# Localised anal squamous cell carcinoma (stage I to III)

Source: https://onco.cc/cancers/localised-anal-cancer/  
OnCo record `localised-anal-cancer` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-18
- Also known as: Non-metastatic anal cancer; Locoregional anal squamous cell carcinoma; Anal canal cancer treated with chemoradiotherapy; Stage I to III anal cancer
- Tags: subtype-page; gastrointestinal
- Group: gastrointestinal
- Burden: The large majority of anal cancers are diagnosed without distant spread, and most are cured without losing the anus.
- Subtypes: 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
- Biomarkers: 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)

## Standard of care

- Staging: Pelvic MRI, PET-CT, examination of the groins, HIV testing and HPV or p16 status; biopsy of suspicious groin nodes. ([MRI](https://onco.cc/technologies/mri/), [PET/CT](https://onco.cc/technologies/pet-ct/), [HPV-positive (p16) head and neck cancer](https://onco.cc/terms/hpv-p16/))
- Stage I to III: 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. ([IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [Mitomycin C](https://onco.cc/drugs/mitomycin/), [ACT II](https://onco.cc/trials/act-ii/), [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/))
- Response assessment: Clinical assessment at 26 weeks; biopsy only if disease persists or grows, because regression continues for months (ACT II). ([Clinical complete response (cCR)](https://onco.cc/terms/clinical-complete-response/), [ACT II](https://onco.cc/trials/act-ii/))
- Persistent or recurrent disease: Salvage abdominoperineal resection with permanent colostomy; inguinal node dissection or radiotherapy for isolated groin recurrence. ([Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/))
- High-risk locally advanced disease: Trials of dose escalation (PLATO ACT5) and adjuvant nivolumab (EA2165); standard care remains chemoradiotherapy alone. ([IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Nivolumab](https://onco.cc/drugs/nivolumab/))

## 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.

## Open problems

- 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.
- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Anal_cancer
- ACT II (Lancet Oncology 2013): https://doi.org/10.1016/S1470-2045(13)70086-X
- NCCN Anal Carcinoma: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1414
- Wikipedia: https://en.wikipedia.org/wiki/Anal_cancer

## Connected records

- cancers: [Anal cancer (squamous cell carcinoma)](https://onco.cc/cancers/anal/), [Anal high-grade squamous intraepithelial lesions (precursor)](https://onco.cc/cancers/anal-hsil-precursor/), [Localised penile cancer (organ-confined, node-negative)](https://onco.cc/cancers/localised-penile-cancer/), [Locally advanced cervical cancer](https://onco.cc/cancers/locally-advanced-cervical-cancer/), [Metastatic and recurrent anal squamous cell carcinoma](https://onco.cc/cancers/metastatic-anal-cancer/)
- technologies: [Circulating tumour HPV DNA (ctHPV-DNA)](https://onco.cc/technologies/cthpv-dna/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [MRI](https://onco.cc/technologies/mri/), [PET/CT](https://onco.cc/technologies/pet-ct/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/)
- drugs: [Capecitabine](https://onco.cc/drugs/capecitabine/), [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [Mitomycin C](https://onco.cc/drugs/mitomycin/), [Nivolumab](https://onco.cc/drugs/nivolumab/)
- terms: [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [Clinical complete response (cCR)](https://onco.cc/terms/clinical-complete-response/), [HPV-positive (p16) head and neck cancer](https://onco.cc/terms/hpv-p16/)
- trials: [ACT II](https://onco.cc/trials/act-ii/)
- key papers: [ACT II: mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for squamous cell carcinoma of the anus](https://onco.cc/key-papers/paper-act-ii-anal-cancer-chemoradiation-lancet-oncol-2013/), [ESMO Clinical Practice Guideline on anal cancer: diagnosis, treatment and follow-up](https://onco.cc/key-papers/paper-esmo-anal-cancer-guideline-ann-oncol-2021/)

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