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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Metastatic anal cancer is squamous cell anal cancer that has spread to the liver, lungs or distant lymph nodes, or come back where surgery can no longer remove it. Carboplatin with paclitaxel became the standard first treatment after the InterAACT trial, the PD-1 antibody retifanlimab was added to it in 2025 after POD1UM-303, and nivolumab or pembrolizumab are options after chemotherapy.
Anal squamous cell carcinoma that has spread beyond the pelvis was for decades treated with cisplatin and fluorouracil on the strength of small series alone. InterAACT (Journal of Clinical Oncology 2020), the first randomised trial in advanced anal cancer, compared that regimen with carboplatin and paclitaxel in 91 patients: response rates were similar, carboplatin and paclitaxel caused fewer serious adverse events and was associated with longer survival, and it became the reference first-line regimen in the NCCN and ESMO guidelines. Because almost all these tumours are HPV-driven and carry PD-L1, checkpoint inhibitors were tested early: the NCI9673 trial of nivolumab (Lancet Oncology 2017) reported responses in 24 percent of 37 previously treated patients, and pembrolizumab showed durable responses in the KEYNOTE-028 and KEYNOTE-158 anal cohorts, so both are guideline options after chemotherapy.
POD1UM-303, also called InterAACT 2 (Lancet 2025), randomised 308 patients with inoperable locally recurrent or metastatic disease to carboplatin and paclitaxel with retifanlimab or placebo and lengthened progression-free survival from 7.4 to 9.3 months, with overall survival favouring the antibody; the United States approved retifanlimab with carboplatin and paclitaxel in May 2025, the first drug approval specific to anal cancer. Oligometastatic disease is sometimes treated with resection or stereotactic radiotherapy of liver or lung metastases, and isolated pelvic recurrence after chemoradiotherapy is treated by salvage surgery rather than as metastatic disease. Circulating HPV DNA is being studied to follow response, and trials of HPV-directed T-cell therapies and vaccines enrol anal cancer alongside cervical and oropharyngeal cancer.
| Setting | Approach | Guideline |
|---|---|---|
| First line | Carboplatin and paclitaxel with retifanlimab (POD1UM-303, approved 2025); carboplatin and paclitaxel alone (InterAACT) where the antibody is unavailable or contraindicated. | not mapped |
| After platinum chemotherapy | Nivolumab (NCI9673) or pembrolizumab (KEYNOTE-158) if no prior PD-1 antibody; fluorouracil-based or taxane chemotherapy otherwise. | not mapped |
| Oligometastatic disease | Resection or stereotactic radiotherapy of limited liver or lung metastases alongside systemic therapy, on a case basis. | not mapped |
| Isolated pelvic recurrence | Salvage abdominoperineal resection when the tumour is resectable; re-irradiation is rarely possible. | not mapped |