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Multimodal Treatment of Advanced Adult Wilms Tumor
0022-5347 /82/1273-0535$02.00/0 Vol. 127, March
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1982 by The Williams & Wilkins Co.
MULTIMODAL TREATMENT OF ADVANCED ADULT WILMS TUMOR MASAMICHI HAGIWARA, MASAAKI TACHIBANA, SEIDO JITSUKAWA, MASARU MURAI, MASAAKI NAKAZONO, MAKOTO HATA AND HIROSHI TAZAKI From the Department of Urology, School of Medicine, Keio University, Tokyo, Japan
ABSTRACT
We report 2 cases of advanced adult Wilms tumor that were treated with surgery, radiation and chemotherapy. The first patient had relapse of a Wilms tumor in the liver 2 years after nephrectomy. Combination chemotherapy, consisting of actinomycin D and vincristine, radiation therapy and final resection of the liver metastasis were successful and the patient has been free of disease for 4 years. The second patient had undergone transcatheter embolization of the renal artery elsewhere with the tentative diagnosis of an inoperable renal cell carcinoma metastatic to both lungs. A left renal tumor, weighing 4,500 gm., and a tumor thrombus in the vena cava extending to the right atrium were removed, and histologically diagnosed as a Wilms tumor. Subsequent chemotherapy and radiotherapy resulted in complete disappearance of the lung metastases. We conclude that multimodal treatment, namely a well timed combination of surgery, chemotherapy and radiotherapy, could potentially eradicate the disease even at an advanced stage. Wilms tumor is one of the most common malignant neoplasms in children. In the last 2 decades a dramatic increase of the survival rate of children with this neoplasm has been achieved as a result of therapeutic advances in the field of oncology. Recent refining of therapeutic approaches to this neoplasm by several cooperative groups has further improved the survival rate and made it possible now to predict a 90 per cent chance of cure for most such children. However, when this neoplasm is found in the adult, guideline for its management is less clear because only a limited number of adult cases have been reported. Herein we report 2 cases of advanced adult Wilms tumor that were treated with surgery, radiation and chemotherapy, and discuss the rational therapeutic approach to this rare disease. CASE REPORTS
Case 1. S. M., 400524, a 22-year-old woman, presented to the outpatient department in January 1974 with painless gross hematuria. She was hospitalized for evaluation of a spaceoccupying lesion of the right kidney suspected on an excretory urogram. A renal angiogram revealed multiple avascular masses at the middle portion of the right kidney. Some of the peripheral vessels surrounding the masses were irregular in caliber and had some neovascularity. Malignancy originating from the cyst wall or tumor with necrosis was the most likely diagnosis. Right nephrectomy was done in March. The right kidney measured 13 x 8 x 7 cm. and weighed 240 gm. Cross sections . showed a multilobulated grayish-white tumor with some hem- ;' orrhagic areas, necrosis and cyst formation at the middle por- ' · tion of the kidney. There was no evidence of capsular or renal vein invasion. Involvement of the regional lymph nodes was not apparent. Microscopic examination revealed a highly cellular tumor, predominantly composed of primitive renal blastematous cells, frequently forming tubular structures with few glomeruli (fig. 1). These histological findings were compatible with• those of a Wilms tumor. Postoperatively, the patient received 6,000 rad of radiation to the tumor bed and was discharged from the hospital in May. Metastatic surveys, including a chest roentgenogram and liver scan, were negative. In June 1976 the patient was rehospitalized because of severe pain at the right upper quadrant. Physical examination revealed Accepted for publication June 24, 1981. Read at annual meeting of American Urological Association, Boston, Massachusetts, May 10-14, 1981.
a large ill-defined tender mass. A celiac angiogram disclosed a huge hypovascular mass occupying the right hepatic lobe, which was interpreted as a liver metastasis of the original Wilms tumor (fig. 2, A). Initially, she was placed on intravenous administration of actinomycin D and vincristine. After completion of 1 course of the combination therapy, which consisted of a daily intravenous push of 0.5 mg. actinomycin D for 7 days and weekly administration of 2 mg. vincristine for 8 weeks, the right upper quadrant mass became nonpalpable and a liver scan confirmed marked shrinkage of the metastatic tumor. Thereafter, treatment consisted of continuous infusion of vincristine into the hepatic artery, which was followed by 6,000 rad of radiation. A celiac angiogram following an additional 2 courses of intravenous vincristine and actinomycin D revealed a solitary residual tumor localized in the right hepatic lobe (fig. 2, B). Since metastatic surveys were negative except for liver metastasis, extended right hepatic lobectomy was done in July 1977. Gross examination of the surgical specimen revealed a centrally necrotic grayish-white nodule, measuring 3 X 3.5 X 4.5 cm., in the right hepatic lobe (fig. 3). Microscopically, the nodule was predominantly composed of fibrous tissue with focal areas of hemorrhage and necrosis. The presence of small islands of renal blastematous cells with tubular differentiation con-
Fm. 1. Case 1. Photomicrograph of renal tumor shows primitive renal blastematous cells frequently forming tubular structures. H & E, reduced from x250. 535
536
HAGIW ARA AND ASSOCIATES
FIG. 2. Case 1. A, celiac angiogram shows huge hypovascular tumor occupying right hepatic lobe. B, celiac angiogram after chemotherapy and radiation therapy demonstrates marked shrinkage of tumor.
FIG. 3. Case 1. Cross sections of right hepatic lobe show grayishwhite tumor with central necrosis.
firmed the diagnosis of metastatic Wihns tumor. The patient refused postoperative adjuvant therapy. She is clinically free of disease and in good health 4 years after resection of the liver metastasis. Case 2. U. Y., 906194, a 37-year-old woman, was initially admitted elsewhere for evaluation of an abdominal mass in May 1979. A retrograde pyelogram showed marked displacement and deformity of the left collecting system (fig. 4, A). Angiographic studies revealed a huge hypervascular tumor of the left kidney, which was interpreted as renal cell carcinoma. Surgical intervention was believed to be impossible and, therefore, transcatheter embolization of the renal artery was done but with little benefit. In November the patient was transferred to this hospital for possible surgical treatment. Physical examination revealed a cachectic woman with a huge left upper quadrant mass. A chest roentgenogram showed multiple metastatic lesions on both lung fields with left pleural effusion. An inferior venacavogram revealed a large tumor thrombus extending to the right atrium (fig. 4, B). In December left nephrectomy with venacavotomy and tumor thrombectomy was done. The left kidney weighed 4,500 gm. and was completely replaced by the tumor. Cross sections showed a yellowish tumor intermixed with hemorrhagic and necrotic areas. Microscopically, the tumor was composed of sheets of undifferentiated spindle-shaped cells with hyperchromatic oval nuclei and scanty indistinct cytoplasms in sparse connective tissue stroma. Examination of the multiple sections revealed a few areas resembling tubular and glomerular structures. Diagnosis was Wihns tumor. The patient was started on a chemotherapeutic regimen, including actinomycin D and vincristine. Following a daily
FIG. 4. Case 2. A, retrograde pyelogram shows marked displacement and deformity of left collecting system. B, inferior venacavogram reveals tumor thrombus extending to right atrium.
intravenous push of 0.5 mg. actinomycin D for 5 days, 2 mg. vincristine was administered weekly for 4 weeks. This course was repeated every 6 weeks. The pulmonary metastases disappeared 2 weeks after initiation of chemotherapy; The patient recovered an appetite and gained 10 kg. in 2 months. However, in June 1980 a chest roentgenogram demonstrated relapse of the pulmonary metastases, which gradually increased in size despite continuation of the chemotherapeutic regimen (fig. 5). Subsequent administration of 75 mg. doxorubicin hydrochloride was ineffective. In September radiation therapy to the pulmonary metastases was started. A total dose of 2,000 rad was given to the whole chest in 4 weeks, which was followed by an additional 2,000 rad to the residual tumors at the left lower lung field in 3 weeks. All the metastatic lesions responded well with complete disappearance of the visible lesions. The patient was discharged from the hospital in good health in December and has been followed at a local hospital. DISCUSSION
Surgery alone offered a 2-year survival to only about 30 per cent of children with Wihns tumor in the 1930s. The addition of routine postoperative. radiotherapy in the 1940s improved the survival rate up to about 50 per cent and the combination of surgery, radiotherapy and chemotherapy in the 1960s further improved it to >80 per cent. 1• 2 Thus, the therapeutic role of surgery is limited in the management of childhood Wihns tumor and it may hold true in the management of adult Wihns tumor. Our first patient, who was thought to have localized disease at the time of nephrectomy and was not placed on postoperative
MULTIMODAL TREATMENT OF ADVANCED ADULT WILMS TUMOR
-
FIG. 5. Chest roentgenograms in case 2. A, before radiation therapy. B, after radiation with 2,000 rad to whole chest and additional 2,000 rad to residual tumors at left lower lung field. Surgery for debulking and histological diagnosis of Wilms' tumor
1 Chemotherapy to convert the disseminated disease to the localized
1 Radiotherapy to the localized disease
1 Surgery for complete removal of the residual tumor
1 Adjuvant chemotherapy and radiotherapy
1 Cure FIG. 6. Rational therapeutic approach to advanced adult Wilms tumor.
chemotherapy, had relapse of the disease in the liver 2 years later. This case might indicate the limited therapeutic role of surgery and the necessity of adjuvant chemotherapy even in the management of localized disease. Surgery is the first step to the possibility of cure for adults with Wilms tumor, that is the diagnostic role of surgery as well as its limited therapeutic role. Our second patient had advanced disease that initially was believed to be renal cell carcinoma and was treated with transcatheter embolization of the renal artery. This case is indicative of the importance of surgical intervention to confirm the histological diagnosis, which makes it possible to select the subsequent treatment modalities. The activity ofradiotherapy for adult Wilms tumor has been
documented in previous reports. 3- 7 Our case 2 also responded well to radiation; However, it was shown by case 1 that even 6,000 rad of radiation could not eradicate the solitary liver metastasis. The recent review of adult Wilms tumor by Kilton and associates demonstrated that radiotherapy alone is unsatisfactory to eradicate the clinically evident diseases, such as inoperable primary tumors, local recurrences and pulmonary metastases. 8 Chemotherapy also has been shown to be effective for adult Wilms tumor. 8 The active agents include vincristine and cyclophosphamide. However, no cases responded to vincristine and/ or cyclophosphamide with complete remission. The effectiveness of actinomycin D has not been documented in adult Wilms tumor,3· 7 ' 9 although the role of this drug in the management of Wilms tumor in childhood is well established. 2• 10 Both of our patients received actinomycin D and vincristine in combination and showed remarkable objective response. However, the degree of response was incomplete in case 1 and its duration was limited in case 2. Doxorubicin hydrochloride has shown varying degrees of effectiveness in children with metastatic Wilms tumor.11 Case 2 showed no response to doxorubicin hydrochloride, which was administrated when the previous 2 drugs became ineffective. Any single treatment modality seems to be unsatisfactory to eradicate Wilms tumor in the adult. The previous reports are suggestive of a less optimistic outlook for this disease in comparison to the counterpart in childhood. 4 • 5 • 8 • 9 • 12 Recently, Kilton and associates suggested the following multimodal treatment for all stages of adult Wilms tumor: 1) surgery for diagnosis, debulking and defining the tumor bed for radiation; 2) postoperative radiation to the tumor bed with additional whole lung radiation if pulmonary metastases are present and 3) combination chemotherapy as used in childhood Wilms tumor, including actinomycin D and vincristine. 8 It was documented by our cases that multimodal treatment, namely the well timed combination of surgery, radiotherapy and chemotherapy, could potentially eradicate even disease of the advanced stage, Our proposal for the management of advanced adult Wilms tumor is summarized in figure 6. REFERENCES 1. Gross, R. E. and Neuhauser, E. B. D.: Treatment of mixed tumors
of the kidney in childhood. Pediatrics, 6: 843, 1950. 2. Farber, S.: Chemotherapy in the treatment of leukemia and Wilms' tumor. J.A.M.A., 198: 826, 1966. 3. Boyer, C. W., Jr., Brickner, T. J., Jr. and Perry, R.H.: Cure of adult Wilms' tumor with distant metastasis? A case report. Amer. J. Roentgen., 103: 823, 1968. 4. Altug, M., Carmichael, F. A., Henry, C. L. and Stockton, R. W.: Wilms tumor in an adult: long-time survival with palliative resection of lung and brain metastases. J. Urol., 91: 212, 1964. 5. Smith, K. H.: Wilms tumor in the adult. Brit. J. Surg., 47: 397, 1960. 6. Livermore, G. R.: Wilms's tumor in an adult: report of a ten year
538
HAGIWARA AND ASSOCIATES
cure. J. Urol., 70: 141, 1953. 7. Sekaran, M. R. and Freedman, S. I.: Wilms' tumor. Treatment in an adult. Urology, 3: 632, 1974. 8. Kilton, L., Matthews, M. J. and Cohen, M. H.: Adult Wilms tumor: a report of prolonged survival and review of literature. J. Urol., 124: 1, 1980. 9. Prat, J., Gray, F. G., Stolley, P. D. and Coleman, J. W.: Wilms tumor in an adult associated with androgen abuse. J.A.M.A., 237: 2322, 1977.
10. Green, D. M. and Jaffe, N.: The role of chemotherapy in the treatment of Wilms' tumor. Cancer, 44: 52, 1979. 11. Sutow, W. W., Hussey, D. H., Ayala, A. G. and Sullivan, M. P.: Wilms' tumor. In: Clinical Pediatric Oncology, 2nd ed. Edited by W. W. Sutow, T. J. Vietti and D. J. Fernbach. St. Louis: C. V. Mosby Co., chapt. 23, p. 556, 1977. 12. Bard, R. H., Greenwald, E. S., Kalnicki, S. and Sablay, L. B.: Adult Wilms tumor treated with radiotherapy and chemotherapy: a case report. J. Urol., 121: 679, 1979.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1982 by The Williams & Wilkins Co.
MULTIMODAL TREATMENT OF ADVANCED ADULT WILMS TUMOR MASAMICHI HAGIWARA, MASAAKI TACHIBANA, SEIDO JITSUKAWA, MASARU MURAI, MASAAKI NAKAZONO, MAKOTO HATA AND HIROSHI TAZAKI From the Department of Urology, School of Medicine, Keio University, Tokyo, Japan
ABSTRACT
We report 2 cases of advanced adult Wilms tumor that were treated with surgery, radiation and chemotherapy. The first patient had relapse of a Wilms tumor in the liver 2 years after nephrectomy. Combination chemotherapy, consisting of actinomycin D and vincristine, radiation therapy and final resection of the liver metastasis were successful and the patient has been free of disease for 4 years. The second patient had undergone transcatheter embolization of the renal artery elsewhere with the tentative diagnosis of an inoperable renal cell carcinoma metastatic to both lungs. A left renal tumor, weighing 4,500 gm., and a tumor thrombus in the vena cava extending to the right atrium were removed, and histologically diagnosed as a Wilms tumor. Subsequent chemotherapy and radiotherapy resulted in complete disappearance of the lung metastases. We conclude that multimodal treatment, namely a well timed combination of surgery, chemotherapy and radiotherapy, could potentially eradicate the disease even at an advanced stage. Wilms tumor is one of the most common malignant neoplasms in children. In the last 2 decades a dramatic increase of the survival rate of children with this neoplasm has been achieved as a result of therapeutic advances in the field of oncology. Recent refining of therapeutic approaches to this neoplasm by several cooperative groups has further improved the survival rate and made it possible now to predict a 90 per cent chance of cure for most such children. However, when this neoplasm is found in the adult, guideline for its management is less clear because only a limited number of adult cases have been reported. Herein we report 2 cases of advanced adult Wilms tumor that were treated with surgery, radiation and chemotherapy, and discuss the rational therapeutic approach to this rare disease. CASE REPORTS
Case 1. S. M., 400524, a 22-year-old woman, presented to the outpatient department in January 1974 with painless gross hematuria. She was hospitalized for evaluation of a spaceoccupying lesion of the right kidney suspected on an excretory urogram. A renal angiogram revealed multiple avascular masses at the middle portion of the right kidney. Some of the peripheral vessels surrounding the masses were irregular in caliber and had some neovascularity. Malignancy originating from the cyst wall or tumor with necrosis was the most likely diagnosis. Right nephrectomy was done in March. The right kidney measured 13 x 8 x 7 cm. and weighed 240 gm. Cross sections . showed a multilobulated grayish-white tumor with some hem- ;' orrhagic areas, necrosis and cyst formation at the middle por- ' · tion of the kidney. There was no evidence of capsular or renal vein invasion. Involvement of the regional lymph nodes was not apparent. Microscopic examination revealed a highly cellular tumor, predominantly composed of primitive renal blastematous cells, frequently forming tubular structures with few glomeruli (fig. 1). These histological findings were compatible with• those of a Wilms tumor. Postoperatively, the patient received 6,000 rad of radiation to the tumor bed and was discharged from the hospital in May. Metastatic surveys, including a chest roentgenogram and liver scan, were negative. In June 1976 the patient was rehospitalized because of severe pain at the right upper quadrant. Physical examination revealed Accepted for publication June 24, 1981. Read at annual meeting of American Urological Association, Boston, Massachusetts, May 10-14, 1981.
a large ill-defined tender mass. A celiac angiogram disclosed a huge hypovascular mass occupying the right hepatic lobe, which was interpreted as a liver metastasis of the original Wilms tumor (fig. 2, A). Initially, she was placed on intravenous administration of actinomycin D and vincristine. After completion of 1 course of the combination therapy, which consisted of a daily intravenous push of 0.5 mg. actinomycin D for 7 days and weekly administration of 2 mg. vincristine for 8 weeks, the right upper quadrant mass became nonpalpable and a liver scan confirmed marked shrinkage of the metastatic tumor. Thereafter, treatment consisted of continuous infusion of vincristine into the hepatic artery, which was followed by 6,000 rad of radiation. A celiac angiogram following an additional 2 courses of intravenous vincristine and actinomycin D revealed a solitary residual tumor localized in the right hepatic lobe (fig. 2, B). Since metastatic surveys were negative except for liver metastasis, extended right hepatic lobectomy was done in July 1977. Gross examination of the surgical specimen revealed a centrally necrotic grayish-white nodule, measuring 3 X 3.5 X 4.5 cm., in the right hepatic lobe (fig. 3). Microscopically, the nodule was predominantly composed of fibrous tissue with focal areas of hemorrhage and necrosis. The presence of small islands of renal blastematous cells with tubular differentiation con-
Fm. 1. Case 1. Photomicrograph of renal tumor shows primitive renal blastematous cells frequently forming tubular structures. H & E, reduced from x250. 535
536
HAGIW ARA AND ASSOCIATES
FIG. 2. Case 1. A, celiac angiogram shows huge hypovascular tumor occupying right hepatic lobe. B, celiac angiogram after chemotherapy and radiation therapy demonstrates marked shrinkage of tumor.
FIG. 3. Case 1. Cross sections of right hepatic lobe show grayishwhite tumor with central necrosis.
firmed the diagnosis of metastatic Wihns tumor. The patient refused postoperative adjuvant therapy. She is clinically free of disease and in good health 4 years after resection of the liver metastasis. Case 2. U. Y., 906194, a 37-year-old woman, was initially admitted elsewhere for evaluation of an abdominal mass in May 1979. A retrograde pyelogram showed marked displacement and deformity of the left collecting system (fig. 4, A). Angiographic studies revealed a huge hypervascular tumor of the left kidney, which was interpreted as renal cell carcinoma. Surgical intervention was believed to be impossible and, therefore, transcatheter embolization of the renal artery was done but with little benefit. In November the patient was transferred to this hospital for possible surgical treatment. Physical examination revealed a cachectic woman with a huge left upper quadrant mass. A chest roentgenogram showed multiple metastatic lesions on both lung fields with left pleural effusion. An inferior venacavogram revealed a large tumor thrombus extending to the right atrium (fig. 4, B). In December left nephrectomy with venacavotomy and tumor thrombectomy was done. The left kidney weighed 4,500 gm. and was completely replaced by the tumor. Cross sections showed a yellowish tumor intermixed with hemorrhagic and necrotic areas. Microscopically, the tumor was composed of sheets of undifferentiated spindle-shaped cells with hyperchromatic oval nuclei and scanty indistinct cytoplasms in sparse connective tissue stroma. Examination of the multiple sections revealed a few areas resembling tubular and glomerular structures. Diagnosis was Wihns tumor. The patient was started on a chemotherapeutic regimen, including actinomycin D and vincristine. Following a daily
FIG. 4. Case 2. A, retrograde pyelogram shows marked displacement and deformity of left collecting system. B, inferior venacavogram reveals tumor thrombus extending to right atrium.
intravenous push of 0.5 mg. actinomycin D for 5 days, 2 mg. vincristine was administered weekly for 4 weeks. This course was repeated every 6 weeks. The pulmonary metastases disappeared 2 weeks after initiation of chemotherapy; The patient recovered an appetite and gained 10 kg. in 2 months. However, in June 1980 a chest roentgenogram demonstrated relapse of the pulmonary metastases, which gradually increased in size despite continuation of the chemotherapeutic regimen (fig. 5). Subsequent administration of 75 mg. doxorubicin hydrochloride was ineffective. In September radiation therapy to the pulmonary metastases was started. A total dose of 2,000 rad was given to the whole chest in 4 weeks, which was followed by an additional 2,000 rad to the residual tumors at the left lower lung field in 3 weeks. All the metastatic lesions responded well with complete disappearance of the visible lesions. The patient was discharged from the hospital in good health in December and has been followed at a local hospital. DISCUSSION
Surgery alone offered a 2-year survival to only about 30 per cent of children with Wihns tumor in the 1930s. The addition of routine postoperative. radiotherapy in the 1940s improved the survival rate up to about 50 per cent and the combination of surgery, radiotherapy and chemotherapy in the 1960s further improved it to >80 per cent. 1• 2 Thus, the therapeutic role of surgery is limited in the management of childhood Wihns tumor and it may hold true in the management of adult Wihns tumor. Our first patient, who was thought to have localized disease at the time of nephrectomy and was not placed on postoperative
MULTIMODAL TREATMENT OF ADVANCED ADULT WILMS TUMOR
-
FIG. 5. Chest roentgenograms in case 2. A, before radiation therapy. B, after radiation with 2,000 rad to whole chest and additional 2,000 rad to residual tumors at left lower lung field. Surgery for debulking and histological diagnosis of Wilms' tumor
1 Chemotherapy to convert the disseminated disease to the localized
1 Radiotherapy to the localized disease
1 Surgery for complete removal of the residual tumor
1 Adjuvant chemotherapy and radiotherapy
1 Cure FIG. 6. Rational therapeutic approach to advanced adult Wilms tumor.
chemotherapy, had relapse of the disease in the liver 2 years later. This case might indicate the limited therapeutic role of surgery and the necessity of adjuvant chemotherapy even in the management of localized disease. Surgery is the first step to the possibility of cure for adults with Wilms tumor, that is the diagnostic role of surgery as well as its limited therapeutic role. Our second patient had advanced disease that initially was believed to be renal cell carcinoma and was treated with transcatheter embolization of the renal artery. This case is indicative of the importance of surgical intervention to confirm the histological diagnosis, which makes it possible to select the subsequent treatment modalities. The activity ofradiotherapy for adult Wilms tumor has been
documented in previous reports. 3- 7 Our case 2 also responded well to radiation; However, it was shown by case 1 that even 6,000 rad of radiation could not eradicate the solitary liver metastasis. The recent review of adult Wilms tumor by Kilton and associates demonstrated that radiotherapy alone is unsatisfactory to eradicate the clinically evident diseases, such as inoperable primary tumors, local recurrences and pulmonary metastases. 8 Chemotherapy also has been shown to be effective for adult Wilms tumor. 8 The active agents include vincristine and cyclophosphamide. However, no cases responded to vincristine and/ or cyclophosphamide with complete remission. The effectiveness of actinomycin D has not been documented in adult Wilms tumor,3· 7 ' 9 although the role of this drug in the management of Wilms tumor in childhood is well established. 2• 10 Both of our patients received actinomycin D and vincristine in combination and showed remarkable objective response. However, the degree of response was incomplete in case 1 and its duration was limited in case 2. Doxorubicin hydrochloride has shown varying degrees of effectiveness in children with metastatic Wilms tumor.11 Case 2 showed no response to doxorubicin hydrochloride, which was administrated when the previous 2 drugs became ineffective. Any single treatment modality seems to be unsatisfactory to eradicate Wilms tumor in the adult. The previous reports are suggestive of a less optimistic outlook for this disease in comparison to the counterpart in childhood. 4 • 5 • 8 • 9 • 12 Recently, Kilton and associates suggested the following multimodal treatment for all stages of adult Wilms tumor: 1) surgery for diagnosis, debulking and defining the tumor bed for radiation; 2) postoperative radiation to the tumor bed with additional whole lung radiation if pulmonary metastases are present and 3) combination chemotherapy as used in childhood Wilms tumor, including actinomycin D and vincristine. 8 It was documented by our cases that multimodal treatment, namely the well timed combination of surgery, radiotherapy and chemotherapy, could potentially eradicate even disease of the advanced stage, Our proposal for the management of advanced adult Wilms tumor is summarized in figure 6. REFERENCES 1. Gross, R. E. and Neuhauser, E. B. D.: Treatment of mixed tumors
of the kidney in childhood. Pediatrics, 6: 843, 1950. 2. Farber, S.: Chemotherapy in the treatment of leukemia and Wilms' tumor. J.A.M.A., 198: 826, 1966. 3. Boyer, C. W., Jr., Brickner, T. J., Jr. and Perry, R.H.: Cure of adult Wilms' tumor with distant metastasis? A case report. Amer. J. Roentgen., 103: 823, 1968. 4. Altug, M., Carmichael, F. A., Henry, C. L. and Stockton, R. W.: Wilms tumor in an adult: long-time survival with palliative resection of lung and brain metastases. J. Urol., 91: 212, 1964. 5. Smith, K. H.: Wilms tumor in the adult. Brit. J. Surg., 47: 397, 1960. 6. Livermore, G. R.: Wilms's tumor in an adult: report of a ten year
538
HAGIWARA AND ASSOCIATES
cure. J. Urol., 70: 141, 1953. 7. Sekaran, M. R. and Freedman, S. I.: Wilms' tumor. Treatment in an adult. Urology, 3: 632, 1974. 8. Kilton, L., Matthews, M. J. and Cohen, M. H.: Adult Wilms tumor: a report of prolonged survival and review of literature. J. Urol., 124: 1, 1980. 9. Prat, J., Gray, F. G., Stolley, P. D. and Coleman, J. W.: Wilms tumor in an adult associated with androgen abuse. J.A.M.A., 237: 2322, 1977.
10. Green, D. M. and Jaffe, N.: The role of chemotherapy in the treatment of Wilms' tumor. Cancer, 44: 52, 1979. 11. Sutow, W. W., Hussey, D. H., Ayala, A. G. and Sullivan, M. P.: Wilms' tumor. In: Clinical Pediatric Oncology, 2nd ed. Edited by W. W. Sutow, T. J. Vietti and D. J. Fernbach. St. Louis: C. V. Mosby Co., chapt. 23, p. 556, 1977. 12. Bard, R. H., Greenwald, E. S., Kalnicki, S. and Sablay, L. B.: Adult Wilms tumor treated with radiotherapy and chemotherapy: a case report. J. Urol., 121: 679, 1979.