Renal cell carcinoma

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Definition

Kidney cancer is a disease in which the cells in certain tissues of the kidney start to grow uncontrollably and form tumors. Renal cell carcinoma, which occurs in the cells lining the kidneys (epithelial cells), is the most common type of kidney cancer. Eighty-five percent of all kidney tumors are renal cell carcinomas. Wilms' tumor is a rapidly developing cancer of the kidney most often found in children under four years of age.

Description

The kidneys are a pair of organs shaped like kidney beans that lie on either side of the spine just above the waist. Inside each kidney are tiny tubes (tubules) that filter and clean the blood, taking out the waste products and making urine. The urine that is made by the kidney passes through a tube called the ureter into the bladder. Urine is held in the bladder until it is discharged from the body. Renal cell carcinoma generally develops in the lining of the tubules that filter and clean the blood. Cancer that develops in the central portion of the kidney (where the urine is collected and drained into the ureters) is known as transitional cell cancer of the renal pelvis. Transitional cell cancer is similar to bladder cancer.

Kidney cancer accounts for 3% of all cancers. According to the American Cancer Society, approximately 30,000 new cases of kidney cancer will be found in 1998. Kidney cancer occurs most often in people between 50 and 60 years old. Men are twice as likely as women to have cancer of the kidney. Other risk factors for the development of kidney cancer include Hispanic heritage, and pre-existing von Hippel-Lindau disease.

— Rosalyn Carson-DeWitt

(medicine) A malignant renal tumor composed principally of large, often hyalin, polygonal cells. Also known as clear-cell carcinoma; Grawitz's tumor; hypernephroma.

Key Terms: Biopsy, Bone scan, Chemotherapy, Computed tomography (CT) scan, Cryoablation, Hematuria, Immunotherapy, Intravenous pyelogram, Magnetic resonance imaging, Nephrectomy, Primary tumor, Radiation therapy.

Definition

Kidney cancer is a disease in which the cells in certain tissues of the kidney start to grow uncontrollably and form tumors. Renal cell carcinoma, sometimes referred to as hypernephroma, occurs in the cells lining the kidneys (epithelial cells). It is the most common type of kidney cancer. Eighty-five percent of all kidney tumors are renal cell carcinomas. Wilms' tumor is a rapidly developing cancer of the kidney most often found in children under four years of age.

Description

The kidneys are a pair of organs shaped like kidney beans that lie on either side of the spine just above the waist. Inside each kidney are tiny tubes (tubules) that filter and clean the blood, taking out the waste products and making urine. The urine that is made by the kidney passes through a tube called the ureter into the bladder. Urine is held in the bladder until it is discharged from the body. Renal cell carcinoma (RCC) generally develops in the lining of the tubules that filter and clean the blood. Cancer that develops in the central portion of the kidney (where the urine is collected and drained into the ureters) is known as transitional cell carcinoma of the renal pelvis. Transitional cell cancer is similar to bladder cancer. Wilms' tumor is the most common type of childhood kidney cancer and is distinct from kidney cancer in adults.

Demographics

Kidney cancer accounts for approximately 2–3% of all cancers. In the United States, kidney cancer is the tenth most common cancer and the incidence has increased by 43% since 1973; the death rate has increased by 16%. According to the American Cancer Society, 35,710 Americans were diagnosed with kidney cancer in 2004, and 12,480 died from the disease. RCC accounts for 90–95% of malignant neoplasms that originate from the kidney.

Kidney cancer occurs most often in men over the age of 40. The median age of diagnosis is 65. The male: female ratio is about 3:2.

Causes and Symptoms

The causes of kidney cancer are unknown, but there are many risk factors associated with kidney cancer. The risk factors listed from greatest to smallest include:

• von Hippel-Lindau disease (>100)
• Chronic dialysis (32)
• Obesity (3.6)
• Tobacco use (2.3)
• First-degree relative with kidney cancer (1.6)
• Hypertension (1.4)
• Occupational exposure to dry cleaning solvents (1.4)
• Diuretics (non-hypertension use) (1.3)
• Trichloroethylene exposure (1.0)
• Heavy phenacetin use (1.1–6.0)
• Polycystic kidney disease (0.8–2.0)
• Cadmium exposure (1.0–3.9)
• Arsenic exposure (1.6)
• Asbestos (1.1–1.8)

The most common symptom of kidney cancer is blood in the urine (hematuria). Other symptoms include painful urination, pain in the lower back or on the sides, abdominal pain, a lump or hard mass that can be felt in the kidney area, unexplained weight loss, fever, weakness, fatigue, and high blood pressure.

Diagnosis

A diagnostic examination for kidney cancer includes taking a thorough medical history and making a complete physical examination in which the doctor will probe (palpate) the abdomen for lumps. Blood tests will be ordered to check for changes in blood chemistry caused by substances released by the tumor. Laboratory tests may show abnormal levels of iron in the blood. Either a low red blood cell count (anemia) or a high red blood cell count (erythrocytosis) may accompany kidney cancer. Occasionally, patients will have high calcium levels.

If the doctor suspects kidney cancer, an intravenous pyelogram (also called an IVP or intravenous urography)) may be ordered. An IVP is an x-ray test in which a dye is injected into a vein in the arm. The dye travels through the body, and when it is concentrated in the urine to be discharged, it outlines the kidneys, ureters, and the urinary bladder. On an x-ray image, the dye will reveal any abnormalities of the urinary tract. The IVP may miss small kidney cancers.

Renal ultrasound is a diagnostic test in which sound waves are used to form an image of the kidneys. Ultrasound is a painless and non-invasive procedure that can be used to detect even very small kidney tumors. Imaging tests such as computed tomography (CT) scans and magnetic resonance imaging (MRI) can be used to evaluate the kidneys and the surrounding organs. These tests are used to check whether the tumor has spread outside the kidney to other organs in the abdomen. If the patient complains of bone pain, a special x ray called a bone scan may be ordered to rule out spread to the bones. A chest x ray may be taken to rule out spread to the lungs.

Akidney biopsy is used to positively confirm the diagnosis of kidney cancer. During this procedure, a small piece of tissue is removed from the tumor and examined under a microscope. The biopsy will give information about the type of tumor, the cells that are involved, and the aggressiveness of the tumor (tumor stage).

Staging, Treatment, and Prognosis

Staging

Staging guidelines for kidney cancer are as follows (2.5 cm equals approximately 1 in):

• Stage I: Primary tumor is 5 cm or less in greatest dimension and is limited to the kidney, with no lymph node involvement.
• Stage II: Primary tumor is larger than 5 cm in greatest dimension and is limited to the kidney, with no lymph node involvement.
• Stage III: Primary tumor may extend into major veins or invade adrenal glands or perinephric tissues, but not beyond Gerota's fascia. There may be metastasis in a single lymph node.
• Stage IV: Primary tumor invades beyond Gerota's fascia. Metastasis in more than one lymph node. Possible metastasis to distant structures in the body.

Treatment

Each person's treatment is different and depends on several factors. The location, size, and extent of the tumor have to be considered in addition to the patient's age, general health, and medical history. In addation, much has changed in the treatment and management of kidney cancer since the 1980s, including new surgical techniques, new anticancer drugs, and the development of effective treatments for advanced disease.

The primary treatment for kidney cancer that has not spread to other parts of the body, which is a Stage I, II, or III tumor, is surgical removal of the diseased kidney (nephrectomy). Because most cancers affect only one kidney, the patient can function well with the remaining one. Two types of surgical procedure are used. Radical nephrectomy removes the entire kidney and the surrounding tissue. Sometimes, the lymph nodes surrounding the kidney are also removed. Partial nephrectomy removes only part of the kidney along with the tumor. This procedure is used either when the tumor is very small or when it is not practical to remove the entire kidney. It is not practical to remove a kidney when the patient has only one kidney or when both kidneys have tumors. There is a small (5%) chance of missing some of the cancer. Nephrectomy can also be useful for Stage IV cancers, but alternative surgical procedures such as transarterial angioinfarction may be used.

The rapid development and widespread use of laparoscopic techniques has made it possible for surgeons to remove small tumors while sparing the rest of the kidney. Most tumors removed by laparoscopy are 4 cm (1.6 in) in size or smaller. Laparoscopy also allows the surgeon to remove small tumors with cryoablation (destroying the tumor by freezing it) rather than cutting.

Radiation therapy, which consists of exposing the cancer cells to high-energy gamma rays from an external source, generally destroys cancer cells with minimal damage to the normal tissue. Side effects are nausea, fatigue, and stomach upsets. These symptoms disappear when the treatment is over. In kidney cancer, radiation therapy has been shown to alleviate pain and bleeding, especially when the cancer is inoperable. However, it has not proven to be of much use in destroying the kidney cancer cells. Therefore radiation therapy is not used very often as a treatment for cancer or as a routine adjuvant to nephrectomy. Radiotherapy, however, is used to manage metastatic kidney cancer.

Treatment of kidney cancer with anticancer drugs (chemotherapy) has not produced good results. However, new drugs and new combinations of drugs continue to be tested in clinical trials. One new drug, semaxanib (SU5416), is reported to have good results in treating patients with kidney cancer. As of 2004, however, semaxanib is still undergoing clinical trials in the United States.

Immunologic therapy (or immunotherapy), a form of treatment in which the body's immune system is harnessed to help fight the cancer, is a new mode of therapy that is being tested for kidney cancer. Clinical trials with substances produced by the immune cells (aldesleukin and interferon) have shown some promise in destroying kidney cancer cells. These substances have been approved for use but they can be very toxic and produce severe side effects. The benefits derived from the treatment have to be weighed very carefully against the side effects in each case. Immunotherapy is the most promising systemic therapy for metastatic kidney cancer.

Prognosis

Because kidney cancer is often caught early and sometimes progresses slowly, the chances of a surgical cure are good. It is also one of the few cancers for which there are well-documented cases of spontaneous remission without therapy.

Alternative and Complementary Therapies

There are several healing philosophies, approaches, and therapies that may be used as supplemental or instead of traditional treatments. All of the items listed may have varying effectiveness in boosting the immune system and/or treating a tumor. The efficacy of each treatment also varies from person to person. None of the treatments, however, have demonstrated safety or effectiveness on a consistent basis. Patients should research such treatments for any potential dangers (laetrile, for example, has caused death due to cyanide poisoning) and notify their physician before taking them.

• 714-X
• antineoplastons
• Cancell
• cartilage (bovine and shark)
• Coenzyme Q10
• Gerson Therapy
• Gonzalez Protocol
• Hydrazine sulfate
• immuno-augementative therapy
• Laetrile
• mistletoe

Coping With Cancer Treatment

Side effects of treatment, as well as nutrition, emotional well-being, and other complications, are all parts of coping with cancer. There are many possible side effects for a cancer treatment that include:

• constipation
• delirium
• fatigue
• fever, chills, sweats
• nausea and vomiting
• mouth sores, dry mouth, bleeding gums
• pruritus (itching)
• sexuality
• sleep disorders

Anxiety, depression, loss, post-traumatic stress disorder, sexuality, and substance abuse are all possible emotional side-effects. Nutrition and eating before, during, and after a treatment can also be of concern. Other complications of coping with cancer include fever and pain.

Questions to Ask the Doctor

• What should I expect from a biopsy test?
• What type of kidney cancer do I have?
• What is the stage of the disease?
• What are the treatment choices? Which do you recommend? Why?
• What are the risks and possible side effects of each treatment?
• What are the chances that the treatment will be successful?
• What new treatments are being studied in clinical trials?
• How long will treatment last?
• Will I have to stay in the hospital?
• Will treatment affect my normal activities? If so, for how long?
• What is the treatment likely to cost?

Clinical Trials

As of 2005, the National Cancer Institute (NCI) listed 73 clinical trials in place across the United States studying new types of radiation therapy and chemotherapy, new drugs and drug combinations, biological therapies, ways of combining various types of treatment for kidney cancer, side effect reduction, and improving quality of life. Immunostimulatory agents and gene-therapy techniques that modify tumor cells, antiangiogenesis compounds, cyclin-dependent kinase inhibitors, and differentiating agents are all being investigated as possible therapies. The reader may consult and a doctor for a list of kidney cancer clinical trials.

Prevention

The exact cause of kidney cancer is not known, so it is not possible to prevent all cases. However, because a strong association between kidney cancer and tobacco has been shown, avoiding tobacco is the best way to lower one's risk of developing this cancer. Using care when working with cancer-causing agents such as asbestos and cadmium and eating a well-balanced diet may also help prevent kidney cancer.

Resources

Books

Beers, Mark H., MD, and Robert Berkow, MD, editors.

"Renal Cell Carcinoma (Hypernephroma; Adenocarcinoma of the Kidney)." Section 17, Chapter 233 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

Periodicals

Brauch, H., G. Weirich, B. Klein, et al. "VHL Mutations in Renal Cell Cancer: Does Occupational Exposure to Trichloroethylene Make a Difference?" Toxicology Letters 151 (June 15, 2004): 301–310.

Dutcher, J.P. "Immunotherapy: Are We Making a Difference?" Current Opinion in Urology September 2000: 435–9.

Godley, P.A., and K.I. Ataga. "Renal Cell Carcinoma." Current Opinion in Oncology May 2000: 260–4.

Griffiths, T. R., and J. K. Mellon. "Evolving Immunotherapeutic Strategies in Bladder and Renal Cancer." Postgraduate Medical Journal 80 (June 2004): 320–327.

Jennens, R. R., M. A. Rosenthal, G. J. Lindeman, and M. Michael. "Complete Radiological and Metabolic Response of Metastatic Renal Cell Carcinoma to SU5416 (Semaxanib) in a Patient with Probable von Hippel-Lindau Syndrome." Urologic Oncology 22 (May-June 2004): 193–196.

Lam, J. S., O. Svarts, and A. J. Pantuck. "Changing Concepts in the Surgical Management of Renal Cell Carcinoma." European Urology 45 (June 2004): 692–705.

Lotan, Y., D. A. Duchene, J. A. Cadeddu, et al. "Changing Management of Organ-Confined Renal Masses." Journal of Endourology 18 (April 2004): 263–268.

Moon, T. D., F. T. Lee, Jr., S. P. Hedican, et al. "Laparoscopic Cryoablation under Sonographic Guidance for the Treatment of Small Renal Tumors." Journal of Endourology 18 (June 2004): 436–440.

Organizations

American Cancer Society (National Headquarters). 1599 Clifton Rd. NE, Atlanta, GA 30329. (800) 227-2345. .

American Foundation for Urologic Disease. E-mail: admin@afud.org.

American Urological Association. 1120 N. Charles St., Baltimore, MD 21201. (410) 727-1100. .

Cancer Research Institute (National Headquarters). 681 Fifth Ave., New York, NY 10022. (800) 992-2623. .

Kidney Cancer Association. 1234 Sherman Ave., Suite 203, Evanston, IL 60202-1375. (800) 850-9132. .

National Cancer Institute (NCI). 9000 Rockville Pike, Building 31, Room 10A16, Bethesda, MD 20892. (800) 422-6237. .

National Kidney Cancer Association. 1234 Sherman Ave., Suite 203, Evanston, IL 60202-1375. (800) 850-9132.

National Kidney Foundation. 30 East 33rd St., New York, NY 10016. (800) 622-9010. .

Other

American Cancer Society (ACS). Cancer Facts & Figures 2004..

—Lata Cherath, Ph.D.; Laura Ruth, Ph.D.; Rebecca Frey, Ph.D.

For more information on renal cell carcinoma, visit Britannica.com.

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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-10	C64.
ICD-9	189.0
ICD-O:	M8312/3
OMIM	144700 605074
DiseasesDB	11245
MedlinePlus	000516
eMedicine	med/2002
MeSH	D002292

Renal cell carcinoma (RCC, also known as hypernephroma) is a kidney cancer that originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that filter the blood and remove waste products. RCC is the most common type of kidney cancer, and the most common type in adults, responsible for approximately 80% of cases.^[1]. Initial treatment is most commonly a radical or partial nephrectomy and remains the mainstay of curative treatment.^[2] Where the tumour is confined to the renal parenchyma, the 5-year survival rate is 60-70%, but this is lowered considerably where metastases have spread. It is resistant to radiation therapy and chemotherapy, although some cases respond to immunotherapy. Targeted cancer therapies such as sunitinib, temsirolimus, bevacizumab, interferon-alpha, and possibly sorafenib have improved the outlook for RCC (progression-free survival), although they have not yet demonstrated improved survival.

Contents 1 Signs and symptoms 2 Classification 3 Headline text 4 Epidemiology 4.1 Risk factors 5 Pathology 6 Radiology 7 Treatment 7.1 Watchful waiting 7.2 Surgery 7.3 Percutaneous therapies 7.4 Medications 7.5 Chemotherapy 7.6 Vaccine 7.7 Cryoablation 8 Prognosis 9 History 10 See also 11 References

Signs and symptoms

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The classic triad is hematuria (blood in the urine), flank pain and an abdominal mass. This is now known, often incorrectly, as the 'too late triad' because by the time patients present with symptoms, their disease is supposedly advanced beyond a curative stage. In addition, whilst this triad is highly suggestive of RCC, it only occurs in around 15% of the sufferers. Today, the majority of renal tumors are asymptomatic and are detected incidentally on imaging, usually for an unrelated cause.

Signs may include:

• Abnormal urine color (dark, rusty, or brown) due to blood in the urine (found in 60% of cases)
• Loin pain (found in 40% of cases)
• Abdominal mass (25% of cases)
• Malaise, weight loss or anorexia (30% of cases)
• Polycythemia (5% of cases)
• Anaemia resulting from depression of erythropoietin (5% of cases)
• The presenting symptom may be due to metastatic disease, such as a pathologic fracture of the hip due to a metastasis to the bone
• Varicocele, the enlargement of one testicle, usually on the left (2% of cases^[3]). This is due to blockage of the left testicular vein by tumor invasion of the left renal vein; this typically does not occur on the right as the right gonadal vein drains directly into the inferior vena cava.
• Vision abnormalities
• Pallor or plethora
• Hirsutism - Excessive hair growth (females)
• Constipation
• Hypertension (high blood pressure) resulting from secretion of renin by the tumour (30% of cases)
• Elevated calcium levels (Hypercalcemia)
• Paraneoplastic disease
• Night Sweats
• Severe Weight Loss

Classification

Micrograph of papillary renal cell carcinoma, showing vascular papillae with foam cells. H&E stain.

Recent genetic studies have altered the approaches used in classifying renal cell carcinoma. The following system can be used to classify these tumors:^[4][5][6]

• Clear cell carcinoma (VHL and others on chromosome 3)
• Papillary carcinoma (MET, PRCC)
• Chromophobe renal carcinoma
• Collecting duct carcinoma

Renal epithelial neoplasms have characteristic cytogenetic aberrations that can aid in classification^[7]. See also Atlas of Genetics and Cytogenetics in Oncology and Haematology.

• Clear cell carcinoma: loss of 3p
• Papillary carcinoma: trisomy 7 and 17
• Chromophobe carcinoma: hypodiploid with loss of chromosomes 1, 2, 6, 10, 13, 17, 21

Array-based karyotyping can be used to identify characteristic chromosomal aberrations in renal tumors with challenging morphology.^[8][9] Array-based karyotyping performs well on paraffin embedded tumors^[10] and is amenable to routine clinical use. See also Virtual Karyotype for CLIA certified laboratories offering array-based karyotyping of solid tumors.

Other associated genes include TRC8, OGG1, HNF1A, HNF1B, TFE3, RCCP3, and RCC17.

Headline text

Epidemiology

The incidence of renal cell cancer has been rising steadily. Nearly 51190 new diagnoses and 12890 deaths reported in the United States in 2007. It is more common in men than women: the male-to-female ratio is 1.6:1 and has been decreasing over the last decade. Blacks have a slightly higher rate of renal cell cancer than whites. The reasons for this are not clear.^[11] Note: in epidemiology, RCC is registered together with renal pelvis carcinoma, which is predominantly transitional cell type.

In Europe the incidence of RCC has doubled in the period from 1975 to 2005.^[12] RCC accounted for 3777 deaths in the UK in 2006; male 2372, female 1820.^[13][14][15]

Risk factors

Cigarette smoking and obesity are the strongest risk factors. Hypertension and a family history of the disease are also risk factors.^[16]

Dialysis patients with acquired cystic disease of the kidney showed a 30 times greater risk than in the general population for developing RCC. ^[17]

Exposure to asbestos, polycyclic aromatic hydrocarbons, gasoline has not been shown to be consistently associated with RCC risk.^[18]

Patients with certain inherited disorders such as von Hippel-Lindau disease, hereditary papillary renal cancer, a hereditary leiomyoma RCC syndrome and Birt-Hogg-Dubé syndrome, show an enhanced risk of RCC.^[19][20][21]

Pathology

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Renal cell carcinoma

Renal cell carcinoma

Gross examination shows a yellowish, multilobulated tumor in the renal cortex, which frequently contains zones of necrosis, hemorrhage and scarring.

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 compresses the surrounding parenchyma, producing a pseudocapsule.^[22]

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

Radiology

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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 highlight the tumor relative to normal renal parenchyma.^{[citation needed]}

In particular, reliably distinguishing renal cell carcinoma from an oncocytoma (a benign lesion) is not possible using current medical imaging or percutaneous biopsy.^{[citation needed]}

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 classification system for cystic renal lesions that classifies them based specific imaging features into groups that are benign and those that need surgical resection is available^[23].

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^[24].

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 adjunctive therapy, including cytoreductive surgery.

Watchful waiting

Small renal tumors (< 4 cm) are treated increasingly by way of partial nephrectomy.^[25][26][27] Most of these small renal masses manifest indolent biological behavior with excellent prognosis.^[28] More centers of excellence are incorporating needle biopsy to confirm the presence of malignant histology prior to recommending definitive surgical extirpation. In the elderly, patients with co-morbidities and in poor surgical candidates, small renal tumors may be monitored carefully with serial imaging. Most clinicians conservatively follow tumors up to a size threshold between 3-5 cm, beyond which the risk of distant spread (metastases) is about 5%.

Surgery

Micrograph of embolic material in a kidney removed because of renal cell carcinoma (cancer not shown). H&E stain.

Surgical removal of all or part of the kidney (nephrectomy) is recommended.^[2] 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^[29], as well as resection of a solitary metastatic lesion. Kidneys are sometimes embolized prior to surgery to minimize blood loss^[1] (see image).

Surgery is increasingly performed via laparoscopic techniques. These have the advantage of being less of a burden for the patient and the disease-free survival is comparable to that of open surgery. ^[2]

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. Therefore, long-term follow-up is crucial to assess completeness of tumour ablation.^[30][31]

Medications

RCC "elicits an immune response, which occasionally results in dramatic spontaneous remissions." This has encouraged a strategy of using immunomodulating therapies, such as cancer vaccines and interleukin-2 (IL-2), to reproduce this response. IL-2 has produced "durable remissions" in a small number of patients, but with substantial toxicity. Another strategy is to restore the function of the VHL gene, which is to destroy proteins that promote inappropriate vascularization. Bevacizumab, an antibody to VEGF, has significantly prolonged time to progression, but phase 3 trials have not been published. Sunitinib (Sutent), sorafenib (Nexavar), and temsirolimus, which are small-molecule inhibitors of proteins, have been approved by the U.S. F.D.A.^[32]

Sorafenib, a protein kinase inhibitor, was FDA approved in December 2005 for treatment of advanced renal cell cancer.

A month later, Sunitinib 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. [1][2]

Recently the first Phase III study comparing an RTKI with cytokine therapy was published in the New England Journal of Medicine. This study showed that Sunitinib offered 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. ^[33]

Temsirolimus (CCI-779) is an inhibitor of mTOR kinase (mammalian 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).

Date of Approval: March 30, 2009 Company: Novartis AG Treatment for: Renal Cell Carcinoma Afinitor (everolimus) is an oral once-daily inhibitor of mTOR indicated for the treatment of patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. Afinitor approved in US as first treatment for patients with advanced kidney cancer after failure of either sunitinib or sorafenib - March 30, 2009

Chemotherapy

Most of the currently available cytostatics are ineffective for the treatment of RCC. Their use can not be recommended for the treatment of patients with metastasized RCC.^[1] The use of Tyrosine Kinase (TK) inhibitors, such as Sunitinib and Sorafenib, and Temsirolimus are described in a different section

Vaccine

Cancer vaccines, such as TroVax, have shown promising results in phase 2 trials for treatment of renal cell carcinoma.^[34] However, issues of tumor immunosuppression and lack of identified tumor-associated antigens must be addressed before vaccine therapy can be applied successfully in advanced renal cell cancer.^[35]

Cryoablation

This involves destroying the kidney tumor without surgery, by freezing the tumor. The process can remove 95% of tumors in one treatment and can be tolerated by patients who are not good candidates for surgery (older or weak patients). ^[36].

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 Fuhrman grading, which measures the aggressiveness of the tumor, may also affect survival, though the data is not as strong to support this.

Prognosis

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%.^{[citation needed]} For tumors that extend through the renal capsule and out of the local fascial investments, the survivability reduces to near 60%.^{[citation needed]} 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 %.^{[citation needed]}

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.^{[citation needed]}

History

Historically, RCC was also known as nephrocellular carcinoma.^[37] [Grawitz] first described renal cell carcinoma in 1883.

See also

• Stauffer syndrome
• Knudson hypothesis^[38]

References

1. ^ ^{a b c} Mulders PF, Brouwers AH, Hulsbergen-van der Kaa CA, van Lin EN, Osanto S, de Mulder PH (February 2008). "[Guideline 'Renal cell carcinoma']" (in Dutch; Flemish). Ned Tijdschr Geneeskd 152 (7): 376–80. PMID 18380384. 
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v • d • e Tumors: urogenital neoplasia: urinary organs (C64-C68/D30, 188-189/223) Abdominal Kidney Glandular and epithelial neoplasm: Renal cell carcinoma · Renal oncocytoma Complex and mixed tumor: Wilms' tumor · Mesoblastic nephroma · Clear-cell sarcoma of the kidney Adipose tissue neoplasm: Angiomyolipoma by location: Renal medullary carcinoma · Juxtaglomerular cell tumor Ureter Ureteral neoplasm Pelvic Bladder Transitional cell carcinoma · Inverted papilloma Urethra transitional cell carcinoma · squamous cell carcinoma · adenocarcinoma · melanoma Retroperitoneum Malignant fibrous histiocytoma See also non-congenital, congenital, symptoms/signs

v • d • e Glandular and epithelial neoplasms (ICD-O 8010-8589) Epithelium Papilloma/carcinoma (8010-8139) Small cell carcinoma · Verrucous carcinoma · Squamous cell carcinoma · Basal cell carcinoma · Transitional cell carcinoma · Inverted papilloma Glands Adenomas/ adenocarcinomas (8140-8429) Gastrointestinal tract: Linitis plastica · Familial adenomatous polyposis pancreas (Insulinoma, Glucagonoma, Gastrinoma, VIPoma, Somatostatinoma) Cholangiocarcinoma · Klatskin tumor · Hepatocellular adenoma/Hepatocellular carcinoma Urogenital Renal cell carcinoma · Endometrioid tumor · Renal oncocytoma Endocrine Prolactinoma · Multiple endocrine neoplasia · Adrenocortical adenoma/Adrenocortical carcinoma · Hurthle cell Other/multiple Neuroendocrine tumor (Carcinoid) · Adenoid cystic carcinoma · Oncocytoma · Clear cell adenocarcinoma · Apudoma · Cylindroma · Papillary hidradenoma Adnexal and skin appendage (8390-8429) sweat gland (Hidrocystoma, Syringoma) · Syringocystadenoma papilliferum Cystic, mucinous, and serous (8440-8499) Cystic general Cystadenoma/Cystadenocarcinoma Mucinous Signet ring cell carcinoma (Krukenberg tumor) · Mucinous cystadenoma/Mucinous cystadenocarcinoma (Pseudomyxoma peritonei) · Mucoepidermoid carcinoma Serous Serous cystadenoma/Serous cystadenocarcinoma/Papillary serous cystadenocarcinoma Ductal, lobular, and medullary (8500-8549) Ductal carcinoma Mammary ductal carcinoma · Pancreatic ductal carcinoma · Comedocarcinoma · Paget's disease of the breast/Extramammary Paget's disease Lobular carcinoma Lobular carcinoma in situ · Invasive lobular carcinoma Medullary carcinoma Medullary carcinoma of the breast · Medullary thyroid cancer Acinar cell (8550-8559) Acinic cell carcinoma Other Complex epithelial (8560-8589) Warthin's tumor · Thymoma

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