Researchers have developed, and now validated, a biomarker test to predict for genitourinary (GU) adverse events induced by stereotactic body radiotherapy (SBRT) in patients with prostate cancer, according to the results of a study published by Kishan et al in Clinical Cancer Research.
The test, developed by investigators at the University of California, Los Angeles (UCLA), is called PROSTOX and consists of 32 microRNA-based germline biomarkers linked to adverse effects from radiation therapy. In a prior study, the investigators used PROSTOX to separate patients into low- and high-risk groups for developing long-term GU effects. Patients in the high-risk group were 10 to 12 times more likely to develop late GU effects.
“We’ve always known that some men develop these life-altering [adverse] 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 study author Joanne Weidhaas, MD, PhD, Professor of Radiation Oncology and Vice Chair of Molecular and Cellular Oncology at the David Geffen School of Medicine at UCLA. “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.”
Methodology and Results
To validate the PROSTOX test, the study authors assessed the relationship between PROSTOX score and late GU adverse effects in 148 patients from the phase III MIRAGE trial, which explored the use of magnetic resonance imaging (MRI)- vs computed tomography–guided SBRT for patients with localized prostate cancer. Predictive models were also created for acute and chronic GU toxicity using PROSTOX scoring.
The study found that PROSTOX can accurately predict late GU toxicity (area under the curve [AUC] = 0.76) and that it has a strong correlation with the grade of GU toxicity that was not influenced by clinical or dosimetric factors. The models also distinguished between acute (AUC = 0.770) and chronic (AUC = 0.763) toxicity; gene ontology analysis differentiated between acute, chronic, and late GU toxicity, showing that each type has a unique biological mechanism.
“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 lead study author Amar Kishan, MD, Executive Vice Chair of Radiation Oncology at the David Geffen School of Medicine at UCLA. “Despite these challenges, this study validated PROSTOX as a predictive biomarker and confirmed that a genetic predisposition to increased toxicity persists with modern, high-precision SBRT, including MRI-guided SBRT. 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.”
“This genre of genetic testing combined with advanced radiation therapy techniques will help personalize treatment for [patients with] prostate cancer, mitigate the risk of serious GU [adverse] effects, as well as give doctors and patients important information to make the best and safest treatment choices,” added co-author Michael Steinberg, MD, 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.
The study authors intend to expand PROSTOX into further patient populations and develop similar biomarker tests to predict for other radiation- and immunotherapy-induced toxicities.
Disclosure: For full disclosures of the study authors, visit aacrjounals.org/clincancerres.
