Journal

of Pediatric

Surgery

\‘Ol,. XII,NO.5

OC'WHER

1977

Survival in Bilateral W ilms’ Tumor- Review of 30 National W ilms’ Tumor Study Cases By Harry 0 Bilateral tients

tumors

or 5.4%

Wilms’

six of

30

tailed

clinical

vived

2 yr after

All

1969,

for

However,

treatment

more

used.

The

course

retrospective

so that

serve as the basis

INDEX

together of this

of this

Between

1969 and

7umor

1000 for local

Recommendations by surgery,

and chemotherapy

radia-

are given.

Bilateral

an attempt

study

conduct

Wilms’

groups

and several

;L national

were to determine

tumor

tumor,

study

I)n

the need ior

LL;I~ contined

tv one kidnq

the beqt maintenance

chemotherapy

local

tumor

disease.

although

committee

The

they

believed

and outcome

of these regarding

was made to gather

study

were

that

an individually

information

did

not

registered

the disease designed

patients

in-

with

in such

treatment

was expected

the various the details.

forms These

01’ d;.\ta

report.

1972. 606 patients

Study (NWTS).

to

whost:

CLINICAL

Wllms

sufficed

cases.

WORDS:

study

that each required

the clinical

valuable

therapy

between

A

advanced

Wilms’

center.

was so complex

to provide

tion therapy,

in children

with

most

and

and to determine

bilateral

but

management

cancer cooperative

goals

with

in

regarding

and

banded

patients

control

Radiation

widely,

rad apparently

sur-

national

removed.

J. D’Angio

used

The

the data and statistical plan.

were

major

Giulio

given

nephrectomy,

irradiation

patients

de-

institutions

and completely

patients

were

ranged

and 2000

agents.

of the

tumors.‘.’

regimen

whom

and

nephrectomies.

doses

Twenty

surgery

procedures

THREE

postoperative

clude

for

E. Evans,

partial

in

is available

patients

only,

additional

Wilms’

in 33 pa-

chemotherapeutic

biopsy

Audrey

enrolled

conservative

of surgical

including

I

(87%)

therapy.

Tefft,

Study.

information

one or more variety

found

children Tumor

patients

radiation

Melvin

were

of 606

the National

N

C. Bishop,

with

DATA

Wllms’

The disease was reported

tumor

were registered

to be hil:ltrral

with

the

Nat~onrll

at the time of diagno\i\

11)

--

Journal

of Ped,ofric

Surgery,

Vol.

12. No. 5 (October). 1977

63 ’

632

BISHOP

ET AL.

33 patients (5.4”,,). In 20 additional patients, disease was subsequently detected in the remaining kidney (3.3?,,,), These latter are not included here since they represent a different stage in the clinical evolution of the disease. To compile the clinical data, a questionnaire was sent to the investigators requesting information concerning the following: age and sex. clinical findings at diagnosis, roentgenographic studies, the extent of initial and subsequent surgery, chemotherapy, radiotherapy. and the status of the patient. Replies were received from ?I institutions reporting 30 patients. Insufficient information was given on the remaining 3 to allow analysis. All patients have been followed for at least 2 yr.

Age and Sex Of the 30 patients analyzed, 18 were girls and I2 were boys. were between I and 2 yr of age and 13 were 24 mo old or more.

Four

were under

I yr of age. 13

Phjlsical Findings Disease was palpated in both kidneys preoperatively in 9 of the 30 patients, while in I9 only one tumor was identified prior to surgery. (This information was not available in two patients.)

Roentgenograms Inferior venacavography was reported for I I patients: in four the cava was displaced, and in two it appeared obstructed. Intravenous pyelograms were performed on all patients and showed bilateral tumors in I7 and a single tumor in 13. Bilateral tumors were identified in 9 of the IO patients with arteriograms; only a single tumor was seen in the tenth. One patient had pulmonary metastases visible at initial examination.

TREATMENT

AND RESULTS

Age and Sex All four patients diagnosed under I yr of age survived 2 or more yr. Twelve of the 13 between 1 and 2 yr of age (9 2”,) and 10 of the 13 patients 24 mo of age or older were disease-free at 2 yr (77”,,). Fifteen of 18 girls and 1 1 of 12 boys lived. Chemotherapy Actinomycin D (AMD), vincristine (VCR), or both were usually administered according to the doses and schedules specified in the NWTS protocol.’ Two patients received VCR prior to surgery and one received both VCR and AMD preoperatively. Postoperatively, two patients had only AMD and both survived. Nineteen had both AMD and VCR (17 survivors), and nine had a combination of AMD, VCR and Adriamycin (ADR)* with 7 survivors. The parents of one patient, who subsequently died, refused the recommended AMD and VCR after two courses. Radiation

Therap)>

All but two children received radiation removed at the first operation and in the maining kidney was resected. Both received had some irradiation to both kidneys, eight

*ADR was prescribed during the latter period Wilms’ tumor became more widely known,

therapy; in one all of the tumor was other the residual tumor in the rechemotherapy and survived. Eleven to only the single remaining kidney,

of the study

(from

mid 1972) when its effect on

BILATERAL

WILMS’

TUMOR

633

SURVIVAL

and in eight patients treatment was given both to the renal fossa following nephrectomy and to the remaining kidney. Details of radiotherapy were not obtained in one other case. An attempt was made to correlate radiation dose with the size of the tumor and with survival. This was possible for I7 kidneys for which detailed radiation therapy and tumor size information was available. In two instances, the tumor measured less than 2 cm. The two patients concerned survived, one following less than 1000 rad to the whole kidney and the other 3000 rad to part of the kidney. In 8 kidneys, tumors measured from 2 5 cm, and the radiation do\e ranged from 1000.m2000 rad. All but one of these patients survived; the patient who expired had disease in the opposite kidney measuring greater than 5 cm (this case is included in the following group of 7 tumors measuring greater than 5 cm), Four kidneys received between 1000 and 2000 rads, and three between 2000 and 3000 rad. Two patients in this latter group died; one previously mentioned received 1300 rads and died of pulmonary metastases, the other one received 2400 rads to the whole abdomen, including both kidneys, and expired of widespread disease and local recurrence. Thus the only two deaths occurred when the residual tumor measured greater than 5 cm and only one of them because of local failure. Sqqical

Management

Three different types of surgical procedure were performed at the time of initial operation. Some had additional surgery in attempts to remove all the remaining tumor following treatment with chemotherapeutic drugs and radiation (Table 1). l All tumor resected initially. Four patients undernent unilateral nephrcctomy and partial resection of the opposite kidney with complete removal of all tumor. All four survived. l Unilateral nephrectomy. Fifteen patients had unilateral nephrectomy at the time of initial surgery. A) One patient had a partial resection of the opposite kidney with incomplete removal of the tumor, and survived. B) Seven patients had confirmatory biopsy of tumor in the opposite kidney but no additional resective surgery and all survived. C) Seven patients had inspection only of the

Tobke 1. Surgical Management

of 30 Patients

With Bilateral

Wilms’

Tumors S”W”Ol

Initial surgery Nephrectomy

with

contralateral heminephrectomy Nephrectomy

with

NOW

5/5*

tieminephrectomy

212

or without contralateral Biopsy

NOW

biopsy

Bilateral

only

Unilateral

10/‘12 tumor tumor

2:2

resections

29

resection

S/S O/11

NOW? Bilateral

lHeminephrectomy tThis

patient

had

left residual bilateral

tumor

nephrectomy

nephrectomy

in one patient. in two

stages

(at 26 and

‘28 mo)

for

persistent

disease

(Cow

4)

BISHOP

634

ET AL.

opposite side. Two of these patients subsequently had all known tumor excised and both survived. Two of the five who had no subsequent resective surgery died (Cases I and 2). l Biopsy only. Eleven patients had single or bilateral biopsies at the time of initial surgery. One had all the known tumor subsequently excised and survived. Nine were left with residual tumor, some even after subsequent surgical procedures with one death (Case 3). One had bilateral nephrectomies for persistent disease at I8 mo and expired (Case 4). In summary, only 7 of the 30 patients had all the tumor excised, 4 initially and 3 at subsequent surgery and all 7 survived. One patient who died had all known disease resected late in his course because of persistent disease (Case 4). Nineteen of the remaining 22 patients who were known to have residual tumor survived. REVIEW

Four of the 30 patients

OF

EXPIRED

PATIENTS

died at 6, 7, I4 and 33 months

following

diagnosis.

Case I The shortest survival time was a 34 yr old female who was treated initially with a right nephrectomy; the lesion in the left kidney was not biopsied. She received AMD, VCK, and II00 rad to the left kidney. Pulmonary metastases failed to respond to additional chemotherapy and radiation therapy, and she died of widespread disease. Case 2 A 5; yr old female had preoperative rupture of a right-sided Wilms’ tumor. the only rupture in the series. Unilateral nephrectomy. radiation to that renal fossa and the remaining kidney, together with AMD. VCR. and ADR failed to halt the progressive disease which was the cause of death 7 mo after the diagnosis. Case 3 A girl, aged 6 yr. had biopsy of a left-sided tumor, and inspection of the right side revealed a mass with direct extension into the liver. She received 2500 rad to the upper abdomen together with AMD, VCR, and ADR. At 9 mo, a left nephrectomy was performed with removal of visible tumor, but inspection of the right kidney revealed no abnormalities. Death occurred at I4 mo with widespread disease including the liver and peritoneal cavity although the right kidney was tumor-free. Case 4 The fourth patient. already reported by David and Lavengood,3 was a 14 yr old male who had bilateral renal biopsies initially. He had received two courses of AMD when the mother refused further treatment. At IX mo, treatment with AMD and VCR was restarted because of persistent disease in both kidneys. Nephrectomies were performed at 26 and 29 mo followed by a renal transplant.

BILATERALWILMA TUMOR SuRVlv~t

Death

occurred

from

6 35

pneumonia

at 33 mo at which

time

there

was no evidence

of tumor.

DISCUSSION This

retrospective the time

ing at

and complexities The

study

of 30 patients

of diagnosis

provides

of retrospective

outstanding

indication

six of 30 (87”,,)

patients

(S7”,,)

from

collected

patients Since

survived

survived,

cessful

management

patients

with initial

or

assume

subsequent

feet the sire the selection ment.

No

resections

radiation

sutlice

chemotherapy

as was

would

seem

(4 of 4 in this

The

to 3000

success

radiation. therapy

true

local

control,

in all

cases

the only

local

tumors

larger

3 patients

with

of

at least

these have led some centers, cases

or

questions

including using

those

both with

roentgenographically,

or

of one or both

can be avoided because

total

kidney

21s recently

when

RT

Even

failure

was

tumor what

cl’-

obviousI! by subseto treat-

described.

in sitlu.

between

1000

and

is combined

some

in the

tumors

with

5 .zm or

IOOO- 3000

rad

after

rad given

3400

than 5 cm. all of whom

The

range

received

look” kidneys.

resections.

They

occasioned

tirst.

by chemosuch

already

as

of Philadelphia. RT

procedures.

its attendant

is reserved

for

clinically. Thus.

renal

have compromised

by the tumors

when

and use of lr-

demonstrated

surgical

and in

even

speculations

Hospital

tumor with

the timing and

and VCR

residual

tumor.

can be produced

Children’s

AMD

in some of these children. loss

lysis

residual

chemotherapy

Observations

at “second

of parenchymul

with

with

regarding

tumor

cases.

hoped that irradiation tion

are

followed

of

child

combined

curative

in some

therapy

RT

raises

It may be that locally

unresponsive

fo-

interext

decisions;

the kidney

that

disease

siLc and its response

by doses

in one nonirradiated doses

were present,

to test sequential

tumors

to analya

doses

into

in those

rad.

modest

alone

take

onlv

and had gross

or biopsy

at least

although

not

out

particular

the surgical

reviewed.

of all gross

residual

surgery.

that

managed

recorded

given

large tumors

for

Of

here were done with data suggest

(KT)

form

for the suc-

favorable

with

resection”

to be well

series),

to one of another

patients

does

was carried

tumor

10 “bench

reported

therapy

rad usually

7000

3 conclusion

it is not possible

by the initial

stud! Seven

some

removal

is essential

heminephrectomy,

were subjected

with

survived.

had upon

of .?I

comparisons.

resection

patients

also

I?

in the present

and therefore

l9/71

survey,

tumors

was intluenced

patients

the tumor

from

In this

of nephrectomy,

resection

larger

surgery

of I7 who did not have resective

quent

2000

and

Twenty-

with

one or more drugs.

resection

localized,

experience,

all but two received

with

Such

surgical

surgery

of the individual

presenl-

the difficulties

favorably

treatment

disease,

patients.

small,

left in one or both kidneys.

The

detinitive

that surgical

possible,

survival

3 patients

who had extirp:ative

sutliciently

tumors

despite

compares Only

of gross

complete

a procedure

the 15 survivors

All

to make

of these

the fact that

lowing

good

This

reports.J,5

resection

one could

account

make such

2 yr.

and all received chemotherapy

all seven patients

tumor

Wilms’

analyses.

previous

had complete

bilateral

information

is the overall

died. so that it is not possible of irradiation,

with

useful

it

i\

damage. func-

and by partidl

or

BISHOP

636

ET AL.

No statement can be drawn regarding the eHicacy or need for the various forms of chemotherapy employed since all patients received one or more drugs. The National Wilms’ Tumor Study has shown that patients given both AMD and VCR have fewer reiapses than those receiving a single drug.? It is probable, therefore, that the overall good survival may have been influenced at least in part by the fact that all but two patients received two or three chemical agents. No conclusion can be drawn from the observation that both patients treated with AMD alone survived whereas two of nine given AMD, VCR and ADR died. The numbers are small; also, three agents may have been selected for these patients because they had more advanced disease. Various clinical facts emerged from the survey. As previously reported,’ survival was better in children under 2 yr of age although this difference, (94”,, vs 77”,,) is not statistically significant because of small sample size. The difference in survival between girls and boys, 79”” vs 92”,,, also is not significant. No attempt was made to analyze the effect that the various treatment combinations had on survival by age or sex since the subgroups are too small. The importance of inspection of the contralateral kidney at operation is reinforced by the fact that in more than one third of the patients the disease was not known to be bilateral prior to the time of exploration. Preoperatively. the bilateral disease was detected by palpation in less than one third of the patients, and an additional one third were demonstrated by IVP. Biopsy of Wilms’ tumors has always been considered dangerous because of possible tumor seeding of the peritoneal cavity, giving rise to recurrent disease. That biopsy has a high risk is not borne out in these patients, where 17/I), with such a biopsy survived; however, one of the two deaths had intraabdominal recurrence.

CONCLUSIONS

Our data show that small tumors present in the second kidney are ditiicult to detect preoperatively. Therefore, not only should the opposite kidney be palpated in all cases, but it also should be exposed for direct inspection by reflection of the colon and its mesentery. The various and disparate methods used in managing these children had almost uniformly good results. It is clear that bilateral Wilms’ tumors are not room for conservative apextremely aggressive lesions. There is therefore proaches designed to preserve as much renal parenchyma as possible. The following suggestions regarding management are based on these considerations and we believe they can be supported by the experience gained from the patients here reported. They apply only to patients with bilateral tumors who may have a different natural history from the unilateral cases. After adequate preoperative work-up, the patient should be explored and resective surgery attempted only if by nephrectomy of the larger side and heminephrectomy of the opposite side all gross tumor can be removed. This was possible in only 5 of 30 cases reviewed here. AMD and VCR are given postoperatively according to the schedule of the N WTS.’ Radiation (RT) is given to the flank if the tumor on either or both sides has penetrated beyond the renal

BILATERAL

WILMS’

capsule.

The

the kidney livered

TUMOR

RT

637

SURVIVAL

dose regimen

has been removed.

to the remaining

of the NWTS

can be followed

but not more

than

kidney

parenchyma

1500

on the side where

rad

in

1.5

2 wk

on the side of the partial

is dc-

nephrec-

tom!. However, tensive

in the majority

bilaterally,

biopsies bined

are advisable.

RT

of patients,

preventing The

as above)

with

resection

experience

and chemotherapy

and VCR

the tumor

complete (e.g.,

here

involvement

reported

subsequent

surgery

ex-

therefore,

indicates

1500 rad in 2 wk to both

or without

is initially

of the tumor;

that

onl!

the

kidneys

com-

plus

AMD

can lead to lonp-term

control. Another RT

approach

routinely.

under

After

investigation

biopsy

of both

at CHP

kidneys,

ing the NWTS

recommendations.

the patient

have received one five day course

jections

will

of VCR.

in those month

Chemotherapy

children

evaluated

showing

if substantial

up to. but not more usually which

of the involved

are helpful

dure performed

will

be dictated

volvement

that a “tumorectomy”

with

the removal If this

attention

of all abnormal

procedure

can be evaluated

for

quent

operation

after

mains

viable

laparotomq

tion

therapy

and drug

to do a local

resection

efTort

is made to preserve as possible.

Only

In summary, tumor therapy should

should should

moved

only

outlined

after

those

uninvolved

followed

undertaking

in

mind

that

two

Rather.

or three

functioning

contain

viable

invol\,ement or at a subseside

TC-

resected

further

irrudilt-

is done hoping

resection

is

not

be performed. renal

tissue

posEver!

on one or

transplantation

be emphasized

that

in a large with

expectancy

Overly

destructive

conservative tissue

not

by renal

the care of children

renal

in-

the treatnumber

of

be established.

the survival

laparotomies,

usual

least

on the tirst

partial

can then

It must

the

greater

laparotomy

functioning

nephrectomy

as a last resort.

If

proce-

Our

may be possible

Postoperatively,

side

resection

side if not surgicalI)

a third

tissue.

involved

be kept to a minimum.

and adequate

both sides.

before

then can its etticacy and safety keep

has

at that time

above has not as yet been tested

not be performed.

hope that

as much

Bilateral

be considered

patients.

be biopsied.

of the more

that

of kidney

involved

evalu-

and bilater:tl

at the time.

with

of the tumor

more

be given

is further

the surgical

may or may kidney

the portion

a

are given

of partial

laparotomy

to the kidney

of an> abnormal

a nephrectomy

ment program

The

should

may

sible.

should

that

and functioning.

at the second

both sides

resection

proving

kidneys

urograms

the feasibility

which

is

is added after

or heminephrectomy

tissue

in-

regimen

2 or 3 mo of treatment,

excretory

goes well the opposite

possible

After

time

weekly

and the patient

Both

by the findings

primarily

by which

therapy

and the patient

At a second

our

tumor.

7 wk.

in determining

choice is to direct hoping

I.5

include

of a kidney.

obviously

size

uxe

folio\\-

to the NWTS

of tumor Radiation

significantly

examinations

portion

in 4 wk

has not occurred.

1500 rad in shrunk

does not

are given

of AM D and three

according

regression

centers

and VCR

is evaluated

2 or 3 mo.

regression

than have

ated. Roentgenographic arteriograms

after

tumor

result

is continued

obvious

for reexploration

the tumors

The

and other

AMD

all

is

operative

resections tumor

will

bilateral good.

tissue

U’ilms’ Radiation

procedures

are advocated will

have

have been preserved

in the

been reon one or

638

BISHOP

ET

AL.

ACKNOWLEDGMENT We are indebted to thia

Study

Paul Baranko. Evans.

to the following

of

Bilateral

St. Joseph’s

The Children’s

Houston;

Hospital

Jack G. Hamilton,

Arbor:

Hospital,

Patricin

Joo.

Baltimore:

Miller.

Cornell

Minneapclis: Patterson. Mexico

School

Jackson; British

W. Sutow.

Columbia.

Babies Hospital.

Thomas York:

Vancouver:

Madison;

Vietti.

Texas

Herbert

Pullen.

University

Univ.

of

Wailington

Univrr-

The Johns

Richard I.lniv.

Louis:

B.

of Ne%

Medical

Teasdale, St.

Denis Hospital,

Ohio:

Mississippi

University,

Hopkins

Minnesota

Pinkerton,

J. Mavis

Hospitals,

Philadelphia;

of

E.

Hospital.

Halpern.

Columbus.

Houston:

Pittsburg: Audrey

of Michigan

Kaifcr,

Donald

of

Children’s

Hospital.

Hospital,

data availahlc

Clinic:

Carolyn

University

Winston-Salem: Hospital.

their

Hospital

The Cleveland

University Nesbit,

Jeanette

Anderson

Theresa

Heyn,

Children‘s

Albequerque:

Children’s

of Los Angeles;

Mark

of Medicine.

M.D.

for making

The

J. Fernbach.

Ruth

Jefferson

Columbus

School

of Medicine,

Wataru

Dallas;

of Wisconsin. New

Newton, Gray

Donald

Hospital

School,

Liebert,

Albo,

Paul G. Dyment.

The Children’s

Center.

William

Phoenix;

University

Medical

and Institutions

Vincent

of Philadelphia;

Medical

Peter

Bowman

Tumor:

Hospital,

sity of Texas. Southwestern Ann

Investigators

Wilms’

Ccntrr.

University Jama

01

Wollf,

New York.

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D’Angio

GJ. Beckwith

al: The National Preliminary can

Wilms’

results.

Association

American

Tumor

Study

Proceedings for

Society

GB. Bishop

Cancer

of Clinical

HC. et

(NWTS):

of the

Ameri-

Research

and

Oncology

15:6X.

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GJ, bvans

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Wllms‘

Wllms’

Tumor

AE.

tumor. Study.

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N, et al: of

Na-

3X:633.

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HS,

tumor.

Lavengood

Urology

3:7l,

RW 1974

Jr:

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HC.

Hope

J Pediatr

J Surec 122:275. 6. fassady Conslderatlons Wilms’

tumor.

resection surgical

of

JW:

Surg I:476

5. DeLorimier et al: Treatment

7. Anderson

1976 Wilms’

4. Bishop tumors.

AA,

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Belrer

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Wilma’

4X7, I966 FO,

Kountz

SL,

Wilms’

tumor.

Am

1971 JR,

Teflt

in

the

Cancer KD.

Filler

RM,

radiation 32:59X

et al:

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01

608. 1973

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malignant

techniques.

M,

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RP:

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using

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