Metastasis-directed radiotherapy without systemic therapy (MRWS) demonstrated promising efficacy with manageable safety in patients with oligometastatic clear cell renal cell carcinoma (ccRCC), according to data from a phase 2 trial (NCT03575611) presented at the 2025 Kidney Cancer Research Summit in Boston, Massachusetts.1
The 2-year PFS and STFS were 40% and 75%, respectively.
“Current treatment for frontline ccRCC focuses on systemic therapy doublets. Although effective, such combinations exhibit substantial toxicities and health care costs,” the authors wrote. “An underutilized option is MRWS, which may facilitate a prolonged systemic therapy-free interval in select patients. Unfortunately, no reliable prognostic markers exist to select patients for MRWS.”
To that end, the investigators enrolled 121 patients with oligometastatic ccRCC to assess the safety and efficacy of MRWS as well as the utility of circulating tumor DNA (ctDNA) as a prognostic biomarker for response.
Most patients in the study had 1 site of metastatic disease (72%) and had never received systemic therapy (70%). Those enrolled in the trial received MRWS, primarily stereotactic radiation therapy, to all sites of disease. Patients were able to receive subsequent rounds of MRWS if limited progression was observed. The trial’s co-primary end points were progression-free survival (PFS) and systemic therapy-free survival (STFS).
Data showed that at a median follow-up of 36 months (range, 13 to 61), the median PFS was 18 months (95% CI, 16 to 25) and the median STFS was 34 months (95% CI, 28 to 54). According to the authors, “The lower bounds of 95% CI of the median STFS exceeded the prespecified 24 [month] threshold for success.”
The 2-year PFS and STFS were 40% and 75%, respectively.
The median overall survival (OS) had not been reached at the time of data report. At 2 and 3 years, OS was 94% and 86%, respectively.
MRWS was also well-tolerated, according to the authors. Overall, 8% of patients (n = 9) experienced grade 3 or higher toxicities that the investigators deemed to be “at least possibly attributed to MRWS.” No grade 5 toxicities were reported.
The investigators then assessed ctDNA as a potential prognostic biomarker for treatment outcomes. At baseline, 56% of patients had molecular residual disease (MRD) detected (MRD+).
Data showed that MRD+ status was associated with significantly shorter STFS (HR, 2.9; 95% CI, 1.4 to 6.1; P = .003). Specifically, the median STFS was 27 months among those who were MRD+ at baseline vs 54 months among those who were MRD- at baseline. Further, MRD+ status at 3-month follow-up was also shown to be strongly associated with a shorter STFS (HR, 4.3; 95% CI, 2.0 to 9.0; P < .001).
According to the authors, this ctDNA approach “appears to be a promising baseline prognostic biomarker for STFS and a dynamic marker of MRWS response.”
“This study demonstrated that metastasis-directed radiation therapy (MDT) can help patients delay or avoid systematic treatments without sacrificing outcomes. Overall survival was not compromised, with survival rates of 94% at 2 years and 87% at 3 years,” said lead author Chad Tang, MD, in a prior news release on the findings.2 “The study also suggests that ultrasensitive ctDNA detection is a promising personalized biomarker that may offer opportunities for de-escalated, personalized care in patients with a cancer type that does not otherwise have many good biomarkers. Our data show those who tested positive on Precise MRD prior to MRWS initiated systemic therapy within a median time of 27 months, whereas those who tested negative on Precise MRD were maintained on MDT for a median time of 54 months.”
The phase 2 trial remains ongoing, with final completion expected in September 2025.3
REFERENCES
1. Tang C, Sherry A, Seo A, et al. Phase 2 trial of metastasis directed radiotherapy without systemic therapy (MRWS) for oligometastatic clear cell renal cell carcinoma (ccRCC) and investigation of circulating tumor DNA (ctDNA). Presented at: 2025 Kidney Cancer Research Summit. July 17-18, 2025. Boston, Massachusetts. https://kcrs.kidneycan.org/wp-content/uploads/2025/07/KCRS25-Abstract-Book-7.14.25.pdf
2. Myriad Genetics highlights MRD clinical validity data at American Association for Cancer Research Annual Meeting. News release. Myriad Genetics. April 25, 2025. Accessed July 25, 2025. https://investor.myriad.com/news-releases/news-release-detail/26286/
3. Stereotactic body radiation therapy in treating patients with oligometastatic renal cell carcinoma. ClinicalTrials.gov. Last updated May 16, 2025. Accessed July 25, 2025. https://clinicaltrials.gov/study/NCT03575611