Kidney: CT of Recurrent Renal Cell Carcinoma

Contrast-enhanced spiral CT is invaluable in the preoperative evaluation and staging of patients with suspected renal cell carcinoma (RCC). Equally important, however, is the role of CT in monitoring patients with RCC after nephrectomy. Timely and accurate detection of recurrent disease provides key prognostic information and assists the oncologist in treatment decisions involving either surgery or immunotherapy, both of which may be beneficial in selected cases.

To maximize the benefit of post-operative CT surveillance, radiologists should understand the unique clinical features of RCC, employ appropriate scanning technique, and become familiar with the common and atypical manifestations of RCC recurrence and metastasis.

Frequency of Recurrence

• Before nephrectomy
  Metastasis is often present at the time the diagnosis is made. Autopsy studies indicate that 21.5% of RCC cases discovered after death already have distant metastasis. Clinical data indicate that up to 30% of patients with RCC have distant metastasis when the diagnosis is first established.
• Post-nephrectomy
  In general, following nephrectomy for localized tumors, 20 to 30% of patients will develop distant metastases, while local failure will occur in about 5%.

Factors increasing the risk of recurrence

• Stage of primary tumor:
  Tumor larger than 7 cm in diameter (T2)
  Tumor invades perinephric fat (T3a) or Gerota's fascia (T4)
• Tumor thrombus in renal vein or IVC (T3b or T3c, respectively)
• Regional nodes positive: (N1 or N2) 64% of these patients will recur locally and/or develop distant metastases.
• Positive surgical margins: higher risk for local recurrence
• Histopathological features:
  High Fuhrman grade
  Spindled (sarcomatoid) tumor architecture

How does RCC recur or metastasize

• Positive surgical margins or incomplete resection: Ô local recurrence.
• Lymphatic route: renal lymphatics drain to regional nodes, which in turn drain via the cisterna chyli (at L1-L2) into the thoracic duct. Responsible for metatases to retroperitoneal, mediastinal, lower cervical and supraclavicular nodes.
• Hematogenous route:

  Antegrade into renal vein, IVC to lungs, brain, and other distant sites

  Retrograde collateral venous flow via lumbar veins into external and internal vertebral venous plexuses of Batson: key route for metastases to axial skeleton and brain.

When does RCC recur or metastasize

• Most patients: within first 6 years after nephrectomy (mean 22-29 months)
• Regional lymph nodes positive (N+): within 3 years of nephrectomy
• Late recurrences: May be observed in up to 11% of patients surviving = 10 years, and have been documented up to 31 years after nephrectomy.

Recurrent and metastatic renal cell carcinoma is highly vascular, just like the primary tumor. Therefore, timely scanning after the administration of intravenous contrast is key to demonstrating contrast enhancement and to differentiating metastasis from other soft tissue structures. Also, since small bowel and colon migrate into the renal fossae after nephrectomy, adequate oral contrast material administration is essential.

Our post-nephrectomy patients receive 750cc of oral contrast material about 30 minutes before scanning. Single-phase scanning of the chest, abdomen and pelvis begins 30 seconds after the start of an injection of 120 ml of non-ionic contrast material delivered at a rate of 3ml/sec by power injector. To maximize detection of vascular liver metastases, the abdomen and pelvis are scanned first, from diaphragm to symphysis pubis. The chest is then immediately scanned from the apices through the liver. Delayed images of the remaining kidney are acquired during the excretory phase. A slice thickness and a reconstruction increment of 5mm are routinely employed.

The frequency of follow-up CT surveillance in many of our patients is driven by the experimental therapy protocol in which they are enrolled. There is no consensus on the frequency of post-nephrectomy CT follow-up in non-protocol patients. A reasonable approach might be to scan high-risk patients (T2, T3, T4, N1, positive surgical margins, high Fuhrman grade) at least yearly for 3 years.

Common

Local Recurrence in Renal Fossa
Recurrent renal carcinoma appears as a posteriorly situated, enhancing mass which often involves the quadratus lumborum and psoas muscles and whose cephalic extent may reach the space once occupied by the adrenal gland. The mass can displace or invade nearby structures and may completely engulf surgical clips from past nephrectomy.

Regional Lymphadenapthy
Renal lymphatics drain medially along the renal veins. The first echelon of defense is the lumbar group of lymph nodes, located in the paraaortic and paracaval retroperitoneum close to the renal vascular pedicle. Identifying regional nodal metastasis is a very important indicator of an unfavorable prognosis.

Distant Metastases (Usual Sites)

Renal carcinoma typically metastasizes to the following distant sites, listed in order of descending frequency: (1) lung and mediastinum; (2) bone; (3) liver; (4) contralateral kidney/adrenal; and (5) brain. Multifocal metastasis is common.

Lung and Mediastinum
The most commonly affected thoracic lymph node groups are the hilar, subcarinal, paratracheal, and left supraclavicular. Lymphangitic metastasis to the pulmonary interstitium may also be observed.

Bone
Bone metastases from renal carcinoma are purely lytic, expansile, and are usually found in the axial skeleton, particularly from T12 through L5. Metastases are more likely on the same side as the primary tumor. Contrast enhancement of the bone lesions can be striking, making tumor encroachment upon the spinal canal easier to detect.

Liver
Since renal metastases to liver are hypervascular, image acquisition early in the arterial phase of contrast administration is essential. Otherwise, the masses may become isodense with normal liver during the portal phase and will be overlooked.

Contralateral Kidney and Adrenal
Metastases to the contralateral kidney or adrenal gland have been frequently reported in both clinical and autopsy series. The metastases may be single or multiple.

Brain
Brain metastases occur in 5% to 10% of patients with advanced renal cancer. Renal cancer shows no predilection for any part of the brain. Acute subarachnoid and intraventricular hemorrhage due to renal metastases has been reported.

Uncommon or Atypical Manifestations

Post-operative surveillance following nephrectomy for RCC is being conducted with constantly improving CT equipment and scanning technique. Delayed and unusual sites of recurrent disease are now recognized more frequently. Some of these recurrences are managed surgically; therefore, accurate CT assessment is crucial.

Pancreatic Metastasis
Metastases to the pancreas may be solitary or multiple and may occur many years after nephrectomy. In contrast to primary ductal adenocarcinoma, pancreatic metastases from RCC are well defined and hypervascular. Smaller metastases may simulate islet cell tumor. Larger lesions often have central areas of low attenuation and may appear to diffusely involve the pancreas. Splenic vein obstruction can occur. Treatment with surgery can improve survival.

Late Metastasis (= 10 Years from Nephrectomy)
This peculiarity of RCC has lead to the following clinical maxim: one can never assume that a patient with RCC is disease-free. The most frequent sites of late metastasis are lung, pancreas, bone, skeletal muscle, and bowel. Aggressive surgical management is generally warranted.

Hemorrhagic Metastasis
Highly vascular metastases may bleed spontaneously or following minor trauma. A high index of suspicion for metastasis is warranted when a hemorrhagic lesion is detected in a patient with known RCC.

Endobronchial Metastasis
These uncommon lesions can be detected incidentally or may be discovered on imaging or bronchoscopy in symptomatic patients with hemoptysis or atelectasis. Like other RCC metastases, the endobronchial lesion may enhance with contrast.

Skeletal Muscle Metastasis
Although skeletal muscle metastases can be symptomatic, the majority of those detected on thoracic and abdominal spiral CT following nephrectomy are neither palpable nor painful. They generally occur in patients with advanced disease. Metastases from RCC tend to be uniformly hyperattenuating. The erector spinae muscle is a favored site.

Peritoneal and Bowel Metastases
Recurrent RCC in the renal fossa may directly invade the adjacent ascending or descending colon. Other more advanced patterns of recurrence include peritoneal carcinomatosis, mesenteric lymphadenopathy, and hematogenous metastases to small bowel. The latter may hemorrhage or serve as the lead point of an intusssusception.

• Failure to scan the liver early during arterial phase may render hypervascular metastases isodense with liver and lead to a false negative examination. Metastases from islet cell and carcinoid tumors can have a similar spiral CT appearance.
• Failure to administer adequate amount of oral contrast material. Non-opacified small bowel loops in the left renal fossa can simulate local recurrence.
• RCC shares certain risk factors with lung and pancreatic cancer (cigarette smoking).
  Discovery of a lung or pancreatic mass in a patient with known RCC raises the question: is it metastasis or a second primary? CT enhancement and morphologic criteria often help. When in doubt, tissue diagnosis will be required.

The clinical course of renal cell carcinoma after nephrectomy is variable and unpredictable. Since RCC metastases are hypervascular, contrast-enhanced spiral CT is an ideal modality for conducting post-operative surveillance. Optimum care is rendered to these patients when radiologists understand the unique clinical features of RCC, appreciate the common and the atypical manifestations of RCC recurrence, and employ appropriate scanning technique.