Next-gen personalised radiotherapy could cure more bladder cancers and cut side effects

Adapting radiotherapy to the ways our bodies change over time could make it possible to cure more bladder cancers while causing fewer side effects, according to one of our latest studies. 

The Phase 2 RAIDER trial, led by a team at The Institute of Cancer Research (ICR) in London, looked at adapting radiotherapy to the size and location of each patient’s bladder at each appointment. By using scan images as a guide to select either a small, medium or large target area, doctors were able to deliver a higher dose of radiation to bladder cancer cells while sparing healthy ones.  

That’s a big step towards kinder and more effective treatments for advanced (or muscle invasive) bladder cancer. The researchers are now planning a Phase 3 study to fully investigate the difference the new treatment can make to patient outcomes. 

More targeted radiotherapy at a higher dose

Radiotherapy, which kills cancer cells by irreversibly damaging their DNA, has been an important part of cancer treatment for over a century. In recent years, a combination of chemotherapy and radiotherapy has become a realistic alternative to bladder removal surgery for many patients with muscle invasive bladder cancer. Avoiding these operations can help support a better quality of life, but, as radiotherapy can also damage nearby healthy cells, it has to be precisely targeted to minimise side effects. 

That’s difficult with the bladder, which can stretch, shrink and even move into slightly different places over time. Standard radiotherapy delivers the same dose of radiation to the same predetermined area of the body in each session. As a result, doctors have to target more of the bladder to ensure that normal changes to its size and position don’t make the treatment any less effective.  

That has two potential downsides. First, the bigger target area increases the risk of damaging healthy cells and leading to difficult long-term side –effects. Second, the dose, which has to balance effectiveness and safety, may not be high enough to kill all the cancer cells. 

By contrast, the personalised technique tested in the RAIDER study allows doctors to choose one of three treatment plans at each radiotherapy appointment based on the size and position of the patient’s bladder at the time. That cuts the amount of healthy tissue in the radiotherapy target area, which, as the trial has now shown, means most patients can receive a higher dose of radiotherapy. 

“Delivering radiotherapy to the bladder is a challenging process,” explained Professor Robert Huddart, lead author of the study. “This work into a potential new way of treating bladder cancers has allowed us to deliver effective treatment safely and allowed us to use a high dose which promises to cure more patients, with relatively few long-term side effects.”   

Fewer side effects than previous bladder cancer studies

In total, the RAIDER trial split 345 patients from the UK, Australia and New Zealand into one of three groups, each receiving a different course of treatment. The first group received standard radiotherapy with a single set treatment plan. The other two groups were given image-guided adaptive treatments, one with a higher radiation dose. 

Most participants in the adaptive groups received treatment with all three plans, confirming just how much people’s bladders can change between appointments. Other improvements in how doctors deliver radiotherapy may also have played a part in the fact that, across all groups of patients, there were fewer serious long-term side effects 6 to 18 months after treatment than in previous studies. There was no evidence that those who received higher dose treatment had any worse side effects compared with those who received standard radiotherapy treatment. 

There were also positive signals about the effectiveness of adaptive radiotherapy with an increased dose, but we’ll need more trials to directly compare it with standard approaches.  

“As medical technologies continue to improve, it means that we can investigate delivering more complicated and personalised forms of radiotherapy to treat certain cancers,” said ICR Professor Emma Hall, the senior author of the paper.  

“We are grateful to those who took part in the RAIDER study, allowing us to determine if adaptive radiotherapy can be given to patients with bladder cancer without substantially worsening their quality of life post-treatment.” 

The RAIDER study was also supported by the National Institute of Health and Care Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust.