Rhabdomyosarcoma involving the genitourinary organs, retroperitoneum, and pelvis

,Journal of Pediatric Surgery VOL XXI, NO 2

FEBRUARY 1986

Rhabdomyosarcoma Involving the Genitourinary Organs, Retroperitoneum, and Pelvis By Cheng-Ju Huang Peking, China 9 W e report on 17 patients with rhabdomyosarcoma of the genitourinary organs, retroperitoneal, pelvic, or perineal regions. T r e a t m e n t was refused by three patients with either bladder or prostatic lesions. The remaining patients were treated with combined modality therapy. Five of 6 patients with bladder lesions are free of tumor 24 to 108 months (mean 51 ) after diagnosis, while one patient died 4 months postoperatively; t w o patients with paratesticular lesions are free of disease 3 years and 10 months following diagnosis, respectively. Of t w o patients with perineal lesions, one patient died, probably due to metastases 21 months after diagnosis, while another patient with local tumor recurrence was treated by reexcision with follow-up for 12 months without evidence of tumor recurrence. The worst results w e r e obtained with the four patients with retroperitoneal pelvic lesions; one patient died 3 months after gross resection of tumor, and the other three patients deteriorated in the 4 months after diagnosis. Overall, 7 of 8 operated patients with bladder or paratesticular lesions are free of disease with folrow-up for 10 to 108 months. The biological behavior of embryonal rhabdomyosarcoma, with the sex and age distribution and the management are discussed. 9 1 9 8 6 by Grune & Stratton, Inc. INDEX W O R D : Rhabdomyosarcoma.

H A B D O M Y O S A R C O M A (RMS) is one of the most common soft tissue sarcomas of childhood. From June 1955 to June 1981, there were 1,320 patients with malignant solid tumors admitted to Peking Children's Hospital (20 patients with malignant tumors of CNS or retinoblastoma, which were diagnosed by biopsy or postmortem examinations were included). Fifty-nine (4.5%) patients were diagnosed as having RMS. RMS was exceeded in frequency only by lymphoma (247), nephroblastoma (222), neuroblastoma (114), embryonal carcinoma (102), and histocytosis X (71), and was the sixth most common malignant tumor in the whole series. In the last two decades since the use of combined therapeutic modalities, the prognosis of children with RMS has improved dramatically.

R

Journal of Pediatric Surgery, Vol 21, No 2 (February), 1986: pp 101-107

MATERIALS AND METHODS Of 59 consecutive pediatric patients with R M S admitted to Peking Children's Hospital, 17 patients have had primary involvement of the genitourinary organs, retroperitoneal tissues, or pelvis. Because the latter lesions frequently involve the bladder wall, they are discussed as one group. The eight female and nine male patients ranged in age from 4 months to 12 years at diagnosis (median age, 3.5 years). There were eight patients with bladder primaries, four with retroperitoneal or pelvic primary tumors, two with paratesticular sarcomas, two with perineal lesions and one with prostatic RMS. The clinical grouping was according to the Intergroup Rhabdomyosarcoma Study. Group I: Localized disease, completely resected (regional nodes not involved). Group 11: Grossly resected tumor with microscopic residual disease. No evidence of gross residual tumor, no evidence of regional node involvement. Regional disease, completely resected (regional nodes involved and/or extension of tumor into an adjacent organ); all tumor completely resected with no microscopic residual tumor. Regional disease with involved nodes grossly resected, but with evidence of microscopic residual. Group lII: Incomplete resection or biopsy with gross residual disease. Group IV: Distant metastic disease present at onset (lung, liver, bone, bone marrow, brain, and distant muscle and nodes). The chemotherapy regimen for R M S used in Peking Children's Hospital is as follows: Vincristine (VCR) 1.5 m g / m 2 x 10 then 1.5 m g / m ~ / 2 weeks x 2 years; Actinomycin (A) 12/ag/kg/d x 7 for 1 course. The interval between first and second courses is 6 weeks, and then one course every 3 months x 6; Cyclophosphamide (C) 2.5 m g / k g / d • 30 for 1 course; 1 course every 3 months x 2 years.

P r i m a r y Bladder T u m o r s The age at diagnosis for four males was 2 to 5 years (mean 3.5 years), and for four female patients, 4 months to 3 years (mean ! 5 months). The clinical presentation, precise site of the tumor, opera-

From the Department of Surgery, Peking Children's Hospital, Peking, China. Address reprint requests to Cheng-Ju Huang, MD, Department of Surgery, Peking Children's Hospital, Peking. China. 9 1986 by Grune & Stratton, Inc. 0022-3468/86/2102~9001503.00/0

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tion performed, chemotherapy regimen, and results are found in Table 1.

Retroperitoneal/Pelvic R M S All four patients with retroperitoneal or pelvic primary tumor (aged 3 to 4 years) presented with a lower abdominal mass. There were three girls and one boy. A summary of clinical data is presented in Table 2.

The mass measured about 12 cm in diameter by bimanual examination. The tumor was considered unresectable RMS so he was started immediately on VCR and cyclophosphamide. Partial regression (40%) of the mass was noted within 8 weeks of chemotherapy. Operation was refused by his parents. Afterwards the mass extended, without response to VCR and cyclophosphamide, and he died ten months after diagnosis. DISCUSSION

Paratesticular The two patients with paratesticular RMS were two and six years of age at diagnosis. They underwent orchiectomy and high ligation of the spermatic cord only, and postoperatively received chemotherapy with VCR and cyclophosphamide. Both of them are free of tumor at follow-up of 3 years and 10 months respectively.

Perineal Lesions A boy aged 1~/2years had a perineal lump measuring 6 x 5 x 5 cm for 2 months. The lump was aspirated in a local hospital but no definite diagnosis was made. We completely resected the tumor and VCR was given postoperatively. Eight months later, the tumor metastasized to the right inguinal nodes and responded well to VCR and cyclophosphamide combined with radiotherapy. Right inguinal node dissection was performed 8 weeks later with no residual tumor found. The patient died one year later, probably due to tumor metastasis although no necropsy was performed. Another girl aged 6 years had a perineal lesion that involved the vulva (Fig 1) and was resected locally. She received only a few weeks of VCR postoperatively. One year later, the tumor recurred locally and extended into the lower third of the vaginal wall. After 6 weeks of chemotherapy with VCR and cyclophosphamide, the tumor was completely resected grossly and followed up by VAC region. Follow-up for 30 months has shown no evidence of disease clinically.

Prostatic Tumor The 12-year-old boy with dysuria and a lump bulging from the perineum was diagnosed as having prostatic RMS by needle biopsy.

Fig 1.

Rhabdomyosarcoma of the vulva,

R h a b d o m y o s a r c o m a has been classified into four pathologic categories: e m b r y o n a l , alveolar, pleomorphic, and mixed. A n u m b e r of investigators ~4 concluded t h a t all childhood forms of r h a b d o m y o s a r c o m a are essentially e m b r y o n a l tumors. T h e variations in growth are due to the different sites of origin. W h e n e m b r y o n a l r h a b d o m y o s a r c o m a involves the soft tissues, because of the restraining influence of the surrounding structures it m a y have a fleshy a p p e a r a n c e and v a r y from firm to cystic in consistency. O n the other hand, these tumors, which grow in hollow viscera, eg, b l a d d e r and vagina, have a g r a p e - l i k e a p p e a r ance, the so-called s a r c o m a botryoides. T h e solid variety usually a p p e a r s to grow more slowly but m a y infiltrate widely beyond the p a l p a b l e mass. T h e deepseated retroperitoneal t u m o r is difficult to detect, so that a p a l p a b l e mass or s y m p t o m s of compression, eg, frequency in urination, a r e not early presentations. A l l four of our retroperitoneal r h a b d o m y o s a r c o m a s were in an advanced clinical group. A l l the t u m o r s were over 10 cm in d i a m e t e r , extended to s u r r o u n d i n g organs and tissues, eg, bladder, colon, uterus, o m e n t u m , and presacral region, peritoneal wall with ascites, a n d had m e t a s t a s i z e d to the inguinal or m e s e n t e r i c l y m p h nodes at diagnosis. Even after p r e p a r a t i o n with preoperative c h e m o t h e r a p y , only one t u m o r was grossly completely resected. In the series of R a n e y et al, ~ only 6 of 24 retroperitoneal r h a b d o m y o s a r c o m a s were grossly completely resected. All lesions showed microscopic t u m o r in the t u m o r bed and the m e a n d i a m e t e r of their 24 t u m o r s was 12 cm. Because of its f r e e d o m to extend into a hollow cavity, the botryoid v a r i e t y m a y grow to an enormous size even though it m a y arise from a small a r e a of the bladder. T h e trigone and posterior vesical wall a r e the most c o m m o n p r i m a r y sites in r h a b d o m y o s a r c o m a of the b l a d d e r . In 6 o f our 8 cases, the p r i m a r y t u m o r was at the trigone and in one case, the t u m o r filled the b l a d d e r except for the dome. One patient presented with the growing t u m o r protruding through the u r e t h r a l m e a t u s ( F i g 2). A l l of our eight patients c o m p l a i n e d of dysuria, due to intermittent obstruction of the internal u r e t h r a l opening. Following a period of s t r a n g u r y , one boy developed urinary retention, while three girls h a d t u m o r prolapse from the external u r e t h r a l orifice causing hydronephrosis and hydroureter, which complicates the m a n -

RHABDOMYOSARCOMA

105

female ratio was 1.47. 3 There were no obvious sex differences in our small group but the retroperitoneal pelvic rhabdomyosarcomas were predominantly in females. There were 14 males and ten females with primary retroperitoneal rhabdomyosarcoma entered in the Intergroup Rhabdomyosarcoma Study 1972 to 1976. s In the series reported by Ransom et al, 6 pelvic rhabdomyosarcoma also occurred predominantly in girls.

Diagnosis and Treatment As a result of combined therapy with surgery, chemotherapy and radiotherapy, 3-year survival rates with no relapse have improved dramatically (83% for Group I; 66% for Group II; 57% for Group III and 29% for Group IVY). Because rhabdomyosarcoma can present at many body sites and is associated with different patterns of biologic behavior, the treatment of children afflicted with this highly malignant tumor continues to present therapeutic challenges to the physicians faced with the diagnosis, determination of extent of tumor, and planning of treatment.

Surgery

Fig 2. Rhabdomyosarcoma of the bladder, protruding through the urethral meatus.

agement. In those patients with bladder outlet or ureteral obstruction early in the disease, the chances of complete tumor resection are good. Of our eight bladder primaries, two patients refused treatment. In one 5-year-old boy with tumor extending to the rectum and pelvic wall, the tumor was grossly completely resected, but microscopically involved margins were left in the tumor bed. The remaining five tumors were completely resected.

Age and Sex Of 636 patients with rhabdomyosarcoma entered in the Intergroup Rhabdomyosarcoma study, 3 67% were 10 years old and under. In our 17 patients, the median age at diagnosis was 3.5 years. Except for the patient with primary prostatic rhabdomyosarcoma who was aged 12 years, all were under 6 years of age. According to Altman and Schwartz 7 the peak incidence of rhabdomyosarcoma is in the 1- to 5-year age group with 10% of cases occurring in the first year of life. Males accounted for almost 60% of the patients (330 of 554 evaluated) who were entered in the Intergroup Rhabdomyosarcoma Study, and the male to

Patients with localized or regional tumor underwent complete surgical excision when this was possible. For patients with unresectable regional, or generalised disease, biopsies were done, and when feasible and safe, the area was explored to determine the extent of the tumor and the structures involved. Then, following treatment with radiotherapy and chemotherapy, reexploration and resection should be considered to afford the patient a better chance of palliation or control of disease.

Rhabdomyosarcoma of the Bladder An intravenous pyelogram will usually outline the polypoid lesions and the condition of the upper urinary tract (Fig 3). A cystogram may help to determine the extent of bladder involvement. Cystoscopy permits evaluation of the bladder, bladder neck, and urethra. Multiple biopsies are taken from any suspicious areas during endoscopy. In our series, treatment was refused by two patients. For one patient, the lesion involved the lateral wall of the bladder, and gross resection of the tumor by partial cystectomy was possible. For the remaining five, total cystectomies were required as the lesions were at the base of the bladder or the tumor occupied almost the whole bladder (Fig 4). Furthermore, two of the five patients received cystostomy first due to prolapse of tumor or urinary retention, which could not be relieved by catheterization.

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CHENG-JU HUANG

Fig 4. der.

Fig 3. Intravenous pyelogram showing a polypoid mass in the bladder w i t h dilated ureters and bilateral hydronephrosis.

Retroperitoneal/Pelvic Rhabdomyosarcoma The retroperitoneal rhabdomyosarcoma almost always has extensive disease at diagnosis, so that even when the tumors were grossly and completely resected, the postoperative tumor bed often showed tumor microscopically. In our series, there was only one patient with grossly completely resected tumor. In all the four patients with complete or incomplete resection, tumor recurred within 4 months after operation.

Paratesticular Rhabdomyosarcoma arising in the distal spermatic cord commonly invades the testis (Fig 5) and has a high incidence of lympatic metastasis. If there is suspected cancer of the testis or paratesticular structures, one should always do an orchiectomy through an inguinal incision with high ligation of the spermatic cord. If the boy had a previous transcrotal biopsy, a hemiscrotectomy should be done with the radical orchiectomy. Our two patients only underwent orchiectomy and high ligation of the spermatic cord, as there was no evidence of tumor metastasis at the time

Rhabdomyosarcoma occupying almost all of the blad-

of operation. According to the majority of investigators, ~'8 all these tumors require unilateral pelvic and retroperitoneal node dissection either at the same time or at a second procedure. If lymphatic metastasis can be excluded then radiotherapy is not necessary.

Perineal Lesions In our series, there were two patients in whom primary perineal lesions were grossly completely resected hut in both of them the tumor metastasized or recurred locally within a year postoperatively. From the Intergroup Rhabdomyosarcoma Study 1972 to 1976, 5 only three of 11 patients with perineal lesions are currently free of disease and seven (64%) have died; the median survival time is only 82 weeks from the beginning of therapy. Sites of recurrence are divided almost equally among local, regional, and distant metastasis.

Chemotherapy Chemotherapy plays an important role in the treatment of the primary tumor and also in the control of clinically evident metastasis or micrometastases. The agents most active against rhabdomyosarcoma are vincristine, actinomycin, cyclophosphamide, and

RHABDOMYOSARCOMA

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Prognosis in Rhabdomyosarcoma

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Rhabdomyosarcoma of the spermatic cord invading the

adriamycin, and they are best administered as 2-4 drugs in combination. At the present time, the basic approach to chemotherapy is the use of less intensive chemotherapy regimens for patients with no residual disease or microscopic residual disease (Group I, II) following surgery, with a more intensive protocol for patients with gross residual or metastatic disease (Group III, IV) at diagnosis. Adriamycin increases the overall toxicity and potential radiation-induced toxicity in the soft tissues, including the mucosa and muscles. 6 Administration of adriamycin with and without radiation increased the morbidity, including infections, in children less than 2 years of age, so that adriamycin should be used cautiously, especially in younger children, and the total dose should be under 450 mg per square meter of body surface.

Radiotherapy Radiation therapy can be withheld safely in patients with clinical stage I lesions and this was demonstrated by the Intergroup Rhabdomyosarcoma Study. They suggested radiotherapy doses in excess of 4,000 rads for older children and 4,000 rads to the "tumor bed" for younger children. Radiotherapy should include all tissues involved by subclinical microscopic and gross residual with a 5 cm margin in all directions. There is an increased risk of failure for children with tumors larger than 5 cm in diameter, especially in patients in clinical group II. 9

The Completeness of Surgical Excision. Although chemotherapy makes an important contribution to treatment, operative resection also plays an important part in the multimodal management. That is, patients with completely resected tumor have the best prognosis, while those with disseminated tumor have the poorest. From the report of Ransom et al, 6 only four of the 18 patients in their series survived, and two of them are free of active disease more than two years after diagnosis. One factor contributing to the poor results of treatment was the high proportion of patients with disseminated tumors at diagnosis. The Site of the Primary Lesion. Patients with disease in the genitourinary or orbital sites had a favorable prognosis, whereas those with disease in the retroperitoneal region had the worst prognosis, for their diagnosis is often made at a later stage. The Presence of Metastases. Patients with nondisseminated tumor, regardless of primary site, have the best opportunity for success from combined modality therapy. 6 REFERENCES

1. Exelby PR: Surgery of soft tissue sarcoma in children. Natl Cancer lnst Monogr56:153-157, 1981 2. Mieran GW, Favara BE: Rhabdomyosarcoma in children: Ultrastructural study of 31 cases. Cancer 46:2035-2040, 1980 3. Maurer HM: The Intergroup Rhabdomyosarcoma Study: Update, November, 1978. Natl Cancer Inst Monogr 56:61-68, 1981 4. Pratt CB, Hustu HO, Kumar APM, et al: Treatment of childhood rhabdomyosarcomaat St. Jude Children's Research Hospital, 1962-78. Natl Cancer Inst Monogr 56:93-101, 1981 5. Raney RB, DonaldsonMH, Sutow WW, et al: Special considerations related to primary site in rhabdomyosarcoma:Experienceof the Intergroup RhabdomyosarcomaStudy 1972-76. Natl Cancer Inst Monogr56:69-74, 1981 6. Ransom JL, Pratt CB, Hustu HO, et al: Retroperitoneal rhabdomyosarcoma in children, results of multimodality therapy. Cancer 45:845-850, 1980 7. Hays DM: Soft tissue sarcoma in childhood. Radiather Oncol 16:114-121, 1982 8. LawrenceW, Hays DM: Surgical lesions from the Intergroup RhabdomyosarcomaStudy. Natl Cancer Inst Monogr56:159-163, 1981 9. Jefft M, Lindberg RD, Gehan EA: Radiation therapy combined with systemic chemotherapy of rhabdomyosarcomain children: local control in patients enrolled in the Intergroup RhabdomyosarcomaStudy. Natl Cancer Inst Monogr56:75-81, 1981