Updates on Management of Anal Cancer: A New Era Has Begun

Squamous cell carcinoma of the anal canal (SCAC) is a rare, human papillomavirus–driven malignancy with a rising global incidence and an increasingly dynamic therapeutic landscape. This review summarizes recent advances and current evidence in the management of SCAC, with a focus on immunotherapy, systemic treatment strategies, and optimization of curative-intent approaches. For locally advanced SCAC, concurrent chemoradiotherapy with fluorouracil and mitomycin C remains the standard of care, on the basis of multiple randomized trials demonstrating improved disease control and organ preservation compared with radiotherapy alone. These studies also show that treatment intensification with alternative chemotherapy, induction therapy, or radiation dose escalation does not improve outcomes. Given the curative intent, maintaining quality of life is a key consideration, and current studies are evaluating radiation dose optimization to reduce treatment-related toxicity, as well as the integration of immunotherapy to improve treatment efficacy. In metastatic SCAC, the combination of carboplatin and paclitaxel is the established first-line chemotherapy backbone. The addition of the PD-1 inhibitor retifanlimab to chemotherapy has demonstrated improved clinical outcomes and is now a preferred first-line approach. In the treatment-refractory setting, anti–PD-1 monotherapy provides modest response rates and remains a standard option for immunotherapy-naïve patients. Together, these findings summarize the current evidence base guiding the management of SCAC.