Investigators at the UCLA Health Jonsson Comprehensive Cancer Center have validated a test that can accurately predict which patients with prostate cancer are at higher risk of developing long-lasting urinary side effects after receiving radiation therapy.
The test, called PROSTOX, is the first of its kind to use microRNAs to predict toxicity from cancer therapy. It could help prevent the burden of long-term complications by identifying patients most at risk before treatment even begins.
In a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research, the UCLA team validated PROSTOX’s ability to predict long-term urinary side effects, which can include urinary tract pain, blood in the urine, increased frequency of urination, and urinary urgency or leakage. The researchers also found that different genetic factors are linked to different types of side effects, reinforcing the need for more personalized approaches to treatment.
A common problem patients may have after radiation is urinary side effects that can disrupt daily life, like frequent trips to the bathroom, pain, and an urgent need to go that doesn’t always come in time.
These side effects can happen right away (acute toxicity), much later (late toxicity), or start early and never go away (chronic toxicity). Even with the most advanced radiation techniques, some patients still develop these side effects, and it’s hard to know how they will respond to the stress of radiation.
In earlier work, Weidhaas and her team discovered that certain inherited genetic differences, especially in areas related to microRNAs, which help control how genes work, can predict how likely someone is to have these side effects. In partnership with MiraDx, the team used this information to develop the genetic test PROSTOX, which identifies 32 unique mirSNPs that are linked to radiation-related side effects and separates patients into low-risk and high-risk groups for developing serious long-term urinary side effects after SBRT. They found people in the high-risk group are about 10 to 12 times more likely to have problems.
In the new study, the researchers set out to confirm that PROSTOX works in a new group of 148 patients with prostate cancer receiving either MRI- or CT-guided SBRT from a phase III clinical trial at UCLA called MIRAGE. In addition, the team used machine learning, a type of artificial intelligence, to develop new models to predict acute and chronic urinary toxicity.
They confirmed that the test can successfully predict which patients will develop significant late urinary toxicity, regardless of whether the radiation was guided by MRI or CT. They also found that PROSTOX wasn’t influenced by other clinical factors, such as age or radiation dose, indicating that it detects an independent, genetic risk for toxicity.
The study also distinguished between two separate types of radiation-induced urinary side effects: chronic toxicity and late toxicity. Using genetic analysis, the team found these forms of toxicity have unique genetic signatures, suggesting they arise from different biological mechanisms.
Late toxicity seems connected to immune system dysfunction and long-term inflammation and chronic toxicity might be more affected by advanced technology, meaning better radiation techniques could help reduce these issues.
