ArticleUrologic oncology2021
Somatic mutations as preoperative predictors of metastases in patients with localized clear cell renal cell carcinoma - An exploratory analysis.
Article in Urologic oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 9 citations in OpenAlex.
- A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170).Cancer research communications · 2024Trial
- Article
- Genomic analysis of small renal masses reveals mutations linked with renal cell carcinoma and fast-growing tumors.Journal of cancer research and clinical oncology · 2025Article
- A Scoping Review of Population Diversity in the Common Genomic Aberrations of Clear Cell Renal Cell Carcinoma.Oncology · 2025Article
- Zebularine showed anti-tumor efficacy in clear cell renal cell carcinoma.Frontiers in pharmacology · 2025Article
- Adjuvant therapy in renal cell carcinoma (RCC): progress, at last.Translational cancer research · 2024Review
- Established and emerging biomarkers of immunotherapy in renal cell carcinoma.Immunotherapy · 2024Review
- Revealing the characteristics of SETD2-mutated clear cell renal cell carcinoma through tumor heterogeneity analysis.Frontiers in genetics · 2024Article
- Current Landscape of Genomic Biomarkers in Clear Cell Renal Cell Carcinoma.European urology · 2023Review
- Prognostic and predictive biomarkers for immunotherapy in advanced renal cell carcinoma.Nature reviews. Urology · 2023Review
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19 authors at 2 institutions in 4 countries.
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Abstract
objectiveRecurrent genomic alterations in clear cell renal cell carcinoma (ccRCC) have been associated with treatment outcomes; however, current preoperative predictive models do not include known genetic predictors. We aimed to explore the value of common somatic mutations in the preoperative prediction of metastatic disease among patients treated for localized ccRCC. MATERIALS AND
methodsAfter obtaining institutional review board approval, data of 254 patients with localized ccRCC treated between 2005 and 2015 who underwent genetic sequencing was collected. The mutation status of VHL, PBRM1, SETD2, BAP1 and KDM5C were evaluated in the nephrectomy tumor specimen, which served as a proxy for biopsy mutation status. The Raj et al. preoperative nomogram was used to predict the 12-year metastatic free probability (MFP). The study outcome was MFP; the relationship between MFP and mutation status was evaluated with Cox-regression models adjusting for the preoperative nomogram variables (age, gender, incidental presentation, lymphadenopathy, necrosis, and size).
resultsThe study cohort included 188 males (74%) and 66 females (26%) with a median age of 58 years. VHL mutations were present in 152/254 patients (60%), PBRM1 in 91/254 (36%), SETD2 in 32/254 (13%), BAP1 in 19/254 (8%), and KDM5C in 19/254 (8%). Median follow-up for survivors was 8.1 years. Estimated 12-year MFP was 70% (95% CI: 63%-75%). On univariable analysis SETD2 (HR: 3.30), BAP1 (HR: 2.44) and PBRM1 (HR: 1.78) were significantly associated with a higher risk of metastases. After adjusting for known preoperative predictors in the existing nomogram, SETD2 mutations remained associated with a higher rate of metastases after nephrectomy (HR: 2.09, 95% CI: 1.19-3.67, P = 0.011).
conclusionIn the current exploratory analysis, SETD2 mutations were significant predictors of MFP among patients treated for localized ccRCC. Our findings support future studies evaluating genetic alterations in preoperative renal biopsy samples as potential predictors of treatment outcome.
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