0022-534 7/78/1205-0586$02 . 00/0

Vol. 120, November Printed in U.S.A.

THE JOURNAL OF UROLOGY

Copyright © 1978 by The Williams & Wilkins Co.

BILATERAL WILMS TUMORS ROBERT A . GARRETT

AND

JOHN P. DONOHUE

From the Department of Urology, Indiana University Medical Center, Riley Hospital for Children, Indianapolis, Indiana

ABSTRACT

~he current management of bilateral Wilms tumor is reviewed and the high incidence of concurrent anomalies with bilateral Wilms tumor is demonstrated in 4 of 5 children. Standardizati~n of management has not been established. Of the 5 patients 3 survived 30 months to 11 years "'.1thout recurrent tumor. Two had unilateral nephrectomy and partial nephrectomy, while 1 had bilateral nephrectomy and allotransplant. All survivors have had adjunctive chemotherapy and radiotherapy. The National Wilms Tumor Study has assigned group V to bilateral Wilms tumors but no protocol for their management has been promulgated. Variations in the mode of presentation as well as methods of management make standardized treatment difficult if not impossible . From 1.5 1 to 13 per cent 2 of all Wilms tumors are bilateral. During the last 25 years 5 (6.5 per cent) bilateral Wilms tumors have occurred in 76 Wilms tumor-bearing children at our institution. 0.fthese 5 tumors 2 were metachronous and 3 were synchronous. Bilaterality manifested at an average age of 15 months,2 corresponding precisely with the average age at discovery of our group and at least a year earlier than unilaterality was noted. Intervals between metachronous manifestations varied from a few months to as long as 19 years. 3 CLINICAL FINDINGS

The most common single manifestation of bilateral Wilms tumor is an abdominal mass. Hematuria is somewhat more likely to occur and hypertension is associated more commonly with bilaterality. Associated congenital abnormalities occur with a frequency at least 10 times at note wit unilater altty.2 Of our 5 children with bilateral Wilms tumors 4 manifested anomalies. Renal abnormalities, such as horseshoe kidney, renal hypoplasia and pyeloureteral duplication, are not uncommon. Sporadic aniridia, hemihypertrophy, hyposp~~ias, especially with pseudohermaphroditism and cryptorch1d1sm, are reported repeatedly. Psychomotor retardation was noted in 2 of our children as well as male pseudohermaphroditism. Patent ductus arteriosis, hemihypertrophy and pyeloureteral duplication also were encountered in our small group. All such concurrences indicate a genetic background. Little emphasis has been placed on the histopathologic study in guidance of management or prognosis. Recent observations strongly suggest that bilateral Wilms tumor stems from multinodular renal blastema, aberrant metanephric tissue, hamartomas or Wilms tumorlets, some of which may or may not progress to overt malignancy. 2 • 4 • 5 Wilms tumors, predominantly sarcomatous or highly anaplastic, have unfavorable outlooks and may justify more intensive therapeutic approaches. 6 DIAGNOSIS

The excretory urogram (IVP) remains the initial definitive diagnostic measure. Angiography assumes a much more important part in bilaterality in defining the nature of the mass lesion but especially in delineating the extent of involvement of each kidney. Accepted for publication March 31, 1978. Read at annual meeting of North Central Section American Urological Association, San Diego, California, Novembe; 6-12, 1977.

MANAGEMENT

It cannot be over-emphasized that a team approach with the oncologist as the primary physician has contributed to the vast improvement in Wilms tumor prognosis during the last decade . Surgical excision remains fundamental to successful management. An atmosphere of aggressive management appears to be rewarding in increasing numbers of survivors. Operation. The extent of renal involvement influences strongly the surgical plan for excision and renal angiography is especially strategic to this evaluation. Broad surgical exposure is achieved best by either the chevron or thoracoabdominal approach carried across to the less involved side. Unilateral nephrectomy with partial contralateral nephrectomy, eillier s1mtrltaneouslyor s taged, is the most common mode of surgi--c-ai-i1mrnrgement~ im ev al uation of renal vasculature at ang10grap y makes partial nephrectomy a comprehensive procedure in many instances. Massive i olvement of both kidneys may call for preliminaryradiothera and/or chemot erapy o c an y urther e mes of demarcation between neoplasm and funchona renal tissue . Reportedly, bilateral par faal nephrectomy has been successful.7 Massive involvement, despite preliminary adjunctive therapy, occasionally calls for bilateral nephrectomy and allotransplantation with a cadaveric kidney. 8 Bench surgery may be necessary in the case of occasional massive involvement when partial nephrectomy is contemplated. 9 Metal clipping of residual or suspected residual tumor tissue guides the radiotherapist in postoperative treatment. Radiotherapy. Except for the use of radiotherapy to reduce tumor size preoperatively the National Wilms Tumor Study guide lines are followed in adjunctive therapy. Radiation alone or in concurrence with actinomycin D to the exclusion of surgical intervention is used rarely, since few children treated with such management have survived. Of 6 children whose tumor-bearing unoperated kidneys following contralateral nephrectomy were managed with chemotherapy and radiotherapy 4 are well .10• 11 Healthy kidney tissue shielding is facilitated by metal clipping and/or angiographic mapping when partial nephrectomy has preceded. Bilateral radiation of diffuse or multinodular renal involvement, especially in precursor renal blastema or hamartomatous phases, may salvage both kidneys or possibly permit selective partial nephrectomy in subsequent surgical attempts . Distant metastases are managed in the conventional pattern. Chemotherapy. Actinomycin D and vincristine are used in all cases of bilateral Wilms tumor for at least 15 months if tolerated . The use of both agents is clearly superior to either alone. Adriainycin may be substituted for vincristine in cases of intolerance or tumor resistance. Actinomycin D and adriam_ycm are radiopotentiators th at may revise total dosa~ of raaiation down}Y!lrd Preoperative chemotherapy may be ....--

586

electea -r,,vhen r_r1assive iTrvolve1nent

acctrrate

PROGNOSIS

a series collected from 8 of 58 survivors (13.8 per cent) at 5 National Wilms Tumor cites (72 cent). 12 This improved outan attitude aggressive - teamwork and additional modalities of intervention. Distant metastases are now eradicated frequently 1 or more Age at significantly influences prognosis. sarcomatous character confers a poor outlook. DISCUSSION

Standardization of bilateral Vviln1s tumor management has not emerged from retrospective analysis and no prospective protocol has been established. Our 5 cases are summarized in the table (cases l and 3 have been reported previously).13· 14 The 3 survivors have been managed since 1966. Those cases prior to that date received no chemotherapy, l antedating the chemotherapy era and the other not surviving the surgical convalescence. Case 2 was an example of over-enthusiastic surgical excision without accurate mapping of tumor tissue with angiography. The patient was oligmic postoperatively and died of cardiac decompensation. Much undetected tumor remained m the residual renal tissue as determined at autopsy. have "'''"'°"'"m to a the reward of &ggressive tumors but also the pulmonary metastasis. is interesting that metastasis occurred in the course of actinomycin D therapy and was nonresponsive to supervoltage radiation. Histology of the metastatic tissue was not significantly different from No. -Age-Sex- Yr. Tumor Concur(mos.) rence

1140

15

-23-M-1950

Probably

24

2- 9-M:-1964

31 1.

15

Yes

tu1nor tissue 2nd vvas not ,u,a1,u,w,,,1s, or sarco1na,. tous. In case 4 a metacl1:conous second tmnor developed 48 months after the initial turnor. Massive involvement defied treatment and bench surgery. Rendering the child anephric was the only hope of Case 5 was associated with male Interval IVPs were interpreted as normal for 54 months but on retrospective study we could detect a expanding renal mass long as l year before the ultimate second tumor discovery. The tumor was located in the line of partial nephrectomy yet after postoperative chemotherapy no tumor was found at laparotomy. Poor survival statistics of several earlier large series include many cases antedating chemotherapy and aggressive surgery. Current optimism, although justified, must be tempered by several modifiers. Radiation exposure of residual renal tissue lead to late renal failure from radiation nephritis. As as 2,000 rads can cause radiation nephritis. Leukemia occurs many times more frequently in Wilms tumor survivors than in a peer group population, 15 Recurrences of tumor as remotely as 19 years after initial management have been reported. Cadaveric transplants suffer a high attrition rate of their own. Consequently, bilateral nephrectomy with allotransplant remains the last resort. Whether immunosuppressive drugs with allotransplant may contribute to emergence of local or distant metastases remains to be seen. From our own experience several lessons are to be learned. Above all aggression has been In both of our metachronous cases pset1d,Jhermai:)h:rn,:ht1 should have warned us that the contralateral to the obvious tumor ~Nas a tumor bearer norrnal n-c,p1nccrc, In neither case was actual renal exposure done at original nephrectomy. Palpation at operation can be erroneous. All bilateral Wiln1s tumors are thought to be multifocal to some degree and must be evaluated angiography preoperatively.

Therapy

as

Chem.otherapy

Survival

Comments

Lt. renal radiation 1,600 rads Lt. nephrectomy, lt. irradis.tion 900 rads Rt. kidney inope::able, further therapy refused

Died 2 1nos.

Rt. pyeloureteral duplication Rt. involvement overiooked at initial laparotomy Pseudohermaphrodite

Bilat. partial nephrectomy

Died 5 days postop. of cardiac decompensation

Cryptorchidism, retardation Multinodular Wilms tumor

l{o evide::-.tc8 of

ivlultinodula:r Wilms tumor Puln1onary rrrntastasis 9 mos.

-17-F-1956

Actinomycin D, mos.

30

A.ctinomycin D, mos.

24

No evidence of disease 6 yrs.

Actinumycin D plus vincristine Azathioprine Prednisone Actinomycin D plus vincristine

2½ yrs. 20 mos. post.. transplant

Actinomycin D, mos.

No evidence of disease 41/zyrs. 21/z yrs.

disease l l yrs.

ra.-:b to

rads to rt. lung 1,500 rads to It. lung Rt. lo~Ner lobectomy 4- 3-F-1971

i'1""o

51

Rt. nephrectomy (stage II) 1;800 rads to renal fossa Interval - 48 rnos. Lt. renal 1-nass anuria Lt. nephrectomy Preop. and postop. ra,ctic,thenrnv 3,000 rads Renal rial

5-23-M-1973

54

No

trnmsnl,mt.

(Chicago Children's Iviemo-

Lt. nephrectomy (stage I) Radiotherapy lt. fossa 2,800 rads Interval 21/z yrs. Rt. mass Partial nephrectomy

vvith Do\vn's syndrome tumor totally necrotic Hemihypertrophy

15

Actinomycin D plus vincristine pl us adriamycin

Creatinine clearance 70 r.al./ min. No antitumor medication now Male pseudohermaphrodite Patent ductus arteriosis Retardation, seizures Normal IVP at age 6 mos. Tumor in line of excision Second look laparotomy biopsy negative Adriamycin replaced vincristine owing to toxicity Creatinine clearance 67 ml./ min.

588

GARRETT AND DONOHUE

As with unilateral Wilms tumors, distant metastases may ultimately require surgical removal if not completely responsive to adjuvant therapy. The concurrence of other anomalies suggests a genetic background for bilateral Wilms tumor. We are particularly impressed that only 1 of our cases escaped concurrent anomalous formations. REFERENCES

1. Abeshouse, B. S.: The management of Wilms' tumor as determined by national survey and review of the literature. J. Urol., 77: 792, 1957. 2. Bond, J. V.: Bilateral Wilms' tumour. Age at diagnosis, associated congenital anomalies, and possible pattern of inheritance. Lancet, 2: 482, 1975. 3. r~ay, R., Brosman, S. and Williams, D. I.: Bilateral nephroblastoma. J. Urol., 110: 119, 1973. 4. Bove, K. E. and McAdams, A. J.: The nephroblastomatosis complex and its relationship to Wilms' tumor: a clinicopathologic treatise. Per. Pediat. Path., 3: 185, 1976. 5. Walker, D. and Richard, G. A.: Fetal hamartoma of the kidney: recurrence and death of patient. J. Urol., 110: 352, 1973. 6. Beckwith, J. B. and Palmer, N. F.: National Wilms Tumor Study. Information Bulletin No. 5, June 15, 1977.

7. Wiener, E. S.: Bilateral partial nephrectomies for large bilateral Wilms' tumors. J. Pediat. Surg., 11: 867, 1976. 8. de Lorimier, A. A., Belzer, F. 0., Kountz, S. L. and Kushner, J. H.: Treatment of bilateral Wilms' tumor. Amer. J. Surg., 122: 275, 1971. 9. Lilly, J. R., Pfister, R.R., Putnam, C. W., Kosloske, A. M. and Starzl, T. E.: Bench surgery and renal autotransplantation in the pediatric patient. J. Pediat. Surg., 10: 623, 1975. 10. White, J. J., Golladay, E. S., Kaizer, H., Pinney, J. D. and Haller, J. A., Jr.: Conservatively aggressive management with bilateral Wilms' tumor. J. Pediat. Surg., 11: 859, 1976. 11. Richards, M. J., Miller, R. C. and Joo, P.: Radical partial renal irradiation. An alternative to partial nephrectomy in bilateral Wilms' tumor. Cancer, 38: 2093, 1976. 12. D'Angio, G. J., Evans, A. E., Breslow, N., Beckwith, B., Bishop, H., Feigl, P., Goodwin, W., Leape, L. L., Sinks, L. F., Sutow, W., Tefft, M. and Wolff, J.: The treatment of Wilms tumor. Cancer, 38: 633, 1976. 13. Stump, T. A. and Garrett, R. A.: Bilateral Wilm's tumor in a male pseudohermaphrodite. J. Urol., 72: 1146, 1954. 14. Garrett, R. A. and Battersby, J. S.: Bilateral Wilms tumor: 4year survival. J. Urol., 106: 942, 1971. 15. Miller, R. W.: Editorial: leukemia in survivors ofWilms tumor. J. Pediat., 87: 505, 1975.