Renal cell carcinoma
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| Renal cell carcinoma Classification and external resources | |
 | |
|---|---|
| Histopathologic image of clear cell carcinoma of the kidney. Nephrectomy specimen. Hematoxylin-eosin stain. | |
| ICD-O: | M8312/3 |
| DiseasesDB | 11245 |
| MedlinePlus | 000516 |
| eMedicine | med/2002 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-525-6884
Associate Editor-In-Chief: Arun Singh, M.D.
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Overview
Renal cell carcinoma is the most common form of kidney cancer arising from the renal tubule. It is the most common type of kidney cancer in adults. Initial treatment is surgery. It is notoriously resistant to radiation therapy and chemotherapy, although some cases respond to immunotherapy. The advent of targeted cancer therapies such as sunitinib has vastly improved the outlook for treatment of RCC.
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, malnourished appearance
- The presenting symptom may be due to metastatic disease, such as a pathologic fracture of the hip due to a metastasis to the bone
- Enlargement of one testicle (usually 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)
- Vision abnormalities
- Pallor or plethora
- Hirsutism or excessive hair growth (females)
- Constipation
- High blood pressure
- Elevated calcium levels (Hypercalcemia)
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, usually affecting men older than 55.
Why the cells become cancerous 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, commonly also develop renal cell carcinoma. Kidney disorders that require dialysis for treatment also increase the risk for developing renal cell carcinoma.
Pathology
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
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
- squamous cell carcinoma
- juxtaglomerular tumor (reninoma)
- transitional cell carcinoma
- angiomyolipoma
- oncocytoma
- Wilm's tumor
In particular, reliably distinguishing renal cell carcinoma from an oncocytoma (a benign lesion) is not possible using current medical imaging or percutaneous biopsy.
Renal cell carcinoma may also be cystic. As there are several benign 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 benign cystic lesion from a malignant 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 benign and those that need surgical resection[1]. 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[1].
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.This is not completely accurate, there are new experimental treatments.
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 treatments.
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. In case of metastases surgical resection of the kidney ("cytoreductive nephrectomy") may improve survival[1], as well as resection of a solitary metastatic lesion.
Percutaneous therapies
Percutaneous, image-guided therapies, usually 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 therapy
Radiation therapy is not commonly used for treatment of renal cell carcinoma because it is usually not successful. Radiation therapy 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. Studies have demonstrated that IL-2 offers the possibility of a complete and long-lasting remission in these diseases. In addition, the anti-VEGF monoclonal antibody bevacizumab has been shown to be promising in advanced disease.
Sorafenib (Nexavar) was FDA approved in December 2005 for treatment of advanced renal cell cancer, the first receptor tyrosine kinase (RTK) inhibitor indicated for this use.
A month later, Sunitinib (Sutent) was approved as well. Sunitinib—an oral, small-molecule, multi-targeted (RTK) inhibitor—and sorafenib both interfere with tumor growth by inhibiting angiogenesis as well as tumor cell proliferation. Sunitinib appears to offer greater potency against advanced RCC, perhaps because it inhibits more receptors than sorafenib. However, these agents have not been directly compared against one another in a single trial. [3][4]
Recently the first Phase III study comparing an RTKI with cytokine therapy was published in the New England Journal of Medicine. This study proved that Sunitinib offers superior efficacy compared with interferon-α. Progression-free survival (primary endpoint) was more than doubled. The benefit for sunitinib was significant across all major patient subgroups, including those with a poor prognosis at baseline. 28% of sunitinib patients had significant tumor shrinkage compared with only 5% of patients who received interferon-α. Although overall survival data are not yet mature, there is a clear trend toward improved survival with sunitinib. Patients receiving sunitinib also reported a significantly better quality of life than those treated with IFNa. [1] Based on these results, lead investigator Dr. Robert Motzer announced at ASCO 2006 that “Sunitinib is the new reference standard for the first-line treatment of mRCC.” [1]
Temsirolimus (CCI-779) is an inhibitor of mTOR kinase (mamallian target of rapamycin) that was shown to prolong overall survival vs. interferon-α in patients with previously untreated metastatic renal cell carcinoma with three or more poor prognostic features. The results of this Phase III randomized study were presented at the 2006 annual meeting of the American Society of Clinical Oncology (www.ASCO.org).
Chemotherapy
Chemotherapy may be used in some cases, but cure is unlikely unless all the cancer can be removed with surgery. The use of Tyrosine Kinase (TK) inhibitors, such as Sunitinib and Sorafenib, and Temsirolimus are described in a different section.
Vaccine
In November 2006, it was announced that a vaccine had been developed and tested with very promising results.(See [5]) The new vaccine, called TroVax, works by harnessing the patient's own immune system to fight the disease. Oxford BioMedica[6]. Further vaccine trials are underway.
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 % to 15 %. If it has spread metastatically to other organs, the 5-year survival rate is less than 5 %.
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.
See also
External links
- Photo at: Atlas of Pathology
- www.411cancer.com - General Cancer Information
- Vaccine for kidney cancer
References
de:Nierenkrebs fr:Cancer du rein hr:Rak bubrega it:Cancro del rene fi:Munuaissyöpä sv:Njurcancer
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
