Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Nov;39(11):791.e17-791.e24.
doi: 10.1016/j.urolonc.2021.08.018. Epub 2021 Sep 25.

Somatic mutations as preoperative predictors of metastases in patients with localized clear cell renal cell carcinoma - An exploratory analysis

Roy Mano  1 , Cihan Duzgol  2 , Maz Ganat  3 , Debra A Goldman  4 , Kyle A Blum  5 , Andrew W Silagy  6 , Aleksandra Walasek  7 , Alejandro Sanchez  8 , Renzo G DiNatale  7 , Julian Marcon  9 , Mahyar Kashan  10 , Maria F Becerra  11 , Nicole E Benfante  7 , Jonathan A Coleman  7 , Michael W Kattan  12 , Paul Russo  7 , Oguz Akin  2 , Irina Ostrovnaya  4 , A Ari Hakimi  13
Affiliations

Somatic mutations as preoperative predictors of metastases in patients with localized clear cell renal cell carcinoma - An exploratory analysis

Roy Mano et al. Urol Oncol. 2021 Nov.

Abstract

Objective: Recurrent 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 methods: After 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).

Results: The 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).

Conclusion: In 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.

Keywords: Gene mutation; Metastases; Outcome; Renal cell carcinoma.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest and disclosure Oguz Akin holds stock options and serves as a scientific advisor for Ezra AI, Inc., which is developing Artificial Intelligence algorithms and software unrelated to the research being reported.

Figures

Figure 1 –
Figure 1 –
Flow-chart of patients selected for the study cohort
Figure 2 –
Figure 2 –
Gene heatmap with mutation frequency among the cohort of clear cell renal cell carcinoma patients who underwent genetic sequencing of their primary renal tumor (n=254)
Figure 3 –
Figure 3 –
Time-dependent ROC curves for metastasis-free probability for patients with clear cell renal tumors and genetic data (n=254) when accounting for (A) the linear predictor alone, and (B) the linear predictor + genetic information. The diagonal line in each of the plots corresponds to random classification. The corresponding AUCs are listed under each plot
See this image and copyright information in PMC

Comment in

References

    1. Herts BR, Baker ME. The current role of percutaneous biopsy in the evaluation of renal masses. Seminars in urologic oncology. 1995;13:254–61. - PubMed
    1. Marconi L, Dabestani S, Lam TB, Hofmann F, Stewart F, Norrie J, et al. Systematic Review and Meta-analysis of Diagnostic Accuracy of Percutaneous Renal Tumour Biopsy. European urology. 2016;69:660–73. - PubMed
    1. Gellert LL, Mehra R, Chen YB, Gopalan A, Fine SW, Al-Ahmadie H, et al. The diagnostic accuracy of percutaneous renal needle core biopsy and its potential impact on the clinical management of renal cortical neoplasms. Archives of pathology & laboratory medicine. 2014;138:1673–9. - PubMed
    1. Richard PO, Jewett MA, Bhatt JR, Kachura JR, Evans AJ, Zlotta AR, et al. Renal Tumor Biopsy for Small Renal Masses: A Single-center 13-year Experience. European urology. 2015;68:1007–13. - PubMed
    1. Richard PO, Jewett MA, Tanguay S, Saarela O, Liu ZA, Pouliot F, et al. Safety, reliability and accuracy of small renal tumour biopsies: results from a multi-institution registry. BJU international. 2017;119:543–9. - PubMed

Publication types