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This algorithm covers anal squamous cell carcinoma and branches on extent of disease: localized versus advanced or metastatic.
Localized disease is treated with definitive, organ-preserving chemoradiation using 5-FU plus mitomycin with radiation (the Nigro regimen). Salvage abdominoperineal resection is reserved for residual or recurrent disease after chemoradiation, so surgery is not the initial treatment. For advanced or metastatic disease, the first-line standard is carboplatin plus paclitaxel plus retifanlimab, supported by POD1UM-303, in which adding retifanlimab improved both progression-free and overall survival over carboplatin plus paclitaxel alone. Carboplatin plus paclitaxel is itself supported by InterAACT, which showed similar disease control to cisplatin plus 5-FU with improved overall survival and less toxicity, establishing it as the preferred chemotherapy backbone for advanced disease. In later lines, the checkpoint inhibitors nivolumab or pembrolizumab are options.