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.
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.
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).
Our findings demonstrated that ctDNA profiling is feasible in mRCC and can predict disease progression after treatment.
British journal of cancer. 2025 May 05 [Epub ahead of print]
Taigo Kato, Masaki Shiota, Koshiro Nishimoto, Nobuaki Matsubara, Takahiro Osawa, Takashige Abe, Yota Yasumizu, Nobuyuki Tanaka, Yoshiyuki Yamamoto, Yu Ishizuya, Hikaru Abutani, Hideaki Bando, Takao Fujisawa, Yoshiaki Nakamura, Mototsugu Oya, Nobuo Shinohara, Masatoshi Eto, Takayuki Yoshino, Norio Nonomura
Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan. ., Department of Urology, Kyushu University Graduate School of Medical Science, Fukuoka, Japan., Department of Uro-Oncology, Saitama Medical University International Medical Center, Saitama, Japan., Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan., Department of Urology, Keio University School of Medicine, Tokyo, Japan., Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan., Chugai Pharmaceutical Co., Ltd, Tokyo, Japan., Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.