肛管直肠黑色素瘤治疗演变：叙述性综述

Anorectal melanoma (ARM) is one of the rarest and most aggressive subtypes of melanoma, representing less than 1% of all melanomas and 0. 1-0. 4% of anorectal malignancies. As a mucosal melanoma arising in sun-shielded sites, ARM exhibits distinct molecular features compared with cutaneous melanoma, including low tumor mutational burden, absent ultraviolet signatures, frequent KIT proto-oncogene Receptor Tyrosine Kinase ( KIT ) mutations (15-25%), and lower immunogenicity. These biological differences contribute to its rapid progression, late diagnosis, and poor response to traditional therapies.

Patients typically present with nonspecific symptoms such as rectal bleeding, often resulting in advanced disease at diagnosis, with up to 67% harboring regional or distant metastases. Management of ARM has evolved significantly over the past decades.

Historically dominated by radical abdominoperineal resection, surgical treatment has shifted toward sphincter-preserving wide local excision when negative margins can be achieved, driven by comparable survival outcomes and superior functional results regarding bowel, urogenital, and psychological quality of life.

However, high positive margin rates remain a major limitation of local excision. Systemic therapy has transitioned from largely ineffective cytotoxic chemotherapy to modern immunotherapy. Immune checkpoint inhibitors have become the cornerstone of treatment, while KIT -mutated tumors may benefit from tyrosine kinase inhibitors. Emerging evidence supports neoadjuvant immunotherapy to improve resectability and downstage tumors, with selected matched cohorts reporting 3-year overall survival rates up to 71-75% when combined with abdominoperineal resection.

Survival gains have been modest and largely confined to specific subgroups. Key challenges include the absence of a dedicated staging system, high local recurrence rates, limited durability of responses in metastatic disease, and an immunologically "cold" tumor microenvironment.

Multidisciplinary team approaches are essential for individualized care. Future progress depends on biomarker-driven trials, integration of novel strategies such as Chimeric Antigen Receptor T-Cell (CAR-T) therapy, and stronger international collaborative research to improve outcomes in this challenging malignancy.