Classic Kaposi Sarcoma: Current Treatment Strategies and Emerging Therapeutic Approaches

Classic Kaposi sarcoma (CKS) is a rare vascular neoplasm driven by infection with Kaposi sarcoma-associated herpesvirus (KSHV) and characterized by a heterogeneous geographic distribution. While the etiology of other Kaposi's sarcoma (KS) variants is well established, the underlying mechanisms of CKS appear multifactorial, with several risk factors, among which advanced age and male sex are most significant. Due to the rarity of CKS and its often indolent clinical course, clinical trials are sparse, and current knowledge of therapeutic approaches remains limited. Most available clinical trials and practice guidelines focus on human immunodeficiency virus (HIV) -related Kaposi sarcoma. Therefore, specific recommendations for the classic form are restricted and rely on a low level of evidence, as categorized by the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines, making disease management more challenging. Current approaches to treating CKS include both local and systemic therapies, selected based on disease stage, patient comorbidities, and individual preferences. Systemic treatment options may include immunotherapy, chemotherapy, or antiangiogenic agents. This review summarizes current management strategies and highlights emerging therapeutic approaches for CKS. It aims to support clinicians in optimizing therapeutic decision-making, including the use of novel and investigational therapies. Although several novel therapies are currently under investigation in clinical trials, significant gaps remain. Therefore, further research is needed to improve disease management.