Prognostic significance of circulating tumor DNA alterations in advanced renal cell carcinoma from SCRUM-Japan MONSTAR-SCREEN: a nationwide genomic profiling project

Journal article

Kato T., Shiota M., Nishimoto K., et al. Prognostic significance of circulating tumor DNA alterations in advanced renal cell carcinoma from SCRUM-Japan MONSTAR-SCREEN: a nationwide genomic profiling project: Genetics and Genomics. British Journal of Cancer, e2200653 (2025); https://doi.org/10.1038/s41416-025-02985-8.Background: Circulating tumor DNA (ctDNA) is a promising tool for diagnosing and predicting cancer prognosis. However, its clinical utility in metastatic renal cell carcinoma (mRCC) remains unclear, particularly in terms of clinical prognosis. Methods: We enrolled 124 patients with mRCC in the MONSTAR-SCREEN study (UMIN 000036749) between August 2019 and February 2022, a national observational ctDNA-based screening study, and performed ctDNA sequencing before and at the time of resistance to systemic therapy. Results: ctDNA were assessed in 178 samples containing 432 mutations. The most frequently altered genes at baseline were VHL (25.0%), PBRM1 (10.9%), TERT2 (8.7%), BAP1 (8.7%), and MTOR (7.6%). Patients receiving first-line therapy with tumor fraction (TF) < 1.2% showed significantly better progression-free survival than those with TF ≥ 1.2% (Hazard ratio (HR) = 0.467; 95% CI 0.229–0.979; p = 0.0425). BAP1 mutational status of ctDNA at baseline led to poor OS (HR = 0.4867; 95% CI 0.322–0.736; p = 0.0003). Serial ctDNA analysis showed that 46.8% of patients developed new ctDNA mutations at disease progression, which was linked to shorter time to progression (p = 0.046). Conclusions: Our findings demonstrated that ctDNA profiling is feasible in mRCC and can predict disease progression after treatment

Authors: Kato, T; Shiota, M; Nishimoto, K; Matsubara, N; Osawa, T

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature [academic journals on nature.com]
• Journal: British Journal of Cancer
• Volume: 133
• Issue: 1
• Pages: 111-120
• Publication date: 2025-05-05
• DOI: 10.1038/s41416-025-02985-8
• EISSN: 1532-1827
• ISSN: 0007-0920
• Language: English
• Keywords: Internal medicine; Liquid biopsy; Medicine; Overall survival; Renal cell carcinoma; Oncology; Confidence interval; Cancer; BAP1; Hazard ratio; Progression-free survival