. While the majority of cSCC cases are low-grade tumors with an excellent prognosis following surgical excision, a minority of cSCC lesions (approximately 5% of patients) progress to locally advanced cSCC (lacSCC) or distant metastatic disease (mcSCC), both of which have an unfavorable prognosis. Recent evidence from studies with checkpoint immunotherapy has changed the systemic treatment landscape for lacSCC and mcSCC patients. While both programmed death-1 (PD-1) receptor inhibitors cemiplimab and pembrolizumab are approved by the FDA, cemiplimab is the only approved systemic therapy for the treatment of nonresectable advanced cSCC in the EU and was recently also approved in Switzerland. Based on the latest evidence from randomized clinical trials, national consensus recommendations for the systemic treatment of advanced cSCC have been defined. For classification and optimal management of patients with lacSCC or mcSCC, an interdisciplinary tumor board discussion should be mandatory. Difficult-to-treat advanced cSCC patients should be referred to and treated by specialized centers. These Swiss recommendations provide guidance for the management of patients aged ≥18 years with lacSCC or mcSCC, specifically systemic therapy with a PD-1 inhibitor in the first-line setting. These up-to-date recommendations will also help Swiss physicians in their decision-making and address treatment variability in Swiss clinical practice. Keywords: cSCC, locally advanced, metastatic, systemic treatment, immunotherapy, cemiplimab

皮肤鳞状细胞癌（cutaneous squamous cell carcinoma, cSCC）是第二大常见的非黑色素瘤皮肤癌（non-melanoma skin cancer）。近年来其发病率持续攀升，在欧洲各国中以瑞士的发病率最高。尽管多数cSCC为低级别肿瘤，经手术切除后预后良好，但仍有少数cSCC病灶（约占患者总数的5%）会进展为局部晚期皮肤鳞状细胞癌（locally advanced cSCC, lacSCC）或远处转移性皮肤鳞状细胞癌（distant metastatic cSCC, mcSCC），这两类疾病的预后均不良。近年来免疫检查点疗法（checkpoint immunotherapy）相关研究的最新证据，改变了lacSCC与mcSCC患者的系统性治疗格局。尽管程序性死亡受体1（programmed death-1, PD-1）抑制剂西米普利单抗（cemiplimab）与帕博利珠单抗（pembrolizumab）均已获得美国食品药品监督管理局（Food and Drug Administration, FDA）批准，但西米普利单抗是欧洲联盟（European Union, EU）境内唯一获批用于治疗不可切除的晚期cSCC的系统性疗法，且近期也在瑞士获批。基于随机对照临床试验（randomized clinical trials）的最新证据，针对晚期cSCC系统性治疗的全国共识指南已正式出台。针对lacSCC或mcSCC患者的分型与优化管理，应强制开展多学科肿瘤会诊讨论。难治性晚期cSCC患者应转诊至专科中心接受治疗。本瑞士共识指南可为年龄≥18岁的lacSCC或mcSCC患者的管理提供指导，尤其是一线治疗中采用PD-1抑制剂的系统性疗法。这份最新指南亦将助力瑞士临床医师制定治疗决策，并解决瑞士临床实践中存在的治疗差异问题。关键词：cSCC、局部晚期、转移性、系统性治疗、免疫治疗、西米普利单抗