Personalising anal cancer treatment cuts side effects

Our PLATO-ACT4 clinical trial has found a kinder and more targeted way of using radiotherapy to treat early-stage anal cancer, showing 98% survival and fewer side effects than traditional treatment.

Anal cancer is a rare cancer that starts in the anus, the last part of the digestive system. The Stand Up To Cancer-funded PLATO study was designed to improve and personalise treatment options for anal cancer, which until now has been treated with a ‘one-size-fits-all’ approach.

As part of PLATO, the ACT4 trial tested a reduced treatment dose and shorter treatment schedule for early-stage anal cancers that haven’t started to spread. Its results show that a lower dose of radiotherapy combined with chemotherapy (also known as chemoradiotherapy) over four-and-a-half weeks still achieves the same high rate of tumour eradication as traditional treatment, which involves a standard dose of chemoradiotherapy over five weeks.

An average of 88 out of 100 patients in the lower dose treatment group had no signs of cancer in the treatment area after three years, and 98 out of 100 were still alive. In the standard dose group of patients, these proportions were slightly lower, with around 84 out of 100 with no signs of cancer in the treatment area and 93 out of 100 still alive.

Patients who received a lower dose also experienced less significant side effects, which can include sore skin, diarrhoea, incontinence, fatigue, vaginal irritation and loss of sexual function.

Professor David Sebag-Montefiore, Chief Investigator of the PLATO study and Clinical Director at the Leeds CRUK Clinical Trials Unit, said: “The side-effects of radiotherapy treatments have a significant impact on the lives of patients, physically, mentally and often financially to attend appointments.

“The current approach for anal cancer treatments is essentially ‘one size fits all’, where the dose of radiotherapy is similar whether the tumour being treated is very small or very large.

“The results will transform the lives of patients with early-stage anal cancer by using a shorter, lower dose of radiotherapy that does not compromise cure rates and reduces the side effects of treatment.”

A better quality of life

RAF veteran Sam Panter, a 48-year-old mother of two, joined ACT4 after she was diagnosed with early-stage anal cancer in 2019. At first, she thought the symptoms she was experiencing were piles (haemorrhoids) and tried to self-treat.

“When that didn’t help, I decided to go back for medical advice and was sent for further examination under a general anaesthetic,” said Sam. “A few days later I was asked to come into hospital to discuss the results and to my utter shock I was told I had anal cancer. Fortunately, they believed it was very treatable as it was still in an early stage.”

Sam was part of the control arm of ACT4, which means she received the standard dose of radiotherapy over five weeks. Although her treatment was successful, the side effects she experienced help show why a kinder option would be such a big step forward.

“I tolerated my treatment well until about the halfway point, when I started to suffer quite badly from side effects. I had big blisters around the radiotherapy site and a constant feeling of having a urine infection, which was extremely uncomfortable,” said Sam.

“I’m so proud to have been part of this work and I really hope it leads to improved treatment options for people around the world who face a diagnosis like me,” Sam said.

Overall, the ACT4 trial was the first in the world to randomise patients with anal cancer between different doses of radiotherapy. Dr Alexandra Gilbert, who led the research, presented data on how that affected quality of life at the 2025 European Society for Radiotherapy and Oncology (ESTRO) congress.

“For the first time, we can see the true impact of anal cancer and treatment from the patient point of view using the two treatment approaches,” she said. “We also see a trend towards improved sexual function in the longer term for men and women using the shorter, lower dose treatment.”