Patients and clinicians have welcomed the results of the ACT4 PLATO trial, which was the first clinical trial in the world to randomly assign patients with anal cancer to receive different doses of radiotherapy.
The research has the potential to change clinical practice for anal cancer treatment internationally, after 30 years of a largely unchanged, one-size-fits-all approach.
In patients who received a lower radiotherapy dose and a shorter course of treatment, the results showed a higher level of complete cancer disappearance and fewer short-term side effects compared to traditional treatment.
It is one of three PLATO clinical trials led by Professor David Sebag-Montefiore and the Leeds Cancer Research UK Clinical Trials Unit at the University of Leeds’ Faculty of Medicine and Health.
Funded by Stand Up to Cancer, PLATO focuses on improved and more personalised treatment options for anal cancer.
Anal cancer is a rare cancer that starts in the anus, the last part of the digestive system.
Around 1,600 people are diagnosed in the UK each year.
Symptoms of anal cancer can include bleeding, bowel changes, severe itching and pain.
Professor Sebag-Montefiore, Chief Investigator of the PLATO study, Audrey and Stanley Burton Professor of Clinical Oncology at the University of Leeds and Honorary Consultant Clinical Oncologist at Leeds Teaching Hospitals NHS Trust, said: “The side effects of radiotherapy treatments have a significant impact on the lives of patients, both physically, mentally and often financially to attend appointments.
“The current approach for anal cancer treatments is essentially a ‘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.”
The current standard of care for anal cancer is radiotherapy combined with chemotherapy over five and a half weeks.
While this practice yields relatively high cure rates, it also results in significant side effects.
A key benefit of this new approach for patients with early-stage anal cancer is the reduction in treatment burden for patients and healthcare systems.
The trial’s long-term results showed that 88 out of 100 (87.6%) patients were successfully treated and remained free of cancer three years later, demonstrating the success of the treatment.
In the standard-dose group, it was 84 out of 100 (83.6%).
Patients in the trial also reported fewer side effects, which can include sore skin, diarrhoea, incontinence, fatigue, vaginal irritation and loss of sexual function.
The study was conducted across 28 sites across the UK, including Leeds Teaching Hospitals NHS Trust, and 163 patients took part.
Sam Panter, an RAF veteran and mother of two who participated in the trial, received the standard dose of radiotherapy across five and a half weeks.
She also received the standard course of chemotherapy.
She started to experience serious side effects midway through her treatment, and has welcomed the results, which could help reduce side effects in the treatment of future patients.
Sam said, “I’m so proud to have been part of this work, and I hope it leads to improved treatment options for people around the world who face a diagnosis like mine.”
IS TISSUE THE ISSUE?
Professor Nick Plant, Pro-Vice Chancellor: Research and Innovation at the University of Leeds, said: “The practice-changing results of the ACT4 PLATO trial are an exemplar of our commitment to excellence in cancer research and innovation in Leeds. Patients in the city, region, and across the globe will directly benefit from this smarter, kinder approach to personalised radiotherapy. Patient-focused, transformational research, such as the ACT4 PLATO trial, is at the heart of our University of Leeds health strategy, providing patients with a high chance of cure with fewer side effects.”
Professor Sebag-Montefiore presented the results last week to cancer experts from around the world at ESTRO 202 (European Society for Radiotherapy and Oncology congress), the largest European radiotherapy conference, and they have been hailed as groundbreaking.
Dr Alexandra Gilbert, Associate Professor at the University of Leeds, who presented data on patient reported quality of life, said: “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. We also see a trend towards improved sexual function in the longer term for men and women using the shorter, lower dose treatment.”
Sam’s experience of traditional treatment
Patients, including trial participant Sam Panter, 48, have welcomed the results of the PLATO trial.
Sam, a former RAF Air Steward, was diagnosed with anal cancer after experiencing symptoms she initially thought were piles (haemorrhoids).
Sam, a mum of two, said: “I first went to see my GP in March that year, after experiencing bleeding, and was sent for a colonoscopy, which came back clear. But after some weeks, the symptoms persisted, and I developed what I thought were haemorrhoids, and I initially tried to treat them myself.
“When that didn’t help, I decided to go back for medical advice and was sent for further examination under a general anaesthetic. 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 joined PLATO ACT4 and received the standard dose of radiotherapy across five and a half weeks and the standard course of chemotherapy.
Sam, who, after leaving the RA, F, worked as a Physiotherapist Assistant, said: “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.
“I remember getting to the halfway point and thinking How am I going to carry on to the end? It had got so uncomfortable, and travelling to and from appointments each day for treatment, which was an hour journey each way, was taking its toll, and I had extreme fatigue.”
“Breakthrough”
The results provide critically important new knowledge and are likely to lead to a change in clinical practice globally.
Professor Sebag-Montefiore said: “These results are a breakthrough for patients like Sam and future anal cancer patients. The shorter, highly effective radiotherapy course not only reduces side effects, but it also reduces hospital visits and optimises the use of healthcare resources.”
Dr Iain Foulkes, Executive Director of Research and Innovation at Cancer Research UK, said: “Anal cancer is a devastating disease, and treatment often comes with severe side-effects. There is a real need for treatments that can help people live a better quality of life.
“The PLATO trial is an outstanding example of harnessing the latest advances in radiotherapy technology to target cancer cells and minimise side effects and personalise radiotherapy treatment in this rare disease.
“The results have been received with great excitement amongst the scientific community at ESTRO. ACT4 is regarded as a practice changing trial that will result in changes in how anal cancer is treated around the world.”
Sam completed her treatment and, in December 2024, was given the all-clear by her clinician after five years cancer-free.
Sam said, “When I was invited to be part of the trial, I decided to take a leap of faith. Without research, we can’t learn, and I put my trust in the clinical team. Knowledge is power, and the results from this trial show how important it is that we all play our part.”
Source: University of Leeds
