Below is an up-to-date overview on Wilms written by Prof Kathy Pritchard-Jones (December 2003).The section on follow-up will be published at a later stage.
We would like to take this opportunity to thank Prof Pritchard-Jones for taking the time to write this article for the website.Thank you very much.
Prof Kathy Pritchard-Jones, PhD, FRCPE, FRCPCH
Consultant Paediatric Oncologist and Senior Lecturer
The Royal Marsden Hospital
Wilms tumour is a kidney cancer that usually affects children aged around 3 to 4 years old. It is also called nephroblastoma, the ending 'blastoma' meaning that it comes from left over cells from the embryo, and the prefix 'nephro' meaning that this is of kidney origin. Wilms tumour is named after Dr Max Wilms, a German surgeon who practised in the 19th Century, and was the first to describe a series of children affected with this tumour.
The commonest way for a Wilms tumour to be discovered is when parents discover a hard lump in the tummy of their child at bath time. Usually the child is fairly well with no other symptoms. Some children have an episode of blood in their urine, and some are more generally unwell with fever, high blood pressure or symptoms arising from the large tumour lump squashing their lungs.
The answer is definitely yes! Wilms tumour is one of the most curable childhood cancers with nine out of ten children being cured in the long term. However, for individual children with Wilms tumour, their chance of being cured depends on many factors, including what their tumour looks like down the microscope (histology), how far the tumour has spread (tumour stage), and age at diagnosis. If the tumour is exposed to chemotherapy before it is removed, then the tumour response to chemotherapy may also be an important factor in determining the long-term outlook.
Wilms tumour is treated by an operation to remove the affected kidney together with chemotherapy. Three chemotherapy agents are commonly used to treat Wilms tumour, vincristine, actinomycin D and doxorubicin (also called adriamycin). The number of drugs used and the need for radiotherapy depends on something called 'tumour stage'. This is a measure of how far the tumour has spread. The different stages are defined as follows
· Stage I is when the tumour is confined within the kidney and is completely removed.
· Stage II is when the tumour has breached through the kidney lining but is still completely removed.
· Stage III is when some of the tumour is left behind, either because the tumour ruptures, because complete surgical removal is not possible or because the tumour has spread to nearby glands (lymph nodes).
· Stage IV is when the tumour has spread to other parts of the body, usually the lungs.
· Stage V is the special case of tumours in both kidneys (bilateral disease).
What is the best treatment for Wilms tumour?
Surgery has always been a mainstay of treatment for Wilms tumour, but additional chemotherapy is very important to stop the tumour from spreading to other sites, and radiotherapy is sometimes necessary to control any residual tumour in the abdomen or at common sites of spread such as the lungs. Even in the pre-chemotherapy era, a small proportion of patients with Wilms tumour were cured by surgery alone. However, unless additional chemotherapy is given, the vast majority of children will have a relapse of their tumour, usually by spreading to the lungs, and will ultimately die of their disease without additional treatment. Hence, the initial approach to treating Wilms is to combine surgery and chemotherapy, sometimes with additional radiotherapy, for all patients to maximise their chance of cure at the beginning. There are several important questions to be considered in deciding how to put together treatment for Wilms tumour.
Timing of Surgery Wilms tumours are often very large at diagnosis and can easily burst at operation. Therefore, investigators in Europe have long used the approach of pre-treating Wilms tumour with chemotherapy prior to operation to remove the affected kidney (nephrectomy), to make the tumour smaller, make the operation safer, and reduce the chance of tumour rupture. The main clinical trials which have used this approach have been run by the International Society of Paediatric Oncology (SIOP Nephroblastoma Studies). In these studies, the amount of treatment required after tumour removal is decided following inspection of the kidney containing the tumour (nephrectomy specimen) by a pathologist.
There has been a different viewpoint taken by doctors in North America, and some other countries around the world. Here it is believed that the most important factor in deciding treatment is to determine how far the tumour has already spread at the time the Wilms tumour is first diagnosed. This means that the North American approach to treatment of Wilms tumour is immediate surgery to remove the kidney, with subsequent treatment being decided after analysis of this nephrectomy specimen. The main clinical trials that have used this approach have been run by the National Wilms Tumour Study Group (NWTSG), the United Kingdom Children's Cancer Study Group (UKCCSG) and the Brazilian Wilms Tumour Group.
The debate about whether the NWTSG or SIOP approaches to the treatment of Wilms tumour are equivalent, or whether one is superior to the other, have gone on for thirty years. Currently all evidence would suggest that whichever approach is used, children with Wilms tumour have about the same chance of survival depending on the tumour stage at diagnosis. The arguments about the relative merits of the two approaches have therefore hinged more on their overall potential for causing long-term side effects and hence the toxicity of treatment.
The UK Children's Cancer Study Group decided in the late 1990's to conduct a
randomised clinical trial comparing these two surgical approaches. This was
known as the UK W3 trial, and finished in March 2001. Its results are currently
being written up for publication in a scientific journal, and will be linked
to this website when they have been published. The results of this trial show
that preoperative chemotherapy causes most tumours to shrink, and increases
the proportion of tumours which are Stage I or II at the time of their removal,
and hence require minimal chemotherapy.
During the 1960's and early 1970's, nearly all children with Wilms tumour were treated with a combination of surgery, chemotherapy, plus radiotherapy to the side of their abdomen where the tumour had been located. Gradually, through a series of successive clinical trials conduced by the childhood specialists in North America and in Europe, it became clear that the majority of children with tumours confined to their flank and kidney did not require radiotherapy. So now, if your child's tumour is described as either Stage I or Stage II, then they will no longer require radiotherapy to their abdomen. This group is more than half of all children with Wilms tumour.
One of the debates in the treatment of Wilms tumour is the significance of tumour 'spill' at the time of operation. As mentioned before, due to their huge size and fragility, it is not uncommon for Wilms tumours to have some spillage at the time of their removal. If the NWTSG approach is being followed, then a minor degree of spillage confined to the kidney bed is not counted as significant, nor does it affect treatment. However, when treated according to the SIOP approach, where tumour spillage is unexpected after preoperative chemotherapy, if it does occur, the child's tumour is 'upstaged' to Stage III. This generally means that they do require radiotherapy, but remember that this is spillage of cells that have survived the first month of chemotherapy, and so they are expected to be somewhat resistant to treatment.
Another group of children with Wilms tumour who sometimes require radiotherapy is children whose tumour has already spread beyond the kidney at the time of their diagnosis (stage IV). The commonest site of distant spread is to the lungs, although metastases sometime occur to distant lymph nodes or to the liver, and occasionally to bones or even the brain. According to the NWTSG approach, all children with metastases require radiotherapy to the site of those metastases, usually the lungs, regardless of how quickly they disappear. The SIOP Nephroblastoma Group has taken a different view which is that if the lung metastases dissolve away during the first few weeks of chemotherapy, then this means that they do not need radiotherapy to ensure long-term cure. However, if the metastases do not disappear with a reasonable amount of chemotherapy and sometimes limited surgery, then the general advice is that these children should receive radiotherapy to the lungs.
For most children with Wilms tumour, the cause is unknown. In about one or two children out of every hundred, there is a history of someone else in the family, usually a distant aunt, uncle or cousin, having been affected with Wilms tumour before. However, in most cases there is no such family history, and the tumour seems to have arisen by chance. About one in twenty children with Wilms tumour also have some type of physical abnormality that they were born with. This usually affects either the genitalia, or the kidney and its drainage system. Very occasionally, children with Wilms tumour also have kidneys that leak a lot of protein (Nephrotic Syndrome), and have abnormally formed genitalia, a combination known as Denys-Drash Syndrome. This is very unusual, and is found in only about one in two hundred children with Wilms tumour. Another type of growth abnormality found in association with Wilms tumour is overgrowth, particularly when it affects one side or part of the body more than the other. This is known as Hemihypertrophy, and is found in about three out of every hundred children with Wilms tumour. In some cases, it is combined with other features such as large body size, large tongue, umbilical hernia, and a history of very low blood sugar as a newborn baby. This constellation of findings is known as the Beckwith Wiedeman Syndrome. Less than one in ten children with Beckwith Wiedeman Syndrome develop Wilms tumour.
About one in a hundred children with Wilms tumour have a condition called Aniridia, where the iris of the eye fails to form properly. These children usually have other problems including abnormal development of the kidney and genitalia, and sometimes slow intellectual development. This constellation of findings is known as the WAGR Syndrome, which stands for Wilms Tumour Aniridia Genito-Urinary Malformation and Mental Retardation. If the chromosomes or genetic material of these children is tested, it is usually found to have a part of chromosome 11 missing. This is the site of two genes, Pax6 and WT1, which code for two proteins that are very important in development of the iris and kidney respectively. Children with this form of Aniridia have a very high risk of developing a Wilms tumour usually by the age of three. Children with familial forms of Aniridia, where abnormalities of the iris are passed on from one generation to the next, do not carry any increased risk of Wilms tumour as their genetic disease is due only to an abnormality of the Pax6 gene which does not affect the WT1 or Wilms tumour gene.
| Stage | a measure of how far a tumour has spread in the body |
| Metastasis | tumour that has spread to another part of the body separate from the original lump |
| Nephrectomy | operation to remove a kidney |
| Chemotherapy | drugs that are designed to kill rapidly growing cancer cells. The drugs used in Wilms tumour are nearly always given by injection into the bloodstream |
contact:monica@wilmsineurope.net
last Updated:14/01/04