ACR Appropriateness Criteria®

Clinical Condition: Renal Cell Carcinoma Staging

Variant 1: Tumor <3 cm.

Note: Abbreviations used in the tables are listed at the end of the "Major Recommendations" field.

Variant 2: Tumor >3 cm.

Note: Abbreviations used in the tables are listed at the end of the "Major Recommendations" field.

Summary of Literature Review

Renal cell carcinoma (RCC) accounts for 2% to 3% of all visceral malignancies. Approximately 36,000 new cases are diagnosed per year in the U.S., resulting in approximately 12,500 deaths. The incidence in men is nearly twice that in women. Metastatic disease at presentation varies with the patient population but typically occurs in about one-third of patients. The most common sites of distant metastases in descending order are the lung, bone, skin, liver, and brain, or in multiple sites.

The traditional treatment for RCC is radical nephrectomy, which involves node dissection and complete removal of the kidney and Gerota's fascia. Nephron-sparing surgery is increasingly used for small tumors. Prognosis is related to tumor size and stage. Robson's staging system (See Appendix 1 in the original guideline document.) was introduced in the 1960s and was much less complex than the TNM system first introduced in 1978 and revised in 1987 and 1997.

The Robson classification has significant limitations in that venous tumoral involvement and lymph node metastases are grouped in the same stage. There are now strong advocates for use of the revised 1997 TNM staging system (See Appendix 2 and 3 in the original guideline document), which is regarded as more accurate and of greater prognostic value. Two significant changes from the 1987 TMN system reflect the importance of tumor size and the extent of inferior vena cava (IVC) involvement. Tumors larger than 7 cm have been upgraded to T2 lesions. For surgical planning of partial elective nephrectomy, further division of T1 tumors into T1a and T1b was added, with a 4.0-cm cutoff separating them, for lesions confined to the kidney. The other significant change in the TNM system regards the extent of IVC involvement. Tumor involving the renal vein with or without IVC involvement below the diaphragm is considered T3b disease, whereas tumor involving the IVC above the diaphragm is classified as T3c.

Approximately 33% of RCCs present in stage I, 10% in stage II, 25% in stage III, and 33% in stage IV. With recent advancements in diagnosis and treatment, median 5-year cancer-specific survival rates have improved to 90% to 95% for stage I, 75% to 85% for stage II, 60% to 70% for stage III, and 20% to 30% for stage IV.

Prognosis is related to the size of the primary tumor as well. In one large study, patients with tumors <2.5 cm had a 100% 5-year survival rate, whereas tumors >10 cm in diameter yielded a median survival rate of 27% at 5 years. Only 5% to 10% of patients present with the classic triad of flank mass, hematuria, and pain. Since the widespread use of ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI), RCCs are increasingly discovered when they are small and therefore at lower stage. Although these incidentally discovered small tumors have a much better prognosis than symptomatic tumors nonaggressive biologic behavior cannot be assumed. In one study of 50 lesions smaller than 3 cm, 38% had extension outside the renal capsule with T3/T4 disease. In another series, 12% of 318 T1 tumors had higher staging due to nodal and distant metastases this was likely related to other factors such as tumor subtype and nuclear grade.

Preoperative staging is important to the surgeon in planning the procedure. Tumor size is accurately determined by CT, MRI, and US. Perinephric tumor extension (T3a) is difficult to discriminate from nonspecific perinephric stranding from edema, vascular engorgement, or fibrosis. High-resolution CT using thin sections (~1 mm) can demonstrate perinephric stranding with 96% sensitivity, 93% specificity, and 95% accuracy, although false positives can be problematic. This determination is often not critical since the tumor and perinephric fat are usually removed at the time of radical nephrectomy. The presence of T3a disease should be excluded, however, if nephron-sparing surgery is planned. CT shows a 100% negative predictive value for T3a disease involving the adrenal gland. Breath-hold MRI showing lack of perinephric fat involvement has high negative predictive value and predicts whether a tumor can be removed by nephron-sparing surgery. In a study of 73 RCCs one group of investigators showed that the presence of a pseudocapsule on MRI had an accuracy of 93% for clear-cell carcinoma in separating T1/T2 tumors from T3a tumors.

Tumor extends into the renal vein in 20% of cases and into renal vein and IVC in 10%, yet with proper surgical treatment, patients with T3b or T3c disease may have survival rates similar to those for stages 1 and II disease. Not only must the involvement of the renal veins and inferior vena be identified, but the cephalic extent of the tumor must also be correctly assessed for preoperative planning. Depending on the level of an IVC thrombus, the surgeon may need to perform a thoracoabdominal incision instead of an abdominal incision. Intra-atrial thrombus may require cardiac bypass. Intrahepatic caval thrombus may require open thrombectomy or, if there is transmural invasion of the caval wall, a graft placement. Thrombus limited to the renal vein ostia may be "milked" back into the vein without the need to open the vein. Therefore, accurate assessment of caval thrombus is important.

Dynamic enhanced CT is the most commonly employed method of identifying caval thrombus. Studies have shown that the technique used influences the success of CT, particularly with regard to the speed of scanning and rate of contrast media administration. Multi-detector-row CT shows very high accuracy rates, achieving equivalence with MRI. Signs suggestive of renal vein or caval thrombus include filling defects, enlargement of the vessel, and rim enhancement. With good technique, helical CT achieves 85% to 91% sensitivity routinely. Problems occur with technically inadequate boluses of contrast media, motion and flow artifact (especially with foot injections), and renal insufficiency. Venous anomalies should be sought, specifically the presence of a retroaortic left renal vein or circumaortic left renal vein, as these have surgical implications.

MRI is 83% to 100% sensitive for tumor thrombus but routinely achieves 90% to 100% sensitivity with modern equipment and may be slightly more accurate than CT in assessing the cephalic extent of the thrombus. Pitfalls of MRI include large tumors compressing the vena cava and flow-related artifacts, which can be reduced with appropriate saturation pulses. With bright blood techniques, rapid or turbulent flow can also lead to artifacts. Intravenous contrast may be helpful in this setting. The highest sensitivity and specificity in assessing venous involvement are achieved with gradient echo sequence. Bland thrombus (low signal intensity) can be distinguished from tumor thrombus, which exhibits intermediate-signal intensity. However, if a good-quality CT is obtained at several phases after contrast administration and the vein is clearly seen, MRI is usually not needed.

Other techniques include US, which is approximately 50% to 75% sensitive for caval thrombus and can be helpful for quickly identifying the cephalad extent of a tumor thrombus. US is limited in obese patients and in the presence of bowel gas, which interferes with the ability to image the renal vein-IVC junction.

Cavography is approximately 85% to 100% sensitive for detecting caval thrombus and is equal to MRI in accuracy. However, multidetector, multiphasic CT or MRI suffices to diagnose caval thrombus, and thus catheter cavography is rarely needed.

Angiography has proved insensitive for tumor thrombus. Its main roles are preoperative embolization to reduce blood loss in hypervascular tumors and for palliation of hematuria in inoperable tumors.

For TxN+ disease (lymph node involvement), CT and MRI are approximately equal, and both are superior to US. All imaging is suboptimal for N staging because of the reliance on node size for assessing metastases. MR lymphography with iron oxide nanoparticles shows promise as a methodology to identify tumor within lymph nodes regardless of their size. The agent is not yet available in the United States, however, and there is no large reported experience with its use in renal cell carcinoma. From a surgical perspective, the identification of nodes is less important because the nodes must be sampled at the time of surgery.

CT-guided aspiration biopsies can be performed if desired for documenting nodal metastases; however; they are rarely needed. Imaging is important for the preoperative detection of bulky adenopathy, which might complicate the surgical approach. This is especially true for laparascopic nephrectomies in which both the vascular anatomy and the nodal pathology may be poorly visualized. Accurate preoperative information becomes even more important, especially for centrally located renal tumors, emphasizing the need for computed tomography angiography (CTA) or magnetic resonance angiography (MRA) prior to such a procedure.

The presence of T4M0–1 disease (metastatic disease with contiguous invasion) is also important to the surgeon. Common sites of contiguous organ invasion include the liver, diaphragm, psoas muscles, pancreas, and bowel. Neither CT nor MRI is ideal, because it is impossible at times to distinguish lack of a fat plane from immediately adjacent but not invasive tumor or from directly invasive tumor; however, both techniques perform well, with a sensitivity and specificity >90%. The multiplanar capabilities of MRI can be useful in this regard; however, neither technique always assesses liver or diaphragmatic invasion correctly. Angiography can also be misleading, since tumors can recruit vessels from the liver or elsewhere without the tumor actually invading the organ.

T4M1N+ disease (distant metastases) principally affects the chest, bone, liver, and brain. Routine chest radiographs are considered necessary, but the routine use of chest CT is more controversial. For small lesions (<3 cm) the risk of metastases is so small as to eliminate the need for chest CT; however, the risk increases with the size of the primary tumor, and although universally accepted guidelines do not yet exist chest CT is justified for larger tumors. When the chest radiograph is suspicious or positive, chest CT is useful for confirming or excluding metastases and defining the extent of disease.

In a study of 119 patients undergoing preoperative CT staging, routine pelvic CT yielded no findings related to the renal cell carcinoma.

Similarly, neither routine bone scans nor bone surveys appear routinely justified. However, if the patient has an elevated alkaline phosphatase, bone pain, or an extremely large and aggressive tumor, bone scans may be helpful. Furthermore, brain MRI does not appear routinely justified, but it is indicated when neurologic symptoms are present, if the primary tumor is large, or if other metastatic disease is already present.

Positron emission tomography (PET) does not yet have an established role in staging renal cancer. Early studies using FDG-PET suggest that it may be difficult to even detect primary renal cancers against the normal background of high activity in the kidneys. PET may be helpful for establishing metastatic disease in lesions detected by CT, MRI, or bone scan, and it may be used to detect unsuspected metastases in high-risk patients. Although negative PET results cannot exclude metastatic disease, a positive PET scan should be considered highly suspicious for local recurrence or metastatic disease due its high specificity.

Summary

Thus, the routine staging of renal cancer should depend on the size of the primary tumor. For small or incidentally detected tumors (≤3 cm), multidetector, multiphasic CT of the abdomen with either CT of the chest or chest radiography is usually sufficient. MRI of the abdomen is a suitable substitute when the patient cannot undergo contrast-enhanced CT. If symptoms of bone pain or neurologic symptoms exist, bone scan or MRI of the brain may be employed.

For larger primary tumors (>3 cm), multidetector, multiphasic CT of the abdomen with chest CT is the diagnostic modality of choice. If the status of the renal veins and inferior vena cava cannot be resolved on CT, contrast-enhanced multiphasic 3D MR venography (MRV) should be performed. MRI of the abdomen is a suitable substitute for staging renal cancer when the patient cannot undergo contrast-enhanced CT.

US may be performed prior to surgery to ascertain the cephalad extent of a previously identified caval tumor thrombus but cannot be relied upon to detect small renal vein or IVC thrombus. Cavography is employed only in unusual circumstances. Prior to any major surgery to remove a locally advanced primary tumor, brain MRI and bone scan should be performed. Lesions detected by any modality that are suspicious for metastatic disease should be either biopsied or examined with an FDG-PET scan.

Although not strictly staging, CTA and MRA should be incorporated into any staging study of the renal cancer, as the vascular information can be helpful to surgeons in planning a resection. Catheter angiography can be performed to embolize large tumors prior to resection.

Anticipated Exceptions

In patients with history of adverse reaction to contrast media or renal insufficiency, MRI and/or US may be preferred to CT. MRI is superior to US in evaluating lymphadenopathy, determining the organ of origin of the mass, diagnosing intracaval and renal venous thrombus, and demonstrating bone metastases.

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