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New Study Published in Clinical Cancer Research Validates PROSTOX ultra Diagnostic Test for Predicting Radiation-Induced Late Toxicity in Prostate Cancer

April 7, 2025 by akarcvane

PROSTOX^TM ultra is the first and only molecular diagnostic test to use biology and genetics to predict radiation toxicity

Study confirms previous published results showing that PROSTOX ultra accurately predicts late genitourinary toxicity and has significant correlation with genitourinary toxicity grade

LOS ANGELES, CA – APRIL 7, 2025 – MiraDx, a molecular diagnostics company advancing personalized medicine through novel germline biomarkers, announced a groundbreaking study published in the journal Clinical Cancer Research, validating previous findings that its PROSTOX ultra test can predict long-term side effects from radiation therapy for prostate cancer, prior to starting treatment. Led by researchers at UCLA’s Department of Radiation Oncology, the study confirms the effectiveness of PROSTOX ultra, the first test capable of predicting long-term radiation side effects based on a patient’s unique genetic profile. The findings reinforce that radiation toxicity is a biologically unique response for each patient, underscoring the potential to personalize and improve cancer treatment using genetics.

The study, titled “Validation and Derivation of MicroRNA-based Germline Signatures Predicting Radiation Toxicity in Prostate Cancer,” is now available online in Clinical Cancer Research, a journal of the American Association for Clinical Research.

In this prospective study of 148 patients enrolled in the Phase 3 MIRAGE clinical trial (Magnetic Resonance Imaging-Guided Stereotactic Body Radiotherapy for Prostate Cancer, NCT 04384770), PROSTOX ultra was assessed. This assay is based on microRNA single-nucleotide polymorphisms (mirSNPs) in non-coding regions of germline DNA, previously shown to play a key role in predicting late genitourinary (GU) toxicity, which typically appears three to six months or later following stereotactic body (SBRT) or conventionally fractionated (CFRT) radiation therapy. The study validated PROSTOX ultra as a biomarker to predict late GU toxicity after SBRT and showed a strong correlation between the PROSTOX ultra score and toxicity grade. In addition, the study identified three separate temporal radiation-induced GU toxicity profiles: acute only, chronic, and late. Notably, these results support the potential of mirSNP-based biomarkers to independently predict different types of toxicity risks prior to radiation therapy, regardless of clinical factors such as age or radiation delivery technique.

“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 Amar Kishan, M.D., primary investigator of the study and Radiation Oncologist at UCLA. “Despite these challenges, this study validated PROSTOX ultra as a predictive biomarker, and that a genetic predisposition to increased toxicity persists with modern, high-precision SBRT, including MRI-guided SBRT. This finding reinforces PROSTOX ultra 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.”

Prostate cancer affects more than a quarter of a million individuals annually, primarily those over 65 years of age. Radiation-induced toxicity remains a significant concern, with late-onset side effects occurring in 15-20% of patients. Currently, no effective interventions exist for these side effects, with the most problematic being late GU toxicity, which includes symptoms such as urinary tract pain, blood in urine, increased frequency of urination, or urinary urgency or leaking. For prostate cancer patients, many of whom live for decades post-treatment, late-onset side effects can persist, be costly to manage and significantly impact their quality of life.

“While severe side effects are uncommon, approximately 15-20% patients do develop moderate toxicity that could require medication and impact quality of life. This underscores the importance of being able to assess a patient’s unique biological suitability for SBRT, since that can influence their risk for long-term side effects,” said Luca Valle, M.D., study investigator and Radiation Oncologist at UCLA. “Fortunately, tools like PROSTOX ultra can help us to individualize and personalize our radiation treatment recommendations and reduce the risk of treatment-related toxicity.”

“These findings represent a very important moment in the treatment of prostate cancer and for the field of oncology treatment as a whole,” said Joanne Weidhaas, M.D., Ph.D., study author, Professor at the David Geffen School of Medicine at UCLA and head of translation research in the Department of Radiation Oncology, and co-founder of MiraDx and founder of MiraKind. “While tumor-based molecular profiling tests that inform treatment selection have contributed to improved patient outcomes, no tests based on germline genetics currently exist to identify toxicity risks to treatment. PROSTOX ultra is the first test that predicts radiation toxicity, giving patients and their physicians important information to make decisions that balance effectiveness with long-term quality of life.”

About PROSTOX ultra Diagnostic Test

PROSTOX ultra is the first and only diagnostic test designed to predict radiation-induced late toxicity in prostate cancer patients. By analyzing microRNA single-nucleotide polymorphisms (mirSNPs) in non-coding germline DNA, PROSTOX ultra identifies patients at higher genetic risk of developing late grade ≥2 genitourinary (GU) toxicity after stereotactic body radiation therapy (SBRT). This toxicity, which can cause long-term urinary complications, typically appears three to six months after radiation therapy and can persist for life. With PROSTOX ultra, patients and clinicians can make more informed treatment choices, minimizing side effects while prioritizing long-term quality of life and health outcomes.

About MiraDx

MiraDx is a Los Angeles-based molecular genetics company that identifies, validates, develops, and delivers novel germline biomarker tests for individualized cancer treatment. Its goal is to improve human health and advance personalized medicine through the application of novel functional germline biomarkers. To learn more about MiraDx, please visit us at miradx.com. To learn about MiraKind, the company’s affiliated non-profit that conducts patient-centric research to better understand novel inherited gene mutations, visit mirakind.org.

Partnership and Other General Inquires

Info@miradx.com

Media Contact

Media@miradx.com

PROSTOX, a signature of late GU toxicity after SBRT radiotherapy in MIRAGE, a prospective trial

May 30, 2024 by akarcvane

MIRAGE trail data poster of PROSTOX signature

This year, approximately 300,000 men in the U.S. were diagnosed with prostate cancer, bringing the total to over 3.3 million cases.¹ Nearly half of those with localized prostate cancer undergo radiation therapy, including stereotactic body radiation therapy (SBRT).

However, about 16% of men treated with SBRT develop genitourinary (GU) toxicity within three to six months after treatment, resulting in urinary frequency, urgency, or incontinence. While often managed with medication, these symptoms may not resolve and can negatively affect one’s quality of life.
Currently, there is no reliable way to predict who will develop late GU toxicity. Identifying patients at high or low risk before therapy starts can help guide safer, more personalized care.

Researchers at UCLA’s Department of Radiation Oncology addressed this need through the MIRAGE prospective clinical trial, confirming the effectiveness of PROSTOX—a genomic test that predicts late grade ≥ 2 GU toxicity from SBRT using a patient’s genetic profile.²

Key findings:

PROSTOX predicts late GU toxicity independent of the delivery method (MRI- vs. CT-guided SBRT).
PROSTOX identifies a genetic signature specific to late toxicity, distinct from acute or chronic toxicity.
Gene ontology analysis³ reveals distinct biological pathways underlying late, acute, and chronic toxicities.

Personalizing Prostate Cancer Treatment

The findings of the MIRAGE study support that PROSTOX is a powerful tool for personalizing prostate cancer treatment. Furthermore, the discovery that there are distinct genetic pathways for acute and chronic GU toxicities suggests the potential to develop therapeutic strategies aimed at toxicity prevention in the future.

Download the MIRAGE poster here.

References

https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html
Kishan AU, et al. Germline variants disrupting microRNAs predict long-term genitourinary toxicity after prostate cancer radiation. Radiother Oncol. 2022 Feb;167:226-232.
Ashburner M, et al. Gene ontology: tool for the unification of biology. Nat Genet. 2000 May;25(1):25-9

Early findings from the GARUDA trial: The impact of a genetic signature of late radiation toxicity on prostate cancer treatment decision-making

June 2, 2023 by akarcvane

As definitive treatments for localized prostate cancer are highly effective, post-treatment quality of life has become a key consideration in patient-physician shared decision-making.¹

A significant side effect of definitive radiotherapy is late grade ≥ 2 genitourinary (GU) toxicity—typically presenting three to six months after treatment as urinary frequency, urgency, or incontinence—which affects approximately 15% of patients.^2,3 These rates appear comparable between conventional fractionation and stereotactic body radiotherapy (SBRT).^4,5

PROSTOX is a diagnostic test that identifies prostate cancer patients at risk for late GU toxicity from SBRT before treatment begins.⁶ It analyzes a patient’s germline DNA for microRNA-associated single nucleotide polymorphisms (mirSNPs). Its purpose is to help guide safer, more personalized treatment choices.

In the GARUDA phase II prospective study, researchers at UCLA’s Department of Radiation Oncology evaluated whether PROSTOX results would influence joint treatment decisions in patients with prostate cancer and their physicians. Patients evaluated for SBRT were tested for PROSTOX, and results were shared. Patients who chose either SBRT or moderately/conventionally fractionated radiation therapy (MHFRT/CFRT) after receiving a low-risk or high-risk PROSTOX score were enrolled in the study.

Key findings:

Treatment choices were impacted based on PROSTOX results.
Observed toxicity aligned with genetic risk prediction.
No significant differences in risk classification by age, race, or ethnicity.

The GARUDA study demonstrates that PROSTOX results influence treatment selection, with patients and physicians adjusting decisions based on predicted toxicity. These results support the utility of using genetic toxicity risk assessment in guiding more personalized approaches to prostate cancer radiation therapy.

References

Hoffman KE, et al. Patient-reported outcomes through 5 years for active surveillance, surgery, brachytherapy, or external beam radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA 2020 Jan;323:149.
Michalski JM, et al. Effect of standard vs dose-escalated radiation therapy for patients with intermediate-risk prostate cancer: The NRG Oncology RTOG 0126 Randomized Clinical Trial. JAMA Oncol 2018 Jun;4:e180039.
Meier RM, et al. Multicenter trial of stereotactic body radiation therapy for low- and intermediate-risk prostate cancer: survival and toxicity endpoints. Int J Radiat Oncol Biol Phys 2018 Oct;102:296-303.
Fransson P, et al. Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Lancet 2019 Feb;394:385-95.
Kishan AU, et al. Long-term outcomes of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer. JAMA Netw Open 2019 Feb;2:e188006.
Kishan AU, et al. Germline variants disrupting microRNAs predict long-term genitourinary toxicity after prostate cancer radiation. Radiother Oncol 2022 Feb;167:226-232.