










































This is an open access article under the terms of a license that permits non-commercial use, provided the original work is properly cited.  
© 2022 The Authors. Société Internationale d'Urologie Journal, published by the Société Internationale d'Urologie, Canada.

Key Words Competing Interests Article Information

Renal cell carcinoma, ultrasound, computed 
tomography, magnetic resonance imaging, 
positron emission tomography

None declared. Received on July 15, 2022 
Accepted on August 31, 2022 
This article has been peer reviewed.

Soc Int Urol J. 2022;3(6):407–423

DOI: 10.48083/SDMV1045

2022 WUOF/SIU International Consultation on  
Urological Diseases: Imaging of Renal Cell Carcinoma

Wai-Kit Lee,1 M. Liza Lindenberg,2 Esther Mena Gonzalez,2 Peter Choyke,2 Kevin G. King,3 
Raghunandan Vikram,4 Vinay A. Duddalwar5

1 Department of Medical Imaging, St. Vincent's Health, University of Melbourne, Fitzroy, Australia 2 Molecular Imaging Branch, Center for Cancer Research, National 
Cancer Institute, NIH, Bethesda, United States 3 Keck School of Medicine of USC, University of Southern California, Los Angeles, United States 4 Department of 
Abdominal Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, United States 5 Keck School of Medicine of USC  
and USC Viterbi School of Engineering, University of Southern California, Los Angeles, United States

Abstract

Imaging plays a central role in the contemporary multidisciplinary management of renal cell carcinoma. This 
article provides an overview of the current imaging modalities, including ultrasound, computed tomography, 
multiparametric magnetic resonance imaging, and molecular imaging, used in the evaluation of renal cell carcinoma. 
A summary of the imaging strategies for renal cell carcinoma staging and restaging post-treatment is provided.

Introduction

Imaging allows for the detection, characterization, staging, treatment planning and guidance, post-treatment 
evaluation, and surveillance of renal cell carcinoma (RCC). An understanding of the advantages and limitations 
of each imaging modality, and the evolving role of imaging in newer management strategies (such as active 
surveillance, ablation, and embolization) and the utility of newer therapeutics (such as antiangiogenic treatments 
and immunotherapy) is critical. The purpose of this narrative review is to provide an overview of the current imaging 
modalities, such as ultrasound (US), multidetector computed tomography (CT), multiparametric magnetic resonance 
imaging (MRI), and molecular imaging, used in the evaluation of RCC; highlight newer imaging techniques, such as 
contrast-enhanced US (CEUS) and novel molecular imaging agents, as well as radiomics with artificial intelligence 
technology; and provide a summary of the imaging strategies for RCC staging and post-treatment restaging. Imaging 
findings following newer treatment techniques, such as ablation and systemic therapy for advanced RCC, are beyond 
the scope of this article.

Detection and Diagnosis
Clear cell renal cell carcinoma (ccRCC) (70%–80%), papillary renal cell carcinoma (pRCC) (10%–15%), and 
chromophobe renal cell carcinoma (chRCC) (5%) are the 3 most common histologic subtypes of RCC[1], which as a 
group show a broad spectrum of imaging appearances. Multiphase contrast-enhanced CT is the imaging modality 
most commonly used for the evaluation of RCC[2]. A systematic review found that the median sensitivity and 
specificity of CT for the diagnosis of RCC were 88% and 75%, respectively[3]. A limitation of CT is the necessity for 
intravenous contrast agent, which may be contraindicated owing to renal dysfunction or iodine allergy.

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Multiparametric MRI is frequently used to further 
characterize renal masses that are indeterminate on CT, 
but can be used as the initial study for the evaluation 
of renal masses, especially in patients with contraindi-
cation to iodinated contrast material[2]. A systematic 
review showed that the median sensitivity and specific-
ity of MR for the diagnosis of RCC were 87.5% and 89%, 
respectively[3]. A limitation of MRI is the contraindica-
tion of intravenous contrast in advanced renal disease 
owing to potential for nephrogenic systemic fibrosis.

Conventional US can be utilized to triage an indeter-
minate renal lesion incidentally detected at single-phase 
CT to determine whether it is a simple or minimally 
complex cyst or a solid lesion. A systematic review 
showed that the sensitivity and specificity of conven-
tional US for the diagnosis of RCC were 46% and 12%, 
respectively[3]. Limitations of conventional US include 
its reduced sensitivity for the detection of small renal 
masses and the inability to further characterize solid 
renal masses. CEUS is superior to CT and MRI for the 
evaluation of septa and mural enhancement in complex 
cystic renal lesions[4,5] (Figure 1), and its median sensi-
tivity and specificity for the diagnosis of RCC in these 
lesions were reported to be 94.5% and 69%, respec-
tively[3]. However, there is no current role for CEUS in 
the Bosniak classification scheme, but proposals for an 
adaptation of the scheme incorporating CEUS features 
have been suggested[6]. Suboptimal image acquisition 
owing to patient factors, such as obesity, inability to 
breath-hold, and acoustic shadowing from bowel gas or 
ribs, can limit the utility of CEUS.

18F-f luorodeox yglucose (FDG) positron emis-
sion tomography/computed tomography (PET/CT) 
is not recommended by major societies, including 

the American Urology Association (AUA), European 
Associat ion of Urolog y (E AU), a nd Nat iona l 
Comprehensive Cancer Network (NCCN), for the 
routine diagnosis or evaluation of RCC because the 
technique is limited by the physiologic excretion of 
radiotracer through the kidneys and the baseline FDG 
uptake in normal renal parenchyma, which can obscure 
part or all of the renal tumor[7–9]. Systematic reviews 
found that FDG PET/CT for RCC detection showed high 
specificity but variable sensitivity depending on the size, 
subtype, and grade of RCC[3,10].

Imaging Features of Common Subtypes  
of RCC
Clear Cell Renal Cell Carcinom
At US, ccRCC has variable appearances. It typically 
appe a rs a s a he terogene ou sly hy poechoic or 
isoechoic mass (Figure 2), but may show hyperechoic 
component s[11,12]. F lu id component s may be 
present due to cystic, necrotic, or hemorrhagic 
change. Doppler flow is readily identified owing to its 
hypervascular nature. At CEUS, ccRCC shows avid, 
early enhancement, followed by washout[13] (Figure 3). 
At CT and MRI, ccRCC is typically exophytic and shows 
vivid early contrast enhancement[14]. It has low-to-
intermediate T1 signal and high T2 signal compared 
to adjacent renal parenchyma[15]. Internal tumor 
heterogeneity can occur owing to areas of hemorrhage, 
necrosis, and/or cystic degeneration, which appear as 
nonenhancing regions[16]. ccRCC may show reduced 
signal on opposed-phase chemical shift MR images 
compared to in-phase images owing to intracellular 
fat[17]. A peritumoral pseudocapsule may be present, 
which appears as a regular low or high attenuation rim 
on CT[18], and low T1 and T2 signal on MR images[19]. 
Calcifications are uncommon[20] (Figures 4 and 5).

Papillary Renal Cell Carcinoma
At US, pRCC may appear as a solid, well-circumscribed 
mass (Figure 6), or sometimes may be partially solid 
with cystic or hemorrhagic components[11]. At CEUS, 
it shows hypoenhancement with a later and lower peak 
of enhancement compared to ccRCC[13] (Figure 7). 
At CT and MRI, pRCC is generally a small peripheral 
homogeneous mass that has low T2 signal compared 
to renal cortex, and shows weak enhancement that 
progressively increases on subsequent phases[21]. pRCC 
may show loss of signal on in-phase images compared 
to opposed phase at chemical shift MRI owing to 
hemosiderin[22]. Some pRCCs appear as hemorrhagic 
cystic masses with enhancing papillary projections[23]. 
Calcifications occur in 7% of cases[21] (Figures 8 and 9). 
Type 1 and 2 pRCCs cannot be reliably differentiated 
on imaging, but type 2 pRCCs are more likely to be 
heterogeneous, show infiltrative margins, and contain 
calcifications[24].

Abbreviations 
AML angiomyolipoma 
AUA American Urological Association
CAIX carbonic anhydrase IX
ccRCC clear cell renal cell carcinoma
CEUS contrast-enhanced US
chRCC chromophobe renal cell carcinoma
CT computed tomography
FDG 18F-fluorodeoxyglucose
MRI magnetic resonance imaging
PET/CT positron emission tomography/computed tomography
pRCC papillary renal cell carcinoma
PSMA prostate-specific membrane antigen
RCC renal cell carcinoma
SUVmax maximum standardized uptake value
US ultrasound

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FIGURE 1. 

Superior ability of CEUS to demonstrate septal enhancement

Contrast-enhanced CT (A) shows a large cystic lesion (arrows) centrally in the right kidney with several internal enhancing septations. CEUS (B) shows 
an even greater number of internal enhancing septations, and with superior detail. Postsurgical pathological evaluation confirmed a mixed epithelial and 
stromal tumor.

FIGURE 2. 

Clear cell renal cell carcinoma 

Chromophobe Renal Cell Carcinoma
At imaging, chRCC is typically a solid, well-circum-
scribed mass that is more homogeneous than ccRCC. 
At CEUS, its enhancement is often nearly isoenhancing 
to renal cortex and can be difficult to discriminate from 
ccRCC, especially with small tumors[13]. chRCC shows 
heterogeneous T2 signal on MRI[25]. At CT and MRI, it 

shows intermediate contrast enhancement in between 
that of ccRCC and pRCC[14,23]. A central scar, spoke-
wheel enhancement pattern and segmental enhancement 
inversion may be present, but these features overlap 
with oncocytoma[25–27]. Calcifications occur in 14% 
to 38% of cases, and perinephric infiltration and venous 
invasion are uncommon[20,26].

Greyscale ultrasound (A) shows a heterogeneous mass (arrows) with solid and cystic components, and color Doppler ultrasound (B) shows flow in the 
solid portion. Contrast-enha eterogeneous mass with avid enhancement.

A

A B C

B

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FIGURE 3. 

Clear cell renal cell carcinoma at CEUS

Corticomedullary phase (A) shows a heterogeneously hyperenhancing (relative to renal cortex) mass (arrows) exophytic from the right kidney (arrowheads). 
At delayed phase (B), the mass shows washout.

Axial unenhanced CT scan (A) shows an expansile mass involving the right kidney. Postcontrast axial CT in corticomedullary phase (B) shows heterogeneous 
and intense enhancement of the mass. Delayed-phase image (90 seconds) (C) shows contrast washout in the mass. This pattern of enhancement and 
contrast washout is typical of clear cell renal cell carcinoma.

FIGURE 4. 

Sixty-year-old male patient with typical features of clear cell renal cell carcinoma on CT 
 

A

A

B

B C

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FIGURE 5. 

Sixty-year-old male patient with typical features of clear cell renal cell carcinoma on MRI 
 

FIGURE 6. 

Papillary renal cell carcinoma 

Axial T2-weighted image (A) shows a right renal mass with heterogeneous high signal. Precontrast fat-suppressed T1-weighted image (B) shows a 
hypointense expansile central mass. Postcontrast T1-weighted image in corticomedullary phase (C) shows intense and heterogeneous enhancement  
of the mass. Diffusion-weighted image (b = 500) (D) and corresponding ADC map (E) show restricted diffusion in the mass.

Greyscale ultrasound (A) shows a small solid, well-circumscribed mass (arrows) that is isoechoic to mildly hyperechoic, and color Doppler ultrasound (B) 
shows internal flow.

A

D

B

E

C

D B

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FIGURE 7. 

Papillary renal cell carcinoma at CEUS 

FIGURE 8. 

Fifty-year-old male patient with an asymptomatic papillary renal cell carcinoma on CT  

Corticomedullary phase (A) shows only slight early enhancement of the mass (arrows), much less than adjacent cortex (arrowheads). The peak of 
enhancement is later, at nephrographic phase (B), but even at its peak, the mass is still slightly hypoenhancing (arrows) relative to the adjacent cortex 
(arrowheads).

Axial unenhanced (A), corticomedullary phase (B), and nephrographic phase (C) CT images show an expansile mass in the upper pole of the right kidney 
with low-grade enhancement. This appearance is commonly seen in type 1 papillary renal cell carcinoma.

A

A B
C

B

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FIGURE 9. 

Fifty-year-old male patient with an asymptomatic papillary renal cell carcinoma on MRI  

Axial T2-weighted image (A) shows an expansile partially exophytic mass in the upper pole of the right kidney with relative low signal compared to  
the renal cortex. Axial precontrast fat-suppressed T1-weighted image (B) and postcontrast fat-suppressed T1-weighted image in nephrographic phase  
(C) show relative hypoenhancement of the mass, compatible with papillary renal cell carcinoma. Diffusion-weighted image (b = 500) (D) and 
corresponding ADC map (E) show restricted diffusion in the mass.

D

A

E

B C

Differentiation of RCC from Benign Renal Tumors
Imaging is unable to reliably discriminate between 
benign and malignant renal masses owing to overlapping 
imaging characteristics in 10% to 15% of cases[28]. RCC 
can be challenging to differentiate from oncocytoma and 
lipid-poor angiomyolipoma (AML). However, composite 
imaging features can suggest a likely diagnosis. AML is a 
typically homogeneous and markedly hyperechoic mass 
on US, but up to 30% of small RCCs may be hyperechoic, 
and a definitive diagnosis of AML cannot be established 
on US appearances alone[12]. At CEUS, AML typically 
shows homogeneous hypoenhancement relative to 
renal parenchyma and can be difficult to distinguish 
from pRCC and chRCC[12,13]. Macroscopic fat within 
a noncalcified renal mass on CT is almost diagnostic 
of an AML. Macroscopic fat rarely occurs in RCC[29]. 
Intracellular fat can be identified in clear cell RCC but 
this feature in isolation does not allow its differentiation 
from lipid-poor AML[30]. A renal mass containing fat 
with calcification or one that shows necrosis is more 
likely to be an RCC than AML[23,29].

pRCC can be differentiated from a hemorrhagic cyst 
and lipid-poor AML because it shows weak progressive 

contrast enhancement. Hemorrhagic cyst shows no 
contrast enhancement[31], and lipid-poor AML shows 
avid early contrast enhancement with subsequent 
contrast washout[32].

chRCC and oncocytoma show multiple overlapping 
imaging features and are most challenging to differenti-
ate from each other[25,33]. At CEUS, oncocytoma typi-
cally shows hyperenhancement and can show persistent 
delayed enhancement, but the features are inadequate 
to allow for confident discrimination from chRCC[12]. 
Quantitative imaging parameters, such as tumor 
enhancement characteristics[34,35], diffusion-weighted 
MRI[36], and texture analysis[37], have shown some 
ability to differentiate between benign and malignant 
renal masses.

Differentiation of Subtypes of RCC
Imaging is as of yet unable to reliably differentiate 
between the subtypes of RCC owing to overlapping 
imaging characteristics. A study showed the perfor-
mance of CT to predict ccRCC and chRCC on morpho-
logic features alone had a positive predictive value 
of less than 75%, but evaluation of their contrast 

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enhancement profile allowed for differentiation of 
ccRCC from other subtypes with a sensitivity, specificity, 
and accuracy of 64%, 87%, and 75%, respectively[34]. 
Dynamic contrast-enhanced MRI studies found that 
RCC subtypes showed contrast enhancement profiles 
concordant with CT findings, but considerable overlap 
occurs and does not allow for definitive tumor histologic 
subtyping[14,35]. The application of algorithmic and 
scoring systems, such as the clear cell likelihood score, 
would help to achieve greater accuracy[38,39]. Type 
1 and 2 pRCCs show overlapping imaging findings 
that do not permit reliable differentiation between 
them on morphological features[14,24] or metabolic 
parameters[40,41]. Early dynamic imaging with FDG 
PET/CT may be more helpful than traditional static 
scanning in distinguishing aggressive RCC subtypes.  
A study showed that the maximum standardized uptake 
value (SUVmax) from dynamic scans was higher in 
ccRCC than non-ccRCC[42]. Another study showed 
that chRCC demonstrated lower SUVmax values than 
ccRCC and pRCC, but there was no significant difference 
between ccRCC and pRCC[43].

Grading of RCC
Nuclea r g rade of RCC correlates w it h pat ient 
survival[44]. Imaging features that act as accurate 
surrogate markers of histologic grade of RCC would 
allow for noninvasive prediction of prognosis and 
triage management. Most studies have attempted to 
differentiate between low- and high-Fuhrman grade 
ccRCC. One study showed that the sensitivity and 
specificity of MRI to diagnose low-grade ccRCC were 
50% and 94%, respectively, and to diagnose high-
grade ccRCC they were 93% and 75%, respectively[45]. 
Another study showed no significant correlation 
between histologic grade and MRI features for pRCC and 
chRCC[46]. Morphologic imaging features suggestive 
of higher grade tumor or sarcomatoid dedifferentiation 
include larger tumors with intratumoral necrosis, 
calcification, infiltrative margins, increased peritumoral 
neovascularity, larger peritumoral vessels, and renal vein 
thrombosis[45,47–48]. An uncommon predominantly 
cystic appearance of ccRCC has been shown to have 
low-grade malignant potential[49]. FDG PET/CT studies 
showed that higher SUVmax and tumor-to-normal 
reference tissue ratios corresponded to more aggressive 
RCC features, such as higher TNM stage and Fuhrman 
grade, as well as presence of venous and lymphatic 
invasion[42,43]. One FDG PET/CT study showed higher 
maximum, mean, and peak standardized uptake values 
in RCC with sarcomatoid differentiation compared 
to ccRCC[50]. Other metabolic measures, such as 
metabolic tumor volume and tumor-to-liver ratios, also 
appear to correlate with RCC grade[51,52]. Quantitative 
imaging parameters, such as tumor enhancement 
characteristics[53], diffusion-weighted MR imaging[54], 

and texture analysis[55,56], have shown some correlation 
with nuclear grading.

Staging
The 8th edition of American Joint Committee on 
Cancer TNM staging manual is the most commonly 
used staging system for RCC[57] (Table 1). The 
American College of Radiology appropriateness criteria 
recommend CT or MRI of the abdomen without and 
with contrast as the most appropriate imaging modalities 
to stage RCC[58]. CT and MRI have similar accuracy for 
the staging of the primary tumor[59,60]. However, CT is 
more commonly utilized owing to its ready availability 
and rapid acquisition time. MRI is generally utilized 
when iodinated contrast medium administration is 
contraindicated. US is generally considered inferior to 
CT or MRI in staging and post-treatment evaluation 
for RCC, but it has a role in select patients. CEUS can 
be helpful in certain situations if CT/MRI remains 
indeterminate, or if CT/MRI cannot be performed with 
contrast (Figure 10). CT chest is recommended at initial 
staging, as the lungs are the most common site of RCC 
metastases[8,61]. Targeted imaging should be considered 
in patients with organ-specific symptoms, such as 
MRI or CT of the brain in patients with neurological 
symptoms, or bone scintigraphy in patients with bone 
pain, elevated alkaline phosphatase, or radiographic 
f indings suggestive of bone metastases[61]. Bone 
metastases from RCC are typically lytic, and the poor 
osteoblastic response may limit the uptake of radiotracer 
at bone scintigraphy. One study of patients with stage IV 
RCC showed that the sensitivity of bone scintigraphy for 
the detection of osseous metastases was 29%[62].

Evaluation of Primary Tumor
Key imaging features of the primary tumor to be 
evaluated include the tumor’s size, location, degree 
of local invasion (into collecting system, perirenal 
fat, perirenal fascia, and adjacent organs), and renal 
vascular anatomy[63]. However, both CT and MRI 
may underestimate tumor size, as well as early urinary 
collecting system, renal sinus fat, and perinephric fat 
invasion, compared to pathologic examination, which 
may result in tumor upstaging[64–67].

Evaluation of Nodes and Distant Metastases
The most common sites of RCC metastases, in 
descending order of frequency, are the lungs, bones, 
liver, lymph nodes, adrenal glands, and brain[68,69]. 
However, metastases to any organ can occur. Cross-
sectional imaging criteria for the diagnosis of metastatic 
lymph nodes rely on size larger than 1 cm in short-axis 
diameter, abnormal shape, disruption of the normal 
lymph node architecture, and abnormal contrast 
enhancement characteristics mirroring those of the 
primary tumor[70]. The accuracy of CT and MRI for 

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FIGURE 10. 

Renal vein tumor invasion on CEUS 

Noncontrast CT (A) shows a left renal lower pole mass (arrow), and a more cranial image (B) shows expansion of the renal vein (arrowheads), concerning 
for tumor invasion or bland thrombus. Greyscale US (C) shows the mass (arrow) and the renal vein (arrowheads) to have similar echogenicity. CEUS (D) 
shows tumor enhancement (arrow) that is contiguous with enhancing tissue in the renal vein (arrowheads), confirming venous invasion by tumor.

B C D

A

lymph node staging is 83% to 88%[69]. Both CT and MRI 
are unable to differentiate enlarged, reactive nodes from 
metastatic lymph nodes or identify micrometastases 
in normal-sized lymph nodes[69,71]. A review showed 
that FDG PET had a sensitivity and specificity of 75% 
and 100%, respectively, for the detection of lymph node 
metastases in RCC[71] (Figure 11).

Imaging in Follow-Up
In RCC, 80% to 85% of tumor recurrence occurs within 
the first 3 years following surgery[69,72]. The incidence 
of local recurrence at the surgical bed following 
surgery for localized RCC is about 2%[69]. Risk for 
tumor recurrence following surgery depends on the 
pathological size, stage, grade, and histologic subtype 
of the primary tumor[69]. Pathological stage and 
grade of the primary tumor enable risk stratification of 
surgical candidates[57,61]. Patients with positive surgical 
margin are considered to be in at least one higher level 
of risk category than that based upon their surgical 
specimen[61].

There is no consensus on the surveillance program 
following treatment. A risk-based postoperative surveil-
lance schedule has been recommended by the AUA[61] 
as well as EAU[8]. Contrast-enhanced CT or MRI of 
the abdomen as well as chest imaging are suggested 
with each follow-up visit[61]. Chest radiograph is 

TABLE 1. 

T staging categories 

Tx Primary tumor cannot be assessed 

T1 
T1a: ≤ 4 cm, limited to the kidney 
T1b: > 4 cm and ≤ 7 cm, limited to the kidney

T2 
T2a: > 7 cm and ≤ 10 cm, limited to the kidney 
T2b: > 10 cm, limited to the kidney

T3 

T3a: invades renal vein/branches, perirenal fat, renal 
sinus fat, or pelvicalyceal system 
T3b: extends into vena cava below the diaphragm 
T3c: extends into vena cava above the diaphragm or 
invades vena cava wall

T4 
Invades beyond Gerota’s fascia, including direct 
extension to adrenal gland 

Amin MB and Edge SB. AJCC Cancer Staging Manual, 8th Edition. 
Springer Nature Switzerland AG; 2017.[57]

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FIGURE 11. 

Papillary renal cell carcinoma metastases on PET/CT 

18F-FDG PET/CT shows focal uptake in the primary left upper pole papillary renal cell carcinoma and in metastatic lesions in the ribs, spine, pelvis, and 
retrocrural lymph nodes. Physiologic activity is within the renal collecting system and bladder. Coronal PET and CT fusion image is on the left, and coronal 
PET is on the right.

recommended for those in low-risk and intermediate- 
risk categories, and chest CT is recommended for those 
in high-risk and very high-risk categories[61]. US alter-
nating with CT or MRI may be considered in low-risk 
and intermediate-risk groups after the initial 2 years of 
follow-up after surgery or ablation, and in active surveil-
lance of localized renal masses[61]. Patients managed 
with ablative treatments are recommended to follow an 
intermediate-risk category surveillance schedule[61]. 
Patients with relapse, stage IV disease, and surgically 
unresectable disease are recommended to undergo CT 
or MRI every 6 to 16 weeks at the physician’s discretion 
and patient’s clinical status[9].

A detailed discussion of the imaging manifestations 
following ablation and systemic therapy with targeted 
agents, such as antiangiogenic agents and immuno-
therapy, is beyond the scope of this article. Traditional 
evaluation of tumor size to determine therapy response 
may be inadequate in these settings. Imaging findings 
supportive of favorable response include development 
of marked necrosis, decrease in tumor attenuation, and 
change in pattern of enhancement[73].

Currently, AUA recommends that PET/CT should not 
be routinely obtained but may be considered in select 
cases[61]. A meta-analysis showed that the pooled sensi-
tivity and specificity were 86% and 88%, respectively, of 
18F-FDG PET/CT for the detection of metastatic disease 
in RCC[74]. Another study showed that PET/CT was 
comparable to CT for the detection of metastatic disease 
after surgery[75]. PET/CT may have prognostic benefit 
and can influence clinical decision. A study showed that 
positive PET/CT scan correlated with lower progres-
sion-free survival at 3 years and lower overall survival 
by 5 years, which affected management decision in 43% 
of patients[76]. Another study showed that the high 
number of FDG-positive RCC metastases or metasta-
ses with high SUVmax at baseline PET/CT were linked 
to shorter overall survival[77]. Furthermore, the study 
showed that disease progression on PET/CT at 16 weeks 
after start of treatment correlated with decreased over-
all survival and progression-free survival. Qualitative 
metrics, such as total lesion glycolysis and metabolic 
tumor volume, were also shown to be predictive of over-
all survival and progression-free survival[78,79].

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A summary of the currently recommended imaging 
modalities to be utilized according to the stage of the 
disease is included (Table 2).

Imaging-Assisted Interventions
Renal mass biopsy, percutaneous tumor ablation, 
and intraoperative surgery can be assisted by real-
time imaging. Image-guided percutaneous renal 
mass biopsy has become more commonly performed 
and can be guided by US or CT. Biopsy may help to 
avoid surgery by demonstrating benign pathology, or 
if showing malignancy can help guide management 
decision to surgery, ablation, or active surveillance. 
Image-guided percutaneous thermal ablation of a 
renal mass is an alternative to surgery in select patients 
with localized tumors and can be potentially curative. 
Intraoperative US can be utilized as an adjunct to assist 
surgery by increasing confidence in selection of the 
site of parenchymal transection, aid in evaluation of 
the relationship of the mass to renal vessels and renal 
collecting system, verify extent of inferior vena caval 
tumor, and aid in detection of additional lesions[80,81]. 
Three-dimensional (3D) imaging technology, such as 3D 
printing model, augmented reality, and mixed reality 
technology, is a novel application of CT or MR imaging 
dataset to produce a visually concise representation of a 
renal tumor to improve its localization within the kidney 
and understand its relationship to relevant anatomical 
structures. Three-dimensional printing models and 
augmented reality have been utilized for preoperative 
surgical planning in complex cases[82] and for patient 
counseling[83].

Future Directions
A number of novel imaging techniques are being 
investigated to further characterize indeterminate renal 
masses including elastography, dual-energy spectral 
CT and perfusion CT, novel PET radiotracers, 99m 
Technetium sestamibi, and the utility of radiomics with 
artificial intelligence[84,85].

Advanced US techniques, such as elastography, are 
being studied for their potential to differentiate between 
benign and malignant renal masses[86]. Advanced CT 
techniques, such as dual-energy spectral CT and perfu-
sion CT, are being studied but their exact role in renal 
mass CT protocol is unclear. Studies have shown mixed 
results in the ability of dual-energy spectral CT and 
perfusion CT to differentiate between benign and malig-
nant renal masses[87], RCC subtypes[88], and RCC 
histologic grade[89]. The higher radiation dose penalty 
and more challenging technique of perfusion CT may 
limit the technique’s wider utility in comparison to 
dual-energy spectral CT[90].

Novel PET radiotracers linked to specific proteins, 
such as prostate-specific membrane antigen (PSMA) and 
carbonic anhydrase IX (CAIX), are under current inves-
tigation for the evaluation of RCC.

A systemic review showed that PSMA PET/CT has 
a potential role in staging, restaging, and predicting 
treatment response, but not for primary tumor evalua-
tion[91]. It appears superior to FDG PET/CT for detec-
tion of local recurrence and bone metastases[92]. CAIX 
is a cell-surface antigen that is highly expressed in 
ccRCC but not found in other RCC subtypes or benign 
renal tissue (Figure 12). Girentuximab is an anti-CAIX 
monoclonal antibody. Preliminary studies showed that 
89Zr-girentuximab PET/CT was able to differentiate 
between ccRCC and non-ccRCC[93], and improved 
detection of RCC metastases compared to CT alone or 
CT in combination with FDG PET/CT[94]. Theragnostic 
applications directed at PSMA and CAIX are being 
explored[95].

99m Technetium sestamibi is a radiotracer that accu-
mulates in mitochondria-rich cells, and is commonly 
utilized in myocardial and parathyroid scintigraphy. 
Renal oncocytoma has high mitochondrial content 
compared to chRCC. A meta-analysis showed that 99m 

TABLE 2. 

Recommended imaging modalities for evaluation at 
each clinical stage of disease 

Recommended imaging 
modality

Suspected renal mass US, CT, MRI

Renal mass 
characterization

CT, MRI, US

RCC staging CT, MRI

Restaging post-treatment CT 

Neurological symptoms MRI, CT

Bone pain/increased 
alkaline phosphatase

Bone scintigraphy

CT: computed tomography; MRI: magnetic resonance imaging; RCC: 
renal cell carcinoma; US: ultrasound.

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Technetium sestamibi scintigraphy had a pooled sensi-
tivity and specificity of 92% and 88%, respectively, for 
detecting renal oncocytomas versus other renal lesions, 
and 89% and 67%, respectively, for detecting renal onco-
cytoma versus chRCC[96]. Novel application of this 
radiotracer to further characterize indeterminate renal 
masses would allow for triage of suspected oncocytomas 
to active surveillance.

Radiomics with artificial intelligence is an emerging 
field that uses computational methods to extract quan-
titative metrics, such as shape, size, and texture, from 
any standard clinical image dataset, such as CT, MRI 
or PET/CT, which can then be used to help differenti-
ate between benign and malignant renal masses, predict 
nuclear grade, and evaluate gene expression profile[97]. 
Preliminary studies have shown that radiomics allows 
for differentiation of benign from malignant renal 
masses with CT[98,99] and MRI[100,101]. One CT study 
showed that sensitivity and accuracy were 85.8% and 
74.4%, respectively, in differentiating ccRCC from onco-
cytoma[98]. Another CT study of 127 patients with RCC 
showed a sensitivity, specificity, and accuracy of 89%, 
92%, and 87%, respectively, for differentiating ccRCC 
from non-ccRCC, and 87%, 92%, and 78%, respectively, 
for differentiating pRCC from chRCC[102]. A further CT 
study of 62 patients with pRCC showed 84% accuracy in 
differentiating between type 1 and type 2 pRCC[103]. An 
MRI study found a sensitivity, specificity, and accuracy 
of 92%, 41%, and 70%, respectively, for distinguishing 
benign from malignant renal masses when utilizing 
deep learning algorithms[100]. Studies have shown 
feasibility of radiomics to differentiate between low- 
and high-grade RCC[104,105]. One study of 53 patients 
showed a sensitivity, specificity, and accuracy of 91.3%, 
80.6%, and 85.1%, respectively, for predicting high-grade 
from low-grade clear cell RCC[106].

Radiogenomic studies have shown that BRCA1-
associated protein 1 mutation is associated with ill-de-
fined tumor margins and presence of calcification, and 
more commonly seen with higher grade RCC[107]. 
Mutation of mucin 4 is found to be associated with 
exophytic tumor growth and reduced survival[107], 
while mutation of lysine demethylase 5C is found to 
be associated with renal vein invasion and reduced 
survival[108]. However, a systemic review of 57 studies 
found that translation of radiomics into clinical practice 
remains technically challenging owing to several factors 
including heterogeneous image acquisition protocols, 
reproducibility of radiomics signature, and big data 
sharing[109].

Conclusion
Imaging plays a central role in the clinical detection, 
stag i ng, a nd fol low-up of pat ients w it h RCC . 
Contemporary management of RCC has emphasized 
the role of imaging in the multidisciplinary care of these 
patients. Clinicians should be cognizant of the strengths 
and limitations of the different imaging techniques. 
Newer imaging techniques and the nascent role of 
artificial intelligence may translate into future clinical 
practice.

FIGURE 12. 

PET/CT targeting carbonic anhydrase IX in patient with 
metastatic clear cell renal cell carcinoma 

Maximum intensity projection image of 18F-VM4-037, a small molecule 
targeting carbonic anhydrase IX, in a patient with metastatic clear 
cell renal cell carcinoma. Physiologic soft palate, and hepatic, renal, 
gastrointestinal, and bladder activity is intense, while metastatic lung 
lesions are focal.

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http://SIUJ.org


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