PROSTOX May Predict Urinary Side Effects Post Prostate Cancer Radiation

PROSTOX uses microRNA to identify genetic predisposal to certain urinary side effects.

Researchers have engineered a test to predict whether patients with prostate cancer are at higher risk of developing urinary side effects following radiation therapy.

The discovery, by investigators from the UCLA Health Jonsson Comprehensive Cancer Center, was announced in a news release from UCLA and detailed in a study published in Clinical Cancer Research outlining the findings regarding the PROSTOX test.

“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,” noted Dr. Joanne Weidhaas, professor of radiation oncology, vice chair of molecular and cellular oncology at the David Geffen School of Medicine at UCLA and senior author of the study, in the news release. “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. This helps doctors and patients choose the safest treatment and avoid unnecessary toxicities.”

The test, as explained in the UCLA news release, is the first of its kind, using microRNAs to predict cancer therapy toxicity. MicroRNAs, as defined by the National Cancer Institute on its website, are a type of RNA found in cells and blood. They can bind to messenger RNAs, or mRNAs, to stop them from producing proteins, and are being studied in the diagnosis and treatment of cancer.

Long-term urinary side effects can include urinary tract pain, blood in the urine, increased frequency of urination and urinary urgency or leakage, and researchers have found that different genetic factors are linked to different types of side effects. This finding, the news release stated, reinforces the need for more personalized approaches to 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 GU side effects as well as give doctors and patients important information to make the best and safest treatment choices,” said co-author Dr. Michael Steinberg, professor and chair of radiation oncology at the David Geffen School of Medicine at UCLA and director of Clinical Affairs at the UCLA Health Jonsson Comprehensive Cancer Center, in the news release.

Weidhaas and colleagues previously found that some inherited genetic differences can predict how likely someone is to experience side effects. They drew on these findings to develop the PROSTOX test to identify 32 unique mirSNPs, or variations within the microRNA, linked to radiation-related side effects.

PROSTOX separates patients into low-risk and high-risk groups for developing serious long-term side effects after stereotactic body radiotherapy (SBRT), revealing that people in the high-risk group are 10 to 12 times more likely to experience problems, according to the news release.

For the new study, researchers confirmed the accuracy of PROSTOX in a group of 148 patients with prostate cancer who received either MRI- or CT-guided SBRT in the phase 3 MIRAGE clinical trial at UCLA.

“Advancements in radiation technology, treatment planning, patient care, and follow-up make it challenging to directly compare toxicity between older and more modern treatment approaches,” said first author of the study Dr. Amar Kishan, executive vice chair of radiation oncology at the David Geffen School of Medicine at UCLA. “This finding reinforces PROSTOX as a true measure of the biological response to radiation, independent of treatment era or technique that can identify the safest course of treatment to avoid toxicity.”

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