All About Kidney Cancer

Ryan P. Smith, MD and Christine Hill-Kayser, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: March 6, 2017

What is the kidney?

The kidneys are two bean-shaped organs that are located in the back of the abdomen, and that have many important functions essential for life. Among the most important are filtering the blood, removing waste products from the blood and ensuring that electrolytes in the blood are correctly balanced. The waste products become urine. In addition, the kidneys produce erythropoietin, a hormone responsible for the production of oxygen carrying red blood cells, and a hormone called rennin, which helps control blood pressure.

Each of the kidneys can be divided into two main functional parts - the cortex and renal pelvis. The outer region of the kidney is called the cortex. The cortex consists of a series of tubes (called collecting tubules) and is responsible for the filtration of blood. The inner region of the kidney is called the renal pelvis. The renal pelvis contains medullary pyramids that collect the filtrate (urine) from collecting tubules in the cortex and send it through the ureters to the urinary bladder. Different types of cancers develop from the two different regions of the kidneys.

The kidneys are located in the back of the abdomen, directly in front of where the lowest ribs can be felt on a person's back. A healthcare provider can feel them in the abdomen at times, though often only if the kidney is enlarged or has a mass on it.

What is kidney cancer?

The definition of a tumor is a mass of abnormally growing cells. Tumors can be either benign or malignant. Benign tumors have uncontrolled cell growth, but without any invasion into normal tissues and without any ability to spread to distant parts of the body. A tumor is called malignant, or cancer, if tumor cells are able to invade tissues and spread locally, as well as to distant parts of the body. Therefore, kidney cancer occurs when cells in either the cortex of the kidney, or cells in the renal pelvis, grow uncontrollably and form tumors that can invade normal tissues and spread to other parts of the body.

Renal cell carcinoma is the most common type of kidney cancer and accounts for about 9 out of 10 cases of kidney cancer. In renal cell cancer, malignant tumors can be growing in either one or both kidneys and there may be multiple tumors. There are several types of renal cell cancer. The type is determined by the appearance of the cancer cell under a microscope. Types of renal cell cancer include:

  • Clear Cell renal cell carcinoma - Accounts for about 7 out of 10 cases of renal cell cancer. Cells appear pale or clear.
  • Papillary renal cell carcinoma - Accounts for about 1 out of 10 renal cell carcinomas. This type of cancer cell forms finger-like projections and when they absorb certain dyes they appear pink.
  • Chromophobe renal cell carcinoma - Accounts for about 5 out of 100 cases of renal cell carcinoma. They appear pale or clear but the cells are much larger than clear cell carcinoma.
  • Rare Types - These subtypes are rare and make up less than 1% of all occurrences of renal cell carcinoma. They include: collecting duct, multilocular cystic, medullary carcinoma, mucinous tubular and spindle cell carcinoma and neuroblastoma-associated renal cell carcinoma.
  • Unclassified - Very rare. They are determined to be unclassified when more than one type of cell exists or the cell does not fit into a specific category.

Transitional cell carcinomas, also known as urothelial carcinomas, account for about 5 to 10 out of every 100 diagnoses of kidney cancer. Transitional cell carcinoma is cancer in the lining of the renal pelvis where urine is stored before it enters the ureter to then travel to the bladder. This type of kidney cancer looks similar to bladder cancer cells when viewed under a microscope.

Wilms Tumor is a tumor commonly found in children and that is very rare in adults. It can affect either one or both kidneys and prior to being diagnosed the tumors are usually quite large.

Renal Sarcoma is a rare type of kidney cancer that begins in the blood vessels or connective tissue of the kidney and accounts for less than 1% of kidney cancers.

Benign kidney tumors are non-cancerous, but can grow very large and have an effect on the body. These include renal adenoma, oncocytoma and angiomyolipoma. They are treated using surgery, radiofrequency ablation and/or arterial embolization.

Am I at risk for kidney cancer?

The American Cancer Society estimates that in 2016 there were about 62,000 new cases of kidney cancer diagnosed, inclusive of all types. It is estimated that there were 14,240 deaths from kidney cancer in 2016. The average age of a person when diagnosed is 64 and kidney cancer is uncommon in people younger than 45. Kidney cancer is more common in men than women. African Americans and American Indians/Alaska Natives have slightly higher rates of renal cell carcinomas than Caucasians.

Risks include:

  • Smoking - The most prominent risk is cigarette smoking. The increased risk is related to how much you smoke. Risk decreases when you stop smoking.
  • Obesity - Obesity changes different hormone levels, which can lead to kidney cancer.
  • Workplace Exposure - Exposure to cadmium, some herbicides and some organic solvents may increase risk of kidney cancer.
  • Family History - The risk for kidney cancer increases in persons with a first-degree relative who has had kidney cancer.
  • Less commonly thought of factors include analgesic (pain killer) abuse, high blood pressure, and several uncommon hereditary diseases, including von Hippel-Lindau disease and polycystic kidney disease.

How can I prevent kidney cancer?

As cigarette smoking doubles the risk of kidney cancer, the best way to decrease your risk of developing kidney cancer is to quit smoking or never start. Maintain a healthy weight. Avoid toxins known to lead to cancer. The only other substantial risk factors for the development of kidney cancer are related to family history. The risk factor of having someone in the family with a history of kidney cancer, or rare genetic syndromes such as von Hippel Lindau and polycystic disease cannot be prevented. If you have this history, be sure your healthcare providers are aware.

What screening tests are available?

There are no screening tests for kidney cancer that are akin to mammography for breast cancer or colonoscopy for colorectal cancer. However, the use of CT scans and ultrasounds have enhanced the early detection of kidney cancer once signs or symptoms have developed (see below). With the advent of CT scans and ultrasounds, 25-40% of kidney cancers are now detected incidentally during the work up of a different problem. These tumors are more likely to be smaller (hence causing no symptoms), and hence more likely to result in a cure.

Other tests that may be used in detecting a kidney tumor include: intravenous pyelogram (IVP), which is used to assess kidney function. IVPs are done by injecting dye into a patient's arm and then taking x-rays of the abdomen to see that dye subsequently excreted by the kidneys as urine. Cytology is simply looking at urine under a microscope and looking for cancerous cells within the urine. Because they may cause early symptoms, kidney cancers that develop in the area of the collecting system may be detected earlier than those in other regions.

What are signs of kidney cancer?

The symptoms seen with kidney cancer can be related to either the tumor in the kidney or as a result of spread of cancer to other locations in the body (metastatic disease). Symptoms resulting from tumor growth in the kidney include hematuria (blood in the urine), abdominal pain, and a flank (side between the ribs and hip) mass. Hematuria, abdominal pain and a flank mass are the classic "triad" of symptoms of kidney cancer, though most patients will not have all three.

Hematuria is the most common symptom and presents as either gross hematuria, where the blood is visible in the urine, or as microscopic hematuria, where the blood is only detected by laboratory testing. Therefore, any presence of blood in the urine that is detected in a urine sample should be investigated.

Symptoms caused by metastatic disease include fever, weight loss, and night sweats (drenching sweats that require changing of clothes or bedsheets). Other symptoms include hypertension, increased calcium in the blood, and liver problems. 

How is kidney cancer diagnosed and staged?

Work up of a kidney cancer usually starts after the patient develops symptoms, with the exception of those cancers that are found incidentally. Tests done prior to treatment of kidney cancer are used to determine the extent of disease that is present so that treatment can be prescribed accordingly. This includes documenting the extent of disease both locally, in the tissues and lymph nodes surrounding the kidney, as well as ensuring there is no spread distantly, outside the area of the kidney (called metastases).

CT scan is most often used to evaluate the tumor size and spread. MRI scans may be used to ensure the tumor has not involved any of the large blood vessels that are in the vicinity of the kidney. Other tests, including basic laboratory blood tests and analysis of the urine may be used to evaluate general health and the extent of the cancer. In addition, chest x-ray and bone scan may be done, to ensure that metastatic spread to the lungs and bones, respectively, has not occurred.

All of these tests are helpful, however, to confirm a diagnosis of any cancer, tissue or cells must be examined by a pathologist. To do this, a biopsy may be done by inserting a needle into the suspected tumor. In some cases, the CT scan and/or MRI is so convincing that cancer is present, that the biopsy is done as part of a surgical procedure to remove the kidney.

The results of these tests are put together to determine the stage of the cancer. The staging of a cancer documents the extent of disease and is often extremely important in terms of what treatment is offered to each individual patient. Before the staging systems are introduced, we will first describe some of the ways that cancers may grow and spread.

Cancers cause problems because they spread and can disrupt the functioning of normal organs. One way kidney cancer can spread is by local extension to invade through the normal structures. This initially includes the kidney, hence causing hematuria, a mass, and abdominal pain. If more growth occurs, cancer can grow to involve the main vein that leaves the kidney (the renal vein), the large vein that returns blood from the bottom half of the body to the heart (the inferior vena cava), or into other organs-most commonly the adrenal glands which sit atop the kidneys.

Kidney cancer can also spread by accessing the lymphatic system. The lymphatic circulation is a complete circulation system in the body (somewhat like the blood circulatory system) that drains into various lymph nodes. When cancer cells access this lymphatic circulation, they can travel to lymph nodes and start new sites of cancer. This is called lymphatic spread. Kidney cancer can spread, at times, into the lymph nodes surrounding the kidney, called the perirenal lymph nodes.

Kidney cancers can also spread through the bloodstream. Cancer cells gain access to distant organs via the bloodstream and cause distant metastases. Cancers of the kidney generally spread locally into the fat surrounding the kidney, the adrenal glands, or the veins prior to spreading via the lymphatic system or the bloodstream. However, tumors, especially larger tumors, can access the bloodstream and spread to the lungs and bones, most commonly. Kidney tumors have also been known to spread to the testis and ovaries through the testicular or ovarian veins that are in close proximity to the kidney.

The staging system used today in kidney cancer is designed to describe the extent of disease within the area of the kidney, in the surrounding lymph nodes, and distantly. This staging system is the "TNM system", as described by the American Joint Committee on Cancer. The TNM systems are used to describe many types of cancers. They have three components: T-describing the size of the "primary" tumor (the tumor in the kidney itself); N-describing the spread to the lymph nodes; M-describing the spread to other organs (metastases). The numbers 0-4 indicate increasing severity.

AJCC Cancer Staging, Kidney Cancer, 7th Edition 2010.

T (Primary Tumor)

TX

Primary tumor cannot be assessed

T0

No evidence of primary tumor

T1

Tumor 7 cm or less in greatest dimension, limited to the kidney

T1a

Tumor 4 cm or less in greatest dimension, limited to the kidney

T1b

Tumor more than 4 cm but not more than 7 cm in greatest dimension, limited to the kidney

T2

Tumor more than 7 cm in greatest dimension, limited to the kidney

T2a

Tumor more than 7 cm but less than or equal to 10 cm in greatest dimension, limited to the kidney

T2b

Tumor more than 10 cm, limited to the kidney

T3

Tumor extends into major veins or perinephric tissues but not into the ipsilateral adrenal gland and not beyond Gerota’s fascia

T3a

Tumor grossly extends into the renal vein or its segmental (muscle containing) branches, or tumor invades perienal and/or renal sinus fat but not beyond Gerota’s fascia

T3b

Tumor grossly extend into the vena cava below the diaphragm

T3c

Tumor grossly extendes into the vena cava above the diaphragm or invades the wall of the vena cava

T3

Tumor invades beyond Gerota’s fascia (including contiguous extension into the ipsilateral adrenal gland

N (Regional Lymph Nodes)

NX

Regional lymph nodes cannot be assessed

N0

No regional lymph node metastasis

N1

Metastasis in regional lymph node(s)

M (Distant Metastasis)

M0

No distant metastasis

M1

Distant metastasis

Staging Groups

Stage

T

N

M

I

T1

N0

M0

II

T2

N0

M0

III

T1 or T2

T2

N1

N0 or N1

M0

M0

IV

T4

Any T

Any N

Any N

M0

M1

 

Though complicated, these staging systems help oncology providers determine the extent of the cancer, and therefore make treatment decisions regarding a patient's cancer.

What are the treatments for kidney cancer?

Once your cancer is staged your care team will determine the best options for treatment. Your care team will be multidisciplinary; including providers from various specialties, such as a primary oncologist, urologist, radiation oncologist, pathologist, nutritionist, social worker and nurses. Your care team will take into consideration the stage of your disease, your overall health, possible side effects of treatment, probability of curing the disease and relief of symptoms when creating your care plan. Treatment options for kidney cancer include: surgery, radiation and chemotherapy. Less frequently used treatments include: ablation, active surveillance (monitoring the disease without active treatment), biologic therapy and targeted therapy. More than one treatment may be prescribed.

Surgery

Surgery is the primary choice of treatment for kidney cancer. There are two types of surgical approaches associated with treatment of kidney cancer. A radical nephrectomy is the removal of the entire kidney, the adrenal gland that sits a top the kidney and the fatty tissue around the kidney. The removal of the kidney may be done through a large incision on the abdomen or back or may be done through a laparoscopic technique in which several small incisions are made rather than one large incision.

A second surgical treatment option is a nephron-sparing nephrectomy, also known as a partial nephrectomy. Only the part of the kidney affected by cancer is removed. It is the preferred treatment for early stage kidney cancer and is often used to remove T1a tumors and some T1b and T2a tumors. The benefit of a partial nephrectomy is to maintain as much kidney function as possible. A partial nephrectomy can be done through an open incision or through a laparoscopic procedure, the same as a radical nephrectomy. Each has benefits and risks associated, but the goal of these surgeries is good long-term renal function and cancer-free survival.

During both a radical and partial nephrectomy the surgeon may choose to perform a regional lymphadenectomy. In this procedure lymph nodes in the same region of the kidney are removed and checked for cancer cells. An adrenalectomy, removal of the adrenal gland, is always done in a radical nephrectomy but is performed during a partial nephrectomy at the surgeon’s discretion.

With any surgery, there are risks and side effects to take into consideration prior to making surgery part of the treatment plan. Possible side effects include: uncontrollable bleeding, blood clots, infections, pain, damage to surrounding organs, hernia, kidney failure, leakage of urine from the kidney, pneumothorax (unwanted air in the chest cavity, and reaction to anesthesia.

Radiation Therapy

Radiation is the use of high-energy x-rays to kill the tumor. This treatment is very complex and should be performed by a radiation team trained in this specialty. Radiation can be given by two different ways: external beam (from a machine outside the body) or brachytherapy (also called internal radiation, from an internally implanted radioactive source). Kidney cancer is not very sensitive to radiation but can be the treatment of choice for a patient who is not healthy enough to withstand surgery. Radiation can also be used to ease symptoms and side effects of kidney cancer including pain and bleeding. Side effects of radiation include skin changes at the site where the radiation is given, nausea, diarrhea and fatigue.

Chemotherapy

Chemotherapies are medications, given either orally or intravenously, that are used to kill tumor cells. Kidney cancer cells are often resistant to standard chemotherapy, so it is not considered a standard treatment for kidney cancer. If your care team decides that chemotherapy will be part of your treatment plan, you may be participating in a clinical trial.

Biologic Therapy (Immunotherapy)

Immunotherapy is the use of medications to enable the body’s immune system to fight and destroy cancer cells. The two immunotherapy medications primarily used to treat kidney cancer are interleukin-2 and interferon-alfa. Potential side effects of interleukin-2 include fatigue, hypotension (low blood pressure), difficulty breathing, heart attack, internal bleeding, fever and chills. Interferon is often used in conjunction with the targeted therapy agent bevacizumab (Avastin) and can cause fever, chills, muscle aches, fatigue and nausea.

Targeted Therapy

Targeted therapies are medications used to treat cancer that "target" a protein or receptor found on the cancer cell and interfere with the cell’s activity or growth. They may cause fewer, yet different, side effects than traditional chemotherapy. These therapies are typically used for metastatic disease, with the goal of shrinking the tumor, slowing the growth of the cancer, and giving patients periods of "stable" disease. Each targeted therapy "targets" a different receptor or cellular function. Some of these medications include: sorafenib, sunitinib, temsirolimus, everolimus, bevacizumab, pazopanib and axitinib.

The goal of your treatment plan will be to cure your kidney cancer or to slow the cancers growth while maintaining quality of life. Your oncology team will determine the best treatment plan based on the extent of the cancer, your health and available therapies.

Clinical Trials

Clinical trials are extremely important in furthering our knowledge of this disease. It is though clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk with your healthcare provider about current clinical trials for colon cancer in your area or use the OncoLink Clinical Trials Matching Service.

Follow-up Care and Survivorship

Your follow-up care will be determined by your care team and will vary depending upon the type of treatment you received for your kidney cancer. If surgery was part of your treatment it is recommended that you visits with your healthcare provider, including a physical exam and blood work, every six months for the first two years and then yearly. A CT scan may be ordered three to six months after surgery to monitor for a recurrence of the cancer. Your care provider will determine a post treatment course that will vary if your cancer has been treated with a technique other than surgery. It is important to attend all of your appointments and to keep a list of any new side effects or symptoms you are experiencing.

Fear of recurrence, relationships and sexual health, financial impact of cancer treatment, employment issues, and coping strategies are common emotional and practical issues experienced by kidney cancer survivors. Your healthcare team can identify resources for support and management of these challenges faced during and after cancer.

Cancer survivorship is a relatively new focus of oncology care. With some 15 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.

Resources for More information

Kidney Cancer Association

Educates families and physicians, and serves as an advocate on behalf of patients at the state and federal levels in the United States and globally. Provides information about kidney cancer and research.

http://www.kidneycancer.org/

References

American Cancer Society, https://www.cancer.org/cancer/kidney-cancer.html, retrieved 7 February 2017.

NCCN Guidelines, https://www.nccn.org/professionals/physician_gls/PDF/kidney.pdf, retrieved 7 February 2017 (log in required).

SEER Statistics, https://seer.cancer.gov/statfacts/html/kidrp.html, retrieved 7 February 2017.

Chandra, A., Snider, J. T., Wu, Y., Jena, A., & Goldman, D. P. (2015). Robot-assisted surgery for kidney cancer increased access to a procedure that can reduce mortality and renal failure. Health Affairs, 34(2), 220-228.

De Meerleer, G., Khoo, V., Escudier, B., Joniau, S., Bossi, A., Ost, P., ... & Spahn, M. (2014). Radiotherapy for renal-cell carcinoma. The Lancet Oncology, 15(4), e170-e177.

Drake, C. G., Lipson, E. J., & Brahmer, J. R. (2014). Breathing new life into immunotherapy: review of melanoma, lung and kidney cancer. Nature Reviews Clinical Oncology, 11(1), 24-37.

Escudier, B., Porta, C., Schmidinger, M., Algaba, F., Patard, J. J., Khoo, V., ... & Horwich, A. (2014). Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 25(Suppl 3), iii49-iii56.

Jonasch, E., Gao, J., & Rathmell, W. K. (2014). Renal cell carcinoma. British Medical Journal, 349, g4797.

Kollmannsberger, C., Bjarnason, G. A., & Ravaud, A. (2015). Toxicity Management of Renal Cell Cancer Patients on Targeted Therapies. In, Kidney Cancer (pp. 365-384). Springer International Publishing.

Larcher, A., Sun, M., Dell'Oglio, P., Trudeau, V., Boehm, K., Schiffmann, J., ... & Montorsi, F. (2016). Mortality, morbidity and healthcare expenditures after local tumour ablation or partial nephrectomy for T1A kidney cancer. European Journal of Surgical Oncology (EJSO).

Motzer, R. J., Escudier, B., McDermott, D. F., George, S., Hammers, H. J., Srinivas, S., ... & Castellano, D. (2015). Nivolumab versus everolimus in advanced renal-cell carcinoma. New England Journal of Medicine, 373(19), 1803-1813.

Thakar, C. V., & Gaitonde, K. (2015). Kidney Function and Injury After Nephrectomy for Kidney Cancer. In Perioperative Kidney Injury (pp. 161-170). Springer New York.


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