Skip to main content
Top
Published in: Abdominal Radiology 10/2020

01-10-2020 | Kidney Cancer | Kidneys, Ureters, Bladder, Retroperitoneum

Association of tumor grade, enhancement on multiphasic CT and microvessel density in patients with clear cell renal cell carcinoma

Authors: Heidi Coy, Jonathan R. Young, Allan J. Pantuck, Michael L. Douek, Anthony Sisk, Clara Magyar, Matthew S. Brown, James Sayre, Steven S. Raman

Published in: Abdominal Radiology | Issue 10/2020

Login to get access

Abstract

Purpose

Clear cell renal cell carcinoma (ccRCC) comprises nearly 90% of all diagnosed RCC subtypes and has the worst prognosis and highest metastatic potential. The strongest prognostic factors for patients with ccRCC include histological subtype and Fuhrman grade, which are incorporated into prognostic models. Since ccRCC is a highly vascularized tumor, there may be differences in enhancement patterns on multidetector CT (MDCT) due to the hemodynamics and microvessel density (MVD) of the lesions. This may provide a noninvasive method to characterize incidentally detected low- and high-grade ccRCCs on MDCT. The purpose of our study was to determine the correlation between MDCT enhancement parameters, ccRCC MVD, and Fuhrman grade to determine its utility and value in assessing tumor vascularity and grade in vivo.

Methods

In this retrospective, HIPAA-compliant, institutional review board-approved study with waiver of informed consent, 127 consecutive patients with 89 low-grade (LG), and 43 high-grade (HG) ccRCCs underwent preoperative four-phase MDCT. A 3D volume of interest (VOI) was obtained for every tumor and absolute enhancement and the wash-in/wash-out of enhancement for each phase was assessed. Immunohistochemistry on resected specimens was used to quantify MVD. Linear regression and Pearson correlation were used to investigate the strength of the association between 3D VOI enhancement and MVD. Stepwise logistic regression analysis determined independent predictors of HG ccRCC. Cut-off values and odds Ratio (OR) with 95% CIs were reported. The clinical, radiomic, and pathologic features with the highest performance in the stepwise logistic regression analysis were evaluated using receiver operator characteristics (ROC) and area under the curve (AUC).

Results

Absolute enhancement in the nephrographic phase < 52.1 Hounsfield Units (HU) (HR 0.979, 95% CI 0.964–0.994, p value = 0.006), lesion size > 4.3 cm (HR 1.450, 95% CI 1.211–1.738, p value < 0.001), and an intratumoral MVD < 15% (HR 0.932, 95% CI 0.867–1.002, p value = 0.058) were independent predictors of HG ccRCC with an AUC of 0.818 (95% CI 0.725–0.911). HG ccRCCs had a significant association between 3D VOI enhancement and MVD in each post-contrast phase (r2 = 0.238 to 0.455, p < 0.05).

Conclusions

Absolute enhancement of the entire lesion obtained from a 3D VOI in the nephrographic phase on preoperative MDCT can provide quantitative data that are a significant, independent predictor of a high-grade clear cell RCC and can be used to assess tumor vascularity and grade in vivo.
Literature
1.
go back to reference Capitanio U, Bensalah K, Bex A, et al. Epidemiology of Renal Cell Carcinoma. European Urology 2019; 75(1): 74-84.CrossRef Capitanio U, Bensalah K, Bex A, et al. Epidemiology of Renal Cell Carcinoma. European Urology 2019; 75(1): 74-84.CrossRef
3.
go back to reference Sun M, Shariat SF, Cheng C, et al. Prognostic factors and predictive models in renal cell carcinoma: a contemporary review. European Urology 2011; 60(4): 644-661.CrossRef Sun M, Shariat SF, Cheng C, et al. Prognostic factors and predictive models in renal cell carcinoma: a contemporary review. European Urology 2011; 60(4): 644-661.CrossRef
4.
go back to reference Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982 Oct; 6(7):655-63.CrossRef Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982 Oct; 6(7):655-63.CrossRef
5.
go back to reference Patard JJ, Kim HL, Lam JS, et al. Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study. J Clin Oncol 2004; 22(16): 3316-22.CrossRef Patard JJ, Kim HL, Lam JS, et al. Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study. J Clin Oncol 2004; 22(16): 3316-22.CrossRef
6.
go back to reference Silverman SG, Israel GM, Trinh QD. Incompletely characterized incidental renal masses: emerging data support conservative management. Radiology 2015 Apr; 275(1):28-42.CrossRef Silverman SG, Israel GM, Trinh QD. Incompletely characterized incidental renal masses: emerging data support conservative management. Radiology 2015 Apr; 275(1):28-42.CrossRef
7.
go back to reference Coy H, Young JR, Douek M, et al. Association of qualitative and quantitative imaging features on multiphasic multidetector CT with tumor grade in clear cell renal cell carcinoma. Abdominal Radiology 2019;44(1):180–189.CrossRef Coy H, Young JR, Douek M, et al. Association of qualitative and quantitative imaging features on multiphasic multidetector CT with tumor grade in clear cell renal cell carcinoma. Abdominal Radiology ​2019;44(1):180–189.​CrossRef
8.
go back to reference Young JR, Margolis D, Sauk S, Pantuck AJ, Sayre J, Raman SS. Clear cell renal cell carcinoma: discrimination from other renal cell carcinoma subtypes and oncocytoma at multiphasic multidector CT. Radiology 2013; 267(2): 444-453.CrossRef Young JR, Margolis D, Sauk S, Pantuck AJ, Sayre J, Raman SS. Clear cell renal cell carcinoma: discrimination from other renal cell carcinoma subtypes and oncocytoma at multiphasic multidector CT. Radiology 2013; 267(2): 444-453.CrossRef
9.
go back to reference Vargas H, Delany H, Delappe E, et al. Multiphasic Contrast-Enhanced MRI: Single-Slice Versus Volumetric Quantification of Tumor Enhancement for Assessment of Renal Clear-Cell Carcinoma Fuhrman Grade. Journal of Magnetic Resonance Imaging 2013; 37: 1160-1167.CrossRef Vargas H, Delany H, Delappe E, et al. Multiphasic Contrast-Enhanced MRI: Single-Slice Versus Volumetric Quantification of Tumor Enhancement for Assessment of Renal Clear-Cell Carcinoma Fuhrman Grade. Journal of Magnetic Resonance Imaging 2013; 37: 1160-1167.CrossRef
10.
go back to reference Young JR, Coy H, Kim HJ, et al. Utility of multiphasic multidetector computed tomography in discriminating between clear cell renal cell carcinomas with high and low carbonic anhydrase-IX expression. Abdominal Radiology 2018; 43(10): 2734-2742.CrossRef Young JR, Coy H, Kim HJ, et al. Utility of multiphasic multidetector computed tomography in discriminating between clear cell renal cell carcinomas with high and low carbonic anhydrase-IX expression. Abdominal Radiology 2018; 43(10): 2734-2742.CrossRef
11.
go back to reference Gerlinger, Rowan, Horswell S, et al. Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing. New England Journal of Medicine 2012; 366(10) 883-92. Gerlinger, Rowan, Horswell S, et al. Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing. New England Journal of Medicine 2012; 366(10) 883-92.
12.
go back to reference Jamshidi N, Jonasch E, Zapala M, et al. The Radiogenomic Risk Score: Construction of a Prognostic Quantitative, Noninvasive Image-based Molecular Assay for Renal Cell Carcinoma. Radiology 2015; 277:114-123.CrossRef Jamshidi N, Jonasch E, Zapala M, et al. The Radiogenomic Risk Score: Construction of a Prognostic Quantitative, Noninvasive Image-based Molecular Assay for Renal Cell Carcinoma. Radiology 2015; 277:114-123.CrossRef
13.
go back to reference Lubner M, Stabo N, Abel EJ, Munoz del Rio A, Pickhardt P. CT Textural Analysis of Large Primary Renal Cell Carcinomas: Pretreatment Tumor Heterogeneity Correlates With Histologic Findings and Clinical Outcomes. AJR 2016; 207: 96-105. Lubner M, Stabo N, Abel EJ, Munoz del Rio A, Pickhardt P. CT Textural Analysis of Large Primary Renal Cell Carcinomas: Pretreatment Tumor Heterogeneity Correlates With Histologic Findings and Clinical Outcomes. AJR 2016; 207: 96-105.
15.
go back to reference Coy H, Young JR, Douek M, et al. Quantitative computer-aided diagnostic algorithm for automated detection of peak lesion attenuation in differentiating clear cell from papillary and chromophobe renal cell carcinoma, oncocytoma, and fat-poor amgiomyolipoma on multiphasic multidetector computed tomography. Abdom Radiol 2017; 42(7): 1919-1928.CrossRef Coy H, Young JR, Douek M, et al. Quantitative computer-aided diagnostic algorithm for automated detection of peak lesion attenuation in differentiating clear cell from papillary and chromophobe renal cell carcinoma, oncocytoma, and fat-poor amgiomyolipoma on multiphasic multidetector computed tomography. Abdom Radiol 2017; 42(7): 1919-1928.CrossRef
16.
go back to reference Zhu YH, Wang X, Zhang J, et al. Low enhancement on multiphase contrast-enhanced CT images: an independent predictor of the presence of high grade tumor of clear cell renal cell carcinoma. Am J Roentgenol 2014; 203: W295-W300.CrossRef Zhu YH, Wang X, Zhang J, et al. Low enhancement on multiphase contrast-enhanced CT images: an independent predictor of the presence of high grade tumor of clear cell renal cell carcinoma. Am J Roentgenol 2014; 203: W295-W300.CrossRef
17.
go back to reference Huhdanpaa H, Hwang D, Cen S, et al. CT prediction of the Fuhrman grade of clear cell renal cell carcinoma (RCC): towards the development of computer-assisted diagnostic method. Abdom Imaging 2015; 40(8): 3168-74.CrossRef Huhdanpaa H, Hwang D, Cen S, et al. CT prediction of the Fuhrman grade of clear cell renal cell carcinoma (RCC): towards the development of computer-assisted diagnostic method. Abdom Imaging 2015; 40(8): 3168-74.CrossRef
18.
go back to reference Kopp RP, Aganovic L, Palazzi KL, Cassidy FH, Sakamoto K, Derweesh IH. Differentiation of clear from non-clear cell renal cell carcinoma using CT washout formula. Can J Urol 2013 Jun; 20 (3): 6790-7.PubMed Kopp RP, Aganovic L, Palazzi KL, Cassidy FH, Sakamoto K, Derweesh IH. Differentiation of clear from non-clear cell renal cell carcinoma using CT washout formula. Can J Urol 2013 Jun; 20 (3): 6790-7.PubMed
19.
go back to reference Wang JH, Min PQ, Wang PJ, et al. Dynamic CT Evaluation of Tumor Vascularity in Renal Cell Carcinoma. AJR 2006; 186:1423-1430.CrossRef Wang JH, Min PQ, Wang PJ, et al. Dynamic CT Evaluation of Tumor Vascularity in Renal Cell Carcinoma. AJR 2006; 186:1423-1430.CrossRef
20.
go back to reference Reiner C, Roessle M, Thiesler T, et al. Computed Tomography Perfusion Imaging of Renal Cell Carcinoma. Invest Radiol 2013; 48: 183-191.CrossRef Reiner C, Roessle M, Thiesler T, et al. Computed Tomography Perfusion Imaging of Renal Cell Carcinoma. Invest Radiol 2013; 48: 183-191.CrossRef
21.
go back to reference Jinzaki M, Tanimoto A, Mukai M et al. Double-Phase Helical CT of Small Renal Parenchymal Neoplasms: Correlation with Pathologic Findings and Tumor Angiogenesis. Journal of Computer Assisted Tomography 2000; 24(6): 835-842.CrossRef Jinzaki M, Tanimoto A, Mukai M et al. Double-Phase Helical CT of Small Renal Parenchymal Neoplasms: Correlation with Pathologic Findings and Tumor Angiogenesis. Journal of Computer Assisted Tomography 2000; 24(6): 835-842.CrossRef
22.
go back to reference Villalobos-Gollas M, Aguilar-Davidov B, Culebro-Garcia C, et al. Pathological implications of areas of lower enhancement on contrast-enhanced computed tomography in renal cell carcinoma: additional information for selecting candidates for surveillance protocols. In Urol Nephrol 2012; 44: 1369-1374.CrossRef Villalobos-Gollas M, Aguilar-Davidov B, Culebro-Garcia C, et al. Pathological implications of areas of lower enhancement on contrast-enhanced computed tomography in renal cell carcinoma: additional information for selecting candidates for surveillance protocols. In Urol Nephrol 2012; 44: 1369-1374.CrossRef
23.
go back to reference Yuan Q, Kapur P, Zhang Y. Intratumor Heterogeneity of Perfusion and Diffusion in Clear-Cell Renal Cell Carcinoma: Correlation With Tumor Cellularity. Clinical Genitourinary Cancer 2016; 14(6) e585-94.CrossRef Yuan Q, Kapur P, Zhang Y. Intratumor Heterogeneity of Perfusion and Diffusion in Clear-Cell Renal Cell Carcinoma: Correlation With Tumor Cellularity. Clinical Genitourinary Cancer 2016; 14(6) e585-94.CrossRef
24.
go back to reference Shinagare A, Krajewski K, Braschi-Amirfarzan M, Ramaiya N. Advanced Renal Cell Carcinoma: Role of the Radiologist in the Era of Precision Medicine. Radiology 2017; 284(2): 333-351.CrossRef Shinagare A, Krajewski K, Braschi-Amirfarzan M, Ramaiya N. Advanced Renal Cell Carcinoma: Role of the Radiologist in the Era of Precision Medicine. Radiology 2017; 284(2): 333-351.CrossRef
25.
go back to reference Hlatky L, Hahnfeldt P, Folkman J. Clinical Application of Antiangiogenic Therapy: Microvessel Density, What it Does and Doesn’t Tell Us. Journal of the National Cancer Institute 2002; 94 (12): 883-893.CrossRef Hlatky L, Hahnfeldt P, Folkman J. Clinical Application of Antiangiogenic Therapy: Microvessel Density, What it Does and Doesn’t Tell Us. Journal of the National Cancer Institute 2002; 94 (12): 883-893.CrossRef
26.
go back to reference Jilaveanu L, Puligandla M, Weiss S, et al. Tumor Microvessel Density as a Prognostic Marker in High-Risk Renal Cell Carcinoma Patients Treated on ECOG-ACRIN E2805. Clinical Cancer Research 2018; 24(1): 217-223.CrossRef Jilaveanu L, Puligandla M, Weiss S, et al. Tumor Microvessel Density as a Prognostic Marker in High-Risk Renal Cell Carcinoma Patients Treated on ECOG-ACRIN E2805. Clinical Cancer Research 2018; 24(1): 217-223.CrossRef
27.
go back to reference Frank I, Blute ML, Cheville JC, Lohse CM, Weaver AL, Zincke H. An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. J Urol. 2002 Dec; 168(6):2395-400.CrossRef Frank I, Blute ML, Cheville JC, Lohse CM, Weaver AL, Zincke H. An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. J Urol. 2002 Dec; 168(6):2395-400.CrossRef
28.
go back to reference Leibovich BC, Blute ML, Cheville JC, Lohse CM, Frank I, Kwon ED, Weaver AL, Parker AS, Zincke H. Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma: a stratification tool for prospective clinical trials. Cancer. 2003 Apr 1; 97(7):1663-71.CrossRef Leibovich BC, Blute ML, Cheville JC, Lohse CM, Frank I, Kwon ED, Weaver AL, Parker AS, Zincke H. Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma: a stratification tool for prospective clinical trials. Cancer. 2003 Apr 1; 97(7):1663-71.CrossRef
29.
go back to reference Sahni VA, Silverman SG. Imaging management of incidentally detected small renal masses. Semin Intervent Radiol. 2014 Mar; 31(1):9-19.CrossRef Sahni VA, Silverman SG. Imaging management of incidentally detected small renal masses. Semin Intervent Radiol. 2014 Mar; 31(1):9-19.CrossRef
30.
go back to reference Sun M, Lughezani G, Jeldres C et al. A proposal for reclassification of the Fuhrman grading system in patients with clear cell renal cell carcinoma. Eur Urol 2009; 56: 775-781.CrossRef Sun M, Lughezani G, Jeldres C et al. A proposal for reclassification of the Fuhrman grading system in patients with clear cell renal cell carcinoma. Eur Urol 2009; 56: 775-781.CrossRef
31.
go back to reference Ouyang A, Wei Z, Su X, et al. Relative Computed Tomography (CT) Enhancement Value for the Assessment of Microvascular Architecture in Renal Cell Carcinoma. Med Sci Monit 2017; 23: 3706-3714.CrossRef Ouyang A, Wei Z, Su X, et al. Relative Computed Tomography (CT) Enhancement Value for the Assessment of Microvascular Architecture in Renal Cell Carcinoma. Med Sci Monit 2017; 23: 3706-3714.CrossRef
32.
go back to reference Jeswani T, Padhani. Imaging tumor angiogenesis. Cancer Imaging 2005; 5(1): 31-138. Jeswani T, Padhani. Imaging tumor angiogenesis. Cancer Imaging 2005; 5(1): 31-138.
33.
go back to reference Garcia-Figueiras R, Padhani AR, Beer AJ, et al. Imaging of Tumor Angiogenesis for Radiologists-Part 1: Biological and Technical Basis. Curr Probl Diagn Radiol 2015; 44(5): 407-24.CrossRef Garcia-Figueiras R, Padhani AR, Beer AJ, et al. Imaging of Tumor Angiogenesis for Radiologists-Part 1: Biological and Technical Basis. Curr Probl Diagn Radiol 2015; 44(5): 407-24.CrossRef
34.
go back to reference Ganeshan B, Miles K. Quantifying tumour heterogeneity with CT. Cancer Imaging 2013; 13(1): 140-149.CrossRef Ganeshan B, Miles K. Quantifying tumour heterogeneity with CT. Cancer Imaging 2013; 13(1): 140-149.CrossRef
35.
go back to reference Qian C, Huang D, Wondergem B, Teh B. Complexity of Tumor Vasculature in Clear Cell Renal Cell Carcinoma 2009; 115(10 Suppl): 2282-9. Qian C, Huang D, Wondergem B, Teh B. Complexity of Tumor Vasculature in Clear Cell Renal Cell Carcinoma 2009; 115(10 Suppl): 2282-9.
36.
go back to reference Cuenod C, Balvay D. Perfusion and vascular permeability: Basic concepts and measurement in DCE-CT and DCE-MRI. Diagnostic and Interventional Imaging 2013; 94: 1187-1204.CrossRef Cuenod C, Balvay D. Perfusion and vascular permeability: Basic concepts and measurement in DCE-CT and DCE-MRI. Diagnostic and Interventional Imaging 2013; 94: 1187-1204.CrossRef
Metadata
Title
Association of tumor grade, enhancement on multiphasic CT and microvessel density in patients with clear cell renal cell carcinoma
Authors
Heidi Coy
Jonathan R. Young
Allan J. Pantuck
Michael L. Douek
Anthony Sisk
Clara Magyar
Matthew S. Brown
James Sayre
Steven S. Raman
Publication date
01-10-2020
Publisher
Springer US
Published in
Abdominal Radiology / Issue 10/2020
Print ISSN: 2366-004X
Electronic ISSN: 2366-0058
DOI
https://doi.org/10.1007/s00261-019-02271-1

Other articles of this Issue 10/2020

Abdominal Radiology 10/2020 Go to the issue

Classics in Abdominal Radiology

“Corn-on-the-cob” sign

Classics in Abdominal Radiology

Fountain sign