PROSTOX ultra Reliably Predicts Long-Term Radiation AEs in Prostate Cancer

Results from the phase 3 MIRAGE trial found that PROSTOX ultra achieved an area under the curve of 0.76, demonstrating a strong correlation with genitourinary toxicity grade.

The PROSTOX ultra test can accurately predict long-term genitourinary (GU) adverse effects (AEs) from radiation therapy (RT) for prostate cancer prior to initiating treatment, according to results from an analysis of the phase 3 MIRAGE trial (NCT04384770) published in Clinical Cancer Research.¹

More specifically, previous findings showing the predictive accuracy of the test were confirmed. Researchers from the Department of Radiation Oncology at UCLA elucidated its effectiveness, establishing it as the first test capable of predicting, based on a patient’s unique genomic profile, the long-term radiation-induced AEs, according to a news release from the drug’s developer, MiraDx.² These findings additionally confirmed that radiation toxicity is biologically unique for patients, revealing the potential for the personalization of RT to improve outcomes through genetics.

Results from the phase 3 MIRAGE trial found that PROSTOX ultra achieved an area under the curve (AUC) of 0.76, demonstrating a strong correlation with GU toxicity grade (P < .0001). Additionally, microRNA single-nucleotide polymorphisms (mirSNP)–based signatures were shown to distinguish acute and chronic RT toxicities, eliciting AUCs of 0.770 and 0.763, respectively. Furthermore, 3 temporal radiation-induced GU toxicity profiles were found: acute only, chronic, and late.

“Advancements in [RT], treatment planning, patient care, and follow-up make it challenging to directly compare toxicity between older and more modern treatment approaches,” primary investigator Amar Kishan, MD, professor of radiation oncology and executive vice chair for the Department of Radiation Oncology at the David Geffen School of Medicine at UCLA and the UCLA Jonsson Comprehensive Cancer Center, said in the news release.² “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 stereotactic body radiation therapy [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.”

The prospective phase 3 MIRAGE trial enrolled 148 patients with prostate cancer to receive either CT-guided SBRT or MRI-guided SBRT.³ The primary end point was incidence of acute grade 2 or greater GU physician-reported toxicity up to 90 days after SBRT. Secondary end points included incidence of gastrointestinal (GI) toxicity up to 90 days after SBRT; incidence of late-grade GI or GU toxicities, defined as occurring up to 5 years after SBRT; patient-reported quality-of-life outcomes; and biochemical recurrence free-survival.

The PROSTOX ultra assay is a diagnostic test designed to predict radiation-induced late toxicities in patients with prostate cancer. Through mirSNP analysis in noncoding germline DNA, PROSTOX ultra identifies patients at a higher genetic risk of developing late grade 2 or higher GU toxicity following SBRT, which typically appears 3 to 6 months after RT, causing long-term urinary complications, and may persist for life.

“While severe [adverse] effects are uncommon, approximately 15% to 20% of 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 [adverse] effects,” study investigator Luca Valle, MD, assistant professor in the Department of Radiation Oncology at the David Geffen School of Medicine at UCLA, said in the news release.² “Fortunately, tools like PROSTOX ultra can help us to individualize and personalize our radiation treatment recommendations and reduce the risk of treatment-related toxicity.”

References

1. Kishan MU, McGreevy K, Valle L, et al. Validation and derivation of microRNA-based germline signatures predicting radiation toxicity in prostate cancer. Clin Cancer Res. Published online April 7, 2025. doi:10.1158/1078-0432.CCR-24-3951
2. New study published in clinical cancer research validates PROSTOX ultra diagnostic test for predicting radiation-induced late toxicity in prostate cancer. News release. MiraDx. April 7, 2025. Accessed April 8, 2025. https://tinyurl.com/4dve5jzj
3. CT-guided stereotactic body radiation therapy and MRI-guided stereotactic body radiation therapy for prostate cancer, MIRAGE study. ClinicalTrials.gov. Updated December 11, 2024. Accessed April 8, 2025. https://tinyurl.com/269stwey