On April 7, 2025 MiraDx, a molecular diagnostics company advancing personalized medicine through novel germline biomarkers, reported 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 (Press release, MiraDx, APR 7, 2025, View Source [SID1234651823]). 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.
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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.