Fall 2014

Evans, T.

Background
Nephroblastoma
Most common childhood abdominal malignancy
80-90% Survival rates in children
40% survival rates in addition to Radiation
Therapy to surgery

Etiology
Thought to be caused by alterations of genes
responsible for normal genitourinary development
Congenital anomalies
Cryptorchidism
Double collecting system
Horseshoe kidney
Hypospadias

WT1

First Wilms tumor

suppressor gene
Chromosomal band 11p13
Direct result of the study of children with
Wilms Tumor

Epidemiology
6-7% of all childhood cancers in North America
450-500 new cases diagnosed each year
5-10% of patients, both kidneys are affected at the same time or one
after the other
More common in blacks than whites
Rare in East Asians
Unilateral Wilms Tumor vs Bilateral male to female ratio
.92:1
.60:1
Median age at diagnosis
3.5 years
Highest for unilateral unicentric and
lowest with syncgronous bilateral tumors

www.medscape.com

Presenting Symptoms
Abdominal swelling
An abdominal mass you can feel
Abdominal pain
Fever
Blood in Urine
Constipation
Loss of appetite
Shortness of breath
Nausea

www.cancer.org
www.mayoclinic.org

Anatomy

Pair of bean shaped, reddish brown organs

about the size of your fist
10-12 cm long, 2.5 cm in thickness, 5-7
cm wide, 120-170 g
Covered by renal capsule
Supply 20-25% of cardiac output
Behind and outside the peritoneal cavity on
the posterior wall of the abdomen from the
12th thoracic vertebra to the 3rd lumbar
vertebra in the adult

3 major regions of Kidney

Renal cortex, renal medulla, renal pelvis
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Physiology

Usually affects only one kidney

5% In both
Diagnosed when tumor is already big, but before metastasize
Kidneys start to develop before baby is born
Maturation process
Can be impaired thus causing tumors to form

Lymph node drainage

Distant metastases
Abdomen
Lung*
Rarely to the liver
Does not spread to the bones, bone marrow, or
brain.

WWW.HOPKINSMEDICINE.ORG

Main types of treatment

Surgery
Radical nephrectomy
-most common
-one kidney
Partial nephrectomy
-both kidneys
Chemotherapy
actinomycin D
vincristine
doxorubicin, cyclophosphamide,etoposide, and carboplatin
Radiation Therapy
External beam radiation therapy
advanced tumors (stages III,IV,V)/ some earlier stage tumors with unfavorable histology
3D-CRT or IMRT

Treatment by type and

stage of Wilms tumor

www.cancer.org

Childrens Oncology Group (COG)

Stage I-V

Stage I
The tumor was contained within
one kidney and was completely
removed by surgery. The tissue
layer surrounding the kidney
(the renal capsule) was not
broken during surgery. The
cancer had not grown into
blood vessels in or next to the
kidney. The tumor was not
biopsied before surgery to
remove it.
About 40% to 45% of all Wilms
tumors are stage I.

Stage IV
The cancer has spread through
the blood to organs away from
the kidneys such as the lungs,
liver, brain, or bone, or to lymph
nodes far away from the
kidneys.
About 10% of all Wilms tumors
are stage IV.

Stage II
The tumor has grown
beyond the kidney, either
into nearby fatty tissue or
into blood vessels in or near
the kidney, but it was
completely removed by
surgery without any
apparent cancer left
behind. Lymph nodes do not
contain cancer. The tumor
was not biopsied before
surgery.
About 20% of all Wilms
tumors are stage II.

Stage V
Tumors are found in both
kidneys at diagnosis.
About 5% of all Wilms tumors are
stage V.

Stage III
This stage refers to Wilms tumors that may not have been
completely removed. The cancer remaining after surgery is
limited to the abdomen (belly). One or more of the
following features may be present:
The cancer has spread to lymph nodes (bean-sized
collections of immune cells) in the abdomen or pelvis but
not to more distant lymph nodes, such as those inside the
chest.
The cancer has invaded nearby vital structures so the
surgeon could not remove it completely.
Deposits of tumor (tumor implants) are found along the
inner lining of the abdominal space.
Cancer cells are found at the edge of the sample removed
by surgery, indicating that some of the cancer still remains
after surgery.
Cancer cells spilled into the abdominal space before or
during surgery.
The tumor was removed in more than one piece for
example, the tumor was in the kidney and in the nearby
adrenal gland, which was removed separately.
A biopsy of the tumor was done before it was removed with
surgery.
About 20% to 25% of all Wilms tumors are stage III.

Treatment option 1
Children with unilateral, favorable histology
2 different approaches
immediate nephrectomy
pre-nephrectomy chemotherapy followed
by delayed nephrectomy

Randomized trials reviewed

Immediate Nephrectomy
Patients eligible for randomization if they had
undergone
initial nephrectomy
pre-operative tumor rupture
undergoing immediate nephrectomy NWTS-1
intra-operative rupture
complicated nephrectomy NWTS-1
12.1% of randomized or
followed NWTS-2 patients
13.3% of randomized or
followed favorable histology NWTS-3 patients
NWTSG (National Wilms Study Group)

Pre-nephrectomy chemotherapy
Patients classified as a surgical emergency

Randomized study #1
The United Kingdom Childrens Cancer Group conducted trial
Randomized 205 patients
Authors recommended pre-nephrectomy chemotherapy be adopted as standard for
management of most children with non-metastatic unilateral favorable histology
Study redefined Stage 1 to include necrotic tumor outside renal capsule but was
completely excised
Local relapses reported more commonly patients treatment with delayed
nephrectomy
-abdominal involvement in a relapse with or without concurrent distant relapse was
5.3% who underwent immediate nephrectomy vs. 10.9% who underwent delayed
nephrectomy
Results demonstrated an 11.4% reduction in percent of patients who required postoperative actinomycin D,based on the assumption that monotherapy with vincristine
was adequate for the post-nephrectomy management of stage 1 tumors
-Although, a subsequent report suggested that monotherapy was in fact not
sufficient treatment for stage 1 favorable histology. Instead two drug chemotherapy
was recommended
-Also concluded, overall burden of treatment was reduced and
resulted in the avoidance of doxorubicin for stage II tumors

Randomized study #1 continued

In summary:
Only patients with unilateral Wilms tumor should undergo
delayed nephrectomy are those with extension of tumor thrombus
into the Inferior Vena Cava
Prior to nephrectomy patients who are poor surgical candidates
should receive appropriate correction prior to nephrectomy
Administration of pre-nephrectomy chemotherapy with unilateral
tumor still require careful assessment of risk and benefits
compared to immediate nephrectomy

Treatment option #2
To determine if patients receiving preoperative chemotherapy with
vincristine and actinomycin D for non-metastatic Wilms tumor
have a more advantageous stage distribution and so need less
treatment compared to patients who have immediate
nephrectomy, without adversely affecting outcome

-Informed consent
was obtained
-Eligible patients
were 6months to 16
years of age
-all patients were
randomized to have
either immediate
nephrectomy or six
weeks of chemotherapy
with Vcr (6 doses) and
Act D (2 doses), with
delayed nephrectomy at
week 6

Methods Between 1991 and 2001, a total of 205 patients with

newly diagnosed non-metastatic renal tumors, 186 had Wilms
histologies, were randomly assigned either to immediate surgery
or to 6 weeks preoperative chemotherapy and then delayed
surgery. Both groups of children received postoperative
chemotherapy according to tumor stage and histology
determined at the time of nephrectomy.

Results There was a significant improvement in the stage distribution

for patients with Wilms histologies receiving delayed surgery
compared to those having immediate nephrectomy
resulted in 20% fewer children receiving radiotherapy or
doxorubicin

Conclusion Six weeks of preoperative chemotherapy with vincristine

and actinomycin D resulted in a significant shift towards a more
advantageous stage distribution and reduction in therapy, while
maintaining overall survival in children with non-metastatic Wilms
tumour.
around 20% of survivors were therefore spared the
late-effects of doxorubicin or radiotherapy. Results suggest that all
children with non-metastatic Wilms tumour should receive
chemotherapy prior to tumor resection.

Possible dietary needs/

complications
Well balanced diet
Exercise

Children are at some

risk of late-effects
including
reduced kidney
function
heart and lung
problems after
chemotherapy or
radiation therapy
slowed or decreased
growth and
development.

www.danafarberbostonchildrens.org

Wilms Tumor 4 year Survival Rates

Tumor Stage

Favorable
Histology

Unfavorable
Histology

99%

83%

II

98%

81%

III

94%

72%

IV

86%

38%

87%

55%

www.cancer.org

Green, D. (2007, July 1). Controversies in the management of Wilms tumour Immediate nephrectomy or delayed
nephrectomy? Retrieved November 16, 2014, from http://www.sciencedirect.com/science/article/pii/
S0959804907005825

References
www.medscape.com
www.cancer.org
www.mayoclinic.org
www.scribd.com
www.hopkinsmedicine.org
www.danafarberbostonchildren.org

Mitchell, C. (2006, May 1). Immediate nephrectomy versus preoperative chemotherapy in the management of
non-metastatic Wilms tumour: Results of a randomised trial (UKW3) by the UK Childrens Cancer Study Group.
Retrieved November 13, 2014, from http://www.sciencedirect.com/science/article/pii/S0959804906005272