What is Wilms Tumor?

Wilms tumor is a type of kidney cancer. While Wilms tumor is considered a relatively rare cancer overall, it is still the most common cancer of the kidneys in children and the fourth most common cause of cancer in children. 90 percent (9 out of 10) cancers of the kidney in children are found to be Wilms tumor. The medical name for Wilms tumor is nephroblastoma (“neh-fro-blast-oh-muh”).

Wilms tumor got its common name from the doctor who discovered this cancer, Max Wilms (see the section titled “Wilms Tumor History” here for more). Ask any person on the street if they know what their “kidneys” are, and chances are, good, you won’t find anyone who doesn’t have an answer for you. But often, it isn’t until you are facing kidney disease that you will discover you really know relatively little about what kidneys do, how they work, and what causes them to stop working. The kidneys are located on the backside of your torso, just above your waistline, and to either side of your spinal column.

The kidneys’ job is to filter the blood and remove extra toxins, salt, and waste matter. The filtered material is then sent from the kidneys to the ureter tubes and out of the body as urine. But this isn’t the kidneys’ only job. They also make two essential hormones, renin and erythropoietin. The former controls blood pressure, and the latter orders new red blood cells from the bone marrow.

One question many people wonder about is why humans have evolved to have two kidneys. Here, while scientists still have not arrived at a single definitive answer, they believe the answer lies in our evolutionary history, with its strong bias towards symmetry. This makes some sense, given that most people can survive perfectly adequately with just one working kidney. This is an especially important point to remember when it comes to Wilms tumor.

Why? Because in most cases, Wilms tumor initially affects just one kidney, not 95 percent of individuals diagnosed with Wilms tumor have it unilaterally (in just one kidney).

Hearing your child’s doctor say, “We think your child has Wilms tumor,” can be terrifying and overwhelming at first.

But thanks to improvements in early detection methods that now lead to faster diagnosis and treatment, in general, the outlook for children diagnosed with Wilms tumor is very favorable, with an up to 90 percent survival rate.

This article offers a thorough history and overview of this type of cancer, including details about diagnosis and treatment, so you can gain your bearings and decide on the next steps.

History

Max Wilms, M.D., was born in 1867 in Hünshoven, Germany. Initially, Wilms followed in his father’s and older brother’s footsteps, pursuing legal studies. But thankfully, it took him just one short semester to change his mind and decide to pursue medicine instead.

As a new practicing physician, Wilms had a strong interest in kidney tumors and cancers in children. He studied case after case and published paper after paper until he finally amassed sufficient data and research to publish what is still considered the defining work on the topic in 1899.

Wilms theorized that renal tumor cells could begin to develop while an infant was still growing inside its mother’s womb. Today, it is known that nephroblastoma arises from immature kidney cells specifically, which is why it is typically only seen in very young children.

Fast forward 27 years, and a passionate and dedicated Polish-American pediatric oncologist, Dr. Sidney Farber, has just graduated from Harvard Medical School and is already hot on the trail of more effective treatments for Wilms tumor and childhood cancers. Today, because of his discoveries, Dr. Farber is honored with the title “Father of Modern Chemotherapy.”

In 1955, Dr. Farber made a historic breakthrough when he discovered that a particular chemotherapy medication called actinomycin D could achieve remission in Wilms tumor patients.

Dr. Farber’s work raised remission rates from just 40 percent to 89 percent during his lifetime. Dr. Farber’s work was also partially responsible for the passage of the National Cancer Act of 1971 under then-President Richard Nixon.

In 1969, a new consortium, the National Wilms Tumor Study (NWTS), was founded to bring together researchers, statisticians, and pediatric oncologists to improve treatment outcomes.

The consortium’s goal from the start was to conduct large-scale case studies to determine which combinations of medications were most effective at achieving remission from Wilms tumor. As a result, the now-renamed Children’s Oncology Group (COG) has studied an estimated 70 percent of all known Wilms tumor cases in the United States. Several ongoing studies continue the work started by the NWTS.

Two of the consortium’s most significant achievements have been reductions in treatment times (from 15 months to just 6 months) that have improved results and helped families save thousands of dollars on treatment costs.

The consortium continues its work today by monitoring the results of The Late Study participants.

The goal of this study, begun by the original NWTS founding board, is to identify late-state serious medical conditions that can arise later on in life in survivors of Wilms tumor.

Risk Factors

It is now known that Wilms tumor cases can include a genetic component. However, this only applies to approximately 1.5 percent of known cases. The patient has a family member who also has a Wilms tumor in these cases. This is called “familial Wilms tumor.”

The risk of developing Wilms tumor has also been linked to three rare syndromes as follows:

• Beckwith-Wiedemann syndrome: This syndrome is linked to a defect in chromosome 11. 10 percent of patients are genetically transmitted. The common name for Beckwith-Wiedemann syndrome is “overgrowth syndrome.” The patient experiences overgrowth from birth, which can also cause the development of Wilms tumor.
• WAGR syndrome: WAGR stands for “Wilms tumor-aniridia-genitourinary malformation-retardation.” Here again, chromosome 11 has been implicated in this rare genetic syndrome, but instead of a defect, there is a deletion.
• Denys-Drash syndrome: This genetic syndrome, which is associated with the gene WT1, specifically targets the kidneys and genitals. 90 percent of Denys-Drash patients are at risk of developing Wilms tumor.

Other conditions that can increase the risk for an infant to develop Wilms tumor includes these:

• Hemihypertrophy: This means that one side of the body develops to be larger than the other.
• Aniridia: This means that the eye’s iris (colored portion) does not form or form only partially.
• Cryptorchidism: When one or both testicles do not descend.
• Hypospadias: The opening where urine comes out is not at the tip of the male genitalia but on the underside.

To date, researchers have yet to identify any lifestyle choices or other predisposing factors that may raise the risk of developing Wilms tumor.

In most cases, the presence of Wilms tumor does not impact the patient’s health otherwise. Currently, the risk is equal in male and female children. The risk is slightly lower in Asian children and slightly higher in black children.

Screening

While current statistics (1 out of every 10,000 children are at risk to develop Wilms tumor) would seem to suggest the necessity of developing an advanced screening test, to date, no such test has been introduced.

The American Cancer Society states that, because Wilms tumor is still considered a rare form of cancer, it is not felt that advanced screening is a practical step to take with all children at this time.

Instead, the interest lies in developing advanced ultrasound screening tests for infants and children that are thought to be at higher risk of developing Wilms tumor.

Infants and young children with known risk factors (see the section here called “Wilms Tumor Risk Factors” for more) could benefit from advanced screening for Wilms tumor.

For infants and young children that are thought to carry a strong genetic or health risk of developing Wilms tumor, pediatricians often do order regular physical exams plus ultrasound-based screening tests (at least four times per year at regular intervals) until the child turns eight.

These advanced screening procedures aim to detect Wilms tumor growth while the tumor(s) are still small and contained within the kidneys.

For infants and young children who have a family member who has been diagnosed with Wilms tumor, the same or similar advanced screening protocol is also highly recommended.

Also, for any parents with a known WT1 genetic mutation (which only requires transmission of a single gene to be passed on to children), genetic testing as a part of family planning or fetal testing can detect the mutation in an unborn child.

Symptoms

One of the main ongoing challenges with diagnosing Wilms tumor is simply detecting it early enough.

Unless the child has known predisposing factors (see section here titled “Wilms Tumor Screening” to learn more), typically, advanced screening is not performed. This means that the presentation of symptoms is the most common way that the presence of Wilms tumor is initially detected and diagnosed.

Because of this, parents must be aware of the symptoms of Wilms tumor as follows:

• Swelling in the abdomen (often painless).
• Mass in the abdomen.
• Pain in the abdominal area.
• Fever.
• Blood present at urination or urine discoloration.
• Nausea and/or loss of appetite.
• Constipation.
• Fatigue or weakness.
• High blood pressure.

While sometimes Wilms tumor is present at birth, in many cases, the first signs and symptoms will appear between the ages of three and four years old.

In younger children, parents often see one of the first warning signs when their infant or baby suddenly needs a larger diaper. This is due to the presence of the abdominal mass that has expanded the width of the waistline.

The first three symptoms – abdominal swelling, pain, or presence of a mass – are typically the direct result of Wilms tumor.

The other symptoms can be directly related to the Wilms tumor but may also be related to a secondary underlying condition that predisposes the patient to develop a Wilms tumor.

It is very important to be aware that, in many cases, patients with Wilms tumor appear perfectly healthy in every other way to save a thickening waistline and/or abdominal area.

It is important not to assume this is just normal growth-oriented weight or girth gain without having a physician do an exam to verify this.

The earlier Wilms tumor is detected and diagnosed, the more hopeful and positive the prognosis becomes.

Diagnosis and Stages

Once the Wilms tumor is suspected, the next step is to do a physical exam and testing to arrive at an accurate diagnosis. The physician will want to take a thorough personal and family medical history during the initial consultation. It is important to reach out to the family to find out if there are any known cases of Wilms tumor or other cancers, as well as urinary tract or genital malformations, as a part of this history-taking.

The physical exam will look for signs of lymph gland enlargement and include abdominal palpation to detect possible swelling or the presence of a mass.

The next step beyond the physical exam typically begins with blood and urine tests. Sometimes, these tests may be done after other tests have narrowed down a possible diagnosis.

The most common blood and urine tests include these:

• Urinalysis

This non-invasive test uses a urine sample and will look for proteins called catecholamines to rule out the possibility of other cancer types.

• CBC (complete blood count/chemistry profile)

This complete blood test will look for possible cancer markers and assess your child’s overall health.

Since neither a urinalysis nor blood work can definitively diagnose Wilms tumor, other tests will be needed to arrive at an accurate diagnosis.

The most common tests used to diagnose Wilms tumor include these:

• Ultrasound

This non-invasive, easy test uses sound waves (sonograms) to give the doctor a picture of what is going on inside the abdomen.

Ultrasound is a preferred test because it can display soft tissue and distinguish between benign cysts and malignant tumors.

• CT (computed tomography) scan

This test uses x-ray technology to look inside of the kidneys themselves to see if there is a tumor and, if so, where it is located and if it has spread to other body systems.

• MRI (magnetic resonance imaging) test

This test uses magnet technology to help the doctor see the kidney in fine detail. This is helpful both to locate Wilms tumor and see if it affects any nearby structures.

• Chest X-ray

If there is a possibility Wilms tumor has spread to the lungs (such as because the patient is reporting shortness of breath), a chest X-ray may be ordered. Sometimes this test is done during a CT scan of the kidneys.

• Bone scan

A bone scan is typically only ordered if Wilms tumor has advanced and is suspected of spreading to the bones.

• Kidney biopsy

Often a biopsy is done during surgery to remove the malignancy. In addition, a small sample of kidney tissue is extracted during surgery and assessed for malignancy. A biopsy may also be ordered to help with treatment planning or confirm the Wilms tumor diagnosis if other tests have been inconclusive.

The last component of the diagnostic process is called “staging. The stage of cancer informs the type of treatment. Wilms tumor, like all cancers, is staged based on the results of physical exams, blood and urine tests, and other diagnostic tests and biopsy procedures.

The work of the Children’s Oncology Group (COG), the organization described here (see the section titled “Wilms Tumor History” to learn more), is used to stage Wilms tumor cases today. In most cases, staging is only done following surgery that attempts to remove all or as much as possible of the malignant tissue.

Here is an overview of the five stages of cancer as outlined by the COG:

• Stage 1

The tumor is contained within the kidney. The outermost layer of the kidney, called the renal layer, was not impacted by the tumor. In addition, the blood vessels and surrounding systems were not impacted by the tumor (up to 45 percent of Wilms tumor cases are diagnosed at stage 1).

• Stage 2

The tumor has grown out of the kidney itself and has impacted nearby fatty tissues or blood vessels. Lymph node biopsies reveal no signs of Wilms tumor cells (20 percent of Wilms tumor cases are diagnosed at stage 2).

• Stage 3

The tumor has impacted nearby abdominal or pelvic lymph nodes, but not more distant lymph nodes. The tumor has impacted nearby tissues or structures such that it could not be completely removed during surgery. Surgeons found tumor tissues in the abdomen lining and at the edges of the biopsy site (up to 25 percent of Wilms tumor cases are diagnosed at stage 3).

• Stage 4

The tumor has spread outwards from the kidney and abdominal area to more distant systems (possible locations include lungs, liver, brain, bones) and/or to more distant lymph nodes outside of the abdomen or pelvic areas.

Here, the bloodstream has carried tumor cells to these outlying systems (10 percent of Wilms tumor cases are diagnosed at stage 4).

• Stage 5

Both kidneys test positive for Wilms tumor during diagnosis (about 5 percent of Wilms tumor cases are diagnosed at stage 5).

There is one more element to diagnosing Wilms tumor with the greatest degree of accuracy, which is obtained by looking at the cancer cells under a microscope. Their appearance, called their “histology,” influences both staging and prognosis.

There are two types of histology as follows:

• Favorable. Favorable histology arises when the doctor sees that the cancer cells maintain a relatively strong inner structure, including intact nuclei with DNA.
• Unfavorable. Unfavorable histology arises when the doctor sees that the cancer cells are losing their inner structure and becoming amorphous in appearance (called “anaplasia”).

Once all of the data from the physical exam, test results, and histology examination is collected and assessed, cancer can be staged, and it is possible to move on to the treatment phase.

Treatments and Drugs

Treatment for Wilms tumor is determined largely by the cancer stage and cell histology (favorable or unfavorable).

For patients residing in and receiving treatment in the United States, much of the treatment is overseen through clinical trials through the Children’s Oncology Group (COG).

These clinical trials aim to achieve maximum remission rates at a lower cost and with a minimum of side effects. In all unilateral (single kidney) cases of Wilms tumor, the very first stage of treatment typically occurs during the diagnostic process, when surgery is performed to remove as much and ideally all of the cancerous tissue, and the kidney is also biopsied to verify Wilms tumor as the diagnosis.

Again in all unilateral cases treated in the United States, the next step is to use chemotherapy and/or radiation to ensure two goals: first, that all of the cancerous tissue has been removed or destroyed, and second, to ensure cancer does not recur. In cases where the Wilms tumor is bilateral (in both kidneys), typically chemotherapy is pursued first, and surgery follows. The goal here is to shrink the tumor as much as possible before surgery is performed.

This allows surgeons to save as much of each kidney as possible during surgery to remove the cancerous tissue.

• Stage 1 Treatment Recommendations

For stage 1 diagnoses where the tumor was able to be completely removed during surgery, and cell histology is deemed favorable, sometimes no further treatment is recommended.

Choosing to simply watch for relapse requires very close monitoring – more so than if chemotherapy was pursued – but it also reduces the risk of side effects and other adverse tissue effects for very young patients in particular.

However, if cell histology was deemed unfavorable, both chemotherapy and radiation are likely to be prescribed following surgery, even if the cancer is only at stage 1.

• Stage 2 Treatment Recommendations

When the diagnosis is stage 2 Wilms tumor, patients will typically be prescribed a course of radiation following surgery, with chemotherapy following radiation.

However, it may be possible to pursue chemotherapy only when cell histology is favorable. When the cell histology is unfavorable, the degree of anaplasia (loss of interior cellular structure) will determine how long radiation treatment lasts.

Typically, any stage 2 Wilms tumor patient will get six months of chemotherapy following radiation treatment.

• Stage 3 Treatment Recommendations

When the diagnosis is stage 3 Wilms tumor, surgery is always followed by a course of radiation and then chemotherapy treatment for about six months. The exception here is if the tumor is very large and cannot be safely removed during surgery. In these cases, chemotherapy is given first to shrink the tumor, and then surgery is done, followed by radiation. Sometimes both chemotherapy and radiation are administered before surgery is done.

• Stage 4 Treatment Recommendations

When the diagnosis is stage 4 Wilms tumor, surgery is done first if possible.

If not possible, chemotherapy and/or radiation is administered in an attempt to shrink the tumor and cancer tissue, and then surgery is done. The location and scope of the chemotherapy and radiation will expand based on where cancerous tissue and/or tumors have been found. Often, the entire abdomen is treated, and the liver and/or lungs if malignancy is found in those locations. Sometimes surgery is done first but only on the liver if there are tumors there that can be safely removed.

• Stage 5 Treatment Recommendations

When the diagnosis is stage 5 Wilms tumor, in most cases, this means the Wilms tumor has been found in both kidneys (bilateral).

The main goal in these cases is to attempt to save at least one kidney. This means that chemotherapy and/or radiation are often done first to shrink the tumors. Then surgery is often done to remove as many or all of the tumors as possible. If there is no possibility to save at least one functioning kidney, the patient will be prescribed kidney dialysis. Dialysis involves the use of technology to filter the blood since the kidneys can no longer do this job.

After 12 to 24 months where the patient is cancer-free, it may be possible to apply for a donor’s kidney.

• When Wilms tumor recurs after treatment

In some cases, Wilms tumor recurs more than once, even if the initial treatment has been a success. In these cases, depending on the nature of the recurrence, the stage of cancer, and whether the cell histology is favorable or unfavorable, surgery, chemotherapy, and/or radiation may be used to treat cancer.

In aggressive recurrent cases, sometimes stem cell therapy (bone marrow transplant) is helpful as a treatment approach.

Coping and Support

Diagnosing and treating Wilms’s tumor can be very stressful and challenging for the patient, carers, and the entire family.

As a parent or relative, you will likely serve as the primary source of support to your child during diagnosis, treatment, and ongoing monitoring for Wilms tumor. But you will also need to support yourself. It is important to remember this and accept help when offered and seek out additional support if you need it.

The National Kidney Cancer Association posts a list of support groups on its website. Also, it offers guidance for starting a support group in your area and for seeking financial assistance to help with treatment costs.

The American Cancer Society offers an online network for caregivers and patients called the Cancer Survivors Network. The website also offers a list of local support programs and services listed by geographic area. In addition, the site is searchable and includes cancer information, lodging programs for carers, rides to treatment sessions, and other options for finding online support.

Cancer.net is another great resource to help carers find information and support. The database includes options to find a support buddy, online support forums, phone and email support, cancer groups, specific resources for rare cancers, counseling suggestions, and contact information for government regulatory agencies. It is also critical to let close friends, relatives, and peers know about what your family is facing. People cannot offer help if they don’t know there is a need.

While it can be difficult to talk about with others, you may want to enlist a close friend or family member to help or even to talk for you on your family’s behalf. In addition, local nonprofits, faith organizations, support groups, and cancer-specific resources may be able to provide you with extra help in areas as diverse as finances, meals, babysitting, rides, prayer, running errands, and emotional support.

By reaching out into your local community, you can begin to build your own support network that can walk with you over the long term and help meet your needs for information and more.

Each year, approximately 500 families find out that one of their youngest family members has contracted a Wilms tumor. When this happens, parents, loved ones, friends, and relatives may feel shocked, disbelief, grief, anger, and many other feelings as well. While it may feel like you are alone in fighting cancer, you are not alone. Help and hope are available to you as well as to your child.