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GENITOURINARY IMAGING

135

Pathways of Lymphatic Spread in Male Urogenital Pelvic Malignancies1 CME FEATURE See www.rsna .org/education /rg_cme.html

LEARNING OBJECTIVES FOR TEST 3 After reading this article and taking the test, the reader will be able to: ■■Describe

the anatomy of the retroperitoneal and inguinopelvic nodal groups by using standard terminology. ■■Identify

the pathways of nodal metastasis that are specific to tumor sites in the prostate, penis, testis, and male bladder. ■■Discuss

the optimal imaging technique and classification system for staging of nodal metastases from male urogenital tumors.

Blanca Paño, MD • Carmen Sebastià, MD • Laura Buñesch, MD • Judit Mestres, MD • Rafael Salvador, MD • Napoleón G. Macías, MD • Carlos Nicolau, MD Regional lymph node involvement in urogenital malignancies (category N in the TNM classification system) is a significant radiologic finding, with important implications for treatment and prognosis. Male urogenital pelvic cancers commonly spread to iliopelvic or retroperitoneal lymph nodes by following pathways of normal lymphatic drainage from the pelvic organs. The most likely pathway of nodal spread (superficial inguinal, pelvic, or paraaortic) depends on the tumor location in the prostate, penis, testis, or bladder and whether surgery or other therapy has disrupted normal lymphatic drainage from the tumor site; knowledge of both factors is needed for accurate disease staging. At present, lymph node status is most often assessed with standard anatomic imaging techniques such as multidetector computed tomography or magnetic resonance (MR) imaging. However, the detection of nodal disease with these techniques is reliant on lymph node size and morphologic characteristics, criteria that provide limited diagnostic specificity. Functional imaging techniques, such as diffusion-weighted MR imaging performed with or without a lymphotropic contrast agent and positron emission tomography, may allow a more accurate nodal assessment based on molecular or physiologic activity. ©

RSNA, 2011 • radiographics.rsna.org

Abbreviations: FDG = fluorine 18 fluorodeoxyglucose, PSA = prostate-specific antigen, USPIO = ultrasmall superparamagnetic iron oxide RadioGraphics 2011; 31:135–160 • Published online 10.1148/rg.311105072 • Content Codes: From the Center for Diagnostic Imaging (CDIC), Hospital Clínic de Barcelona, Villarroel 170, 08036 Barcelona, Spain. Presented as an education exhibit at the 2009 RSNA Annual Meeting. Received March 22, 2010; revision requested May 6 and received July 1; accepted July 26. For this CME activity the authors, editors, and reviewers have no relevant relationships to disclose. Address correspondence to B.P. (e-mail: [email protected]). 1

©

RSNA, 2011

136 January-February 2011

radiographics.rsna.org

Figure 1. Schematic shows the major pelvic and retroperitoneal lymph node groups: the inguinal (red), external iliac (green), internal iliac (yellow), common iliac (pink), and paraaortic (blue) nodes.

Introduction

The detection of metastases to lymph nodes is crucial for the accurate staging of male urogenital pelvic malignancies. Accurate nodal staging is important for clinical management and is frequently an independent prognostic factor. Moreover, the rate of cancer recurrence increases with nodal spread. Knowledge of the anatomic pathways by which these tumors spread may facilitate identification of the most likely sites of nodal involvement, helping improve nodal assessment and, thus, aiding in the management of each patient according to specific radiologic findings. Current multidetector computed tomography (CT) and magnetic resonance (MR) imaging techniques, which rely on nonspecific morphologic criteria, have only a limited capability for differentiating between benign and malignant changes in lymph nodes. Innovative functional imaging techniques such as MR imaging with the use of ultrasmall paramagnetic iron oxide (USPIO) particles, diffusion-weighted sequences, or both, and positron emission tomography (PET), might help overcome this significant limitation by providing information about molecular or physiologic activity.

The article describes the anatomy and nomenclature of the iliopelvic and paraaortic lymph nodes and outlines common pathways of metastasis from tumors of the male urogenital system to these regional nodes. The advantages and limitations of anatomic and functional imaging techniques for the detection and classification of nodal disease are discussed in detail.

Normal Anatomy of the Paraaortic and Iliopelvic Nodes

A solid understanding of the anatomy and nomenclature of the inguinopelvic and retroperitoneal nodal groups is essential for accurate staging of male urogenital pelvic neoplasms. These nodal groups are described briefly in the next five sections (Fig 1).

Paraaortic Nodes The paraaortic nodes can be divided into seven subgroups on the basis of the relationship of the node to the aorta and the inferior vena cava (Fig 2). The lateroaortic, preaortic, and retroaortic nodes surround the aorta. The right lateroaortic subgroup is further divided into aortocaval, laterocaval, precaval, and retrocaval subgroups, with the nomenclature reflecting the location of the nodes in relation to the inferior vena cava (1).

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Figure 2. Schematic shows the seven subgroups of paraaortic lymph nodes. The subgroups are distinguished from one another on the basis of their positions in relation to the aorta and the inferior vena cava.

Figure 3. Common iliac lymph nodes. Schematic (a) and axial contrast material–enhanced CT image (b) show the common iliac nodal group, which consists of three chains. These are, as depicted in b, the lateral chain (L), which is located lateral to the common iliac artery (a) and forms an extension from the lateral external iliac nodal chain; the medial chain (M), which occupies the triangular area bordered by both common iliac arteries and includes nodes at the sacral promontory; and the middle chain (Mi), which consists of nodes within the lumbosacral fossa. The relation of these nodes to the common iliac vein (v in b) also is shown.

Common Iliac Nodal Group The common iliac nodal group consists of three chains: lateral, middle, and medial (Fig 3). The first chain is an extension of the lateral chain of external iliac nodes located lateral to the common iliac artery. The medial chain occupies the triangular area bordered by both common iliac arteries from the aortic bifurcation to the bifurcations of the external and internal iliac arteries. Nodes at the sacral

promontory are included in this chain. The middle chain nodes are located in the lumbosacral fossa (the area bordered posteromedially by the lower lumbar or upper sacral vertebral bodies, anterolaterally by the psoas muscle, and anteromedially by the common iliac vessels) and between the common iliac artery and common iliac vein (1).



Figure 4. Internal iliac lymph nodes. Schematic (a) and axial contrast-enhanced CT image (b) show the chains of internal iliac lymph nodes that accompany the visceral branches of the internal iliac vessels. In b, the central location of the sacral (S) nodes within the pelvis and the position of the junctional (J) nodes between the internal (a) and external (a´) iliac arteries are clearly visible. v = internal iliac veins.

Figure 5. External iliac lymph nodes. Schematic (a) and axial contrast-enhanced CT image (b) show the three chains of the external iliac nodal group. These are, as depicted in b, the lateral (L) chain, positioned laterally along the external iliac artery; the middle (Mi) chain, situated between the external iliac artery (a) and external iliac vein (v); and the medial (M) chain (also known as obturator nodes), positioned medial and posterior to the external iliac vein.

Internal Iliac (Hypogastric) Nodal Group The internal iliac nodal group, also known as the hypogastric nodal group, consists of several

nodal chains accompanying each of the visceral branches of the internal iliac artery (Fig 4). Among the nodes of this group are the junctional nodes that are located at the junction between the internal and external iliac nodal groups. The junctional nodes have relevance for various path-


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Figure 6. Inguinal lymph nodes. (a, b) Schematic (a) and axial contrast-enhanced CT image (b) show the locations of the superficial (S) and deep (D) inguinal nodes in relation to the common femoral artery (a), common femoral vein (v), and saphenous vein (v´). The sentinel nodes in the superficial inguinal group are those located at the saphenofemoral junction. (c) Axial contrast-enhanced CT image shows the origin of the inferior epigastric and circumflex iliac (cx) vessels, a landmark that allows differentiation between deep inguinal nodes (D) and medial-chain external iliac nodes (M). v = external iliac vein.

ways of lymphatic dissemination, as described in the section on “Common Pathways of Nodal Metastasis” (1).

External Iliac Nodal Group The external iliac nodal group consists of three chains: lateral, middle, and medial (Fig 5). The lateral chain includes nodes that are located along the lateral aspect of the external iliac artery. The middle chain comprises nodes located between the external iliac artery and the external iliac vein. The medial chain contains nodes located medial and posterior to the external iliac vein. The medial chain nodes are also known as the obturator nodes (1).

Inguinal Lymph Nodes This group consists of superficial inguinal and deep inguinal nodes (Fig 6). The superficial inguinal nodes, which are located in the subcutaneous tissue anterior to the inguinal ligament, accompany the superficial femoral vein and the saphenous vein. The sentinel nodes for the super-

ficial subgroup are those situated at the saphenofemoral junction, where the great saphenous vein drains into the common femoral vein. The deep inguinal nodes are those located along the common femoral vessels. The landmarks that allow differentiation between the deep inguinal nodes and the medial chain of the external iliac nodes are the inguinal ligament and the origins of the inferior epigastric and circumflex iliac vessels (1).

Common Pathways of Nodal Metastasis

The lymphatic spread of male urogenital pelvic tumors usually occurs via one of three general pathways of lymphatic drainage: superficial inguinal, pelvic, or paraaortic. The most likely pathway in each case depends largely on the location of the tumor. However, the expected pathway may be altered in patients who have undergone treatment for cancer.



Superficial Inguinal Pathway The superificial inguinal pathway is the primary route of metastasis from perineal tumors, including penile cancer (Fig 7). The saphenofemoral junction node is the sentinel node along this pathway; from that node, metastatic tumor cells may ascend to the deep inguinal and external iliac nodes (1).

Pelvic Pathways Pelvic tumors may metastasize along four pelvic lymphatic drainage pathways: (a) the anterior pelvic route, which drains lymph from the anterior wall of the bladder along the obliterated umbilical artery to the internal iliac (hypogastric) nodes (Fig 8a); (b) the lateral route, which drains lymph from the pelvic organs to the medial chain of the external iliac nodal group (a characteristic route of spread from carcinomas at the lateral aspect of the bladder and from prostate adenocarcinomas); (c) the internal iliac (hypogastric) route, which drains lymph from most of the pelvic organs along the visceral branches of the internal iliac lymphatic ducts to the junctional nodes located at the junction between the internal and external iliac vessels; and (d) the presacral route, which includes the lymphatic plexus anterior to the sacrum and coccyx and extending upward to the common iliac nodes (Fig 8b). Late-stage tumors of lower pelvic organs such as the prostate may spread to the presacral space either via the perirectal lymphatics or by direct extension (1).

Paraaortic Pathway Metastases from testicular carcinoma most commonly occur along the paraaortic pathway, a route that bypasses the pelvic lymph nodes (Fig 9). The lymphatic vessels of the testis follow the gonadal blood vessels, ascending through the spermatic cord. At the inguinal ring the lymphatic vessels continue upward along the gonadal blood vessels, anterior to the psoas muscle, ending in the paraaortic and paracaval nodes at the renal hilum. From these nodes, metastatic disease may spread downward in a retrograde fashion, toward the aortic bifurcation (1).

Modified Posttherapeutic Pathways Knowledge about any previous treatment of the primary tumor is important because surgery, chemotherapy, and radiation therapy may modify the

Figure 7. Superficial inguinal lymphatic drainage pathway. Schematic shows the location of the saphenofemoral junction nodes, sentinel nodes for the superficial inguinal pathway, along which metastatic tumor cells from the penis can ascend toward the deep inguinal (red) and external iliac (green) nodes.

pattern of nodal disease. Nodal dissemination follows a different pathway when normal lymphatic drainage has been disrupted by nodal dissection or therapeutic irradiation, as often occurs in the treatment of germ cell tumors of the testis. Pelvic nodes are not usually involved in testicular cancer unless scrotal surgery or retroperitoneal nodal dissection has taken place (2,3). After radical cystectomy for bladder cancer, metastatic disease is seen more frequently in the common iliac and paraaortic nodes than in the expected nodal chains (4). Similarly, after therapeutic irradiation of the prostate or radical prostatectomy, recurrent disease usually is seen in extrapelvic nodes (5).

Anatomic Imaging Evaluation Multidetector CT and MR Imaging Anatomic imaging techniques are the techniques most widely used for the staging of nodal disease in patients with urogenital pelvic malignancies. Multidetector CT and MR imaging enable direct visualization of lymph nodes, allowing evaluation of those that are related to the primary tumor. The most common sign of nodal involvement in malignancy is the enlargement of lymph nodes. However, normal-sized or minimally enlarged lymph nodes also may represent metastases,


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Figure 8. Schematics show pelvic pathways of nodal metastasis. (a) By the anterior route (arrows), lymph drains from the anterior wall of the bladder along the obliterated umbilical artery to the internal iliac or hypogastric nodes. (b) By the lateral route (purple arrow), lymph drains from the pelvic organs to the external iliac (green) nodes; by the internal iliac or hypogastric route (pink arrow), it drains along the visceral branches of the internal iliac vessels to the junctional nodes; and by the presacral route (yellow arrow), it drains through the lymphatic plexus anterior to the sacrum and coccyx. Figure 9. Schematic shows the paraaortic pathway of metastasis (arrows), by which malignant cells from testicular tumors can proceed upward through lymphatic ducts that follow the gonadal vessels to nodes at the renal hilum, completely bypassing the pelvic nodes.


and other signs, such as the shape or location of nodes, should be considered. The combined use of these morphologic criteria could help improve the detection of nodal metastases at multidetector CT and MR imaging. Multidetector CT is the modality most often used for the initial staging of urogenital malignancies because of its high spatial resolution and capability for acquisition of a large image dataset within a brief time. Multiplanar reconstruction of the near-isotropic multidetector CT image datasets provides three-dimensional views of nodal shape and allows accurate nodal measurement and accurate calculation of the ratio of the longitudinal nodal diameter to the transverse diameter. Moreover, the high spatial resolution provided by multidetector CT is beneficial for illustrating the relations between lymph nodes and vessels. MR imaging provides excellent soft-tissue contrast and is therefore helpful for the staging of tumors in sites such as the bladder and prostate, where the regional lymph nodes are those within the pelvis.

Imaging-based Criteria for Identifying Nodal Metastases Lymph Node Size.—The ability to distinguish

between malignant and benign change in lymph nodes by using morphologic imaging techniques is reliant on nodal size criteria. The criterion that is generally accepted is a maximum short-axis diameter of more than 10 mm (6–11). However, size-based nodal assessment has several limitations. Findings of lymph node involvement in malignancy are often inaccurate because a substantial proportion of nodes that harbor metastases from urogenital cancers are not enlarged to a size considered to exclude normalcy. Furthermore, the size of a node does not allow differentiation between nodal metastasis and nodal hyperplasia. The sensitivity of CT for the detection of nodal metastases on the basis of node size ranges from 24% to 78%, and that of MR imaging, from 24% to 75%. The results of many studies have shown that the use of a node size smaller than 10 mm as the criterion for identifying nodal metastases from urogenital malignancies resulted in a reduction in the falsenegative rate; however, this benefit was offset by diminished specificity (12–15). Another limitation of using node size to identify metastatic disease is the variability of the size


Figure 10. Axial contrast-enhanced CT image shows an enlarged junctional node (arrow) with a maximum short-axis diameter of 14 mm. The node has irregular borders and demonstrates inhomogeneous enhancement, characteristics that are strongly suggestive of metastasis.

criterion according to the location of the node and the primary tumor. On the basis of their experience with MR imaging, Grubnic et al (6) advocated that lymph nodes with a maximum short-axis diameter of more than 5 mm in the retroperitoneum and 6 mm in the pelvis be considered abnormal. Vinnicombe et al (7) proposed that the upper limit of the maximum short-axis diameter for normal lymph nodes in patients with testicular tumors be 9 mm for the common iliac region, 10 mm for the external iliac region, and 7 mm for the internal iliac region. Koh et al (3) described as “suspicious” a maximum short-axis diameter of 8 mm for abdominal retroperitoneal lymph nodes in patients with testicular cancer. The results of a study by Oyen et al (9) in patients with prostate cancer showed that with 6 mm used as the upper limit of normal node size at CT, sensitivity of 78% and specificity of 97% were achieved in the detection of nodal metastases. We were unable to find in the literature any specific recommendations regarding size criteria for identifying nodal metastases from penile or bladder cancer. Shape and Contour of Nodes.—Most benign

nodes are ovoid, whereas malignant nodes tend to have a rounded shape. However, the use of combined criteria of size and shape did not improve the accuracy of radiologic assessment of urogenital pelvic cancers beyond that achieved with size as the single criterion (16). Another useful sign of nodal involvement might be an irregular node border, which occurs in some cases


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age from a primary tumor and that are borderline in size or recently increased in size have a higher probability of metastatic infiltration and should be evaluated more carefully than other nodes. Number of Nodes.—The presence of a group

of normal-appearing nodes may be suggestive of malignancy, as was found in a study of nonHodgkin lymphoma. However, the specificity of this sign is low, particularly in the pelvis, where nodal asymmetry is common and may lead to false-positive findings (3). Figure 11. Axial contrast-enhanced CT image obtained in a patient who had undergone treatment for a seminomatous tumor of the right testis shows an enlarged, calcified aortocaval node (arrow) with a diameter of 15 mm in its greatest dimension, a finding indicative of N1 disease. Nodal calcification in this case is nonspecific.

Figure 12. Magnified axial contrastenhanced CT image shows an enlarged external iliac node (arrow) with a central region of low attenuation, an appearance produced in this case by tuberculosis and not pathognomonic of malignant infiltration.

because of extracapsular extension of metastatic disease (Fig 10). However, this sign is rarely observed in small nodal metastases. Nodal Location.—The location of a node should

be considered to determine whether it lies along a specific lymphatic drainage pathway. Nodes that are located along the pathway of lymphatic drain-

Internal Nodal Architecture.—Internal archi-

tectural features such as calcifications and accumulations of fat or fluid, which are well depicted with anatomic imaging techniques (especially MR imaging, which provides better soft-tissue contrast resolution than CT), may be helpful for identifying nodal metastases. The MR signal intensity of an involved node may resemble that of a primary malignancy; this finding is suggestive of nodal involvement. Nodal calcifications may be observed in the presence of metastases from bladder cancer. However, calcifications also may be seen in nodes affected by benign inflammatory disease such as tuberculosis or by posttherapeutic changes such as occur after treatment for seminoma (Fig 11). It is important to remember that nodal calcifications are not a reliable sign of either malignancy or benignity. Some metastatic nodes, especially those arising from nonseminomatous germ cell tumors of the testes, have an internal cystic appearance due to central areas of necrosis that have low attenuation at CT and high signal intensity at T2-weighted MR imaging. Large metastatic nodes also frequently appear heterogeneous, with a low-density component (perhaps due to necrosis) at their centers. However, the appearance of a central area of lower density within a lymph node is not pathognomonic of malignant infiltration and may be observed also in the presence of tuberculosis and various fungal infections (17–19) (Fig 12). Lymph nodes frequently enhance after the administration of a contrast agent. Homogeneous enhancement of a node may result from both benign and malignant conditions. However, inhomogeneous enhancement of an enlarged node should arouse the suspicion that malignant infiltration may be present (20) (Fig 10).


radiographics.rsna.org Table 1 Incidence of Nodal Metastases from Male Urogenital Tumors according to Primary Tumor Location and Classification Tumor Classification

Tumor Location

T1

T2

T3

T4

Prostate Penis Bladder

< 5% 16%–60%† < 5%

< 5% 82% 10%–20%‡

15%–30%* 100% 30%–50%

> 40% 100% 40%–45%

Sources.—References 20, 22, and 23. *Incidence is 15% in early T3 disease and 30% in late T3 disease. †Incidence is 16% in T1 G1 disease and 60% in T1 G2 and T1 G3 disease. ‡Incidence is 10%–15% in T2a and 15%–20% in T2b disease.

Metastatic nodes may demonstrate contrast enhancement similar to that of the primary tumor, a finding that represents malignant infiltration with the same grade and aggressiveness (3,20). Noworolski et al (21) recently reported that it is possible to discriminate between benign change and malignancy on the basis of semiquantitative or quantitative analysis of the rate of nodal contrast enhancement at both CT and MR imaging. However, the use of this approach is still confined to the research setting. Accumulated fat within a node is more likely to represent benign change than malignancy. Other Indicators.—Various characteristics of a

primary tumor, such as its anatomic location, stage, grade, histologic makeup, and biologic behavior, affect both the frequency of occurrence and the individual characteristics of nodal metastases. Among patients with urogenital cancers, as among those with most other abdominal or pelvic cancers, the prevalence of nodal disease increases with the stage of the primary tumor. The relationship between the tumor stage and the likelihood of nodal metastasis is summarized in Table 1. Other biologic indicators also may signal the likelihood of nodal metastases. For example, a Partin nomogram based on the preoperative serum level of prostate-specific antigen (PSA), clinical TNM classification, and Gleason score at biopsy in a patient with prostate cancer may be predictive of the histopathologic grade at radical prostatectomy and the likelihood of nodal disease. Partin nomograms that indicate a high risk of nodal disease provide an alert to the radiologist to exercise caution during nodal evaluation (24).

Functional Imaging Evaluation

A number of functional imaging techniques have been or are being developed to overcome the limitations of anatomic imaging techniques for cancer staging. As mentioned earlier, nodal assessment with anatomic imaging techniques relies on nonspecific criteria that are of limited use for differentiating benign change in lymph nodes from malignant involvement. Functional imaging techniques, which allow assessments of metabolic and physiologic activity, may provide more reliable information.

Lymphotropic Nanoparticle–enhanced MR Imaging This emerging technique represents one of the most promising approaches for the detection of lymph node metastases in patients with urologic cancers, although lymphotropic nanoparticle– based contrast agents have not yet been approved for clinical use in the United States and Europe. The results of MR imaging experiments performed with the use of ultrasmall superparamagnetic iron oxide (USPIO) particles, also known as ferumoxtran-10, show that this technique allows indirect evaluation of macrophage function within the lymph nodes. Normal lymph nodes contain macrophages that engulf the USPIO nanoparticles, whereas lymph nodes affected by a malignancy lack the phagocytic cells needed to take up these nanoparticles. Thus, normal lymph nodes show homogeneous uptake of USPIO particles and appear dark at MR imaging because of T2 and T2* shortening, whereas lymph nodes affected by metastatic disease do not take up the contrast material, and therefore appear bright. Since the image interpretation is based on nodal function rather than nodal structure, it is possible to detect subcentimeter metastases in normal-sized nodes and to accurately characterize enlarged, reactive nodes.


False-positive results may occur in the presence of reactive nodal hyperplasia, inflammation, or granulomatous disease with central necrosis, conditions in which the relative scarcity or absence of macrophages results in decreased nanoparticle uptake and thus incorrect characterization of lymph nodes as malignant. Falsepositive results also may be caused by focal lipomatosis or focal nodal fibrosis; however, the acquisition and review of T1-weighted images, which allow accurate identification of fat in the nodal hilum, can help reduce the frequency of false-positive findings (25). False-negative results have been reported to occur in the presence of nodal metastases smaller than 5 mm (26), the minimum spatial resolution threshold for depiction by the currently available MR imaging systems (25). Nevertheless, in a recent trial in which USPIO particle–enhanced MR imaging was compared with iodinated contrast material–enhanced CT in 80 men with clinically localized prostate carcinoma, a high level of accuracy was achieved with USPIO particle–enhanced MR imaging, with increases in both sensitivity (from 35% to 90%) and specificity (from 90% to 98%) for the detection of nodal metastases. Similarly, the sensitivity and negative predictive value of MR lymphangiography with the use of USPIO particles were as high as 82% and 96% in 375 patients with prostate cancer with an intermediate to high risk of nodal metastases (>5% risk according to nomograms) (26). High levels of accuracy in the identification of nodal metastases also have been found with the use of USPIO particle–enhanced MR imaging in patients with testicular (27), bladder (28), and penile (29,30) cancers. Results obtained in different trials are not directly comparable because of overall heterogeneity in study designs, MR imaging techniques used, and body parts imaged. Results obtained in the pelvis may not be applicable to the mediastinum, where image degradation due to motion artifact may lead to a decrease in sensitivity for the detection of small metastases. Experimental studies have shown that the quality of image interpretation with this technique also varies according to the learning curve of the individual interpreter. Furthermore, interpretation is time consuming because the evaluation of each lymph node requires a comparison between unenhanced and contrast-enhanced acquisitions in order to determine whether low signal intensity in a single lymph node is caused by uptake of USPIO particles (27,28).

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Diffusion-weighted MR Imaging Diffusion-weighted MR imaging sequences are designed to depict alterations in thermally induced random (Brownian) motion of water molecules within tissues. The degree of this motion is known as diffusion. Diffusion-weighted MR imaging can be performed quickly, without the necessity of administering an exogenous contrast medium. The technique yields qualitative and quantitative information that reflects changes at a cellular level and provides unique insight into tumor cellularity and cellular membrane integrity. High cellularity and cell membrane integrity restrict diffusion. With clinical MR imaging systems, diffusion sensitivity can easily be varied by changing the b value used during image acquisition. Quantitative analysis of diffusion may be performed by obtaining and mapping apparent diffusion coefficient (ADC) values. Diffusion-weighted imaging has been reported to allow differentiation between malignant and nonmalignant change in lymph nodes, with good sensitivity and specificity. Normal lymph nodes exhibit relatively restricted diffusion because of their high cellular density. Metastatic lymph nodes may contain areas of increased cellular density or necrosis that further restrict or increase diffusion. Thus, lymph node abnormalities can be detected more quickly and more easily by using this technique. Nevertheless, it is as yet unknown whether nonmalignant change in lymph nodes can be differentiated from malignant involvement by using diffusion-weighted MR images and calculated ADC values. There are major challenges to the widespread adoption of diffusion-weighted MR imaging, including the standardization of protocols for image data acquisition and analysis (31,32). Although diffusion-weighted imaging shows promise as a noninvasive technique for evaluation of nodal involvement in pelvic malignancies, the interpretation of diffusion-weighted images is difficult because of limited spatial resolution, limited morphologic information, and artifacts. Thoeny et al (33) recently reported the results of their study of USPIO nanoparticle–enhanced MR imaging performed with diffusion-weighted sequences. The major advantage of this approach, in comparison with USPIO particle–enhanced non–diffusion-weighted MR imaging, was the average time needed for image evaluation (13 minutes instead of 80 minutes). However, further studies are needed to verify these results.



PET/CT and PET/MR Imaging with Metabolically Active Compounds PET/CT is used with increasing frequency for cancer staging because it provides a useful combination of metabolic (functional) information with anatomic information. By contrast, the fusion of PET with MR imaging for oncologic evaluations has yet to be validated in clinical studies (34–36). The radiopharmaceutical most commonly used at PET/CT for oncologic imaging is fluorine 18 fluorodeoxyglucose (FDG), which allows the detection of tissues with abnormally high glucose uptake, such as tumors. However, FDG PET/CT is not considered useful for the staging of most male urogenital malignancies, because there is little metabolic activity in the prostate and because excretion of the radiotracer via the urinary tract and bowel may hinder accurate evaluation of pelvic nodes. Clinical studies of PET/CT performed with the use of alternative radiotracers such as carbon 11 (11C)-acetate or -choline have shown promising results in the staging of prostate cancer (37–39). Studies performed with choline showed high accuracy for the detection of lymph node invasion in patients with an intermediate to high risk of regional metastasis from prostate carcinoma (according to available nomograms) who underwent pelvic lymph node dissection. The sensitivity, specificity, negative predictive value, positive predictive value, and percentage of correctly recognized cases with PET/CT were 60%, 97.6%, 87.2%, 90%, and 87.7% (40). In addition, the alternative use of 11C-choline at PET/CT to overcome the limitations of FDG trace excretions to the urinary system has been tested in patients with bladder cancer. Several studies were recently reported in which a limited number of patients were assessed with 11Ccholine PET/CT for the preoperative detection of nodal metastases from bladder cancer. The reported sensitivity of this technique was between 60% and 99%, slightly higher than that of CT alone. However, larger clinical studies are needed to clarify the value of PET for the preoperative staging of bladder cancer (41). FDG PET/CT is useful for the staging and posttreatment follow-up of testicular cancer. Albers et al (42) compared the accuracy of CT

Figure 13. Schematic shows common pathways of metastasis from prostate cancer. The obturator nodes in the external iliac (green) nodal group are sentinel nodes along the lateral route (dashed purple arrows), and the junctional nodes in the internal iliac (yellow) nodal group are sentinel nodes along the hypogastric route (dashed yellow arrows).

and FDG PET for TNM classification of stage I or II seminomatous and nonseminomatous germ cell tumors of the testis and concluded that FDG PET had a higher sensitivity (70% versus 40%) and a higher specificity (100% versus 78%). A study by Hain et al (43) demonstrated comparable results. One limitation of FDG PET in these studies was its inability to depict metastatic lesions with a diameter of less than 5 mm (42). However, CT is similarly limited; it does not allow accurate detection of nodal metastases until the node size reaches 1 cm. No substantial progress has been made in the development of new radiotracers for the staging of testicular cancer.

TNM Classification of Male Urogenital Pelvic Malignancies

Urogenital tumors usually spread first to regional lymph nodes. The specific nodal groups most likely to be affected by metastatic disease vary according to the location of the primary tumor (prostate, penis, testis, or bladder). In the TNM classification system, regional nodal metastases


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Figure 14. Schematics show unilateral (a) and bilateral (b) regional metastases (N1 lesions) from prostate cancer. Regional metastases (represented as red nodes) may occur in both the internal and the external iliac nodal groups, and their laterality does not affect their categorization as N lesions. Horizontal line through the pelvis shows the division between sites of N and M1 disease.

Table 2 Clinical Determinants of Risk of Nodal Metastasis from Prostate Carcinoma Parameter

High Risk

Low Risk

PSA level (ng/mL) Gleason score Clinical disease stage

≥ 20 ≥7 T3 or T4

< 20