Abstract
Anal cancer, although rare, has seen an increasing incidence and mortality, primarily due to high-risk sexual behaviors, HIV, and low HPV vaccination coverage. This review examines current treatment strategies for non-metastatic squamous cell carcinoma of the anus, with a focus on chemoradiation therapy (CRT) and emerging therapies. The historical and scientific basis for chemoradiation therapy using 5-fluorouracil and mitomycin C (MMC) is discussed as the standard treatment, although alternatives such as cisplatin and capecitabine show promise, particularly in settings where MMC is unavailable or when access to infusion pumps is restricted. Negative data regarding treatment intensification, induction or maintenance chemotherapy, and combinations with targeted therapies that have not demonstrated significant benefits are also reviewed. Ongoing research on immune checkpoint inhibitors presents new opportunities to improve patient outcomes. Surgical interventions may be recommended for very early disease but are usually reserved for cases of recurrence or failure after CRT. Despite challenges related to immunization efforts and high-risk behaviors, advancements in CRT and the development of novel therapies offer hope for improved outcomes with reduced toxicity.