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

Kato, Taigo; Shiota, Masaki; Nishimoto, Koshiro; Matsubara, Nobuaki; Osawa, Takahiro; Abe, Takashige; Yasumizu, Yota; Tanaka, Nobuyuki; Yamamoto, Yoshiyuki; Ishizuya, Yu; Abutani, Hikaru; Bando, Hideaki; Fujisawa, Takao; Nakamura, Yoshiaki; Oya, Mototsugu; Shinohara, Nobuo; Eto, Masatoshi; Yoshino, Takayuki; Nonomura, Norio

doi:https://doi.org/10.1038/s41416-025-02985-8

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

Kato, Taigo; Shiota, Masaki; Nishimoto, Koshiro et al.

British Journal of Cancer, 2025, e2200653

Number of Access:163（2025-10-12 17:10 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/102248

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Title	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
Creator	NRID 1000070648021 1000070648021 researchmap permalink taigokato taigokato Scopus Author ID 55414697500 55414697500 ORCID 0000-0002-8681-1407 0000-0002-8681-1407 CreatorName Kato, Taigo
	NRID 1000020635445 1000020635445 CreatorName Shiota, Masaki
	NRID 1000000365363 1000000365363 CreatorName Nishimoto, Koshiro
	CreatorName Matsubara, Nobuaki
	NRID 1000060374443 1000060374443 CreatorName Osawa, Takahiro
	NRID 1000010399842 1000010399842 CreatorName Abe, Takashige
	NRID 1000040464854 1000040464854 CreatorName Yasumizu, Yota
	NRID 1000060445244 1000060445244 CreatorName Tanaka, Nobuyuki
	NRID 1000090759557 1000090759557 researchmap permalink yoshi229 yoshi229 ORCID 0000-0002-1271-3521 0000-0002-1271-3521 CreatorName Yamamoto, Yoshiyuki
	NRID 1000000783854 1000000783854 researchmap permalink okiishi okiishi CreatorName Ishizuya, Yu
	CreatorName Abutani, Hikaru
	NRID 1000000630948 1000000630948 CreatorName Bando, Hideaki
	CreatorName Fujisawa, Takao
	NRID 1000060776384 1000060776384 CreatorName Nakamura, Yoshiaki
	NRID 1000000213885 1000000213885 CreatorName Oya, Mototsugu
	NRID 1000090250422 1000090250422 CreatorName Shinohara, Nobuo
	NRID 1000090315078 1000090315078 CreatorName Eto, Masatoshi
	NRID 1000020469969 1000020469969 CreatorName Yoshino, Takayuki
	NRID 1000030263263 1000030263263 researchmap permalink read0185096 read0185096 Scopus Author ID 7005880662 7005880662 CreatorName Nonomura, Norio
Description	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.
Abstract	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.
Publisher	Springer Nature
Source Title	British Journal of Cancer
Page	e2200653
Date of Issued	2025-05-05
Language	English
Handle URL	https://hdl.handle.net/11094/102248
PISSN	00070920
eISSN	15321827
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41416-025-02985-8
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	British Journal of Cancer. 2025, p. e2200653
DC.title	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
DC.creator	Kato, Taigo
	Shiota, Masaki
	Nishimoto, Koshiro
	Matsubara, Nobuaki
	Osawa, Takahiro
	Abe, Takashige
	Yasumizu, Yota
	Tanaka, Nobuyuki
	Yamamoto, Yoshiyuki
	Ishizuya, Yu
	Abutani, Hikaru
	Bando, Hideaki
	Fujisawa, Takao
	Nakamura, Yoshiaki
	Oya, Mototsugu
	Shinohara, Nobuo
	Eto, Masatoshi
	Yoshino, Takayuki
	Nonomura, Norio
DC.publisher	Springer Nature
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-05-05
DC.identifier	https://doi.org/10.1038/s41416-025-02985-8
DC.description	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.
DCTERMS.abstract	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.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	102248
citation_title	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
citation_author	Kato, Taigo
	Shiota, Masaki
	Nishimoto, Koshiro
	Matsubara, Nobuaki
	Osawa, Takahiro
	Abe, Takashige
	Yasumizu, Yota
	Tanaka, Nobuyuki
	Yamamoto, Yoshiyuki
	Ishizuya, Yu
	Abutani, Hikaru
	Bando, Hideaki
	Fujisawa, Takao
	Nakamura, Yoshiaki
	Oya, Mototsugu
	Shinohara, Nobuo
	Eto, Masatoshi
	Yoshino, Takayuki
	Nonomura, Norio
citation_publisher	Springer Nature
citation_language	English
citation_date	2025-05-05
citation_journal_title	British Journal of Cancer
citation_firstpage	e2200653
citation_doi	https://doi.org/10.1038/s41416-025-02985-8
citation_public_url	https://hdl.handle.net/11094/102248

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

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