Localised anal squamous cell carcinoma (stage I to III)
Localised anal cancer is squamous cell cancer of the anal canal that has not spread beyond the pelvis and groin, one of the few cancers cured mainly by chemotherapy and radiotherapy together rather than by surgery. Fluorouracil with mitomycin during radiotherapy has been standard since the ACT II trial; surgery to remove the anus is kept for the minority whose cancer persists or returns.
Overview
Anal squamous cell carcinoma confined to the anal canal, the pelvic nodes and the groin nodes is treated to keep the anus. Before 1974 the standard was abdominoperineal resection with a permanent colostomy; Norman Nigro then showed that fluorouracil and mitomycin given during radiotherapy made most tumours disappear, and the UKCCCR ACT I and EORTC trials in the 1990s proved chemoradiotherapy beat radiotherapy alone. ACT II (Lancet Oncology 2013), the largest anal cancer trial with 940 patients, found that cisplatin was no better than mitomycin alongside fluorouracil and radiotherapy, that maintenance chemotherapy added nothing, and that tumours keep regressing for months, so response should be judged at 26 weeks rather than 11 before anyone is sent for surgery. RTOG 98-11 had likewise found induction cisplatin inferior to mitomycin-based treatment.
Today's treatment is intensity-modulated radiotherapy with concurrent fluorouracil (or capecitabine) and mitomycin, with the dose scaled to stage; very small well-differentiated perianal tumours can be excised alone. Salvage abdominoperineal resection is offered when biopsy confirms persistent or recurrent disease. HPV or p16 status is favourable and HIV is no longer a bar to full-dose treatment when CD4 counts are adequate. The UK PLATO programme (ACT3, ACT4 and ACT5) is testing lower doses for early tumours and higher doses for locally advanced ones, EA2165 tests nivolumab after chemoradiotherapy for high-risk disease, and circulating HPV DNA is being studied as a way to tell early who is cured.
State of the art
- Organ-preserving chemoradiotherapy cures most patients and has been standard for fifty years.
- ACT II settled the chemotherapy partner (mitomycin), the futility of maintenance and the timing of response assessment.
- Radiotherapy dose is now being tailored to stage in the PLATO trials.
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 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.
- 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.
- 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 combiningKidneys: Fluorouracil (5-FU)
Capecitabine: reduce to 75% for CrCl 30-50; contraindicated below 30.
- Good to knowImmune-related endocrinopathies (thyroiditis, hypophysitis)
Immunotherapy can attack hormone-producing glands: most often the thyroid (usually ending in an under-active thyroid needing lifelong tablets), and less often the pituitary (hypophysitis) or adrenal glands, which can be life-threatening if missed.
See all on the product pages:Fluorouracil (5-FU)Mitomycin CNivolumab·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)Stage I anal canal squamous cell carcinoma (T1 N0, lower radiotherapy dose) · Stage II anal squamous cell carcinoma (T2 to T3 N0) · Stage III node-positive or T4 anal squamous cell carcinoma (locally advanced, higher dose) · Perianal (anal margin) squamous cell carcinoma (small tumours excised alone) · HPV-negative anal squamous cell carcinoma (worse prognosis) · Anal cancer in people living with HIV
- 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), Metastatic and recurrent anal squamous cell carcinoma, 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
The large majority of anal cancers are diagnosed without distant spread, and most are cured without losing the anus.
- MRIStandard of care
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
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.
Pelvic MRI, PET-CT, examination of the groins, HIV testing and HPV or p16 status; biopsy of suspicious groin nodes.
Intensity-modulated radiotherapy with concurrent fluorouracil (or capecitabine) and mitomycin, dose scaled to stage (ACT II, RTOG 98-11); small perianal tumours may be excised alone.
Clinical assessment at 26 weeks; biopsy only if disease persists or grows, because regression continues for months (ACT II).
Salvage abdominoperineal resection with permanent colostomy; inguinal node dissection or radiotherapy for isolated groin recurrence.
Trials of dose escalation (PLATO ACT5) and adjuvant nivolumab (EA2165); standard care remains chemoradiotherapy alone.
Subtypes & biomarkers
top- Stage I anal canal squamous cell carcinoma (T1 N0, lower radiotherapy dose)
- Stage II anal squamous cell carcinoma (T2 to T3 N0)
- Stage III node-positive or T4 anal squamous cell carcinoma (locally advanced, higher dose)
- Perianal (anal margin) squamous cell carcinoma (small tumours excised alone)
- HPV-negative anal squamous cell carcinoma (worse prognosis)
- Anal cancer in people living with HIV
- HPV and p16 status (favourable)
- T and N stage on MRI and PET-CT
- HIV status and CD4 count
- Clinical complete response at 26 weeks (ACT II)
- Circulating HPV DNA (investigational)
- PD-L1 (not required)
How often this target appears
- 1974Nigro reports complete responses to fluorouracil, mitomycin and radiotherapy, sparing the anus
- 1996UKCCCR ACT I: chemoradiotherapy beats radiotherapy alone
- 2008RTOG 98-11: mitomycin-based chemoradiotherapy beats induction cisplatin
- 2013ACT II published: mitomycin equals cisplatin, no maintenance, assess response at 26 weeks
- 2016Intensity-modulated radiotherapy becomes standard after RTOG 0529 reduces toxicity
- 2019PLATO trials open to personalise radiotherapy dose by stage
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 8 changes by month →- 2026-09-18This recordLocalised anal squamous cell carcinoma (stage I to III)Facts on this page last checked
When this page itself was last checked or edited.
- 2019MilestoneIMRT / IGRT (modern external beam)PLATO trials open to personalise radiotherapy dose by stage
A milestone in how this cancer is treated.
- 2016MilestoneIMRT / IGRT (modern external beam)Intensity-modulated radiotherapy becomes standard after RTOG 0529 reduces toxicity
A milestone in how this cancer is treated.
- 2013Trial resultACT IIACT II reported
Complete response about 90% with either mitomycin or cisplatin; no benefit from maintenance chemotherapy.
- 2013MilestoneACT IIACT II published: mitomycin equals cisplatin, no maintenance, assess response at 26 weeks
A milestone in how this cancer is treated.
- 2008MilestoneMitomycin CRTOG 98-11: mitomycin-based chemoradiotherapy beats induction cisplatin
A milestone in how this cancer is treated.
What is in development for Localised anal squamous cell carcinoma (stage I to III), drawn from the whole corpus: 1 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.
Trials reported · 1
- ACT II · phase 3 · 2013 · positive
Open problems and what is being done
Radiotherapy dose for early and for locally advanced tumours is still being settled in PLATO.
About a quarter of patients with locally advanced disease relapse and need major surgery.
and how the field plans to fix it →What is being done about thisAdvanced and metastatic diseaseAvailable now- IMRT / IGRT (modern external beam)Standard of care
- MRIStandard of care
- PET/CTStandard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Atlas of advanced disease · Invasion and metastasis.
Late bowel, sexual and bladder effects of pelvic chemoradiotherapy are common and under-measured.
Whether adding a PD-1 antibody to chemoradiotherapy improves cure is untested outside EA2165.
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.
Landmark trials
Expert centres
topExpert centres
Seoul · hospital | South Korea | none recorded | 0 | 464 | 3,248 | #22 | |
London · consortium | United Kingdom | none recorded | 1 | not matched | - | none recorded | - |
Shanghai · hospital | China | none recorded | 0 | 2,872 | 31,534 | - | |
Sydney · cancer center | Australia | none recorded | 0 | 2,222 | 33,278 | - | |
Beijing · hospital | China | none recorded | 0 | 1,784 | 18,230 | - | |
Utrecht · cancer center | Netherlands | none recorded | 0 | 1,422 | 20,323 | - | |
Guangzhou · hospital | China | none recorded | 0 | 1,245 | 12,931 | - | |
Tianjin · cancer center | China | none recorded | 0 | 1,219 | 11,455 | - | |
Hangzhou · cancer center | China | none recorded | 0 | 1,219 | 17,635 | - | |
Beijing · hospital | China | none recorded | 0 | 1,154 | 11,808 | - | |
Rozzano (Milan) · hospital | Italy | none recorded | 0 | 1,031 | 10,720 | - | |
Naples · cancer center | Italy | none recorded | 0 | 961 | 15,028 | - | |
Changsha · cancer center | China | none recorded | 0 | 930 | 14,477 | - | |
Jinan · cancer center | China | none recorded | 0 | 920 | 7,804 | - | |
Rotterdam · cancer center | Netherlands | none recorded | 0 | 852 | 12,180 | - |
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 Localised 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 Localised 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, T and N stage on MRI and PET-CT, HIV status and CD4 count, Clinical complete response at 26 weeks, Circulating HPV DNA), 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 Stage I anal canal squamous cell carcinoma, Stage II anal squamous cell carcinoma, Stage III node-positive or T4 anal squamous cell carcinoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Staging
- For my situation (staging), which of the standard options do you recommend and why?Why: Guideline options include: Pelvic MRI, PET-CT, examination of the groins, HIV testing and HPV or p16 status; biopsy of suspicious groin nodes.
Stage I to III
- For my situation (stage i to iii), which of the standard options do you recommend and why?Why: Guideline options include: Intensity-modulated radiotherapy with concurrent fluorouracil (or capecitabine) and mitomycin, dose scaled to stage (ACT II, RTOG 98-11); small perianal tumours may be excised alone.
- Am I a candidate for Fluorouracil (5-FU), Mitomycin C, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ACT II apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Response assessment
- For my situation (response assessment), which of the standard options do you recommend and why?Why: Guideline options include: Clinical assessment at 26 weeks; biopsy only if disease persists or grows, because regression continues for months (ACT II).
- How do the results of ACT II apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Persistent or recurrent disease
- For my situation (persistent or recurrent disease), which of the standard options do you recommend and why?Why: Guideline options include: Salvage abdominoperineal resection with permanent colostomy; inguinal node dissection or radiotherapy for isolated groin recurrence.
High-risk locally advanced disease
- For my situation (high-risk locally advanced disease), which of the standard options do you recommend and why?Why: Guideline options include: Trials of dose escalation (PLATO ACT5) and adjuvant nivolumab (EA2165); standard care remains chemoradiotherapy alone.
- Am I a candidate for Nivolumab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Circulating tumour HPV DNA (ctHPV-DNA), Nivolumab, IMRT / IGRT (modern external beam)?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 “Radiotherapy dose for early and for locally advanced tumours is still being settled in PLATO”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “About a quarter of patients with locally advanced disease relapse and need major surgery”. 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 Localised 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
9targets
1drugs
4companies
3terms
3trials
1key 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.
Fluorouracil and mitomycin with radiotherapy remains the standard for localised anal cancer, without maintenance, and patients whose tumour has not vanished at three months should be watched to six months rather than sent straight to surgery.
Latest papers
topQuery for this cancer: (TITLE:"Localised anal squamous cell carcinoma" OR ABSTRACT:"Localised anal squamous cell carcinoma" OR TITLE:"stage I to III" OR ABSTRACT:"stage I to III" OR TITLE:"Non-metastatic anal cancer" OR ABSTRACT:"Non-metastatic anal cancer" OR TITLE:"Locoregional anal squamous cell carcinoma" OR ABSTRACT:"Locoregional anal squamous cell carcinoma" OR TITLE:"Anal canal cancer treated with chemoradiotherapy" OR ABSTRACT:"Anal canal cancer treated with chemoradiotherapy" OR TITLE:"Stage I to III anal cancer" OR ABSTRACT:"Stage I to III anal cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Localised anal squamous cell carcinoma (stage I to III), not a curated reading list.
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