Vol. 115, June Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright 1976 by The Williams & Wilkins Co.
UROGENITAL RHABDOMYOSARCOMA IN CHILDHOOD PAUL C. J. ROGERS,* STUARTS. HOWARDS
AND
DIANE M. KOMP
From the University of Virginia Hospital, Charlottesville, Virginia
ABSTRACT
Recent advances in chemotherapy and radiotherapy have improved the prognosis of urogenital rhabdomyosarcoma. Preliminary reports suggest that a mutilative operation may no longer be essential to cure this disease. Rhabdomyosarcoma is the most frequent cancer involving the bladder, prostate and vagina in children, and 13 to 20 per cent of all rhabdomyosarcomas are situated within the pelvic area. 1 As with Wilms tumor, studies now indicate that the combined modalities of operation, radiation therapy and chemotherapy are producing dramatically increased survival rates in this tumor. Because new advances in the therapeutic approach have not been sufficiently noted in the urological literature we present a brief summary of this important information. PROGNOSTIC BACKGROUND
Treatment of rhabdomyosarcoma from all sites with radiation or operation alone yielded 9 to 35 per cent survival rates. 2 • 5 These results were modestly improved as chemotherapy was added but significant progress has only come about since multidrug, multimodal therapy has been practiced. Significant prognostic factors relating to age, race, site, histology and stage have been described. 1 • 3 • 7 Age: The prognosis for infants less than 1 year old is generally considered to be worse in contrast to Wilms tumor and neuroblastoma. Some authors claim a decreased survival in patients more than 7 years old but this has not been confirmed by others. 5 Site: Genitourinary tumors have an intermediate prognosis compared to orbital tumors, which have the best and extraorbital rhabdomyosarcomas of the head and neck, which have the worst prognosis. Extent of disease: The most important factor for prognosis is the stage and survival data can only be interpreted in the context of stage. Histology: The majority of urogenital tumors are of the embryonal type, which has a more favorable prognosis compared to · alveolar and pleomorphic rhabdomyosarcoma. Sarcoma botryoides is a polypoid embryonal sarcoma that has the best survival rate. Sex: No correlation has been made between sex and survival. Rate of relapse: Recurrences have been noted in 70 per cent of patients within 1 year and' in 90 per cent within 2 years of diagnosis. UROGENITAL RHABDOMYOSARCOMA
Rhabdomyosarcoma probably arises embryologically from the urogenital sinus, from the non-specific mesenchyme, incorporated in the mesonephric duct. 8 Vagina: 1• • This tumor usually occurs during the first 3 years of life with symptoms of prolapsing polyp, vaginal mass, discharge or bleeding. It most commonly arises from the anterior vaginal wall. Bladder and urethra: 1• 10• 11 The incidence of this tumor is Accepted for publication October 10, 1975. * Requests for reprints: Department of Pediatric Hematology/ Oncology, Box 201, University of Virginia Hospital, Charlottesville, Virginia 22901. 738
increased in boys and approximately 75 per cent will be seen before the child is 5 years old. Of the bladder tumors 65 per cent arise from the region of the trigone and bladder neck. Since the tumor tends to be more in the superficial tissues until late in the disease distant metastases are a late occurrence. Urinary obstruction occurs and presenting symptoms may be frequency, urgency and incontinence. Urinary tract infection is frequent and hematuria is a late sign. Prostate: 1• 10• 11 Tumors of the vagina, bladder and urethra generally cause symptoms sooner than those of the prostate. Rhabdomyosarcoma of the prostate produces similar symptoms to those of the bladder but the average age of onset is older. The tumor compresses the base of the bladder and infiltrates directly the bladder neck and urethra, resulting in symptoms of bladder neck obstruction. Rectal compression or infiltration may cause symptoms of lower bowel obstruction. Dissemination is rapid by local direct invasion and distant dissemination is noticed earlier than in bladder lesions. Whether, in fact, this tumor of the prostate is more aggressive or rather that detection is more often delayed is unclear. Para testicular: 1• 12 These tumors present as an expanding non-tender mass in the scrotum. They tend to grow rapidly, spread early to regional lymph nodes and usually arise above the testicle and below the inguinal canal. A secondary hydrocele may well be present. CURRENT THERAPY
The traditional approach has been that of surgery first with a radical operation, usually an extensive local resection or an anterior, posterior or total pelvic exenteration. The aim has been to excise all tumor with margin of normal tissue and inguinal node dissection if possible. Irradiation follows if microscopic tumor is detected in the margins of resection or if the regional nodes are positive. By adding chemotherapy to operation and radiation, survival rates of up to 84 per cent of patients with rhabdomyosarcoma of all sites have been reported. 4 • 5 , 13 Ghavimi and associates treated patients with pelvic tumors with combined therapy and reported that 17 of 27 patients (63 per cent) were free of tumor during 18 months to 10 years of followup. 14 Chemotherapy approaches have varied but generally involve cyclic combination therapy for as long as 2 years. The drugs most favored in combination are vincristine, cyclophosphamide, actinomycin D and, recently, adriamycin. •·&, 1 •· 13 The rationale for chemotherapy is that residual tumor cells may remain outside the areas of operation and radiotherapy and occult distant metastases may be present. Chemotherapy and radiotherapy can reduce bulk in previously inoperable situations. Amazingly successful management of inoperable or metastatic rhabdomyosarcoma by radiation and concomitant vincristine, actinomycin D and cyclophosphamide has been reported by Wilbur and associates. Of 21 children 16 (76 per cent) were without evidence of disease during 1 to 4 years of followup. 19
UROGENITAL RH ABDO f1;1IY OS AH.CO f,,ifA
The resuits w1tt, chemotherapy and radiation have raised the question of whether radical operation is necessary or desirable for complete eradication of the tumor. 6 • 15 • 20 A less radical operation has been advocated either as the primary therapy followed by effective irradiation and chemotherapy or for residual tumor removed post-chemotherapy and radiation.•. 20 - 2 • Rivard and associates reported on 9 patients with pelvic tumor unresectable without sacrificing other pelvic structures. 22 • 23 They were treated by a preoperative multidrug regimen followed by local radiation therapy and/or operation. Of these patients 7 with unresectable tumor showed a 75 per cent decrease of tumor volume after 2 courses of chemotherapy and 5 are surviving 12 to 60 months. The deaths had only occurred in stage IV disease, that is disseminated disease. Thus, all 5 children with stages I to HI pelvic tumors are well 1 to 5 years after presentation, having had only minimal surgical intervention. Mutilative operation with its associated morbidity and reduced quality of life may no longer be essential to cure this disease. The urologist will be well advised to follow the progress of chemotherapy for this tumor and consult the oncologists before embarking on therapy. REFERENCES
1. Sutow, W. W., Vietti, T. and Fernbach, D. J.: Clinical Pediatric Oncology, 1st ed. St. Louis: The C. V. Mosby Co., pp. 450467 and 500-504, 1973. 2. Mahour, G. H., Soule, E. H., Mills, S. D. and Lynn, H. B.: Rhabdomyosarcoma in infants and children: a clinicopathological study of 75 cases. J. Pediat. Surg., 2: 402, 1967. 3. Sutow, W. W., Sullivan, M. P., Ried, H. L., Taylor, H. G. and Griffith, K. M.: Prognosis in childhood rhabdomyosarcoma. Cancer, 25: 1384, 1970. 4. Heyn, R. M., Holland, R., Newton, W. A., Jr., Tefft, M., Breslow, N. and Hartmann, J. R.: The role of combined chemotherapy in the treatment of rhabdomyosarcoma in children. Cancer, 34: 2128, 1974. 5. Ghavimi, F., Exelby, P. R., D'Angio, G. J., Cham, W., Lieberman, P. H., Tan, C., Mike, V. and Murphy, M. L.: Multidisciplinary treatment of embryonal rhabdomyosarcoma in children. Cancer, 35: 677, 1975. 6. Kilman, J. W., Clatworthy, H. W., Jr., Newton, W. A., Jr. and Grosfeld, J. L.: Reasonable surgery for rhabdomyosarcoma. Ann. Surg., 178: 346, 1973. 7. Ehrlich, F. E., Haas, J. E. and Kiesewetter, W. B.: Rhabdomyosarcoma in infants and children: factors affecting long term survival. J. Pediat. Surg., 6: 571, 1971.
CHiLuHuOD
8. Batsakis J. G.: Urogenital rhabdomyosarcoma: histogenesis and classification. J. Urol., !10: 180, 1963. 9. Hilgers, R. D.: Pelvic exenteration for vaginai embryonal rhabdomyosarcoma. Obst. Gynec., 45: 175, 1975. 10. Tefft, M. and Jaffe, N.: Sarcoma of the bladder and prostate in children: rationale for the role of radiation therapy based on a review of the literature and a report of fourteen additional patients. Cancer, 32: 1161, 1973. 11. Timmons, J. W., Jr., Burgert, E. 0., Jr., Soule, E. H., Gilchrist, G. S. and Kelalis, P. P.: Embryonal rhabdomyosarcoma of the bladder and prostate in childhood. J. Urol., 113: 694, 1975. 12. Burrington, J. D.: Rhabdomyosarcoma of the para testicular tissues in children. Report of eight cases. J. Pediat. Surg., 4: 503, 1969. 13. Heyn, R. M.: The role of chemotherapy in the management of soft tissue sarcomas. Cancer, 35: 921, 1975. 14. Ghavimi, F., Exelby, P. R., D'Angio, G. J., Whitmore, W. F., Jr., Lieberman, P. H., Lewis, J. L., Jr., Mike, V. and Murphy, M. L.: Combination therapy of urogenital embryonal rhabdomyosarcoma in children. Cancer, 32: 1178, 1973. 15. Sutow, W. W., Johnson, D. E. and Fernandez, C. H.: Chemotherapy in multimodal management of rhabdomyosarcoma of bladder and prostate in children. Urol. Clin. N. Amer., 1: 607, 1974. 16. Exelby, P. R.: Management of embryonal rhabdomyosarcoma in children. Surg. Clin. N. Amer., 54: 849, 1972. 17. Jaffe, N., Filler, R. M., Farber, S., Traggis, D. G., Vawter, G. F., Tefft, M. and Murray, J. E.: Rhabdomyosarcoma in children. Improved outlook with a multidisciplinary approach. Amer. J. Surg., 125: 482, 1973. 18. Pratt, C. B., Hustu, H. 0., Fleming, I. D. and Pinke!, D.: Coordinated treatment of childhood rhabdomyosarcoma with surgery, radiotherapy, and combination chemotherapy. C>incer Res., 32: 606, 1972. 19. Wilbur, J. R., Sutow, W. W., Sullivan, M. P., Castro, J. R., Kaizer, H. and Taylor, H. G.: Successful treatment of inoperable embryonal rhabdomyosarcoma. Pediat. Res., 5: 408, 1971. 20. Johnson, D. G.: Trends in surgery for childhood rhabdomyosarcoma. Cancer, 35: 916, 1975. 21. Clatworthy, H. W., Jr., Braren, V. and Smith, J. P.: Surgery of bladder and prostatic neoplasms in children. Cancer, 32: 1157, 1973. 22. Rivard, G. E., Ortega, J. A., Nitschke, R. and Karon, M.: Chemotherapy, not exenteration for pelvic rhabdomyosarcoma (abstract). Pediat. Res., 7: 352/124, 1973. 23. Rivard, G. E., Ortega, J., Hittle, R., Nitschke, R. and Karon, M.: Intensive chemotherapy as primary treatment for rhabdomyosarcoma of the pelvis. Cancer, 36: 1593, 1975. 24. Mackenzie, A. R., Sharma, T. C., Whitmore, W. F., Jr. and Melamed, M. R.: Non-extirpative treatment of myosarcomas of the bladder and prostate. Cancer, 28: 329, 1971. 1
THE JOURNAL OF UROLOGY
Copyright 1976 by The Williams & Wilkins Co.
UROGENITAL RHABDOMYOSARCOMA IN CHILDHOOD PAUL C. J. ROGERS,* STUARTS. HOWARDS
AND
DIANE M. KOMP
From the University of Virginia Hospital, Charlottesville, Virginia
ABSTRACT
Recent advances in chemotherapy and radiotherapy have improved the prognosis of urogenital rhabdomyosarcoma. Preliminary reports suggest that a mutilative operation may no longer be essential to cure this disease. Rhabdomyosarcoma is the most frequent cancer involving the bladder, prostate and vagina in children, and 13 to 20 per cent of all rhabdomyosarcomas are situated within the pelvic area. 1 As with Wilms tumor, studies now indicate that the combined modalities of operation, radiation therapy and chemotherapy are producing dramatically increased survival rates in this tumor. Because new advances in the therapeutic approach have not been sufficiently noted in the urological literature we present a brief summary of this important information. PROGNOSTIC BACKGROUND
Treatment of rhabdomyosarcoma from all sites with radiation or operation alone yielded 9 to 35 per cent survival rates. 2 • 5 These results were modestly improved as chemotherapy was added but significant progress has only come about since multidrug, multimodal therapy has been practiced. Significant prognostic factors relating to age, race, site, histology and stage have been described. 1 • 3 • 7 Age: The prognosis for infants less than 1 year old is generally considered to be worse in contrast to Wilms tumor and neuroblastoma. Some authors claim a decreased survival in patients more than 7 years old but this has not been confirmed by others. 5 Site: Genitourinary tumors have an intermediate prognosis compared to orbital tumors, which have the best and extraorbital rhabdomyosarcomas of the head and neck, which have the worst prognosis. Extent of disease: The most important factor for prognosis is the stage and survival data can only be interpreted in the context of stage. Histology: The majority of urogenital tumors are of the embryonal type, which has a more favorable prognosis compared to · alveolar and pleomorphic rhabdomyosarcoma. Sarcoma botryoides is a polypoid embryonal sarcoma that has the best survival rate. Sex: No correlation has been made between sex and survival. Rate of relapse: Recurrences have been noted in 70 per cent of patients within 1 year and' in 90 per cent within 2 years of diagnosis. UROGENITAL RHABDOMYOSARCOMA
Rhabdomyosarcoma probably arises embryologically from the urogenital sinus, from the non-specific mesenchyme, incorporated in the mesonephric duct. 8 Vagina: 1• • This tumor usually occurs during the first 3 years of life with symptoms of prolapsing polyp, vaginal mass, discharge or bleeding. It most commonly arises from the anterior vaginal wall. Bladder and urethra: 1• 10• 11 The incidence of this tumor is Accepted for publication October 10, 1975. * Requests for reprints: Department of Pediatric Hematology/ Oncology, Box 201, University of Virginia Hospital, Charlottesville, Virginia 22901. 738
increased in boys and approximately 75 per cent will be seen before the child is 5 years old. Of the bladder tumors 65 per cent arise from the region of the trigone and bladder neck. Since the tumor tends to be more in the superficial tissues until late in the disease distant metastases are a late occurrence. Urinary obstruction occurs and presenting symptoms may be frequency, urgency and incontinence. Urinary tract infection is frequent and hematuria is a late sign. Prostate: 1• 10• 11 Tumors of the vagina, bladder and urethra generally cause symptoms sooner than those of the prostate. Rhabdomyosarcoma of the prostate produces similar symptoms to those of the bladder but the average age of onset is older. The tumor compresses the base of the bladder and infiltrates directly the bladder neck and urethra, resulting in symptoms of bladder neck obstruction. Rectal compression or infiltration may cause symptoms of lower bowel obstruction. Dissemination is rapid by local direct invasion and distant dissemination is noticed earlier than in bladder lesions. Whether, in fact, this tumor of the prostate is more aggressive or rather that detection is more often delayed is unclear. Para testicular: 1• 12 These tumors present as an expanding non-tender mass in the scrotum. They tend to grow rapidly, spread early to regional lymph nodes and usually arise above the testicle and below the inguinal canal. A secondary hydrocele may well be present. CURRENT THERAPY
The traditional approach has been that of surgery first with a radical operation, usually an extensive local resection or an anterior, posterior or total pelvic exenteration. The aim has been to excise all tumor with margin of normal tissue and inguinal node dissection if possible. Irradiation follows if microscopic tumor is detected in the margins of resection or if the regional nodes are positive. By adding chemotherapy to operation and radiation, survival rates of up to 84 per cent of patients with rhabdomyosarcoma of all sites have been reported. 4 • 5 , 13 Ghavimi and associates treated patients with pelvic tumors with combined therapy and reported that 17 of 27 patients (63 per cent) were free of tumor during 18 months to 10 years of followup. 14 Chemotherapy approaches have varied but generally involve cyclic combination therapy for as long as 2 years. The drugs most favored in combination are vincristine, cyclophosphamide, actinomycin D and, recently, adriamycin. •·&, 1 •· 13 The rationale for chemotherapy is that residual tumor cells may remain outside the areas of operation and radiotherapy and occult distant metastases may be present. Chemotherapy and radiotherapy can reduce bulk in previously inoperable situations. Amazingly successful management of inoperable or metastatic rhabdomyosarcoma by radiation and concomitant vincristine, actinomycin D and cyclophosphamide has been reported by Wilbur and associates. Of 21 children 16 (76 per cent) were without evidence of disease during 1 to 4 years of followup. 19
UROGENITAL RH ABDO f1;1IY OS AH.CO f,,ifA
The resuits w1tt, chemotherapy and radiation have raised the question of whether radical operation is necessary or desirable for complete eradication of the tumor. 6 • 15 • 20 A less radical operation has been advocated either as the primary therapy followed by effective irradiation and chemotherapy or for residual tumor removed post-chemotherapy and radiation.•. 20 - 2 • Rivard and associates reported on 9 patients with pelvic tumor unresectable without sacrificing other pelvic structures. 22 • 23 They were treated by a preoperative multidrug regimen followed by local radiation therapy and/or operation. Of these patients 7 with unresectable tumor showed a 75 per cent decrease of tumor volume after 2 courses of chemotherapy and 5 are surviving 12 to 60 months. The deaths had only occurred in stage IV disease, that is disseminated disease. Thus, all 5 children with stages I to HI pelvic tumors are well 1 to 5 years after presentation, having had only minimal surgical intervention. Mutilative operation with its associated morbidity and reduced quality of life may no longer be essential to cure this disease. The urologist will be well advised to follow the progress of chemotherapy for this tumor and consult the oncologists before embarking on therapy. REFERENCES
1. Sutow, W. W., Vietti, T. and Fernbach, D. J.: Clinical Pediatric Oncology, 1st ed. St. Louis: The C. V. Mosby Co., pp. 450467 and 500-504, 1973. 2. Mahour, G. H., Soule, E. H., Mills, S. D. and Lynn, H. B.: Rhabdomyosarcoma in infants and children: a clinicopathological study of 75 cases. J. Pediat. Surg., 2: 402, 1967. 3. Sutow, W. W., Sullivan, M. P., Ried, H. L., Taylor, H. G. and Griffith, K. M.: Prognosis in childhood rhabdomyosarcoma. Cancer, 25: 1384, 1970. 4. Heyn, R. M., Holland, R., Newton, W. A., Jr., Tefft, M., Breslow, N. and Hartmann, J. R.: The role of combined chemotherapy in the treatment of rhabdomyosarcoma in children. Cancer, 34: 2128, 1974. 5. Ghavimi, F., Exelby, P. R., D'Angio, G. J., Cham, W., Lieberman, P. H., Tan, C., Mike, V. and Murphy, M. L.: Multidisciplinary treatment of embryonal rhabdomyosarcoma in children. Cancer, 35: 677, 1975. 6. Kilman, J. W., Clatworthy, H. W., Jr., Newton, W. A., Jr. and Grosfeld, J. L.: Reasonable surgery for rhabdomyosarcoma. Ann. Surg., 178: 346, 1973. 7. Ehrlich, F. E., Haas, J. E. and Kiesewetter, W. B.: Rhabdomyosarcoma in infants and children: factors affecting long term survival. J. Pediat. Surg., 6: 571, 1971.
CHiLuHuOD
8. Batsakis J. G.: Urogenital rhabdomyosarcoma: histogenesis and classification. J. Urol., !10: 180, 1963. 9. Hilgers, R. D.: Pelvic exenteration for vaginai embryonal rhabdomyosarcoma. Obst. Gynec., 45: 175, 1975. 10. Tefft, M. and Jaffe, N.: Sarcoma of the bladder and prostate in children: rationale for the role of radiation therapy based on a review of the literature and a report of fourteen additional patients. Cancer, 32: 1161, 1973. 11. Timmons, J. W., Jr., Burgert, E. 0., Jr., Soule, E. H., Gilchrist, G. S. and Kelalis, P. P.: Embryonal rhabdomyosarcoma of the bladder and prostate in childhood. J. Urol., 113: 694, 1975. 12. Burrington, J. D.: Rhabdomyosarcoma of the para testicular tissues in children. Report of eight cases. J. Pediat. Surg., 4: 503, 1969. 13. Heyn, R. M.: The role of chemotherapy in the management of soft tissue sarcomas. Cancer, 35: 921, 1975. 14. Ghavimi, F., Exelby, P. R., D'Angio, G. J., Whitmore, W. F., Jr., Lieberman, P. H., Lewis, J. L., Jr., Mike, V. and Murphy, M. L.: Combination therapy of urogenital embryonal rhabdomyosarcoma in children. Cancer, 32: 1178, 1973. 15. Sutow, W. W., Johnson, D. E. and Fernandez, C. H.: Chemotherapy in multimodal management of rhabdomyosarcoma of bladder and prostate in children. Urol. Clin. N. Amer., 1: 607, 1974. 16. Exelby, P. R.: Management of embryonal rhabdomyosarcoma in children. Surg. Clin. N. Amer., 54: 849, 1972. 17. Jaffe, N., Filler, R. M., Farber, S., Traggis, D. G., Vawter, G. F., Tefft, M. and Murray, J. E.: Rhabdomyosarcoma in children. Improved outlook with a multidisciplinary approach. Amer. J. Surg., 125: 482, 1973. 18. Pratt, C. B., Hustu, H. 0., Fleming, I. D. and Pinke!, D.: Coordinated treatment of childhood rhabdomyosarcoma with surgery, radiotherapy, and combination chemotherapy. C>incer Res., 32: 606, 1972. 19. Wilbur, J. R., Sutow, W. W., Sullivan, M. P., Castro, J. R., Kaizer, H. and Taylor, H. G.: Successful treatment of inoperable embryonal rhabdomyosarcoma. Pediat. Res., 5: 408, 1971. 20. Johnson, D. G.: Trends in surgery for childhood rhabdomyosarcoma. Cancer, 35: 916, 1975. 21. Clatworthy, H. W., Jr., Braren, V. and Smith, J. P.: Surgery of bladder and prostatic neoplasms in children. Cancer, 32: 1157, 1973. 22. Rivard, G. E., Ortega, J. A., Nitschke, R. and Karon, M.: Chemotherapy, not exenteration for pelvic rhabdomyosarcoma (abstract). Pediat. Res., 7: 352/124, 1973. 23. Rivard, G. E., Ortega, J., Hittle, R., Nitschke, R. and Karon, M.: Intensive chemotherapy as primary treatment for rhabdomyosarcoma of the pelvis. Cancer, 36: 1593, 1975. 24. Mackenzie, A. R., Sharma, T. C., Whitmore, W. F., Jr. and Melamed, M. R.: Non-extirpative treatment of myosarcomas of the bladder and prostate. Cancer, 28: 329, 1971. 1
