Metastatic and recurrent anal squamous cell carcinoma
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.
Overview
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.
State of the art
- Retifanlimab with carboplatin and paclitaxel is the first regimen approved specifically for anal cancer.
- InterAACT gave the disease its first randomised first-line standard.
- PD-1 antibodies produce durable responses in a minority after chemotherapy.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
- Emergency services nowBlood clot (lenalidomide, pomalidomide, thalidomide)
A swollen painful calf, or sudden breathlessness with chest pain; venous and arterial thromboembolism is a boxed warning and blood-thinning prophylaxis is recommended.
- Check before combiningFood and drink: Fluorouracil (5-FU)
Capecitabine: take within 30 minutes after a meal. DPD deficiency (DPYD variants) causes severe toxicity: pre-treatment genotyping is recommended in Europe.
- Check before combiningFood and drink: Pembrolizumab
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
- Check before combiningKidneys: Carboplatin
Dose by Calvert formula using GFR (see the calculators).
See all on the product pages:CarboplatinFluorouracil (5-FU)NivolumabPaclitaxel / nab-paclitaxelPembrolizumabRetifanlimab·Printable cards in the navigator
Anatomy and lymph node drainage
- Right colon (MSI-high, BRAF commoner)
- Left colon and sigmoid
- Rectum
- Anal canal (HPV squamous)
- Appendix
- Peritoneum and omentum (mesothelioma, peritoneal spread)
- Nodes: pericolic
- Nodes: mesenteric root
- Nodes: para-aortic
- Nodes: mesorectal
- Nodes: lateral pelvic and inguinal (anal)
Right-sided tumours behave differently from left-sided and rectal ones; the colon drains along its mesenteric vessels, the rectum into the mesorectum and pelvic side wall.
- Right colon (MSI-high, BRAF commoner)
- Left colon and sigmoid
- Rectum
- Anal canal (HPV squamous)Synchronous metastatic anal squamous cell carcinoma (liver, lung, distant nodes) · Inoperable locally recurrent anal cancer · Oligometastatic anal cancer (local treatment considered) · HPV-negative metastatic anal squamous cell carcinoma
- Appendix
- Peritoneum and omentum (mesothelioma, peritoneal spread)
- pericolic
- mesenteric root
- para-aortic
- mesorectal
- lateral pelvic and inguinal (anal)
Same organ: Peritoneal mesothelioma, Colorectal cancer, Rectal cancer, Mismatch-repair deficient (MSI-high) colorectal cancer, BRAF V600E-mutant colorectal cancer, HER2-amplified colorectal cancer, KRAS G12C-mutant colorectal cancer, Early-onset colorectal cancer (under 50), Anal cancer (squamous cell carcinoma), Appendiceal cancer and pseudomyxoma peritonei, Small intestine cancer (small bowel adenocarcinoma), Small intestinal neuroendocrine tumours, Anal high-grade squamous intraepithelial lesions (precursor), Localised anal squamous cell carcinoma (stage I to III), Low-grade appendiceal mucinous neoplasm and pseudomyxoma peritonei, Appendiceal adenocarcinoma (mucinous and non-mucinous, including signet ring cell), Goblet cell adenocarcinoma of the appendix, Localised small bowel adenocarcinoma (stage I to III, resected), Advanced and metastatic small bowel adenocarcinoma
A minority of patients present with distant spread or relapse beyond the pelvis after chemoradiotherapy; the liver, lungs and distant nodes are the usual sites.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Carboplatin and paclitaxel with retifanlimab (POD1UM-303, approved 2025); carboplatin and paclitaxel alone (InterAACT) where the antibody is unavailable or contraindicated.
Nivolumab (NCI9673) or pembrolizumab (KEYNOTE-158) if no prior PD-1 antibody; fluorouracil-based or taxane chemotherapy otherwise.
Resection or stereotactic radiotherapy of limited liver or lung metastases alongside systemic therapy, on a case basis.
Salvage abdominoperineal resection when the tumour is resectable; re-irradiation is rarely possible.
Subtypes & biomarkers
top- Synchronous metastatic anal squamous cell carcinoma (liver, lung, distant nodes)
- Metachronous relapse after chemoradiotherapy
- Inoperable locally recurrent anal cancer
- Oligometastatic anal cancer (local treatment considered)
- HPV-negative metastatic anal squamous cell carcinoma
- HPV and p16 status
- PD-L1 (not required for retifanlimab)
- Circulating HPV DNA (investigational monitoring)
- HIV status and CD4 count
- Mismatch repair and tumour mutational burden (rarely relevant)
How often this target appears
- 2017NCI9673: nivolumab responses in refractory anal cancer
- 2020InterAACT: carboplatin and paclitaxel becomes the first-line standard
- 2025POD1UM-303 published; retifanlimab with carboplatin and paclitaxel approved in the United States
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 4 changes by month →- 2026-09-18This recordMetastatic and recurrent anal squamous cell carcinomaFacts on this page last checked
When this page itself was last checked or edited.
- 2025MilestoneRetifanlimabPOD1UM-303 published; retifanlimab with carboplatin and paclitaxel approved in the United States
A milestone in how this cancer is treated.
- 2020MilestoneCarboplatinInterAACT: carboplatin and paclitaxel becomes the first-line standard
A milestone in how this cancer is treated.
- 2017MilestoneNivolumabNCI9673: nivolumab responses in refractory anal cancer
A milestone in how this cancer is treated.
What is in development for Metastatic and recurrent anal squamous cell carcinoma, drawn from the whole corpus: 0 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Nothing recorded in development for this cancer yet.
Open problems and what is being done
Median survival remains under two years even with a PD-1 antibody added to chemotherapy.
No second-line standard exists after chemo-immunotherapy.
Whether local treatment of oligometastases improves survival has never been randomised.
HPV-directed cell therapies and vaccines are promising but early.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Expert centres
topExpert centres
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Seoul · hospital | South Korea | none recorded | 0 | 464 | 3,248 | #22 | |
Stanford · university | United States | 0 | 3,000 | 50,162 | #30 | ||
Amsterdam · cancer center | Netherlands | none recorded | 0 | 1,451 | 25,873 | #45 | |
Shanghai · hospital | China | none recorded | 0 | 2,872 | 31,534 | - | |
Wuhan · hospital | China | none recorded | 0 | 2,478 | 31,527 | - | |
Sydney · cancer center | Australia | none recorded | 0 | 2,222 | 33,278 | - | |
Beijing · hospital | China | none recorded | 0 | 1,784 | 18,230 | - | |
Dallas, TX · cancer center | United States | 0 | 1,744 | 19,757 | - | ||
Utrecht · cancer center | Netherlands | none recorded | 0 | 1,422 | 20,323 | - | |
Beijing · cancer center | China | none recorded | 0 | 1,344 | 18,195 | - | |
Guangzhou · hospital | China | none recorded | 0 | 1,245 | 12,931 | - | |
Leiden · university | Netherlands | none recorded | 0 | 1,245 | 16,125 | - | |
Tianjin · cancer center | China | none recorded | 0 | 1,219 | 11,455 | - | |
Hangzhou · cancer center | China | none recorded | 0 | 1,219 | 17,635 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Metastatic and recurrent anal squamous cell carcinoma but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Metastatic and recurrent anal squamous cell carcinoma
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example HPV and p16 status, PD-L1, Circulating HPV DNA, HIV status and CD4 count, Mismatch repair and tumour mutational burden), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Synchronous metastatic anal squamous cell carcinoma, Metachronous relapse after chemoradiotherapy, Inoperable locally recurrent anal cancer.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
First line
- For my situation (first line), which of the standard options do you recommend and why?Why: Guideline options include: Carboplatin and paclitaxel with retifanlimab (POD1UM-303, approved 2025); carboplatin and paclitaxel alone (InterAACT) where the antibody is unavailable or contraindicated.
- Am I a candidate for Carboplatin, Paclitaxel / nab-paclitaxel, Retifanlimab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
After platinum chemotherapy
- For my situation (after platinum chemotherapy), which of the standard options do you recommend and why?Why: Guideline options include: Nivolumab (NCI9673) or pembrolizumab (KEYNOTE-158) if no prior PD-1 antibody; fluorouracil-based or taxane chemotherapy otherwise.
- Am I a candidate for Nivolumab, Pembrolizumab, Fluorouracil (5-FU), and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Oligometastatic disease
- For my situation (oligometastatic disease), which of the standard options do you recommend and why?Why: Guideline options include: Resection or stereotactic radiotherapy of limited liver or lung metastases alongside systemic therapy, on a case basis.
Isolated pelvic recurrence
- For my situation (isolated pelvic recurrence), which of the standard options do you recommend and why?Why: Guideline options include: Salvage abdominoperineal resection when the tumour is resectable; re-irradiation is rarely possible.
Any stage
- Are there clinical trials I could join, for example of Retifanlimab, Circulating tumour HPV DNA (ctHPV-DNA), Nivolumab, Pembrolizumab?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Median survival remains under two years even with a PD-1 antibody added to chemotherapy”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “No second-line standard exists after chemo-immunotherapy”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Metastatic and recurrent anal squamous cell carcinoma, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
6targets
2drugs
6companies
5terms
2key papers
2Most decisions on the localised and metastatic anal cancer pages, from the chemoradiotherapy schedule to when to operate and what to give for metastatic disease, follow this guideline or its American counterpart.
Carboplatin and paclitaxel is the first-line chemotherapy for metastatic anal cancer, and the platform to which PD-1 antibodies such as retifanlimab were added.
Latest papers
topQuery for this cancer: (TITLE:"Metastatic and recurrent anal squamous cell carcinoma" OR ABSTRACT:"Metastatic and recurrent anal squamous cell carcinoma" OR TITLE:"Advanced anal cancer" OR ABSTRACT:"Advanced anal cancer" OR TITLE:"Stage IV anal squamous cell carcinoma" OR ABSTRACT:"Stage IV anal squamous cell carcinoma" OR TITLE:"Inoperable recurrent anal cancer" OR ABSTRACT:"Inoperable recurrent anal cancer" OR TITLE:"Metastatic SCAC" OR ABSTRACT:"Metastatic SCAC") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Metastatic and recurrent anal squamous cell carcinoma, not a curated reading list.
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