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Background <p>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.</p> Methods <p>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.</p> Results <p>ctDNA were assessed in 178 samples containing 432 mutations. The most frequently altered genes at baseline were <i>VHL</i> (25.0%), <i>PBRM1</i> (10.9%), <i>TERT2</i> (8.7%), <i>BAP1</i> (8.7%), and <i>MTOR</i> (7.6%). Patients receiving first-line therapy with tumor fraction (TF) &lt; 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; <i>p </i>= 0.0425). <i>BAP1</i> mutational status of ctDNA at baseline led to poor OS (HR = 0.4867; 95% CI 0.322–0.736; <i>p </i>= 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 (<i>p </i>= 0.046).</p> Conclusions <p>Our findings demonstrated that ctDNA profiling is feasible in mRCC and can predict disease progression after treatment.</p>

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

  • 期刊论文

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  • 发表日期：

    2025年5月5日

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  • 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

摘要

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.