UCLA researchers have validated a new genetic test that can predict which prostate cancer patients are most likely to develop urinary complications following radiation therapy, potentially transforming treatment decision-making for one of the most common male cancers.
The test, called PROSTOX, successfully identified men at higher risk of developing urinary side effects after radiation treatment in a study of 148 patients published in the journal Clinical Cancer Research.
"We've always known that some men develop these life-altering side effects that they will carry through the remainder of their lives, but until now, we didn't have a way to predict who," said senior researcher Dr. Joanne Weidhaas, vice chair of molecular and cellular oncology at the David Geffen School of Medicine at UCLA.
How PROSTOX Works
PROSTOX evaluates 32 unique genetic factors related to radiation side effects. The test analyzes microRNA single-nucleotide polymorphisms (mirSNPs) in non-coding germline DNA to identify patients with higher genetic risk for developing genitourinary toxicity following radiation therapy.
"What makes PROSTOX different is that it looks at a patient's unique genetics to estimate their personal risk of developing side effects from radiation," Dr. Weidhaas explained. "This helps doctors and patients choose the safest treatment and avoid unnecessary toxicities."
Early testing found that men identified by the test as high-risk were approximately 10 to 12 times more likely to develop urinary side effects compared to those at lower risk.
Study Validates Predictive Accuracy
The research team set out to confirm PROSTOX's effectiveness in a new cohort of 148 patients who received stereotactic body radiotherapy (SBRT) for their prostate cancer. SBRT is a highly precise form of radiation therapy delivered over just five sessions.
Results from the phase 3 MIRAGE trial (NCT04384770) demonstrated that PROSTOX achieved an area under the curve of 0.76, showing a strong correlation with genitourinary toxicity grade (P < .0001).
"Despite advances in radiation therapy techniques, this study validated PROSTOX as a predictive biomarker, confirming that genetic predisposition to increased toxicity persists even with modern, high-precision stereotactic body radiation therapy, including MRI-guided SBRT," said Dr. Amar Kishan, professor of radiation oncology and executive vice chair for the Department of Radiation Oncology at UCLA.
Different Types of Side Effects Have Different Causes
Interestingly, the study also revealed different genetic signatures between urinary side effects that develop late but eventually fade, and those that start early and never resolve.
This suggests these two types of side effects likely occur for different biological reasons. Late-onset urinary symptoms appear to be connected to immune system problems and long-term inflammation, while persistent side effects seem to be associated with the type of radiation technology used in treatment.
Clinical Implications
Radiation therapy for prostate cancer can irritate the bladder, causing urinary incontinence, frequent urination, or painful urination. While the initial risk is low following treatment, it increases each year for several years.
"While severe adverse effects are uncommon, approximately 15% to 20% of patients develop moderate toxicity that could require medication and impact quality of life," noted study investigator Dr. Luca Valle, assistant professor in the Department of Radiation Oncology at UCLA. "This underscores the importance of being able to assess a patient's unique biological suitability for SBRT."
The ability to predict these complications before treatment begins could significantly improve quality of life for prostate cancer survivors.
Future Directions
The research team plans to continue validating PROSTOX in larger patient populations and is exploring similar genetic tests to predict side effects in other cancers following treatment.
"This genre of genetic testing combined with advanced radiation therapy techniques will help personalize treatment for prostate cancer patients, mitigate the risk of serious genitourinary side effects, and give doctors and patients important information to make the best and safest treatment choices," said Dr. Michael Steinberg, chair of radiation oncology at the David Geffen School of Medicine at UCLA.
Dr. Weidhaas added, "With further research, we hope to apply these genetic insights across cancer care. Ultimately, we want patients to survive cancer and live well after treatment."
The PROSTOX test is being developed by MiraDx, a precision medicine company focused on microRNA-based diagnostics.
