Renal cell carcinoma

Renal cell cancer, also called renal adenocarcinoma, or hypernephroma, can often be cured if it is diagnosed and treated when still localized to the kidney and to immediately surrounding tissue. The probability of cure is directly related to the stage or degree of tumor dissemination. Even when regional lymphatics or blood vessels are involved with tumor, a significant number of patients can achieve prolonged survival and probable cure. When distant metastases are present, disease-free survival is poor; however, occasional selected patients will survive after surgical resection of all known tumor. Because a majority of patients are diagnosed when the tumor is still relatively localized and amenable to surgical removal, approximately 40% of all patients with renal cancer survive 5 years. Occasional patients with locally advanced or metastatic disease may exhibit indolent courses lasting several years. Late tumor recurrence a number of years after initial therapy occasionally occurs.

Renal cell cancer is one of the few tumors in which well-documented cases of spontaneous tumor regression in the absence of treatment exist, but this occurs very rarely and may not lead to long-term survival. Surgical resection is the mainstay of therapy of this disease. Even in patients with disseminated tumor, locoregional forms of treatment may play an important role in palliating symptoms of the primary tumor or of ectopic hormone production. Systemic treatment has demonstrated only limited effectiveness.

Renal cell carcinoma s the most common type of kidney cancer in adults. Initial treatment is with surgery. It is notoriously resistant to radiation treatment and chemotherapy, eventhough some cases respond to immunotherapy.

Signs and symptoms

The classic triad is hematuria (blood in the urine), flank pain and an abdominal mass. This "classic triad" is infrequently present when the patient first presents for medical attention.

Other signs may include:

• Abnormal urine color (dark, rusty, or brown) due to blood in the urine
• Weight loss of more than 5% of body weight with emaciated, thin, malnourished appearance
• More and more frequently, renal cell carcinoma is identified as an incidental finding on a medical imaging study of the abdomen (e.g. computed tomography a.k.a. CT) done for an unrelated purpose
• The presenting symptom may be due to to metastatic disease, such as a pathologic fracture of the hip due to a metastasis to the bone
• Enlargement of one testicle (commonly the left, due to blockage of the left gonadal vein by tumor invasion of the left renal vein -- the right gonadal vein drains directly into the inferior vena cava)
• Paraneoplastic phenomena (not directly due to the mass, but due to secreted substances with hormonal activity):
  • Vision abnormalities
  • Pallor or plethora
  • Excessive hair growth (females)
  • Constipation
  • Cold intolerance
• High blood pressure

Causes

Renal cell carcinoma affects about three in 10,000 people, resulting in about 31,000 new cases in the US per year. Every year, about 12,000 people in the US die from renal cell carcinoma. It is more common in men than women, commonly affecting men older than 55.

Why the cells become malignant is not known. A history of smoking greatly increases the risk for developing renal cell carcinoma. Some people may also have inherited an increased risk to develop renal cell carcinoma, and a family history of kidney cancer increases the risk.

People with von Hippel-Lindau disease, a hereditary disease that also affects the capillaries of the brain, usually also develop renal cell carcinoma. Kidney disorders that require dialysis for therapy also increase the risk for developing renal cell carcinoma.

Pathology

Renal cell carcinoma.

Gross examination shows a hypervascular lesion in the renal cortex, which is frequently multilobulated, yellow (because of the lipid accumulation) and calcified.

Light microscopy shows tumor cells forming cords, papillae, tubules or nests, and are atypical, polygonal and large. Because these cells accumulate glycogen and lipids, their cytoplasm appear "clear", lipid-laden, the nuclei remain in the middle of the cells, and the cellular membrane is evident. Some cells may be smaller, with eosinophilic cytoplasm, resembling normal tubular cells. The stroma is reduced, but well vascularized. The tumor grows in large front, compressing the surrounding parenchyma, producing a pseudocapsule.[1]

Secretion of vasoactive substances (e.g. renin) may cause arterial hypertension, and release of erythropoietin may cause polycythemia (increased production of red blood cells).

Radiology

A Computerized axial tomography scan showing bilateral renal cell carcinomas.

The characteristic appearance of renal cell carcinoma (RCC) is a solid renal lesion which disturbs the renal contour. It will frequently have an irregular or lobulated margin. 85% of solid renal masses will be RCC. 10% of RCC will contain calcifications, and some contain macroscopic fat (likely due to invasion and encasement of the perirenal fat). Following intravenous contrast administration (computed tomography or magnetic resonance imaging), enhancement will be noted, and will increase the conspicuity of the tumor relative to normal renal parenchyma.

A list of solid renal lesions includes:

• renal cell carcinoma
• metastasis from an extra-renal primary neoplasm
• renal lymphoma
• oncocytoma

In particular, reliably distinguishing renal cell carcinoma from an oncocytoma (a non-malignant lesion) is not possible using current medical imaging or percutaneous biopsy.

Renal cell carcinoma may also be cystic. As there are several non-malignant cystic renal lesions (simple renal cyst, hemorrhagic renal cyst, multilocular cystic nephroma, polycystic kidney disease), it may occasionally be difficult for the radiologist to differentiate a non-malignant cystic lesion from a cancerous one. A famous radiologist named Dr. Morton Bosniak developed a classification system for cystic renal lesions that classifies them based specific imaging features into groups that are non-malignant and those that need surgical resection.

At diagnosis, 30% of renal cell carcinoma has spread to that kidney's renal vein, and 5-10% has continued on into the inferior vena cava. (Refer to Oto, Herts, Remer, Novick "Inferior Vena Cava Tumor Thrombus in Renal Cell Carcinoma: Staging by MR Imaging and Impact on Surgical Treatment", American Journal of Radiology 1998:171:1619-1624)

Percutaneous biopsy can be performed by a radiologist using ultrasound or computed tomography to guide sampling of the tumor for the purpose of diagnosis. However this is not routinely performed because when the typical imaging features of renal cell carcinoma are present, the possibility of an incorrectly negative result together with the risk of a medical complication to the patient make it unfavorable from a risk-benefit perspective.

Treatment

If it is only in the kidneys, which is about 40% of cases, it can be cured roughly 90% of the time with surgery. If it has spread outside of the kidneys, often into the lymph nodes or the main vein of the kidney, then it must be treated with chemotherapy and other therapys.

Surgery

Surgical removal of all or part of the kidney (nephrectomy) is recommended. This may include removal of the adrenal gland, retroperitoneal lymph nodes, and possibly tissues involved by direct extension (invasion) of the tumor into the surrounding tissues. In cases where the tumor has spread into the renal vein, inferior vena cava, and possibly the right atrium (angioinvasion), this portion of the tumor can be surgically removed, as well. Surgical resection is commonly not offered to patients with distant metastases (such as to the bones, lungs, or brain).

Noninvasive therapies

Noninvasive, image-guided therapies, commonly managed by radiologists, are being offered to patients with localized tumor, but who are not good candidates for a surgical procedure. This sort of procedure involves placing a probe through the skin and into the tumor using real-time imaging of both the probe tip and the tumor by computed tomography, ultrasound, or even magnetic resonance imaging guidance, and then destroying the tumor with heat (radiofrequency ablation) or cold (cryotherapy). These modalities are at a disadvantage compared to traditional surgery in that pathologic confirmation of complete tumor destruction is not possible.

Radiation treatment

Radiation treatment is not usually used for therapy of renal cell carcinoma because it is commonly not successful. Radiation treatment may be used to palliate the symptoms of skeletal metastases.

Medications

Medications such as alpha-interferon and interleukin-2 (IL-2) have been successful in reducing the growth of some renal cell carcinomas, including some with metastasis. IL-2 (Proleukinandreg;) is presently the only treatment FDA-approved for the therapy of metastatic renal cell carcinoma (kidney cancer). Studies have demonstrated that IL-2 offers the possibility of a complete and long-lasting remission in these diseases.

Chemotherapy

Chemotherapy may be used in some cases, but cure is unlikely unless all the cancer can be removed with surgery.

Prognosis

The outcome varies depending on the size of the tumor, whether it is confined to the kidney or not, and the presence or absence of metastatic spread. The Furhman grading, which measures the aggressiveness of the tumor, may also affect survival, though the data is not as strong to support this.

The five-year survival rate is around 90-95% for tumors less than 4 cm. For larger tumors confined to the kidney without venous invasion, survival is still relatively good at 80-85%. For tumors that extend through the renal capsule and out of the local fascial investments, the survivability reduces to near 60%. If it has metastasized to the lymph nodes, the 5-year survival is around 5 percent to 15 percent. If it has spread metastatically to other organs, the 5-year survival at less than 5 percent.

For those that have tumor recurrence after surgery, the prognosis is generally poor. Renal Cell Carcinoma does not generally respond to chemotherapy or radiation. Immunotherapy, which attempts to induce the body to attack the remaining cancer cells, has shown promise. Recent trials are testing newer agents, though the current complete remission rate with these approaches are still low, around 12-20% in most series.