A new trial with patients with advanced rectal cancer has found that the addition of immunotherapy treatment alongside extended radiotherapy led to better rates of remission.
The findings from the UK-wide trial – released at the ESTRO 2025 conference in Vienna this week – reported high rates of complete response to treatment among patients participating in the trial, particularly in the group where immunotherapy was combined with short course radiotherapy.
Overall, a high rate of 52% complete remission was observed in patients across the trial, exceeding pre-trial expectations of 30%.
The colorectal cancer team based at Aberdeen Royal Infirmary, led by Dr Leslie Samuel, Honorary Clinical Chair in Oncology at the University of Aberdeen and Consultant Oncologist for NHS Grampian, collaborated in the study. Colorectal cancer patients from across Grampian took part in both the main trial as well as the initial safety trial.
The randomised phase II PRIME-RT trial, led by the University of Glasgow and NHS Greater Glasgow & Clyde, tested extended pre-surgical radiotherapy regimens, both of short course and long course periods, used in addition to immunotherapy in patients with locally-advanced rectal cancer (patients with larger and more aggressive tumours), marking the first time this combination of treatments has been evaluated in the same patient population.
The trial also found that the addition of immunotherapy treatment for these patients did not appear to significantly add any negative side effects.
Rectal cancer kills around 4,100 people in the UK (around 410 in Scotland) every year.* Over the last 20 years, incidence of early-onset rectal cancer has increased by 50.5% in the UK (53.6% in Scotland) for people aged 25-49 and rates are rising faster in young women than young men, particularly in Scotland and Northern Ireland.**
Each year around 12,000 people are diagnosed with rectal cancer in the UK. Around 1,100 people are diagnosed each year in Scotland.*** Bowel cancer, also known as colorectal cancer, is the second most common cause of cancer deaths in the UK.**** Rectal cancer makes up around a quarter of bowel cancer deaths.* Despite this, treatment options remain limited, particularly for patients who are diagnosed at later stages of the disease.
The usual treatment for rectal cancer is surgery, with most patients requiring a temporary stoma or ostomy. Up to one third of patients with colorectal cancer often require a permanent colostomy.
Seeking to find better treatments and outcomes for patients the phase II PRIME-RT trial investigated the possibility of increasing the number of patients with complete remission from the disease, using a combination of immunotherapy and radiotherapy, whilst also avoiding the need for surgery.
The trial involved 46 patients across multiple centres across the UK for whom their rectal cancer was locally-advanced. The trial tested two different radiotherapy strategies – short and long-course regimes – in combination with Durvalumab, a common immunotherapy treatment. For patients reaching the end of treatment, high rates of complete remission were observed in both of the two arms of the trial (67% and 48%); and at 18 months follow-up, 56% and 33% of patients respectively exhibited sustained complete responses.
Chief Investigator of the trial, Campbell Roxburgh, Professor of Colorectal Surgical Oncology at the University of Glasgow’s School of Cancer Sciences, said: “We are extremely encouraged by the findings of our PRIME-RT trial, which provides positive evidence of a more successful treatment option for patients with advanced rectal cancer.
“Our trial specifically aimed to increase rates of complete remission in these patients, and to allow more patients to be managed without the need for life-altering surgery. The success of our findings went beyond our expectations, adding to growing evidence that immunotherapy synergises with radiotherapy regimens to enhance rates of remission in this group of patients. In particular, our findings add weight to emerging evidence that indicate a short-course radiation schedule may represent the best treatment partner for immunotherapy.
“Going forward, we are planning follow-up trials in rectal cancer, with the aim of further enhancing responses informed by these results. Although patient response rates have improved, some patients still do not respond completely to these treatments and continue to require surgery. More still needs to be done to understand the biology underpinning treatment response, to help us to deliver a more ‘precision medicine’ biology approach to rectal cancer.”
Dr Leslie Samuel who led the Aberdeen arm of the trial added: “In a group of patients with significantly locally advanced rectal cancers, we were amazed by the impressive response.
“A significant proportion of our patients achieved a complete clinical response, with no evidence of residual cancer.
“Fundamentally, this means those patients did not require radical surgery including the formation of a permanent colostomy.”
Cancer Research UK Director of Research, Dr Catherine Elliott, welcomed the news and said: “Harnessing our own immune system to help us tackle cancer is a growing area of cancer research and in combination with other therapies, such as radiotherapy, it can be even more effective.
“It’s encouraging news that this clinical trial combining these therapies can not only reduce the need for life-changing surgery but can help increase the number of people with rectal cancer in remission.”
The phase II PRIME-RT trial is funded by AstraZeneca UK and was carried out in collaboration with Glasgow’s Experimental Cancer Medicine Centre (ECMC). Glasgow’s ECMC is funded by a partnership between Cancer Research UK, the Scottish Government Chief Scientist Office and the Little Princess Trust. The trial was led by the University of Glasgow and NHS Greater Glasgow & Clyde in collaboration with The Christie NHS Foundation Trust, NHS Grampian, The University of Aberdeen, the University of Oxford and NHS Ayrshire and Arran.
- *Based on the average annual number of deaths from rectal cancer (ICD10 C20) in the years 2017-2019
- **Based on the percentage change in incidence rates from 3 cases per 100,000 people between 1997-1999 to 4 cases per 100,000 people between 2017-2019
- ***Based on the average annual number of new cases of rectum cancer (ICD10 C20) diagnosed in the years 2017-2019
- ****Based on the European age-standardised mortality rate of 26.7 bowel cancer deaths per 100,000 population in the UK in 2017-2019. The leading cause of cancer death in the UK is lung cancer, based on the European age-standardised mortality rate of 55.5 lung cancer deaths per 100,000 population in the UK in 2017-2019.