**2. Common techniques of characterization of renal lesions**

### **2.1. Ultrasound**

Ultrasound (US) is one of the most common techniques used in the initial evaluation of re‐ nal lesions. It is a low cost and easy access technique and it also allows avoiding the expo‐ sure to ionizing radiation and the use of contrast (Figure 1).

**Figure 1.** Solid mass in right upper kidney (5 x 3.7 cm).

Although it is an observer-dependent technique, it allows monitoring renal lesions growth and distinguish between cystic and solid lesions. Ultrasonographic features of cystic lesions that allow distinction with malignant lesions or abscesses are:


One of its limitations is the evaluation and characterization of small lesions. Jamis found that CT detected more renal lesions, especially if they were noncontour deforming. 5% of 2 cm lesions were not detected with CT, an 30% were missed in US. Of lesions under 1 cm, 24% were not detected in TC versus 80% with US [4]. Moreover, given the variability in the echogenicity of malignant kidney, it can be difficult, in the case of isoechoic images, the identification and distinction of these lesions.

In recent years it has become increasingly important the use of contrast-enhanced ultra‐ sound (CEUS). Current CEUS consist of intravenously injected microbubbles that increase the number of reflectors in the vascular space. It has different utilities. It is useful in the dif‐ ferential diagnosis of solid and cystic lesions so as to characterize cystic lesions in benign or malignant [5]. Solid lesions show early arterial enhancement, normally lower than sur‐ rounding parenchyma. The delayed enhancement varies and after an arterial phase lesions are isoechoic relative to parenchyma. Often because of intralesional necrosis, there are intra‐ lesional areas without contrast enhancement.

It is of particular interest the characterization of complex cystic lesions. Some studies have reported a sensitivity and specificity similar to CT [6] [7]. It can be considered a valid alter‐ native to CT and MRI in monitoring these lesions that need prolonged follow [8]. It may also be useful in detecting small renal masses, improving the accuracy of simple ultrasound, since it allows to observe changes in the thickness of the cortical pyramidal space, not visible in simple US.

### **2.2. CT scan**

including oncology pathways due to a specific driver mutations: silencing von-Hippel Lindau gene, angiogenesis alterations, evasion of apoptosis or sustained angiogenesis.These features have enabled the emergence of a wide spectrum of novel oncology drugs that are designed to target and interfere with specific aberrant biological pathways. Therefore, morphological crite‐ ria may not provide meaningful data in this setting and the incorporation of new imaging tech‐ niques (MRI diffusion, perfusion CT, PET scan, etc....) in the diagnosis of extension and assessment of efficacy of this drugs may provide unique physiological data that can be correlat‐

In this chapter we will review the main techniques of radiological diagnosis and staging, the role of new imaging techniques and we will also discuss the validity of the classical criteria

Ultrasound (US) is one of the most common techniques used in the initial evaluation of re‐ nal lesions. It is a low cost and easy access technique and it also allows avoiding the expo‐

ed with histopathological changes and may provide functional information.

**2. Common techniques of characterization of renal lesions**

sure to ionizing radiation and the use of contrast (Figure 1).

**Figure 1.** Solid mass in right upper kidney (5 x 3.7 cm).

of interpretation of response.

**2.1. Ultrasound**

46 Renal Tumor

Computed tomography (CT) is the modality of choice for the diagnosis and study of exten‐ sion of renal carcinoma, with a sensitivity greater than 95% (Figure 2) [9]. In addition, the development of multidetector CT has allowed an increase in the rate of detection and diag‐ nosis in early stages [10].

For the evaluation of suspicious lesions, it is advisable to have a specific protocol. This should include a scan without contrast to determine the presence of calcification or fatty tis‐ sue within the tumor, and will serve as baseline study to study if these lesions enhance after contrast administration.

Tumors less than 3 cm sometimes have a smooth contour, they are homogeneous and diffi‐ cult to distinguish from some benign lesions. Renal cystic carcinomas usually have thick‐ ened walls and septa, sometimes with calcification. Three-dimensional CT is important in staging renal cell carcinoma, with the objective of identifying patients having a resectable tu‐ mor and to define the best therapeutic option. The value of CT is limited to the study of the perirenal fat. Various criteria have been used to describe the appearance of perirenal fat in‐ filtration. Trabeculation of perirenal fat is not a reliable sign of tumor involvement, and is found in approximately 50% of patients with localized tumors T1 and T2. It can be caused by edema, vascular congestion, or prior inflammation [14]. The presence of a nodule uptake in perirenal fat, is considered the most specific finding of perirenal invasion, with high spe‐

Imagen Thecniques in Renal-Cell Carcinoma http://dx.doi.org/10.5772/54190 49

Helical CT has also been shown to have high accuracy in the diagnosis of renal vein in‐ vasion with a negative predictive value of 97% and a positive predictive value of 92%

The adrenal evaluation is important because if no abnormalities are detected on CT, adrena‐ lectomy can be avoided. CT has a high negative predictive value in the detection of adrenal involvement by RCC. When the adrenal gland is enlarged, displaced or not displayed an

The study of lymph node is based primarily on its size. It is considered that a lymph node could be metastatic when its diameter is greater than 1 cm. However this approach has a limited specificity and sensitivity (between 3 and 43% in different studies) because the size

The nodal enhancement pattern helps differentiate between reactive and malignant lympha‐ denopathy. Metastatic lymph nodes can be enhanced after administration of contrast, espe‐

Finally, given that CT plays an important role in detecting distant disease, it is necessary to

conduct a study of the chest and abdomen in the staging of metastatic disease.

cificity (98%) but low sensitivity (46%) [15].

**Figure 3.** Renal cell carcinoma with thrombosis of the inferior cava vein.

adrenalectomy should be considered [17].

increase may be due to inflammatory changes.

cially if the primary tumor is highly vascularized.

(Figure 3) [16].

**Figure 2.** CT scan, right renal cell carcinoma.

The three perfusion renal phases defined in CT diagnosis are: corticomedullary phase, neph‐ rographic phase, and renal elimination phase (or excretory phase) [11].

The images in the corticomedullary phase help to identify the lesion and its vascular supply, being optimal for detecting or excluding tumor invasion of the renal veins [12]. The nephro‐ graphic and elimination phase help detecting renal masses, especially those of small size.

The appearance of renal carcinoma in CT varies depending on the size of the tumor vascula‐ ture, the extent of necrosis or intratumoral cystic changes. Enhancement of a renal lesion shows that it is hypervascular; this is the most important finding in the evaluation of renal masses, being a useful parameter in differentiating histological subtypes.

Different groups have shown as clear cell carcinoma has a higher contrast enhancement than other histological subtypes, especially papillary carcinomas [13]. Zhang et al show that 90% of the clear cell renal carcinoma are hypervascular and heterogeneous (with sol‐ id hypervascular foci and low attenuation foci by necrotic or cystic changes). Seventy five % of papillary carcinomas were hypovascular and 90% had an uniform pattern or peripheral uptake while chromophobe tumors often show a moderate and homogeneous enhancement [10].

Tumors less than 3 cm sometimes have a smooth contour, they are homogeneous and diffi‐ cult to distinguish from some benign lesions. Renal cystic carcinomas usually have thick‐ ened walls and septa, sometimes with calcification. Three-dimensional CT is important in staging renal cell carcinoma, with the objective of identifying patients having a resectable tu‐ mor and to define the best therapeutic option. The value of CT is limited to the study of the perirenal fat. Various criteria have been used to describe the appearance of perirenal fat in‐ filtration. Trabeculation of perirenal fat is not a reliable sign of tumor involvement, and is found in approximately 50% of patients with localized tumors T1 and T2. It can be caused by edema, vascular congestion, or prior inflammation [14]. The presence of a nodule uptake in perirenal fat, is considered the most specific finding of perirenal invasion, with high spe‐ cificity (98%) but low sensitivity (46%) [15].

Helical CT has also been shown to have high accuracy in the diagnosis of renal vein in‐ vasion with a negative predictive value of 97% and a positive predictive value of 92% (Figure 3) [16].

**Figure 3.** Renal cell carcinoma with thrombosis of the inferior cava vein.

**Figure 2.** CT scan, right renal cell carcinoma.

48 Renal Tumor

enhancement [10].

The three perfusion renal phases defined in CT diagnosis are: corticomedullary phase, neph‐

The images in the corticomedullary phase help to identify the lesion and its vascular supply, being optimal for detecting or excluding tumor invasion of the renal veins [12]. The nephro‐ graphic and elimination phase help detecting renal masses, especially those of small size.

The appearance of renal carcinoma in CT varies depending on the size of the tumor vascula‐ ture, the extent of necrosis or intratumoral cystic changes. Enhancement of a renal lesion shows that it is hypervascular; this is the most important finding in the evaluation of renal

Different groups have shown as clear cell carcinoma has a higher contrast enhancement than other histological subtypes, especially papillary carcinomas [13]. Zhang et al show that 90% of the clear cell renal carcinoma are hypervascular and heterogeneous (with sol‐ id hypervascular foci and low attenuation foci by necrotic or cystic changes). Seventy five % of papillary carcinomas were hypovascular and 90% had an uniform pattern or peripheral uptake while chromophobe tumors often show a moderate and homogeneous

rographic phase, and renal elimination phase (or excretory phase) [11].

masses, being a useful parameter in differentiating histological subtypes.

The adrenal evaluation is important because if no abnormalities are detected on CT, adrena‐ lectomy can be avoided. CT has a high negative predictive value in the detection of adrenal involvement by RCC. When the adrenal gland is enlarged, displaced or not displayed an adrenalectomy should be considered [17].

The study of lymph node is based primarily on its size. It is considered that a lymph node could be metastatic when its diameter is greater than 1 cm. However this approach has a limited specificity and sensitivity (between 3 and 43% in different studies) because the size increase may be due to inflammatory changes.

The nodal enhancement pattern helps differentiate between reactive and malignant lympha‐ denopathy. Metastatic lymph nodes can be enhanced after administration of contrast, espe‐ cially if the primary tumor is highly vascularized.

Finally, given that CT plays an important role in detecting distant disease, it is necessary to conduct a study of the chest and abdomen in the staging of metastatic disease.

### **2.3. Magnetic resonance imaging**

Magnetic resonance imaging (MRI) is useful when computed tomography cannot be per‐ formed, but it has not proved to be superior to CT in the detection or characterization of renal masses. The study should include T1 and T2 sequences and opposed-phase images to detect intratumoral fat. Dynamic study after paramagnetic contrast administration is essential.

Both CT and MRI have high reliability in delineating the extent of intratumoral thrombus, since it could change the surgical approach. However, MRI is more sensitive than CT to dif‐ ferentiate between tumoral and non-tumoral thrombus. The tumoral thrombus is heteroge‐ neous or hyperintense on T2-weighted images, with marked enhancement on the postcontrast images, and, sometimes, it is seen the continuity with the renal tumor. The tu‐ mor thrombus is hypointense, not homogeneous and and does not enhance after contrast administration [18].

Also, as discussed below, MRI can help us to distinguish between different histological sub‐ types of renal cell carcinoma (RCC), and between these ones and benign tumors such as on‐ cocytomas and angiomyolipomas.

**Figure 4.** Clear cell RCC. Heterogeneous tumor with focal posterior bleeding. T2 (left side) and T1 sequence (right

Imagen Thecniques in Renal-Cell Carcinoma http://dx.doi.org/10.5772/54190 51

The MR Imaging appearance of oncocytomas is variable and nonspecific. They are typically spherical and well-defined masses with hyposignal on T1-weighted images and hypersignal on T2-weighted images, in most cases. The central scar, when present, has a stellate appear‐ ance with low signal intensity on T1-weighted images and high signal intensity on T2 weighted images, and it may show delayed enhancement after contrast administration.

Angiomyolipoma with a predominant fatty component is isointense relative to fat on all MR Imaging sequences and its signal intensity is higher than that of the renal parenchyma on T1-weighted images. Fat-suppression sequences are also useful. Lipid-poor angiomyolipo‐ mas are difficult to distinguish from clear cell RCC with current imaging methods, so may occasionally be required histopathological evaluation to establish the correct diagnosis [21].

Diffusion-weighted imaging may be useful in differentiating between RCC and oncocytoma and in the characterization of the different histological subtypes of RCC. Angiomyolipoma, due to the presence of fat, can give false positives, but it is characterized through conven‐

The whole-body MRI, at present, is positioning itself as one of the techniques of choice for evaluation of bone marrow in patients with suspected bone metastases with a sensitivity / specificity (> 90%) higher than the radiology conventional CT and bone scans, and similar to

Complement the study with diffusion-weighted imaging, besides allowing a faster interpre‐ tation and greater detection of subtle findings could add specificity to the study [28]. This is particularly relevant with the progressive increased use of new anti tumor drugs in which

side) with fast gradient contrast, showing renal vein invasion. Courtesy Dr. Armesto-Pérez.

Sometimes are surrounded by a well-defined hypointense capsule [24].

this technique may allow better assessment of tumor response [29].

tional sequences [25] [26].

PET-CT (Figure 5) [27].

Clear cell RCC usually shows a signal intensity similar to that of the renal parenchyma on T1-weighted images and it´s high intensity on T2-weighted images (Figure 4). Central ne‐ crosis is common, and it is typically seen as a homogeneus hypointense area in the center of the mass on T1-weighted images, and hyperintense, rarely hypointense, on T2-weighted im‐ ages [19]. If intratumoral hemorrhage occurs, the appearance of this will depend on the de‐ gree of degradation of its components. A hypointense ring, or pseudocapsule, is sometimes seen on both T1 and T2-weighted images, and is due to compression of the adjacent renal parenchyma by the tumor growth. Breakage of this pseudocapsule correlates with advanced stage and higher nuclear grade [20]. This histological subtype tends to be hypervascular, with heterogeneous enhancement during the arterial phase. You can also appreciate renal vein thrombus in more aggressive and advanced tumors. They can also be predominantly cystic, with only a few areas of solid component [21].

The type I papillary RCC is characterized by a homogeneous hyposignal on T2-weighted images, with homogeneous low-level enhancement after contrast administration [22]. Some‐ times they show necrosis and hemorrhage. Type II papillary RCC have a more complex ap‐ pearance, with hemorrhage and necrosis. It is common to see a hemorrhagic cystic mass with enhancing papillary projections at the periphery. In both types is frequent the presence of a fibrous capsule [23].

Chromophobe RCC may show cystic changes within a solid mass. It is not common the presence of necrotic foci, even in large tumors. Its appearance on MR can be identical to those of clear cell RCC [23].

**2.3. Magnetic resonance imaging**

essential.

50 Renal Tumor

administration [18].

of a fibrous capsule [23].

those of clear cell RCC [23].

cocytomas and angiomyolipomas.

cystic, with only a few areas of solid component [21].

Magnetic resonance imaging (MRI) is useful when computed tomography cannot be per‐ formed, but it has not proved to be superior to CT in the detection or characterization of renal masses. The study should include T1 and T2 sequences and opposed-phase images to detect intratumoral fat. Dynamic study after paramagnetic contrast administration is

Both CT and MRI have high reliability in delineating the extent of intratumoral thrombus, since it could change the surgical approach. However, MRI is more sensitive than CT to dif‐ ferentiate between tumoral and non-tumoral thrombus. The tumoral thrombus is heteroge‐ neous or hyperintense on T2-weighted images, with marked enhancement on the postcontrast images, and, sometimes, it is seen the continuity with the renal tumor. The tu‐ mor thrombus is hypointense, not homogeneous and and does not enhance after contrast

Also, as discussed below, MRI can help us to distinguish between different histological sub‐ types of renal cell carcinoma (RCC), and between these ones and benign tumors such as on‐

Clear cell RCC usually shows a signal intensity similar to that of the renal parenchyma on T1-weighted images and it´s high intensity on T2-weighted images (Figure 4). Central ne‐ crosis is common, and it is typically seen as a homogeneus hypointense area in the center of the mass on T1-weighted images, and hyperintense, rarely hypointense, on T2-weighted im‐ ages [19]. If intratumoral hemorrhage occurs, the appearance of this will depend on the de‐ gree of degradation of its components. A hypointense ring, or pseudocapsule, is sometimes seen on both T1 and T2-weighted images, and is due to compression of the adjacent renal parenchyma by the tumor growth. Breakage of this pseudocapsule correlates with advanced stage and higher nuclear grade [20]. This histological subtype tends to be hypervascular, with heterogeneous enhancement during the arterial phase. You can also appreciate renal vein thrombus in more aggressive and advanced tumors. They can also be predominantly

The type I papillary RCC is characterized by a homogeneous hyposignal on T2-weighted images, with homogeneous low-level enhancement after contrast administration [22]. Some‐ times they show necrosis and hemorrhage. Type II papillary RCC have a more complex ap‐ pearance, with hemorrhage and necrosis. It is common to see a hemorrhagic cystic mass with enhancing papillary projections at the periphery. In both types is frequent the presence

Chromophobe RCC may show cystic changes within a solid mass. It is not common the presence of necrotic foci, even in large tumors. Its appearance on MR can be identical to

**Figure 4.** Clear cell RCC. Heterogeneous tumor with focal posterior bleeding. T2 (left side) and T1 sequence (right side) with fast gradient contrast, showing renal vein invasion. Courtesy Dr. Armesto-Pérez.

The MR Imaging appearance of oncocytomas is variable and nonspecific. They are typically spherical and well-defined masses with hyposignal on T1-weighted images and hypersignal on T2-weighted images, in most cases. The central scar, when present, has a stellate appear‐ ance with low signal intensity on T1-weighted images and high signal intensity on T2 weighted images, and it may show delayed enhancement after contrast administration. Sometimes are surrounded by a well-defined hypointense capsule [24].

Angiomyolipoma with a predominant fatty component is isointense relative to fat on all MR Imaging sequences and its signal intensity is higher than that of the renal parenchyma on T1-weighted images. Fat-suppression sequences are also useful. Lipid-poor angiomyolipo‐ mas are difficult to distinguish from clear cell RCC with current imaging methods, so may occasionally be required histopathological evaluation to establish the correct diagnosis [21].

Diffusion-weighted imaging may be useful in differentiating between RCC and oncocytoma and in the characterization of the different histological subtypes of RCC. Angiomyolipoma, due to the presence of fat, can give false positives, but it is characterized through conven‐ tional sequences [25] [26].

The whole-body MRI, at present, is positioning itself as one of the techniques of choice for evaluation of bone marrow in patients with suspected bone metastases with a sensitivity / specificity (> 90%) higher than the radiology conventional CT and bone scans, and similar to PET-CT (Figure 5) [27].

Complement the study with diffusion-weighted imaging, besides allowing a faster interpre‐ tation and greater detection of subtle findings could add specificity to the study [28]. This is particularly relevant with the progressive increased use of new anti tumor drugs in which this technique may allow better assessment of tumor response [29].

ty of skeletal involvement with underestimation of the extension of the extension of the meta‐ static involvement, being clearly inferior to other techniques such magnetic resonance imaging or PET scan [31]. Because most bone metastases are symptomatic, most of authors recommend the use of bone scintigraphy only in symptomatic patients with or without raised level of alka‐ line phosphatase [32,33], although others believe that because its poor sensitivity, the routine

Imagen Thecniques in Renal-Cell Carcinoma http://dx.doi.org/10.5772/54190 53

**Figure 6.** Bone scan of a patient with renal cancer showing metastases in the right tibia, left femur, pelvis and rib

We can study the PET role of in RCC from three points of view: localized disease, extensive

**Localized disease:** Most of publications in this patient subset have been made in a retrospec‐ tive way and many of them studied patients from the PET archive and not from the popula‐

cage.

**2.5. PET**

disease and monitoring treatment response.

use of bone scintigraphy in RCC needs to be questioned [34,35].

**Figure 5.** Whole body MRI. Bone, lung and liver metastases. Courtesy Dr. Armesto-Pérez.

#### **2.4. Bone scan**

Bone metastases in RCC is reported in 17-37% of patients and its early identification may have prognosis importance because its early intervention leads to significant reduction in patient morbidity. Bone scintigraphy is a very useful tool in diagnosis of bone metastases when those lesions have sufficient osteoblastic reaction (Figure 6). However, bone metastases in RCC usu‐ ally appear as large expansive lytic lesions, most commonly in the axial skeleton and are poorly visualized in bone scintigraphy [30], showing variable uptake, with a sensitivity between 10-60% in the diagnosis of this metastases in preselected patients with RCC and high probabili‐ ty of skeletal involvement with underestimation of the extension of the extension of the meta‐ static involvement, being clearly inferior to other techniques such magnetic resonance imaging or PET scan [31]. Because most bone metastases are symptomatic, most of authors recommend the use of bone scintigraphy only in symptomatic patients with or without raised level of alka‐ line phosphatase [32,33], although others believe that because its poor sensitivity, the routine use of bone scintigraphy in RCC needs to be questioned [34,35].

**Figure 6.** Bone scan of a patient with renal cancer showing metastases in the right tibia, left femur, pelvis and rib cage.

### **2.5. PET**

**Figure 5.** Whole body MRI. Bone, lung and liver metastases. Courtesy Dr. Armesto-Pérez.

Bone metastases in RCC is reported in 17-37% of patients and its early identification may have prognosis importance because its early intervention leads to significant reduction in patient morbidity. Bone scintigraphy is a very useful tool in diagnosis of bone metastases when those lesions have sufficient osteoblastic reaction (Figure 6). However, bone metastases in RCC usu‐ ally appear as large expansive lytic lesions, most commonly in the axial skeleton and are poorly visualized in bone scintigraphy [30], showing variable uptake, with a sensitivity between 10-60% in the diagnosis of this metastases in preselected patients with RCC and high probabili‐

**2.4. Bone scan**

52 Renal Tumor

We can study the PET role of in RCC from three points of view: localized disease, extensive disease and monitoring treatment response.

**Localized disease:** Most of publications in this patient subset have been made in a retrospec‐ tive way and many of them studied patients from the PET archive and not from the popula‐ tion of patients with a suspicious kidney mass. More recently we have knows the result of a prospective study that examined 18 patients with renal lesions suspicious for malignancy di‐ agnosed on CT, MRI or ultrasound [36]. In all patients, a FDG-PET/CT was made and diag‐ nosis of malignancy was suspected when intensity on PET was greater than intensity in the renal parenchyma and it was different from the physiological excretion in the collecting sys‐ tem. Patients underwent nephrectomy or surgical resection of the renal mass with the re‐ spective histological analysis. PET showed a sensitivity of 46,6% and a specificity of 66,6%. The median diameter and Furhman grade of FDG positive malignant lesions were signifi‐ cantly higher than in FDG-negative malignant lesions (p< 0,05). It is difficult to draw conclu‐ sions with a study involving a sample of patients so small, but we can see that about half of the patients could not be diagnosed by PET, so probably we will have to expect better re‐ sults with this diagnostic technique before introducing it as part of a routine preoperative diagnosis of RCC. A modification of the technique is the immunological PET, using 124IcG250 (chimeric girentuximab labeled with 124I) because cG250 functions as an epitope of CAIX, a transmembrane enzyme that is almost universally expressed in clear cells RCC cells. With this modality has been observed a 94% sensitivity and 100% specificity, with positive and negative predictive values of 100% and 90% respectively, in a population of 26 patients with renal masses suspicious for malignancy [37].

tients had metabolic disease progression, which correlated with decreased OS and PFS 8HR: 5.96 [95% CI: 2.43-19-02] and 12,13 [95% CI:3,72-46,51]), respectively [41]. With these results, we can conclude that the FDG-PET probably may be more useful in diagnosing tumor pro‐ gression than treatment response. Another point that deserves to be examined is whether

Imagen Thecniques in Renal-Cell Carcinoma http://dx.doi.org/10.5772/54190 55

the cutoff of 20% is appropriate to differentiate responders from those who do not.

**Figure 7.** PET scan showing loco-regional recurrence (red arrows), in a patient with a previous left nephrectomy.

The introduction of functional imaging techniques have allowed us to study in vivo physio‐ logical processes of tissues and tumors. Techniques such as computed tomography (CT) or magnetic resonance (MR) allow us to study tumor perfusion (angiogenesis). Positron emis‐ sion tomography (PET) scan or spectroscopy RM is useful in the evaluation of tumor metab‐ olism while difusion RM allows the study of the diffusion of water molecules through the diffusion sequences (cellularity) to assess hypoxia phenomena or changes in the lymph no‐ des function. All these techniques can obtain information on the tumor microenvironment, including levels of oxygenation, tumor cell proliferation or vascularization and open a dif‐ ferent dimension in the study of patients: diagnosis, staging, treatment planning, evaluation

**3. New techniques in imaging of renal tumors**

of response or follow-up [42] [43].

**Extensive disease:** Although in the metastatic RCC PET has better sensitivity (63-100%) than in localized disease, some authors believe that FDG-PET currently appears to be too unrelia‐ ble to recommend is routine use in the staging of RCC, because it is less sensitive than radio‐ logical imaging for retroperitoneal lymphadenopathy and bone or lung metastases [38]. However, this technique may have a place detecting recurrence and probably an associated prognostic value (Figure 7). In a recent study, the authors found a sensitivity and specificity of 81% and 71% respectively, for FDG-PET in the diagnosis of recurrence, with correct diag‐ nosis in all cases of intra-abdominal (lymph nodes, local recurrence and adrenal glands) and bone recurrence, with a clear trend for better 5-year survival in PET-negative patients com‐ pared with PET-positive patients: 83% versus 46% respectively [39].

**Monitoring treatment response:** Systemic treatment in metastatic RCC is represented for multikinase inhibitors like sorafenib and sunitinib. This drugs are actives because its capaci‐ ty of inhibition on the tyrosine kinase receptor VEGF and the platelet-derived growth factor receptor, in the endothelial cells and pericytes. Because expression of Glut (a downstream product of HIF transcriptional activity), it is conceivable that intensity of FDG uptake may be reflective of the magnitude of the entire pathway [40]. In other words, the variable inten‐ sity of FDG-PET in RCC may reflect variable strength of the HIF signaling pathway. Kayani et al. studied prospectively 44 treatment naive metastatic RCC. A basal (pretreatment) FDG-PET was made and them repeated it at 4 and 16 weeks of treatment. The most intense lesion of each patient (SUV > 2.5) was used as the index lesion and they defined metabolic re‐ sponse as a decrease of > 20% in SUV and metabolic disease progression as an increase of >20 % or development of new metastatic lesions. In the first comparison (after 4 treatment weeks) they found a metabolic response in 24 (57%) patients but without correlation with the PFS or overall survival. In the second comparison (16 treatment weeks), 12 (28%) pa‐ tients had metabolic disease progression, which correlated with decreased OS and PFS 8HR: 5.96 [95% CI: 2.43-19-02] and 12,13 [95% CI:3,72-46,51]), respectively [41]. With these results, we can conclude that the FDG-PET probably may be more useful in diagnosing tumor pro‐ gression than treatment response. Another point that deserves to be examined is whether the cutoff of 20% is appropriate to differentiate responders from those who do not.

tion of patients with a suspicious kidney mass. More recently we have knows the result of a prospective study that examined 18 patients with renal lesions suspicious for malignancy di‐ agnosed on CT, MRI or ultrasound [36]. In all patients, a FDG-PET/CT was made and diag‐ nosis of malignancy was suspected when intensity on PET was greater than intensity in the renal parenchyma and it was different from the physiological excretion in the collecting sys‐ tem. Patients underwent nephrectomy or surgical resection of the renal mass with the re‐ spective histological analysis. PET showed a sensitivity of 46,6% and a specificity of 66,6%. The median diameter and Furhman grade of FDG positive malignant lesions were signifi‐ cantly higher than in FDG-negative malignant lesions (p< 0,05). It is difficult to draw conclu‐ sions with a study involving a sample of patients so small, but we can see that about half of the patients could not be diagnosed by PET, so probably we will have to expect better re‐ sults with this diagnostic technique before introducing it as part of a routine preoperative diagnosis of RCC. A modification of the technique is the immunological PET, using 124

CAIX, a transmembrane enzyme that is almost universally expressed in clear cells RCC cells. With this modality has been observed a 94% sensitivity and 100% specificity, with positive and negative predictive values of 100% and 90% respectively, in a population of 26 patients

**Extensive disease:** Although in the metastatic RCC PET has better sensitivity (63-100%) than in localized disease, some authors believe that FDG-PET currently appears to be too unrelia‐ ble to recommend is routine use in the staging of RCC, because it is less sensitive than radio‐ logical imaging for retroperitoneal lymphadenopathy and bone or lung metastases [38]. However, this technique may have a place detecting recurrence and probably an associated prognostic value (Figure 7). In a recent study, the authors found a sensitivity and specificity of 81% and 71% respectively, for FDG-PET in the diagnosis of recurrence, with correct diag‐ nosis in all cases of intra-abdominal (lymph nodes, local recurrence and adrenal glands) and bone recurrence, with a clear trend for better 5-year survival in PET-negative patients com‐

**Monitoring treatment response:** Systemic treatment in metastatic RCC is represented for multikinase inhibitors like sorafenib and sunitinib. This drugs are actives because its capaci‐ ty of inhibition on the tyrosine kinase receptor VEGF and the platelet-derived growth factor receptor, in the endothelial cells and pericytes. Because expression of Glut (a downstream product of HIF transcriptional activity), it is conceivable that intensity of FDG uptake may be reflective of the magnitude of the entire pathway [40]. In other words, the variable inten‐ sity of FDG-PET in RCC may reflect variable strength of the HIF signaling pathway. Kayani et al. studied prospectively 44 treatment naive metastatic RCC. A basal (pretreatment) FDG-PET was made and them repeated it at 4 and 16 weeks of treatment. The most intense lesion of each patient (SUV > 2.5) was used as the index lesion and they defined metabolic re‐ sponse as a decrease of > 20% in SUV and metabolic disease progression as an increase of >20 % or development of new metastatic lesions. In the first comparison (after 4 treatment weeks) they found a metabolic response in 24 (57%) patients but without correlation with the PFS or overall survival. In the second comparison (16 treatment weeks), 12 (28%) pa‐

cG250 (chimeric girentuximab labeled with 124

54 Renal Tumor

with renal masses suspicious for malignancy [37].

pared with PET-positive patients: 83% versus 46% respectively [39].

I-

I) because cG250 functions as an epitope of

**Figure 7.** PET scan showing loco-regional recurrence (red arrows), in a patient with a previous left nephrectomy.
