A study from the University of Manchester has made a significant advancement in the treatment of prostate cancer by identifying genetic variants that affect patient sensitivity to radiation. This groundbreaking research holds the potential to reduce severe bowel complications, known as rectal toxicity, associated with radiotherapy. The findings were published on October 13, 2025, in the journal Clinical Cancer Research.
Led by PhD researcher Artemis Bouzaki, who is affiliated with both the University of Manchester and The Christie NHS Foundation Trust, the study uniquely combines genetic data with detailed spatial maps of radiation delivery in the rectum. Previous studies had established that the lower posterior region of the rectum is significant for rectal toxicities, but this is the first research to incorporate genetic information into this analysis.
“Rectal toxicity is a significant concern for patients receiving radiotherapy for prostate cancer, the most common cancer in men and now the most common cancer in England,” Bouzaki stated. She emphasized that while guidelines limit rectal toxicity rates to around 10%, many patients still experience a deterioration in bowel function, leading to severe complications such as incontinence and rectal bleeding.
The research analyzed data from 1,293 prostate cancer patients as part of the international REQUITE study, which collected outcomes from 17 hospitals across Europe and the USA between 2014 and 2016. Patients were grouped based on three genetic variants linked to increased radiation sensitivity and were assessed alongside dose maps detailing radiation exposure across the rectum. This methodology, developed by the research team in earlier work, revealed that the risk of complications was consistently highest in the lower posterior rectum.
Utilizing a technique called Voxel Based Analysis, the researchers examined three-dimensional image data in minute volume units known as voxels, allowing for a more precise assessment of radiation dose distribution. This approach enables identification of smaller regions within organs where specific radiation doses correlate with various treatment side effects.
Co-author and study supervisor Dr. Alan McWilliam noted, “Our work has revealed that patients with certain genetic variants may benefit from lower radiation doses in those specific parts of the rectum, which could make a significant difference to their recovery.” He cautioned that these findings are preliminary and emphasized the need for clinical studies to confirm their safety and effectiveness before any modifications to standard treatment protocols can be implemented.
One reason for the heightened sensitivity of the lower rectum may stem from anatomical and functional differences between its upper and lower parts, which could influence responses to radiation. These differences likely impact inflammation and immune response, potentially interacting with various genetic variants studied by the researchers.
Dr. Hayley Luxton, Head of Research Impact and Engagement at Prostate Cancer UK, highlighted the importance of personalized treatment approaches. “No two men’s prostate cancers will be the same, and different men will opt for different treatment,” she stated. Luxton acknowledged that while radiotherapy is highly effective for treating prostate cancer, it can lead to life-altering side effects.
The study points toward two primary strategies for minimizing these side effects: adjusting radiation dosages based on genetic profiles or reducing doses to particular areas of the body. Thanks to funding from Prostate Cancer UK and Movember, the Manchester team has successfully integrated both methods, paving the way for more tailored radiotherapy treatments.
“This study helps bring us that much closer to ensuring that the right men receive the right treatment at the right time,” Luxton concluded. The implications of these findings could transform prostate cancer care, making it more personalized and effective for patients worldwide.
