Kidney: Current Concepts In The Diagnosis and Management of Renal Cell Carcinoma: Role of Multidetector CT and Three Dimensional CT

SHEILA SHETH, M.D., JOHN C SCATARIGE, M.D. , KAREN M HORTON, M.D. FRANK CORL , ELLIOT K. FISHMAN, M.D.

INTRODUCTION

Renal cell carcinoma is the most common malignancy of the kidney and accounts for 2% of all cancers. It is estimated that, in 1999, there will be 29,990 new cases diagnosed in the United States and 11,600 deaths due to the disease. To this day, surgical resection remains the only curative treatment for RCC.

The past two decades have witnessed significant changes in the presentation, diagnosis and management of RCC. With the wide spread use of cross sectional imaging, as many as one half of RCC are discovered serendipitously and many are early stage lesions. Paralleling this clinical stage migration, there is a growing trend for more limited surgical resection, such as adrenal sparing radical nephrectomy, laparoscopic nephrectomy or partial nephrectomy.

The challenges of renal tumor imaging include not only reliable differentiation between benign and malignant lesions, but also accurate delineation of the extent of the disease to ensure optimal treatment planning. Spiral CT has significantly improved imaging of renal masses by decreasing volume averaging artifacts and respiratory misregistration artifacts and allowing image acquisitions during optimal contrast enhancement. Further advances, particularly optimization of volume data sets, are anticipated with Multidetector CT which provides data acquisitions speeds at least four times greater then single detector spiral CT with better resolution.

TECHNIQUES

A major breakthrough offered by of spiral and multidetector CT is the ability to image the kidney during various phases of contrast enhancement.

Non contrast phase
· Part of protocol for evaluation of suspected renal mass
· Baseline to measure enhancement characteristics of a lesion
· Enhancement of more then 10 to 12 HU in the mass is suspicious for malignancy
· Calcifications are seen in up to 30% of RCC

Arterial phase (early corticomedullary phase)
· Scan delay of 30 seconds
· Brightly enhancing renal cortex, limited enhancement of the medulla
· Peak contrast in the renal artery
· Optimal imaging of renal arterial anatomy (donor nephrectomy)

Corticomedullary phase (CMP)
· Scan delay of 50 to 60 seconds
· Enhanced renal cortex, limited enhancement of the medulla
· Pitfalls in the diagnosis of small, less then 3cm renal masses
- False positive: hypodense medulla mistaken for lesion
- False positive: pseudo enhancement of a renal cyst
- False negative: small central hypodense masses easier to miss
· Peak contrast in the renal vein, best phase to assess tumor extension
· Optimal evaluation of liver, spleen, pancreas, best phase to exclude metastases

Nephrographic phase (NP)
· Scan delay of 70 (early nephrographic) to 180 seconds
· Homogeneous enhancement of renal parenchyma
· Often some contrast in the collecting system at 180 seconds
· Optimal detection, maximum diagnostic confidence for small renal masses
· Suboptimal evaluation of renal vessels and abdominal organs.

Excretory phase (EP)
· Scan delay of more then 180 seconds
· Contrast in the collecting system
· Helpful for central masses or suspected transitional cell carcinoma

Accurate imaging of the patient with suspected RCC requires a combination of sequences. Many different protocols have been described in the literature and the optimal sequence to evaluate patients with renal tumors is still the subject of some controversy. In order to optimize efficiency and minimize radiation exposure to the patient and cost, we carefully tailor the study to the clinical indication.

Our standard protocols are outlined below.

Note: the thinner slice thickness and reconstruction intervals (in bold) are used for vascular mapping.

• Additional sequences are obtained as required:
  · In patients with a suspected renal mass, the goal of the study is to characterize the lesion and differentiate benign masses from RCC. Our protocol includes non contrast scans through the kidneys in addition to dual phase CT. In selected cases, particularly if a suspected mass is small and central, we add a late nephrographic or excretory phase to better delineate the lesion and determine its relationship with the collecting system.
  · When staging for renal cell carcinoma, the goal of the study is to identify patients who have resectable disease and can be cured by surgical intervention. The extent of disease must be accurately delineated to allow optimal surgical planning. This is best accomplished by 3D CT. Our Urology colleagues find the interactive display of a three dimensional model of the affected kidney and its vascular supply invaluable in helping them select the most appropriate surgical approach.

STAGING FOR RENAL CELL CARCINOMA

Two staging systems, the Robson (older classification) and the TNM classifications, are commonly used. The TNM system defines the anatomic extent of the tumor more precisely and has gained wide acceptance despite its complexity.
Accurate staging at the time of diagnosis is essential for 2 main reasons:
1) Treatment decisions hinge on the extent and stage of the tumor.
2) Numerous studies have shown that the pathological stage of the tumor at the time of diagnosis is the single most important factor in determining prognosis. Disease free survival is inversely correlated with increasing pathologic stage, falling from 60 to 90% 5 years survival for patients with organ confined lesions to 5 to 10% for those with distant metastases.

CT criteria for staging.

Perinephric spread of tumor:
Perinephric invasion is the most common cause of staging errors on CT. Spread of tumor within the perinephric fat cannot be reliably diagnosed and differentiation between stage T2 and T3a tumors is problematic. Microscopic spread of tumor to the perinephric fat cannot be identified on CT. The most specific finding of stage T3a disease, the presence of an enhancing nodule in the perinephric space, is highly specific but only 46% sensitive. Perinephric stranding does not reliably indicate tumor spread and is also found in about half of patients with localized T1 or T2 tumors. In these patients, perinephric stranding may be caused by edema, vascular engorgement or previous inflammation. This limitation of CT does have prognostic implications but does not impact on patient management since patients with stage T3a disease are candidates for radical or partial nephrectomy.

Imaging of the ipsilateral adrenal gland.
The incidence of ipsilateral adrenal malignant involvement is low, reported at 10% or less in radical nephrectomy specimen, regardless of the size and location of the primary tumor. Evaluation of the adrenal gland is important for surgical management because the current trend is to spare the ipsilateral adrenal gland unless an abnormality is suggested on CT. In one study of 157 patients with RCC who underwent radical nephrectomy, visualization of a normal adrenal gland on CT was associated with a 100% negative predictive value for tumor spread to the gland at pathology. By contrast, adrenal enlargement, displacement or non-visualization was associated with malignant spread in 24 % of cases and adrenelectomy should be performed in these patients.

Venous spread of tumor.
Because RCC has a propensity to extend into the venous system, accurate preoperative evaluation of the renal vein and inferior vena cava is crucial. Renal vein extension occurs in approximately 23% of RCC and spread of the thrombus into the IVC is found in 10% of patients. Tumor extension into the IVC is more common with right-sided RCC. The thrombus is usually intra luminal, without invasion of the vessel endothelium. Patients with extensive venous involvement and no nodal or distant metastases carry a relative good prognosis with 5 years survival of 30 to 64%. In these patients, aggressive surgical resection for cure is justified. On CT, venous extension is optimally visualized during the corticomedullary phase of enhancement, when contrast enhancement of the renal vein is at its peak. The most reliable sign of venous extension is the presence of a low density-filling defect within the vein. Enhancement pattern within the thrombus helps distinguish tumor from bland thrombus. Exact determination of the superior extent of the thrombus is critical because the level of IVC involvement dictates the surgical approach. It is important to determine if the tumor remains infrahepatic and can be removed via an abdominal approach or extends into the retrohepatic IVC requiring a thoraco abdominal incision. Extension in the right atrium does not preclude resection, but requires cardiopulmonary bypass. Although MRI is currently the preferred modality to image venous extension, in our experience, 3D CT is also very effective.

Regional lymph node metastases.
The presence of regional lymph node metastases carries a poor prognosis with reported 5 years survival rates of 5 to 30%. The CT diagnosis of lymph node metastases relies on nodal enlargement above 1 cm short axis diameter. This criterion was associated with a 4% false negative rate in a series of 163 patients with RCC who underwent nephrectomy and regional lymph node dissection. This study also showed that in more then half of the patients, nodal enlargement was caused by benign inflammatory changes. This reactive nodal enlargement is often associated with extensive tumor necrosis. Nodal enlargement demonstrated on CT should not disqualify patients for nephrectomy unless metastatic spread is confirmed by fine needle aspiration. Enhancement pattern within the node may also help differentiate reactive from malignant adenopathy: metastatic nodes may enhance, particularly if the primary tumor is very vascular.

Local extension and distant metastases.
The prognosis for these patients is dismal, with reported 5 years survival of 5 to 10%. However, patients with a solitary metastasis may benefit from aggressive management with nephrectomy and surgical removal of the metastatic lesion. Renal cell carcinoma metastasizes most frequently to the lungs and mediastinum, bones and liver. Less common sites include the controlateral kidney, the adrenal gland, the brain, pancreas mesentery and abdominal wall. Like the primary tumor, metastatic lesions tend to be hypervascular. Hepatic metastases are most conspicuous in the hepatic arterial phase and may become obscured and isodense to the liver parenchyma in the portal venous phase.
Loss of tissue planes between the tumor and surrounding organs raises the possibility of direct extension. Unfortunately, this diagnosis is often difficult. In equivocal cases, 3D CT is valuable to increase diagnostic confidence and help plan surgical resection.

ROLE OF 3D CT FOR SURGICAL PLANNING

Three dimensional (3D) CT combined with CT angiography has the potential to provide the urologist with all the critical information needed to plan the surgical procedure.
The ability to interactively review the imaging data in multiple planes and orientations is particularly helpful in the following circumstances:
· Before undertaking venous thrombectomy
· For planning extensive abdominal resection to remove locally invasive tumor
· Prior to partial or nephron sparing nephrectomy

Nephron sparing surgery
Nephron sparing surgery (NSS) entails complete excision of the renal cancer while preserving the largest amount of functioning renal parenchyma. Its use is being increasingly advocated for the management of small (<4cm) RCC as long term studies show survival rates comparable to radical nephrectomy.
Current indications include:
· Multicentric RCC. While 7 to 15 % of sporadic RCC may be bilateral, multicentric RCC are much more common in patients with Von Hippel Lindau disease and hereditary RCC.
· Single RCC in a solitary functioning kidney
· Single RCC in a patient with compromised renal function.
· Single RCC with a normal controlateral kidney. This indication is still somewhat controversial.

Role of 3D CT for planning NSS
3D CT helps delineate the precise location of the renal mass, its relationship to the surface of the kidney, the collecting system and the renal hilum. The arterial and venous anatomy of the kidney is depicted on the 3D CT angiogram. The ideal lesion for NSS is small, less then 4cm, polar, cortical and far from the renal hilum and collecting system.

CONCLUSIONS

In the year 2002, spiral and multidetector CT remains the single most effective imaging modality for the diagnosis and staging of renal cell carcinoma. In the majority of patients, it is the only imaging test needed prior to surgical management.