DOI:10.2214/AJR.07.3568
AJR 2008; 191:1220-1232
© American Roentgen Ray Society
Renal Cell Carcinoma: Diagnosis, Staging, and Surveillance
Chaan S. Ng1,
Christopher G. Wood2,
Paul M. Silverman1,
Nizar M. Tannir3,
Pheroze Tamboli4 and
Carl M. Sandler1
1 Department of Radiology, Box 368, The University of Texas M. D. Anderson
Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030-4009.
2 Department of Urology, The University of Texas M. D. Anderson Cancer Center,
Houston, TX.
3 Department of Medical Oncology, The University of Texas M. D. Anderson Cancer
Center, Houston, TX.
4 Department of Pathology, The University of Texas M. D. Anderson Cancer Center,
Houston, TX.
Received December 20, 2007;
accepted after revision April 10, 2008.
Address correspondence to C. S. Ng
(cng{at}mdanderson.org).
C. G. Wood is a consultant for Pfizer, Inc.; Antigenics, Inc.;
Bristol-Myers Squibb; Ethicon, Inc.; and Bayer Healthcare.
CME
The article is available for CME credit. See
www.arrs.org
for more information.
Abstract
OBJECTIVE. This educational review focuses on the staging and
radiologic evaluation of renal cell carcinoma. It includes discussion of the
epidemiology, pathology, and therapeutic options of renal cell carcinoma and
the implications for radiologic follow-up.
CONCLUSION. The incidence of renal cell carinoma has been
increasing. Imaging plays a central role in its detection, staging, and
treatment evaluation and follow-up.
Keywords: imaging • renal cell carcinoma • staging
Introduction
Renal cell carcinoma (RCC), the eighth most common malignancy affecting
adults, accounts for between 3% and 4% of new cancer cases in the United
States. It is the seventh most common cancer in men and the ninth most common
in women [1]. We now know that
RCC actually represents a family of related disorders with distinct
cytogenetic and immunohistochemical properties that have differing prognoses,
imaging characteristics, and potential morbidities.
The classic clinical presentation of flank pain, hematuria, and a palpable
flank mass is comparatively uncommon (5–10% of cases). However, clinical
symptomatology may be quite nonspecific—for example, anorexia,
tiredness, weight loss, or fever of unknown origin
[2]. Other presentations
include varicocele formation (from tumor thrombus in the left renal vein or
the inferior vena cava [IVC]) and disseminated malignancy. RCC may also
present with a variety of paraneoplastic syndromes, such as polycythemia
secondary to excessive secretion of erythropoietin, hypercalcemia secondary to
factors regulating calcium, and hepatic dysfunction (Stauffer syndrome).
Incidentally detected tumors in asymptomatic individuals have been steadily
increasing with the dissemination of imaging techniques, including CT, MR, and
sonography, accounting for approximately 60% of renal tumors in the 1990s,
compared with approximately 10% in the early 1970s
[3,
4].
Besides identifying these incidental lesions, diagnostic imaging plays an
increasing role in this disease, particularly in the context of newer surgical
approaches such as laparoscopic and nephron-sparing approaches. MDCT has been
a major advance, providing angiographic and 3D imaging essential for
presurgical planning.
This article focuses on the epidemiology, pathology, staging, radiologic
evaluation, and therapeutic options of RCC and the implications for radiologic
follow-up.
Epidemiology
There were an estimated 51,190 new cases of, and 12,890 deaths from, renal
cancer in 2007 in the United States, accounting for 2.3% of all cancer deaths
in the United States [1]. The
incidence has steadily increased during the past 50 years in the United States
and has occurred in 9.1/100,000 population in 1997, with a mortality rate of
3.5/100,000
[5–7].
Reported worldwide incidence rates range from 0.6/100,000 to 14.7/100,000
[8]. Most tumors present in the
fifth to seventh decade of life, with a median age at diagnosis of 66 years
and median age at death of 70 years. The incidence is two to three times
higher in men and is slightly more common in blacks than in whites
[5]. The incidence of renal
tumors at autopsy is approximately 2%
[9]. The tumors are usually
solitary but may be multifocal (6–25%), with bilateral RCC occurring
sometime in the course of life in 4% of patients
[10].
Certain genetic conditions are associated with an increased incidence of
RCC, including von Hippel-Lindau disease, hereditary papillary renal cancer,
and, possibly, tuberous sclerosis
[11]. RCC occurs in von
Hippel-Lindau disease in 35–40% of patients, occurs at a younger age,
and is frequently bilateral (75%) or multifocal (87%)
[12]. RCC is also more common
in acquired cystic renal disease. Long-term dialysis carries a three- to
sixfold increased risk compared with the normal population. Hereditary
papillary RCC is an autosomal dominant form of the disease that is associated
with multifocal papillary renal tumors. The disease has a 5:1 male
predominance. Other suggested risk factors include cigarette smoking; obesity;
diuretic use; exposure to petroleum products, chlorinated solvents, cadmium,
lead, asbestos, and ionizing radiation; high-protein diets; hypertension;
kidney transplantation; and HIV infection
[5,
10,
13–15].
Survival Statistics
Despite the increasing incidence of the disease in recent decades, survival
has steadily improved, with a current overall 5-year survival of approximately
62% [7]. Prognosis is
influenced by the extent of disease at diagnosis, with a 5-year survival rate
in the absence of metastases exceeding 50%; in the presence of distant
metastases, the 5-year survival rate decreases to 10% (with a 10-year survival
rate of < 5%).
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Fig. 1B —Histopathologic slides of renal cell carcinoma (RCC). (H and
E) Papillary RCC type I. Tumor papillae are lined by short cuboidal cells with
basophilic cytoplasm. Nuclei are small with few inconspicuous nucleoli.
Collection of foamy histiocytes is present in middle of lower half of
image.
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Fig. 1C —Histopathologic slides of renal cell carcinoma (RCC). (H and
E) Papillary RCC type II. Tumor shows papillae lined by columnar to
pseudostratified cells that have striking eosinophilic cytoplasm.
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Fig. 1D —Histopathologic slides of renal cell carcinoma (RCC). (H and
E) Chromophobe RCC. Note sheet of tumor cells with focal necrosis (upper left
corner). Tumor cells have abundant pale flocculent cytoplasm, prominent cell
membranes, perinuclear halos, and wrinkled nuclei.
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The possible factors that have contributed to improved survival include
advances in renal imaging and surgical techniques, stage migration to smaller
and lower-stage disease as a result of earlier diagnosis in asymptomatic
individuals, and the introduction of immunotherapy for advanced disease. Tumor
size has been found to be an independent predictor of outcome, with larger
tumors having a poorer survival; for example, 5- and 10-year disease-free
survivals after surgery for T1, T2, T3a, T3b, and T3c tumors are approximately
95% and 91%, 80% and 70%, 66% and 53%, 52% and 43%, and 43% and 42%,
respectively [16].
Regarding the potential contribution from incidentally detected tumors, the
overall 5-year survival rate is approximately 85% for such cases, compared
with 53% in symptomatic cases. Although data are not available, this may very
well increase in the new era in which tumors are being detected incidentally
at an earlier stage and smaller size. Evidence suggests, although not
conclusively, that asymp tomatic tumors are smaller and of lower grade and
earlier stage [3,
7].
Pathology
RCC (hypernephroma or Grawitz's tumor) is the most common tumor to affect
the adult kidney, accounting for 80–90% of primary malignant renal
neoplasms in adults.
On gross pathology, tumors most often appear encapsulated. Tumors may be
solid, cystic, or mixed, including or engulfing fat and calcification
[17]. As many as 10% of tumors
have some cystic component
[18], and such tumors may be
more aggressive [19].
Histologic subtypes according to the Heidelberg classification
[20] include clear cell
("conventional") adenocarcinoma (80%), papillary (15%),
chromophobe (5%), collecting duct (1%), and unclassified (4%)
[21,
22]. Each of these subtypes
has differing cytogenetic and immunohistochemical profiles as well as
differing prognoses. Histopathologic grading of the nuclei of the tumor is
made by dividing them into the four-tier Fuhrman nuclear classification
[23], with grade I being the
best-differentiated and grade IV the most anaplastic.
Clear cell carcinoma displays large uniform cells with abundant clear
cytoplasm rich in glycogen and lipid (Fig.
1A). Clear cell carcinoma is typically highly vascular. Papillary
tumors are subdivided into type I tumors
(Fig. 1B), which occur
sporadically and metastasize somewhat later, and type II
(Fig. 1C), which are more
likely inherited, may be multiple, and often present with a higher Fuhrman
grade and poorer prognosis. Collecting duct tumors, which arise from the
medullary collecting duct, often occur in younger patients and are associated
with a poor overall prognosis. Renal medullary carcinoma is a rare subtype,
closely related to collecting duct carcinoma and having a poor prognosis,
which occurs in young patients with sickle cell anemia or sickle trait.
Chromophobe tumors and oncocytomas, both of which arise from collecting duct
epithelium, may be confused on histologic examination but have differing
immunohistochemical profiles (Fig.
1D). Chromophobe tumors have the best overall prognosis, and
oncocytomas are benign.
The tumor can extend directly into the perinephric fat, ipsilateral adrenal
gland, or adjacent musculature, and, less frequently, the liver, spleen,
pancreas, and colon. Rarely, the tumor may invade the renal collecting system.
RCC has a propensity for extending, as tumor thrombus, into the tributaries of
the renal veins and subsequently to the main renal vein, the IVC, the hepatic
veins, and potentially the right atrium. Hematogenous metastases are more
common and occur earlier than lymphatic dissemination, the former most
commonly to the lungs and bone, but essentially to any organ, including the
subcutaneous tissues and skeletal muscle.
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Fig. 2C —Schematic diagrams of TNM staging of renal cell carcinoma.
(© 2008 The University of Texas M. D. Anderson Cancer Center) Stage T3a
tumors involving perinephric fat (C) and adjacent adrenal gland
(D).
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Fig. 2D —Schematic diagrams of TNM staging of renal cell carcinoma.
(© 2008 The University of Texas M. D. Anderson Cancer Center) Stage T3a
tumors involving perinephric fat (C) and adjacent adrenal gland
(D).
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Fig. 2E —Schematic diagrams of TNM staging of renal cell carcinoma.
(© 2008 The University of Texas M. D. Anderson Cancer Center) Stage T3b
tumor involving renal vein or inferior vena cava (IVC) inferior to
diaphragm.
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Staging
Staging systems are designed to reflect the modes of spread (Fig.
2A,
2B,
2C,
2D,
2E,
2F) and are used to stratify
treatment options and to assess prognoses and survival characteristics. The
current version of the 2002 TNM staging of the American Joint Committee on
Cancer (AJCC) and the International Union Against Cancer (UICC) is presented
in Tables 1 and
2
[24].
In light of the increasing trend for the discovery of very small tumors as
incidental findings on imaging studies performed for other purposes, revisions
to this 1997 version have been proposed, including subclassification of T1
into T1a < 2.5 cm; T1b, 2.5–4.0 cm; and T1c, 5.0–7.0 cm tumors.
The Robson classification
[25]is an alternative staging
system no longer used but still referred to in some of the older
literature.
Prognosis is generally reflected in staging severity, with lower-stage
disease being associated with longer survival rates. Five-year survival rates
by TNM stage are shown in Table
3. The prognosis is noticeably adversely affected by spread of the
tumor beyond the renal fascia and into the retroperitoneum (TNM T3a and
higher). The natural history of the disease, however, is often unpredictable,
and there are wide ranges in survival. There are reports, albeit rare (<
1:600), of stabilization or even spontaneous remissions in the face of
metastatic disease [10,
26].
Crotty et al. [27] reported
that 86% of chromophobe tumors in their series were Robson stage I at
presentation. Beck et al. [28]
reported that chromophobe and papillary histology were associated with an
improved disease-free survival at 5 years compared with patients with clear
cell RCC. When controlled for size and stage of tumor, however, chromophobe,
but not papillary, carcinoma offered a significantly improved survival. The
times from nephrectomy to metastasis and from metastasis to death were twice
those for patients with chromophobe histology when compared with those with
clear cell or papillary subtypes.
It has been suggested that there are other potentially important
determinants of survival that should be included in staging, including
recognition of RCC tumor variants, sarcomatoid histology, histopathologic
grade, molecular proliferation markers (silver-staining nucleolar organizer
regions, proliferating cell nuclear antigen, and Ki-67 antigen), performance
status, weight loss, hypercalcemia, and erythrocyte sedimentation rate
[7,
10,
29,
30]. However, current staging
does not incorporate these factors.
Twenty-five to 33% of patients have overt metastases at presentation
[2,
13,
31]. The more common sites of
metastases as reported in stage IV disease (TNM T4 or N1+ M1 disease) are the
lung (69%), bone (43%), liver (34%), lymph nodes (22%), adrenal gland (19%),
brain (7%), and thyroid, skin, and bladder (< 1% each)
[32]. Rarer sites include
skeletal muscle, bowel, gallbladder, pancreas, and orbits
[10,
13,
33]. Large tumors tend to be
associated with more advanced dissemination.
Radiologic Evaluation
The goals of radiologic imaging are to detect and stage the primary tumor.
In most institutions, CT is the main imaging technique for the evaluation of
the intraabdominal component of renal tumors. In some specific instances, such
as allergy to iodinated contrast medium, MRI and sonography can provide
complementary information. The risks of nephrogenic systemic fibrosis (NSF) in
patients with significantly impaired renal function, which is considered to be
associated with some gadolinium-based MRI contrast agents, should be
considered carefully when staging with MRI is deemed advisable
[34].
It is generally considered that a risk-adapted approach is used for workup
of other possible sites of metastases. Chest CT should be performed if the
primary tumor is large or locally aggressive because metastases are more
common in these patients [35].
Chest radiography without CT should be reserved for patients with a low risk
of metastatic disease or for those in long-term follow-up
[36,
37]. Brain MRI and nuclear
medicine bone scanning are generally justified only if there are symptoms and
signs to suggest disease at these sites or if the tumor is large and locally
aggressive, although even the latter is debated
[31]. Technetium-99m-methylene
diphosphonate (MDP) bone scanning, however, may be limited in detecting the
typical osteolytic bone metastases from RCC. The value of pelvic CT in staging
is also limited [38].
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Fig. 3A —CT reformations of bilateral renal tumors in 60-year-old
woman. Large arrows indicate primary renal tumor. CT scan shows solid left
renal mass (large arrow) and complex cystic right renal mass
(small arrow).
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Fig. 3B —CT reformations of bilateral renal tumors in 60-year-old
woman. Large arrows indicate primary renal tumor. Coronal multiplanar
reformation (MPR) during arterial phase shows one left and two right renal
arteries (small arrows).
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Fig. 3C —CT reformations of bilateral renal tumors in 60-year-old
woman. Large arrows indicate primary renal tumor. Coronal maximum intensity
projection during arterial phase shows bilateral tumors (large
arrows) and renal arteries (small arrows).
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Fig. 3D —CT reformations of bilateral renal tumors in 60-year-old
woman. Large arrows indicate primary renal tumor. Volume-rendered image during
arterial phase also shows renal arteries (small arrows).
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Fig. 3E —CT reformations of bilateral renal tumors in 60-year-old
woman. Large arrows indicate primary renal tumor. Coronal MPR during delayed
phase shows inferior vena cava (large thin arrows) and left renal
vein (arrowheads), renal collecting system, aorta, and renal arteries
(small thin arrows).
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CT Evaluation
Suggested protocols for preoperative evaluation and follow-up using MDCT
are presented in the text that follows. In addition to assessing tumor stage,
preoperative evaluation focuses on delineating the tumor with particular
attention to the relationship of the tumor to adjacent structures, including
vascular relationships. In comparison, follow-up evaluation is directed toward
surveillance for residual or recurrent disease. In general, 100–150 mL
of iodinated IV contrast medium is used at a flow rate of 2–3 mL/s.
Preoperative Evaluation
For an MDCT protocol, unenhanced images of the liver and kidneys are
obtained with 5-mm collimation in 5-mm increments. Unenhanced images of the
kidneys allow detection of calcification or fat in the kidney, enable
assessment of contrast enhancement, and assist in characterizing the lesion.
IV contrast-enhanced images targeted on the kidneys are obtained in the
arterial, late arterial (corticomedullary and portal venous), nephrographic,
and excretory phases at 15–30, 45–60, 80–90, and 180
seconds, respectively, after commencement of the IV infusion. Imaging of the
liver and the remaining abdominal structures is performed in the portal venous
phase. Excretory phase images from the kidneys through the bladder are
generally obtained to complete the evaluation of the entire urinary tract when
requested by the referring clinician.
Multiplanar reformatted and 3D volume-rendered presentations of the renal
phase images are helpful in allowing visualization of the relationships of
structures, particularly for surgeons
[39–41].
Such reformations are best obtained with the thinnest possible images and some
degree of reconstruction interval overlap (typically, < 1.5-mm interval and
10–50% overlap) and are transferred to a workstation for creating
multiplanar reformatted images, 3D volume rendering, and
maximum-intensity-projection (MIP) images (Figs.
3A,
3B,
3C,
3D). The late arterial phase
provides a useful angiographic image of arterial and venous supply to the
kidney but has limited additional usefulness for lesion detection and
characterization when a nephrographic phase is used. The combination of
excretory and nephrographic phases has been shown to improve lesion detection
and staging [42,
43].
Several investigators have shown that clear cell RCC enhances to a greater
extent and is more heterogeneous in appearance than other histologic subtypes
(Figs. 4A and
4B). Kim et al.
[44] showed that an increase
in attenuation of 84 HU in the corticomedullary phase differentiates clear
cell RCC from non–clear cell tumors with a sensitivity of 74% and a
specificity of 100%. Herts et al.
[45] showed that papillary
tumors were more homogeneous and had a much lower tumor-to-parenchyma
enhancement ratio than was present in non-papillary subtypes, particularly
with tumors smaller than 3 cm in diameter (Figs.
4C and
4D). Chromophobe tumors also
are less hypervascular than clear cell tumors and tend to have a more
peripheral pattern of enhancement; however, their appearance is not
sufficiently characteristic to allow them to be reliably differentiated from
papillary lesions (Figs. 4E
and 4F). Oncocytomas cannot be
reliably differentiated from RCC by imaging and thus are also considered to be
surgical lesions. The well-known prominent central scar that can be used to
suggest the diagnosis of oncocytoma may also be present in necrotic clear cell
tumors. Medullary RCC tumors are located centrally in the kidney and show
variable, typically limited, contrast enhancement
(Fig. 4G). They cannot be
reliably distinguished from other RCCs or urothelial tumors but may be
suggested when an aggressive tumor in a young patient with sickle cell disease
or trait is encountered.
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Fig. 4A —CT appearances of various cell types of renal cell carcinoma
(RCC). Conventional clear cell RCC in 59-year-old woman. CT scans of TNM stage
T1a tumor in corticomedullary and nephrogenic phases show typical
hypervascularity of tumor (arrow, A) and subsequent washout
(arrow, B).
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Fig. 4B —CT appearances of various cell types of renal cell carcinoma
(RCC). Conventional clear cell RCC in 59-year-old woman. CT scans of TNM stage
T1a tumor in corticomedullary and nephrogenic phases show typical
hypervascularity of tumor (arrow, A) and subsequent washout
(arrow, B).
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Fig. 4C —CT appearances of various cell types of renal cell carcinoma
(RCC). Papillary RCC in 48-year-old man. CT scans of TNM stage T1a tumor in
corticomedullary (C) and nephrogenic (D) phases show typical
hypovascularity of tumor (arrow).
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Fig. 4D —CT appearances of various cell types of renal cell carcinoma
(RCC). Papillary RCC in 48-year-old man. CT scans of TNM stage T1a tumor in
corticomedullary (C) and nephrogenic (D) phases show typical
hypovascularity of tumor (arrow).
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Fig. 4E —CT appearances of various cell types of renal cell carcinoma
(RCC). Chromophobe RCC in 61-year-old man. CT scans of TNM stage T2 tumor in
corticomedullary (E) and nephrogenic (F) phases show
hypovascularity of tumor (arrow).
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Fig. 4F —CT appearances of various cell types of renal cell carcinoma
(RCC). Chromophobe RCC in 61-year-old man. CT scans of TNM stage T2 tumor in
corticomedullary (E) and nephrogenic (F) phases show
hypovascularity of tumor (arrow).
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Fig. 4G —CT appearances of various cell types of renal cell carcinoma
(RCC). Medullary RCC (large arrow) and adjacent paraaortic adenopathy
(small arrows) in 36-year-old man. CT shows TNM stage T1b N1
tumor.
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Follow-Up Evaluation
For an MDCT protocol, unenhanced images of the liver and kidneys are
obtained with 5-mm collimation in 5-mm increments. Unenhanced images of the
liver assist in the detection of hypervascular metastases (which are typical
of renal metastases) that might otherwise be obscured on contrast-enhanced
images. IV contrast-enhanced images of the abdomen and pelvis are obtained
70–80 seconds after the beginning of the IV infusion, acquired at 5-mm
slice thickness, and reconstructed at 2.5-mm intervals. Late arterial phase
images can assist in identifying hypervascular liver metastases. Delayed
excretory phase images are obtained at approximately 180 seconds.
MRI Evaluation
MRI is generally only used when optimal CT cannot be performed, as in the
case of a severe allergy to iodinated contrast medium or pregnancy. MRI has
similar reported overall staging accuracies to those of CT
[46]. Its multiplanar
capability, however, is particularly useful for delineating the superior
extent of tumor in the IVC [2,
14,
17].
We use coronal and axial conventional T1-weighted (TR/TE, 600/60) and axial
dual-echo fast spin-echo T2-weighted (6,000/first -echo TE, 136; second-echo
TE, 68)fat-suppressed images of the abdomen. Images are supplemented by
dynamic contrast-enhanced 3D fast spoiled gradient-recalled echo sequences
(FSPGR) to further delineate the primary tumor and liver lesions and to
evaluate any vascular thrombus identified. In particular, tumor, rather than
bland, thrombus is indicated by the presence of enhancing vessels in the
thrombus. Multiple dynamic acquisitions can be used to obtain arterial,
nephrogenic, and pyelographic-like images
[47–50].
MDCT with 3D reformations and MRI have similar overall staging accuracies for
RCC [51].
Sonographic Evaluation
Sonography can be useful for assessing the presence and extent of venous
thrombus. It can also be helpful in distinguishing cysts from hypovascular
solid tumors seen on CT (e.g., papillary RCC). Sonography can reveal the
septations better because of complex interfaces to the ultrasound beam.
Sonography has reported accuracies for T staging of 77–85%
[52,
53] and for detection of
venous thrombus of 87% [54].
However, it has limitations in visualizing the retroperitoneum and perinephric
tissues [54,
55], although some proponents
argue otherwise [53].
Intraoperative sonography has been effectively used in patients undergoing
nephron-sparing surgery to identify multifocal lesions and intrarenal tumor
anatomy [56,
57].
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Fig. 5 —Tumor involvement of perinephric fat in 72-year-old woman. CT
scan shows tumor with associated perinephric nodularity (arrow). TNM
stage T3a disease was confirmed on resection specimen.
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Fig. 6 —Metastases to regional lymph node (TNM stage N2) in
81-year-old woman. CT scan shows enlarged left paraaortic node (small
arrows) and adjacent stage T1b papillary renal cell carcinoma (large
arrow).
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Percutaneous Biopsy
Preoperative percutaneous biopsy of the renal lesion is generally not
undertaken because the results usually do not affect what therapy will be
recommended except in patients with multiple tumors or occasionally in
patients with an underlying predisposing condition. Percutaneous biopsies may
be considered in selected cases—for example, when an abscess or
metastatic disease from a known primary tumor is suspected, especially from
lymphoma or melanoma [10,
17]. Percutaneous biopsy is
also generally performed in patients who will undergo ablative or thermal
therapy to determine the underlying histologic subtype of the tumor.
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Fig. 7A —Venous involvement of renal vein and inferior vena cava
(IVC). CT scan in 45-year-old woman shows enhancing tumor thrombus in expanded
left renal vein (large arrows) (TNM stage T3b) and IVC (small
arrow).
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Fig. 7B —Venous involvement of renal vein and inferior vena cava
(IVC). Thrombus in left renal vein extends to origin of renal vein at IVC on
coronal contrast-enhanced MR image (arrows) (TNM stage T3b) in
68-year-old woman. Arrowheads indicate left renal tumor.
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Fig. 7C —Venous involvement of renal vein and inferior vena cava
(IVC). Thrombus in expanded right renal vein extends to supradiaphragmatic IVC
on coronal contrast-enhanced MR image (arrows) (TNM stage T3c) in
82-year-old woman. Note aorta and renal artery origins are also visible
(arrowheads).
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Angiography
Approximately 20% of patients have multiple renal arteries, and many
surgeons find preoperative CT or MR angiograms to be valuable, particularly
when partial nephrectomy or laparoscopic approaches are planned.
Three-dimensional and multiplanar reformatted images, as well as angiographic
displays, aid appreciation of the relationships of the tumor to the collecting
system, adjacent normal parenchyma, and vascular supply
[10,
37,
38,
57].
PET
The efficacy of PET in renal malignancy remains under investigation. It
shows some potential in staging, the detection of unsuspected metastases,
follow-up, and the evaluation of indeterminate renal masses
[7,
58–61].
Recommendations for Preoperative Imaging
Patients must be adequately staged in order to plan appropriate management
options. Abdominal CT and MRI are the mainstay of staging the primary tumor
and of evaluating the possibility of locoregional nodal or abdominal visceral
metastases, such as to the adrenal glands, liver, pancreas, and contralateral
kidney. Delineation of vascular anatomy and evaluation of venous thrombosis,
best provided by a multiphasic evaluation as discussed previously, are helpful
when surgery is being contemplated. CT or MRI can be used, depending on local
preferences and patient factors.
Controversies exist as to whether, and how best, to evaluate for the
possibility of intrathoracic metastases. A stage-directed strat egy is
probably reasonable: For small primary tumors (T1), in which the risk of
metastatic disease is small, simple chest radiography is probably
satisfactory. For stage T2 or higher primary tumors, chest CT should probably
be performed. Screening for bone or brain metastases is probably re quired
only when there are suggestive symptoms.
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Fig. 8A —Metastatic disease (TNM stage M1). Note hypervascular nature
of most metastases. Pulmonary metastases in 76-year-old man. CT scan shows
typical well-defined "cannonball" nodules (arrows).
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Fig. 8D —Metastatic disease (TNM stage M1). Note hypervascular nature
of most metastases. CT scan shows lytic lesion in left iliac bone and
associated hypervascular soft-tissue metastasis (arrows) in same
patient as in C.
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Fig. 8E —Metastatic disease (TNM stage M1). Note hypervascular nature
of most metastases. Hypervascular liver metastases (arrows) are seen
on CT scan in 72-year-old man. Note that these must be differentiated from
hemangiomas.
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Therapeutic Options and Implications for Radiologic Follow-Up
Surgical resection is the only effective means of cure for clinically
localized renal tumors [10,
62]. Classically, this
involves total nephrectomy, but more recently, partial or
"nephron-sparing" nephrectomy has been shown to be equally
effective in selected groups. The indications for partial nephrectomy include
a tumor < 4 cm, peripheral location, absence of the contralateral kidney,
bilateral renal tumors, and renal insufficiency. Another consideration is
whether there is a risk of future impairment of renal function from another
condition or a risk of bilateral renal tumors (e.g., patients with von
Hippel-Lindau disease in whom future surgeries may be required).
Radical Nephrectomy
Total nephrectomies are typically undertaken via a retroperitoneal
posterolateral approach [10].
It is "radical" when it classically includes excision of the
perirenal fat, including the ipsilateral adrenal gland, and a lymph node
dissection. The dissection involves the region from the diaphragmatic crus to
the aortic bifurcation of the ipsilateral—and possibly the
contralateral—aspects of the IVC or the aorta
[7]. The sensitivity,
specificity, and accuracy for the detection of perinephric extension of
disease by high-resolution CT have been reported to be 96%, 93%, and 95%,
respectively [63]
(Fig. 5). Surgical management
is not directly affected by the presence of perinephric extension of disease
because a radical nephrectomy includes en bloc removal of all the contents of
Gerota's fascia.
Ipsilateral adrenalectomy is included in the classic radical nephrectomy.
However, ipsilateral adrenal metastases occur in only 1–10% of patients.
It occurs especially in large left-sided upper pole tumors, usually by direct
extension (i.e., T3a tumors)
[64]. One of the roles of
imaging is to assist in allowing adrenal-sparing nephrectomies in order to
reduce the risk of future adrenal insufficiency
[7].
Surgery, although substantially more challenging, is not necessarily
excluded in the presence of contiguous organ invasion, which typically
involves the liver, diaphragm, psoas muscles, pancreas, and bowel (Robson
stage IVA, or TNM T4 disease). Both CT and MRI may have difficulty in
distinguishing abutment of tumor from invasion of adjacent organs.
Partial (Nephron-Sparing) Nephrectomy
Partial nephrectomy is a relatively new technique. When evaluating this
possibility, the relationship of the tumor to the rest of the kidney and, in
particular, to the arterial supply to the tumor and the remainder of the
kidney, is important. Nephron-sparing surgery has been shown to be equally as
efficacious as total nephrectomy, with reported local recurrence rates of <
2% [10] and 5-year survival
rates of 87–90%, which are comparable to those from radical nephrectomy
[57]. However, in the case of
a solitary kidney, a risk of developing proteinuria, focal segmental
glomerulosclerosis, and progressive renal failure exists if more than 50% of
the renal mass is removed
[57].
Both total and partial nephrectomies can be undertaken laparoscopically.
Some surgeons supplement the laparoscopic approach with direct "hand
assistance" in the operative field. Laparoscopic approaches reduce
perioperative morbidity and length of the hospital stay. However, operation
times are generally longer, and morcellation of the sample leads to
difficulties in pathologic staging and introduces the risk of tumor seeding
[10]. Cryoablation and
radiofrequency ablation, which may be undertaken laparoscopically or
percutaneously, are promising techniques for treating small tumors
[30,
57,
65].
Nodal Status and Dissection
The presence of nodal metastases is an adverse prognostic factor
[66,
67]. Using a cutoff of 1 cm
for short-axis nodal size, sensitivity and specificity have been reported to
be 83% and 88% [68] and
overall accuracies have been reported to be 83–89%
[68,
69]
(Fig. 6). However, radiologic
assessment of nodal status, in common with other tumors, has its limitations.
Enlarged (> 1 cm) nodes are not necessarily metastatic but may be
reactive—that is, false-positive (58% in one series by Studer et al.
[70]—which may be more
common in necrotic tumors or tumors that involve the renal vein. Conversely,
small nodes may contain micrometastases—that is, false-negative
metastases (4% in the series by Studer et al.).
It is reported that 3–22.5% of patients who undergo radical
nephrectomy without clinically evident metastases have regional nodal
involvement at surgery [67,
71]. In pathologic series, the
prevalence of metastatic nodes in cases of occult RCC diagnosed only at
autopsy is reported at 14%
[72].
Accurate determination of nodal staging requires tissue; some surgeons
therefore advocate routine retroperitoneal nodal dissection. However, the
clinical value of this is controversial, in particular as to whether it
affects survival, and surgeons vary in their approach
[10,
26,
57,
67,
73].
Venous Involvement
Extension of tumor into the renal veins has been reported to occur in
20–35% of patients, and into the IVC, in 4–10%
[74–76],
the latter being infrahepatic (50%), intrahepatic (40%), or intraatrial (10%)
[77] (Figs.
7A,
7B,
7C). IVC thrombus is more
common from right-sided tumors because of the shorter renal vein on the right
[53,
76].
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Fig. 9A —Local recurrence after nephrectomy as seen on CT.
Postsurgical appearances in left nephrectomy bed (lower arrow) in
52-year-old man resolved at follow-up. Note associated surgical vascular clips
(upper arrow).
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Fig. 9C —Local recurrence after nephrectomy as seen on CT. Pitfall of
unopacified small bowel is seen in left nephrectomy bed of 58-year-old man,
which could be misinterpreted as adenopathy (large arrow) and local
tumor recurrence (small arrow) without careful tracing of bowel.
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Identification of thrombus in the venous system, especially the IVC, is
particularly important because it affects surgical management, typically
necessitating an anterior abdominal approach. Furthermore, if thrombus extends
into the heart, a combined thoracic and intracardiac approach with cardiac
bypass may be required.
Current CT techniques have reported sensitivities and specificities for
detecting renal vein thrombus of 85% and 98%, respectively
[78]. Color Doppler sonography
has reported sensitivities and specificities for detecting thrombus in the
renal veins of 75% and 96%, respectively, with 100% accuracy for detection of
thrombus in the IVC [54]. MRI
has similar reported sensitivity and specificity for detecting thrombus in the
renal vein of 86–94% and 75–100%, respectively, as well as 100%
accuracy for detecting IVC thrombus
[79,
80]. MRI, with its multiplanar
capability, is probably the best technique for identifying the superior extent
of IVC involvement [49,
81].
Fortunately, prognosis is not adversely affected by tumor in the venous
system or by its level in the IVC, provided the tumor is free-floating and can
be successfully removed (5-year survival rates of 50–69% in the absence
of metastatic disease). However, prognosis is severely impaired if tumor
invades the wall of the IVC (5-year survival rate, 25%), although this can
improve if the involved IVC can be resected completely (5-year survival rate,
57%) [2,
66,
82]. Unfortunately, current
imaging techniques have some limitations in distinguishing bland thrombus from
tumor thrombus and in distinguishing invasive from noninvasive tumor with
respect to the vessel wall [2].
Intravascular tissue that enhances after IV contrast administration or that
contains neovascularization (the thread-and-streak sign) is good evidence of
tumor thrombus rather than bland thrombus
(Fig. 7D).
Metastatic Disease and Palliation
In the context of metastatic disease, a nephrectomy may still be indicated
for sympto matic relief—for example, severe pain or hematuria; in a
small number of cases (
0.3%), regression of metastases has been reported
after resection of the primary tumor. Cytoreductive nephrectomy has been shown
to offer a survival benefit in selected patients with metastatic disease
[83]. Preoperative
embolization can provide symptomatic relief and reduce intraoperative bleeding
in large tumors. Also, resection is sometimes performed to obtain material
needed in immunotherapy. Radiation therapy is sometimes used for
palliation—for example, pain from bone metastases.
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Fig. 11A —CT appearances after partial nephrectomy in 55-year-old man.
CT scan obtained 6 weeks after left partial nephrectomy shows low-density
lesion (arrow) at surgical site that could be confused with mass
lesion.
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Fig. 11B —CT appearances after partial nephrectomy in 55-year-old man.
Six months after partial nephrectomy, note resolution of postoperative changes
(arrow). Also note previous right nephrectomy.
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Immunotherapy and Targeted Therapies
The mainstay of systemic therapy for metastatic RCC has historically been
immunotherapy (or cytokine therapy) with interleukin-2 (IL-2) and
interferon-
(IFN-). High-dose IL-2 has consistently produced a
15–20% response rate, 6–8% complete remission rate, and
approximately 5% cure rate
[84,
85]; however, it is a fairly
toxic regimen. IFN- has provided modest survival benefit, has a more
favorable toxicity profile, and is more easily administered than IL-2. As a
result, IFN- has been adopted as the control arm in many clinical
trials of novel agents.
Novel therapies for metastatic RCC have targeted the consequences of von
Hippel-Lindau (VHL) gene inactivation and the resulting up-regulation
of hypoxia-inducible factor (HIF) target genes, notably vascular
endothelial growth factor (VEGF) and platelet-derived growth factor
(PDGF). Four targeted agents are presently in clinical use for
metastatic RCC: sunitinib, sorafenib, temsirolimus, and bevacizumab. Sunitinib
(Sutent, Pfizer), a multi tyrosine kinase inhibitor (MKI), has shown an
objective response rate (ORR) of 31% and a median progression-free survival of
11 months for sunitinib-treated patients
[86,
87]. It is considered the
standard-of-care treatment for patients with advanced, good- and
intermediate-risk, conventional clear cell RCC. Sorafenib (Nexavar, Bayer
HealthCare), another MKI, is considered second-line therapy after cytokine
failure [88]. Temsirolimus
(Torisel, Wyeth), an inhibitor of mammalian target of rapamycin (mTOR), is
considered the standard of care for patients with poor-risk metastatic RCC,
irrespective of histology [89,
90]. Bevacizumab (Avastin,
Genentech), a humanized antibody to VEGF, has shown promise in
patients with good- and intermediate-risk metastatic RCC
[91] but has not yet been
approved for metastatic RCC by the U.S. Food and Drug Administration
(FDA).
Postoperative Surveillance and Recurrent Disease
Local recurrence in the nephrectomy bed occurs in approximately
20–40% of patients, typically in the first 5 years after nephrectomy
[17,
36]; the risks are highest
when the resection margins are incomplete. Isolated recurrences in the
nephrectomy bed are uncommon (1.8%)
[92], and resection is
typically difficult [10] but
in selected patients may improve survival.
Chae et al. [93] analyzed
the patterns of recurrence in 194 patients with RCC who had undergone complete
resection. Tumor recurrence was found in 21% of the patients within a mean
time of 17 months. Tumor recurrence occurred within 2 years in 83% of the
patients. The recurrence rate was highest for those with an original tumor
greater than 5 cm and, as expected, for those with a higher Fuhrman grade and
higher stage at the time of presentation.
Metastasectomies are of uncertain value
[10,
94] but may be efficacious in
certain subgroups—for example, those with a solitary site of disease and
a prior disease-free interval of greater than 1 year
[26]. Resection of solitary
metastases, typically to the lung, can result in 5-year survival of
25–60% [10].
The likelihood of developing metastases is directly related to tumor stage.
In one series after radical nephrectomy, metastatic disease occurred in 7.1%
of patients with stage T1 disease, 26.5% with stage T2, and 39.4% with stage
T3 disease, with the chance of developing recurrent metastases greatest in the
first three postoperative years
[95]. Sites of metastatic
disease include the lung (Figs.
8A and
8B), bone (Figs.
8C and
8D), liver
(Fig. 8E), adrenal gland
(Fig. 8F), skeletal muscle
(Fig. 8G), and pancreas
(Fig. 8H).
CT is the most sensitive imaging technique for follow-up in the abdomen. A
meticulous technique is required; for example, unopacified small-bowel loops,
which inevitably occupy the nephrectomy bed, can mimic local recurrence (Fig.
9A,
9B,
9C,
9D). Sonography has not been
found to be reliable in assessing the nephrectomy bed. During the surveillance
period, it is recommended that evaluation of potential intrathoracic disease
be undertaken by chest radiography, with chest CT, bone scanning
(Fig. 10), and brain MRI
reserved for patients with suspicious clinical symptoms, signs, and abnormal
blood chemistries. A suggested stage-specific postoperative imaging
surveillance protocol after radical nephrectomy for localized RCC is presented
in Table 4, although some argue
for more intensive surveillance
[71].
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TABLE 4: Stage-Specific Postoperative Imaging Surveillance After Radical
Nephrectomy for Localized Renal Cell Carcinoma
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Fig. 12B —Local recurrence after cryoablation as seen on CT of
61-year-old man. Scan 2 months after ablation shows low-density lesion with
minimal marginal enhancement, typical of postablation changes
(arrow).
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The follow-up strategy after nephron-sparing surgery is similar, except
that particular attention should be paid to the remnant kidney, where local
recurrence rates are in the region of 4–6% (Fig.
11A,
11B). These occur a maximum of
6–24 months after surgery in patients with stage T3 disease, and later
than 48 months in stage T2 disease. Recurrences are most likely the result of
undetected microscopic multifocal RCC in the remnant kidney
[57]. In pathologic series,
multifocality in primary tumors < 5 cm in size is 19%
[96]. A suggested
stage-specific postoperative imaging surveillance protocol after partial
nephrectomy for localized RCC is presented in
Table 5. Careful follow-up is
also required for patients who have undergone ablation therapies (Fig.
12A,
12B,
12C).
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TABLE 4: Stage-Specific Postoperative Imaging Surveillance After Radical
Nephrectomy for Localized Renal Cell Carcinoma
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More specialized follow-up may be required for patients with end-stage
renal disease, acquired cystic disease of the kidney, or von Hippel-Lindau
disease [10]. One of the
features of RCC is that it can have an unpredictable time course, with
recurrence-free intervals of up to 30 years; prolonged periods of follow-up
may therefore be needed
[53].
References
- Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer
statistics, 2007. CA Cancer J Clin 2007;57
: 43–66[Abstract/Free Full Text]
- Choyke Pl, Newhouse JH, Bluth EI, et al. ACR appropriateness
criteria: renal cell carcinoma staging, 2002. American College of Radiology
Website.
www.acr.org.
Accessed December 9, 2002
- Luciani LG, Cestari R, Tallarigo C. Incidental renal cell
carcinoma: age and stage characterization and clinical
implications—study of 1092 patients (1982–1997).
Urology 2000; 56:58
–62[CrossRef][Medline]
- Jayson M, Sanders H. Increased incidence of serendipitously
discovered renal cell carcinoma. Urology1998; 51:203
–205[CrossRef][Medline]
- Chow WH, Devesa SS, Warren JL, Fraumeni JF Jr. Rising incidence of
renal cell cancer in the United States. JAMA1999; 281:1628
–1631[Abstract/Free Full Text]
- Katner HP, Baynham SA. Increasing incidence of renal cell cancer.
JAMA 1999; 282:2119
–2120; discussion 2121[Free Full Text]
- Pantuck AJ, Zisman A, Belldegrun AS. The changing natural history
of renal cell carcinoma. J Urol 2001;166
:1611
–1623[CrossRef][Medline]
- Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence
of 25 major cancers in 1990. Int J Cancer1999; 80:827
–841[CrossRef][Medline]
- Choyke PL, Amis ES Jr, Bigongiari LR, et al. Renal cell carcinoma
staging. American College of Radiology. ACR appropriateness criteria.
Radiology 2000;215
[suppl]:721
–725[Medline]
- Russo P. Renal cell carcinoma: presentation, staging, and surgical
treatment. Semin Oncol 2000;27
: 160–176[Medline]
- Bjornsson J, Short MP, Kwiatkowski DJ, Henske EP. Tuberous
sclerosis-associated renal cell carcinoma: clinical, pathological, and genetic
features. Am J Pathol 1996;149
:1201
–1208[Abstract]
- Levine E, Weigel JW, Collins DL. Diagnosis and management of
asymptomatic renal cell carcinomas in von Hippel-Lindau syndrome.
Urology 1983; 21:146
–150[CrossRef][Medline]
- Figlin RA. Renal cell carcinoma: management of advanced disease.
J Urol 1999; 161:381
–386; discussion 386–387[CrossRef][Medline]
- Pretorius ES, Wickstrom ML, Siegelman ES. MR imaging of renal
neoplasms. Magn Reson Imaging Clin N Am2000; 8:813
–836[Medline]
- Godley P, Kim SW. Renal cell carcinoma. Curr Opin
Oncol 2002; 14:280
–285[CrossRef][Medline]
- American Cancer Society. How is kidney cancer staged? 2007.
American Cancer Society Website.
www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_kidney_cancer_staged_22.asp?rnav=cri.
Accessed October 16, 2007
- Hilton S. Imaging of renal cell carcinoma. Semin
Oncol 2000; 27:150
–159[Medline]
- Parienty RA, Pradel J, Parienty I. Cystic renal cancers: CT
characteristics. Radiology 1985;157
: 741–744[Abstract/Free Full Text]
- Brinker DA, Amin MB, de Peralta-Venturina M, Reuter V, Chan DY,
Epstein JI. Extensively necrotic cystic renal cell carcinoma: a
clinicopathologic study with comparison to other cystic and necrotic renal
cancers. Am J Surg Pathol 2000;24
: 988–995[CrossRef][Medline]
- Kovacs G, Akhtar M, Beckwith BJ, et al. The Heidelberg
classification of renal cell tumours. J Pathol1997; 183:131
–133[CrossRef][Medline]
- Shanks JH. Pathology of renal cell carcinoma: recent developments.
Clin Oncol (R Coll Radiol) 1999;11
: 263–268[Medline]
- Bostwick DG, Eble JN. Diagnosis and classification of renal cell
carcinoma. Urol Clin North Am 1999;26
: 627–635[CrossRef][Medline]
- Fuhrman SA, Lasky LC, Limas C. Prognostic significance of
morphologic parameters in renal cell carcinoma. Am J Surg
Pathol 1982; 6:655
–663[Medline]
- American Joint Committee on Cancer. AJCC cancer staging
manual. New York, NY: Springer-Verlag,2002
- Robson CJ. Staging of renal cell carcinoma. Prog Clin
Biol Res 1982; 100:439
–445[Medline]
- Rini BI, Vogelzang NJ. Prognostic factors in renal carcinoma.
Semin Oncol 2000;27
: 213–220[Medline]
- Crotty TB, Farrow GM, Lieber MM. Chromophobe cell renal carcinoma:
clinicopathological features of 50 cases. J Urol1995; 154:964
–967[CrossRef][Medline]
- Beck SD, Patel MI, Snyder ME, et al. Effect of papillary and
chromophobe cell type on disease-free survival after nephrectomy for renal
cell carcinoma. Ann Surg Oncol 2004;11
: 71–77[CrossRef][Medline]
- Delahunt B. Histopathologic prognostic indicators for renal cell
carcinoma. Semin Diagn Pathol 1998;15
: 68–76[Medline]
- Tsui KH, Shvarts O, Smith RB, Figlin RA, deKernion JB, Belldegrun
A. Prognostic indicators for renal cell carcinoma: a multivariate analysis of
643 patients using the revised 1997 TNM staging criteria. J
Urol 2000; 163:1090
–1095; quiz 1295[CrossRef][Medline]
- Staudenherz A, Steiner B, Puig S, Kainberger F, Leitha T. Is there
a diagnostic role for bone scanning of patients with a high pretest
probability for metastatic renal cell carcinoma?
Cancer 1999; 85:153
–155[CrossRef][Medline]
- Zagoria RJ, Bechtold RE. The role of imaging in staging renal
adenocarcinoma. Semin Ultrasound CT MR1997; 18:91
–99[CrossRef][Medline]
- Ng CS, Loyer EM, Iyer RB, David CL, DuBrow RA, Charnsangavej C.
Metastases to the pancreas from renal cell carcinoma: findings on three-phase
contrast-enhanced helical CT. AJR 1999;172
:1555
–1559[Abstract/Free Full Text]
- Broome DR, Girguis MS, Baron PW, Cottrell AC, Kjellin I, Kirk GA.
Gadodiamide-associated nephrogenic systemic fibrosis: why radiologists should
be concerned. AJR 2007;188
: 586–592[Abstract/Free Full Text]
- Choyke Pl, Amis ES, Bigongiari LR, et al. ACR appropriateness
criteria: renal cell carcinoma staging, 1998. American College of Radiology
Website:
www.acr.org.
Accessed December 9, 2002
- Chin AI, Lam JS, Figlin RA, Belldegrun AS. Surveillance strategies
for renal cell carcinoma patients following nephrectomy. Rev
Urol 2006; 8:1
–7[Medline]
- Curry NS, Francis IR, Baumgarten DA, et al. ACR appropriateness
criteria: renal cell carcinoma staging, 2007. American College of Radiology
Website:
www.acr.org.
Accessed March 27, 2008
- Fielding JR, Aliabadi N, Renshaw AA, Silverman SG. Staging of 119
patients with renal cell carcinoma: the yield and cost-effectiveness of pelvic
CT. AJR 1999; 172:23
–25[Abstract/Free Full Text]
- Sheth S, Scatarige JC, Horton KM, Corl FM, Fishman EK. Current
concepts in the diagnosis and management of renal cell carcinoma: role of
multidetector CT and three-dimensional CT.
RadioGraphics 2001;21
[spec no]:S237
–S254[Abstract/Free Full Text]
- Urban BA, Ratner LE, Fishman EK. Three-dimensional volume-rendered
CT angiography of the renal arteries and veins: normal anatomy, variants, and
clinical applications. RadioGraphics2001; 21:373
–386; questionnaire
549–555[Abstract/Free Full Text]
- Wunderlich H, Reichelt O, Schubert R, Zermann DH, Schubert J.
Preoperative simulation of partial nephrectomy with three-dimensional computed
tomography. BJU Int 2000;86
: 777–781[CrossRef][Medline]
- Kopka L, Fischer U, Zoeller G, Schmidt C, Ringert RH, Grabbe E.
Dual-phase helical CT of the kidney: value of the corticomedullary and
nephrographic phase for evaluation of renal lesions and preoperative staging
of renal cell carcinoma. AJR 1997;169
:1573
–1578[Abstract/Free Full Text]
- Yuh BI, Cohan RH. Different phases of renal enhancement: role in
detecting and characterizing renal masses during helical CT.
AJR 1999; 173:747
–755[Abstract/Free Full Text]
- Kim JK, Kim TK, Ahn HJ, Kim CS, Kim KR, Cho KS. Differentiation of
subtypes of renal cell carcinoma on helical CT scans.
AJR 2002; 178:1499
–1506[Abstract/Free Full Text]
- Herts BR, Coll DM, Novick AC, et al. Enhancement characteristics of
papillary renal neoplasms revealed on triphasic helical CT of the kidneys.
AJR 2002; 178:367
–372[Abstract/Free Full Text]
- Beer AJ, Dobritz M, Zantl N, Weirich G, Stollfuss J, Rummeny EJ.
Comparison of 16-MDCT and MRI for characterization of kidney lesions.
AJR 2006; 186:1639
–1650[Abstract/Free Full Text]
- Choyke PL. Detection and staging of renal cancer. Magn
Reson Imaging Clin N Am 1997;5
: 29–47[Medline]
- Zhang J, Israel GM, Krinsky GA, Lee VS. Masses and pseudomasses of
the kidney: imaging spectrum on MR. J Comput Assist
Tomogr 2004; 28:588
–595[CrossRef][Medline]
- Hallscheidt PJ, Fink C, Haferkamp A, et al. Preoperative staging of
renal cell carcinoma with inferior vena cava thrombus using multidetector CT
and MRI: prospective study with histopathological correlation. J
Comput Assist Tomogr 2005;29
: 64–68[CrossRef][Medline]
- Tuite DJ, Geoghegan T, McCauley G, Govender P, Browne RJ,
Torreggiani WC. Three-dimensional gadolinium-enhanced magnetic resonance
breath-hold FLASH imaging in the diagnosis and staging of renal cell
carcinoma. Clin Radiol 2006;61
: 23–30[CrossRef][Medline]
- Hallscheidt PJ, Bock M, Riedasch G, et al. Diagnostic accuracy of
staging renal cell carcinomas using multidetector-row computed tomography and
magnetic resonance imaging: a prospective study with histopathologic
correlation. J Comput Assist Tomogr 2004;28
: 333–339[CrossRef][Medline]
- Frohmuller HG, Grups JW, Heller V. Comparative value of
ultrasonography, computerized tomography, angiography and excretory urography
in the staging of renal cell carcinoma. J Urol1987; 138:482
–484[Medline]
- Bos SD, Mensink HJ. Can duplex Doppler ultrasound replace
computerized tomography in staging patients with renal cell carcinoma?
Scand J Urol Nephrol 1998;32
: 87–91[CrossRef][Medline]
- Habboub HK, Abu-Yousef MM, Williams RD, See WA, Schweiger GD.
Accuracy of color Doppler sonography in assessing venous thrombus extension in
renal cell carcinoma. AJR 1997;168
: 267–271[Abstract/Free Full Text]
- Fritzsche PJ, Millar C. Multimodality approach to staging renal
cell carcinoma. Urol Radiol 1992;14
: 3–7[Medline]
- Campbell SC, Fichtner J, Novick AC, et al. Intraoperative
evaluation of renal cell carcinoma: a prospective study of the role of
ultrasonography and histopathological frozen sections. J
Urol 1996; 155:1191
–1195[CrossRef][Medline]
- Novick AC. Advances in the management of localized renal cell
cancer. Can J Urol 2000;7
: 960–966[Medline]
- Montravers F, Grahek D, Kerrou K, et al. Evaluation of FDG uptake
by renal malignancies (primary tumor or metastases) using a coincidence
detection gamma camera. J Nucl Med 2000;41
: 78–84[Abstract/Free Full Text]
- Ramdave S, Thomas GW, Berlangieri SU, et al. Clinical role of F-18
fluorodeoxyglucose positron emission tomography for detection and management
of renal cell carcinoma. J Urol 2001;166
: 825–830[CrossRef][Medline]
- Shvarts O, Han KR, Seltzer M, Pantuck AJ, Belldegrun AS. Positron
emission tomography in urologic oncology. Cancer
Control 2002; 9:335
–342[Medline]
- Majhail NS, Urbain JL, Albani JM, et al. F-18 fluorodeoxyglucose
positron emission tomography in the evaluation of distant metastases from
renal cell carcinoma. J Clin Oncol 2003;21
:3995
–4000[Abstract/Free Full Text]
- Marshall FF, Stewart AK, Menck HR. The National Cancer Data Base:
report on kidney cancers. The American College of Surgeons Commission on
Cancer and the American Cancer Society. Cancer1997; 80:2167
–2174[CrossRef][Medline]
- Catalano C, Fraioli F, Laghi A, et al. High-resolution
multidetector CT in the preoperative evaluation of patients with renal cell
carcinoma. AJR 2003;180
:1271
–1277[Abstract/Free Full Text]
- Sandock DS, Seftel AD, Resnick MI. Adrenal metastases from renal
cell carcinoma: role of ipsilateral adrenalectomy and definition of stage.
Urology 1997; 49:28
–31[CrossRef][Medline]
- Hafron J, Kaouk JH. Ablative techniques for the management of
kidney cancer. Nat Clin Pract Urol 2007;4
: 261–269[CrossRef][Medline]
- Giberti C, Oneto F, Martorana G, Rovida S, Carmignani G. Radical
nephrectomy for renal cell carcinoma: long-term results and prognostic factors
on a series of 328 cases. Eur Urol 1997;31
: 40–48[Medline]
- Blom JH, van Poppel H, Marechal JM, et al.; EORTC Genitourinary
Group. Radical nephrectomy with and without lymph node dissection: preliminary
results of the EORTC randomized phase III protocol 30881. Eur
Urol 1999; 36:570
–575[CrossRef][Medline]
- Johnson CD, Dunnick NR, Cohan RH, Illescas FF. Renal
adenocarcinoma: CT staging of 100 tumors. AJR1987; 148:59
–63[Abstract/Free Full Text]
- Fein AB, Lee JK, Balfe DM, et al. Diagnosis and staging of renal
cell carcinoma: a comparison of MR imaging and CT. AJR1987; 148:749
–753[Abstract/Free Full Text]
- Studer UE, Scherz S, Scheidegger J, et al. Enlargement of regional
lymph nodes in renal cell carcinoma is often not due to metastases.
J Urol 1990; 144:243
–245[Medline]
- Saidi JA, Newhouse JH, Sawczuk IS. Radiologic follow-up of patients
with T1-3a,b,c or T4N+M0 renal cell carcinoma after radical nephrectomy.
Urology 1998; 52:1000
–1003[CrossRef][Medline]
- Johnsen JA, Hellsten S. Lymphatogenous spread of renal cell
carcinoma: an autopsy study. J Urol 1997;157
: 450–453[CrossRef][Medline]
- Schafhauser W, Ebert A, Brod J, Petsch S, Schrott KM. Lymph node
involvement in renal cell carcinoma and survival chance by systematic
lymphadenectomy. Anticancer Res 1999;19
:1573
–1578[Medline]
- Kearney GP, Waters WB, Klein LA, Richie JP, Gittes RF. Results of
inferior vena cava resection for renal cell carcinoma. J
Urol 1981; 125:769
–773[Medline]
- Davits RJ, Blom JH, Schroder FH. Surgical management of renal
carcinoma with extensive involvement of the vena cava and right atrium.
Br J Urol 1992;70
: 591–593[Medline]
- Kallman DA, King BF, Hattery RR, et al. Renal vein and inferior
vena cava tumor thrombus in renal cell carcinoma: CT, US, MRI and
venacavography. J Comput Assist Tomogr1992; 16:240
–247[Medline]
- Oto A, Herts BR, Remer EM, Novick AC. Inferior vena cava tumor
thrombus in renal cell carcinoma: staging by MR imaging and impact on surgical
treatment. AJR 1998;171
:1619
–1624[Free Full Text]
- Welch TJ, LeRoy AJ. Helical and electron beam CT scanning in the
evaluation of renal vein involvement in patients with renal cell carcinoma.
J Comput Assist Tomogr 1997;21
: 467–471[CrossRef][Medline]
- Hricak H, Thoeni RF, Carroll PR, Demas BE, Marotti M, Tanagho EA.
Detection and staging of renal neoplasms: a reassessment of MR imaging.
Radiology 1988;166
: 643–649[Abstract/Free Full Text]
- Roubidoux MA, Dunnick NR, Sostman HD, Leder RA. Renal carcinoma:
detection of venous extension with gradient-echo MR imaging.
Radiology 1992;182
: 269–272[Abstract/Free Full Text]
- Goldfarb DA, Novick AC, Lorig R, et al. Magnetic resonance imaging
for assessment of vena caval tumor thrombi: a comparative study with
venacavography and computerized tomography scanning. J
Urol 1990; 144:1100
–1103; discussion
1103–1104[Medline]
- Hatcher PA, Anderson EE, Paulson DF, Carson CC, Robertson JE.
Surgical management and prognosis of renal cell carcinoma invading the vena
cava. J Urol1991; 145:20
–23; discussion 23–24[Medline]
- Kassouf W, Sanchez-Ortiz R, Tamboli P, et al. Cytoreductive
nephrectomy for T4NxM1 renal cell carcinoma: the M. D. Anderson Cancer Center
experience. Urology 2007;69
: 835–838[CrossRef][Medline]
- Yang JC, Sherry RM, Steinberg SM, et al. Randomized study of
high-dose and low-dose interleukin-2 in patients with metastatic renal cancer.
J Clin Oncol 2003;21
:3127
–3132[Abstract/Free Full Text]
- McDermott DF, Regan MM, Clark JI, et al. Randomized phase III trial
of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in
patients with metastatic renal cell carcinoma. J Clin
Oncol 2005; 23:133
–141[Abstract/Free Full Text]
- Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus
interferon-alfa in metastatic renal-cell carcinoma. N Engl J
Med 2007; 356:115
–124[Abstract/Free Full Text]
- Motzer RJ, Figlin RA, Hutson TE, et al. Sunitinib versus
interferon-alfa (IFN-) as first-line treatment of metastatic renal cell
carcinoma (mRCC): updated results and analysis of prognostic factors.
J Clin Oncol 2007;25
[meeting abstracts suppl]:5024[Free Full Text]
- Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced
clear-cell renal-cell carcinoma. N Engl J Med2007; 356:125
–134[Abstract/Free Full Text]
- Hudes G, Carducci M, Tomczak P, et al. Temsirolimus,
interferon-alfa, or both for advanced renal-cell carcinoma. N Engl
J Med 2007; 356:2271
–2281[Abstract/Free Full Text]
- Dutcher JP, Szczylik C, Tannir N, et al. Correlation of survival
with tumor histology, age, and prognostic risk group for previously untreated
patients with advanced renal cell carcinoma (adv RCC) receiving temsirolimus
(TEMSR) or interferon-alpha (IFN). J Clin Oncol2007; 25[meeting abstracts
suppl]: 5033
- Escudier B, Koralewski P, Pluzanska A, et al. A randomized,
controlled, double-blind phase III study (AVOREN) of
bevacizumab/interferon-{alpha}2a vs placebo/interferon-{alpha}2a as first-line
therapy in metastatic renal cell carcinoma. J Clin
Oncol 2007; 25[meeting
abstracts suppl]: 3[Free Full Text]
- Itano NB, Blute ML, Spotts B, Zincke H. Outcome of isolated renal
cell carcinoma fossa recurrence after nephrectomy. J
Urol 2000; 164:322
–325[CrossRef][Medline]
- Chae EJ, Kim JK, Kim SH, Bae SJ, Cho KS. Renal cell carcinoma:
analysis of postoperative recurrence patterns.
Radiology 2005;234
: 189–196[Abstract/Free Full Text]
- Sella A, Swanson DA, Ro JY, et al. Surgery following response to
interferon-alpha-based therapy for residual renal cell carcinoma. J
Urol 1993; 149:19
–21; discussion 21–22[Medline]
- Levy DA, Slaton JW, Swanson DA, Dinney CP. Stage-specific
guidelines for surveillance after radical nephrectomy for local renal cell
carcinoma. J Urol 1998;159
:1163
–1167[CrossRef][Medline]
- Baltaci S, Orhan D, Soyupek S, Beduk Y, Tulunay O, Gogus O.
Influence of tumor stage, size, grade, vascular involvement, histological cell
type and histological pattern on multifocality of renal cell carcinoma.
J Urol 2000; 164:36
–39[CrossRef][Medline]
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Abstract
Introduction
