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© 2002 American Society for Clinical Oncology Paratesticular Rhabdomyosarcoma: Report From the Italian and German Cooperative GroupByFrom the Pediatric Oncology and Pediatric Surgery Units, Istituto Nazionale Tumori, Milan, and Hematology-Oncology Division, University of Padova, Padova, Italy; and Pediatric Oncology Division, Olga Hospital, Stuttgart, Germany. Supported in part by a grant from Fondazione Città della Speranza.Address reprint requests to Andrea Ferrari, MD, Pediatric Oncology Unit, Istituto Nazionale Tumori, Via G Venezian, 1, 20133 Milan MI, Italy; email: ferrari{at}istitutotumori.mi.it
PURPOSE: We report the experience of the German-Italian Cooperative Group with 216 pediatric patients with paratesticular rhabdomyosarcoma treated over 20 years. PATIENTS AND METHODS: At diagnosis, 198 patients had localized disease and 18 had distant metastases. Among the nonmetastatic patients, complete tumor resection was performed in 83% of cases. Evaluation of the retroperitoneal lymph nodes changed over the years from routine surgical staging to radiologic assessment. All patients received chemotherapy, which was reduced in intensity and duration for patients with low-risk features in subsequent protocols. Radiotherapy was administered to 10% of patients. RESULTS: Among 72 patients with a negative retroperitoneal computed tomography (CT) scan, surgical assessment detected nodal involvement in only one case. Among 23 patients with enlarged nodes on CT scans, surgery confirmed nodal spread in 65% of patients. No differences in the rate of nodal involvement were observed over the years. With a median follow-up of 110 months, 5-year survival was 85.5% for the series as a whole, 94.6% for patients with localized disease, and 22.2% for metastatic cases. Retroperitoneal nodal recurrence was the major cause of treatment failure. Univariate analysis revealed the prognostic value of tumor invasiveness, size, and resectability, as well as of nodal involvement and age, in patients with localized tumor. CONCLUSION: The outcome for patients with localized paratesticular rhabdomyosarcoma is excellent, despite the reduction in chemotherapy over the years: an alkylating agent–free and anthracycline-free regimen is adequate treatment for low-risk patients. Surgical assessment of the retroperitoneum must be reserved for patients with enlarged nodes on CT scans. Children over 10 years old carry a higher risk of nodal involvement and relapse.
PARATESTICULAR rhabdomyosarcoma accounts for approximately 7% of all rhabdomyosarcomas and is the most common soft tissue sarcoma in childhood, with an annual incidence of four to seven cases per million.1 It arises from mesenchymal elements of the spermatic cord, epididymis, and testicular envelopes, producing a painless scrotal mass. This superficial location usually enables an early diagnosis and, in most cases, complete surgical resection. These characteristics and the fact that almost all paratesticular rhabdomyosarcomas are of the more favorable embryonal subtype account for the good prognosis for these children.2 All recently published series have reported an overall survival of more than 80% at 5 years, using a multimodality approach with surgery, chemotherapy, and radiation therapy.3-10 Reducing the morbidity of the treatment without jeopardizing its efficacy is one of the most important aims in the treatment of these patients. Retroperitoneal lymph node dissection has been used as a routine staging procedure, but significant sequelae have been reported.11,12 The feasibility of omitting anthracyclines and alkylating agents from chemotherapy regimens and the identification of patients with high-risk features requiring a more aggressive approach are also relevant matters awaiting a solution. We report our findings in a large series of patients with paratesticular rhabdomyosarcoma with a view to investigating these issues. Patients were recruited over 20 years according to the protocols of the German Cooperative Soft Tissue Sarcoma Group (CWS), the Italian Cooperative Group (ICG) on childhood soft tissue sarcoma, and the Istituto Nazionale Tumori (INT) of Milan.
A total of 216 previously untreated patients under 21 years of age was enrolled onto different protocols from September 1978 to June 1999. Complete clinical data and treatment details were available on all patients. Histopathologic review was done by each study group’s own panel of pathologists. The German studies (CWS-81, CWS-86, CWS-91, and CWS-96) included 111 children, while 105 patients were treated at Italian centers (60 according to the RMS-79,13 RMS-88,9 and RMS-96 protocols coordinated by the ICG; 45 according to the INT protocols8 up until 1996; thereafter, INT patients were included in the ICG studies). The median age at diagnosis was 7 years (range, 1 month to 21 years); 133 patients were under and 83 were over 10 years of age. All enrolled patients were white.
Clinical Grouping
Staging of disease was done according to both the tumor-nodes-metastases (TNM) pretreatment staging classification14 and the Intergroup Rhabdomyosarcoma Study (IRS) postsurgical grouping system.15 The definition of TNM T1 refers to tumors confined to the organ or tissue of origin, while T2 lesions invade contiguous structures; T1 and T2 groups are further divided into subsets A or B according to tumor diameter In the IRS system, group I defines completely excised tumors; group II indicates grossly resected tumors with microscopic residual disease and/or regional lymph nodal spread; group III includes patients with gross residual disease after incomplete resection or biopsy; and group IV comprises patients with distant metastases at onset.15
Treatment Therapeutic guidelines advocated the use of local radiotherapy in the case of microscopic or macroscopic residual tumor after initial or delayed surgery. Clinically or pathologically involved retroperitoneal nodes had to be irradiated. Chemotherapy was used in all patients. Various chemotherapeutic regimens were adopted over the years, according to ongoing protocols and the extent of the disease (Table 1). The German group used the vincristine, dactinomycin, cyclophosphamide, and doxorubicin (VACA) regimen in the CWS-81 protocol,16 replacing cyclophosphamide with ifosfamide in the vincristine, dactinomycin, ifosfamide, and doxorubicin (VAIA) regimen adopted in the subsequent CWS-86 and CWS-91 studies. The INT protocols8 used the VACA regimen for 12, 9, or 6 months in relation to the initial extent and the degree of primary surgery. The Italian group switched from the vincristine, dactinomycin, and cyclophosphamide (VAC)/cyclophosphamide, doxorubicin, and vincristine (CAV) regimen adopted in the RMS-79 study9,13 to the VAIA, ifosfamide, vincristine, and dactinomycin (IVA), and vincristine and dactinomycin (VA) regimens (depending on the IRS group involved) in the RMS-88 protocol. Finally, VA was adopted in CWS-96 and RMS-96 protocols for low-risk patients, who were defined as those with (a) favorable histology (embryonal or spindle cells), (b) no local invasiveness or nodal or distant spread (T1N0M0), and (c) completely resected tumor (IRS group I). Eight patients with metastatic disease were treated according to the European MMT4 protocol17 using the carboplatin, epidoxorubicin, vincristine, dactinomycin, ifosfamide, and etoposide (CEVAIE) regimens, followed by high-dose melphalan (200 mg/m2) with autologous peripheral-blood stem-cell rescue in two cases.
Statistical Methods Prognosis was defined according to survival and event-free survival (EFS), using the Kaplan-Meier18 method to calculate the curves. Survival was estimated from diagnosis to death or last follow-up evaluation, and EFS was evaluated from diagnosis to disease progression, relapse, death for any cause, or last follow-up. The log-rank test19 was used to compare the survivals curves of the patient subgroups in univariate analyses in order to ascertain the potential value of prognostic factors. The small number of events prevented a comparison of survival with a multivariate analysis.  2 tests were used to compare the frequency of patient characteristics. Follow-up was updated as of December 2000 and ranged from 19 to 266 months (median follow-up, 110 months).
According to the International Classification,20 the histologic subtype was embryonal in 181 (84%) of 216 patients, alveolar in 18, spindle cells in 10, and not otherwise specified in seven. Data on the amount of time that elapsed between the onset of symptoms (usually a unilateral painless intrascrotal mass) and diagnosis were available for 91 Italian patients and ranged from 1 week to 12 months (median elapsed time, 6 weeks). In the patients younger than 10 years, the median delay was 3 weeks (range, 1 week to 9 months), which differed significantly (P < .01) from the situation among older patients, in whom the median latency period was 3 months (range, 2 weeks to 12 months). At onset, 198 patients (92%) had localized disease and 18 (8%) had distant metastases, compared with approximately 25% for rhabdomyosarcomas at other sites. For the whole series of 216 patients, 5-year survival and EFS rates were 88.5% and 85%, respectively. Because clinical characteristics and outcome differed significantly, we performed separate analyses for patients with locoregional disease and for those with metastases.
Patients With Localized Disease
Retroperitoneal lymph node assessment. Retroperitoneal lymph node involvement was detected in 21 patients (10%), while 177 were categorized as N0. Among the N1 patients, six had T1A primary lesions, three had T1B lesions, three had T2A lesions, and nine had T2B lesions. Nine patients were in IRS group II, and 12 were in group III. The rate of nodal involvement differed significantly in relation to the patient’s age: seven (5%) of 132 children under 10 years old were N1, as opposed to 14 (21%) of 66 children over 10 years old (P < .01). The retroperitoneal evaluation was radiologic assessment alone in 103 patients, and five patients were diagnosed as having nodal involvement (cN1). In 95 patients, the radiologic evaluation was followed by surgical exploration of the lymph nodes, and a comparison was subsequently performed between the radiologic findings and the pathological assessment (Table 3). In this subset, tumor involvement was detected in 16 patients (pN1).
In 72 patients, the CT scan was negative and retroperitoneal surgical evaluation was done as a routine staging procedure: pathologic nodal involvement was found in only one patient (cN0 pN1). Among these 72 patients, 13 were older than 10 years and none of them showed pathologic nodal spread. Laparotomy was performed in 23 patients because the nodes were enlarged (from 1.5 to 2.5 cm in size) but not clearly involved on CT scans. At pathologic examination, tumor involvement was confirmed in 65% (15 patients, cN1 pN1), whereas in 35% (eight patients, cN1 pN0), nodal spread was not found. If we consider only patients over the age of 10 (17 patients), the rate of nodal involvement was the same: 11 (65%) of 17 were pN1, and six (35%) of 17 were pN0. The surgical assessment consisted of multiple samplings in 35 cases and nodal dissection in 60 (unilateral lymphadenectomy in nearly all cases). In particular, 22 of 23 patients submitted to surgery for radiologically enlarged nodes underwent dissection. The data failed to support a comparison between the accuracy of multiple samplings and nodal dissection in the pathologic detection of micrometastases. No significant difference was observed in the rate of positive node detection when lymph node staging changed from the first period when a surgical assessment was required (10 N1 out of 88 patients, or 11%) to the second one when a radiologic approach was used (11 N1 out of 110 patients, or 10%). Surgery. Initial surgery was complete in 164 patients (83%). In 35 patients, the microscopically complete resection with histologically free margins was obtained on primary re-excision performed within 2 months of the first inadequate operation (due to a trans-scrotal approach in 24 patients). In another eight patients who had undergone trans-scrotal tumor resection, no re-excision with hemiscrotectomy was performed despite the recommendations of the protocol to do so. None of these eight patients received any further local treatment and were all alive in first complete remission (CR). Initial surgery was incomplete in 34 patients. In 19 of them, a second surgery was performed after chemotherapy (generally after 12 to 14 weeks of treatment). In five, delayed local surgery was combined with laparotomy and dissection of the involved retroperitoneal nodes. Radiotherapy. Given the high number of patients who achieved complete tumor resection, radiotherapy was only delivered to 20 patients (10%). The dose ranged from 32 Gy to 60 Gy (median dose, 40.5 Gy). External-beam irradiation was administered in concomitance with chemotherapy; conventional fractionation (2 Gy/d) was adopted in 12 children and hyperfractionation (1.6 Gy twice daily) in eight. Twelve patients were irradiated at the site of local microscopically or macroscopically evident residual disease, five at the primary site and retroperitoneal positive nodes, and three at the involved nodes. Contrary to the protocol guidelines, only eight of the 21 N1M0 patients received nodal radiotherapy. Retroperitoneal irradiation was not administered to five children because of their young age (< 3 years), while in the eight patients the physicians probably considered retroperitoneal dissection as adequate local treatment. In this subgroup of 21 patients, three retroperitoneal relapses were observed in one of eight children who were irradiated and in two of 13 children who were not. Chemotherapy. All patients received chemotherapy according to the different regimens: the VACA combination was used in 85 patients, VAIA in 39, IVA in 23, and VAC/CAV in 14. After 1988, 36 children considered to be low risk were treated with VA. CEVAIE was administered to one child. Results of treatment. The 5-year survival and EFS rates in patients with localized disease were 94.6% and 90.7%, respectively, with a median follow-up of 110 months (range, 19 to 266 months). According to IRS grouping, 5-year survival and EFS rates were 96.1% and 91.3% in group I, 94.4% and 95.2% in group II, and 75.5% and 76.2% in group III, respectively. At the time of this report, 180 children were alive in first CR and 18 had relapsed 3 to 33 months (median, 17 months) after diagnosis. Retroperitoneal lymph node disease recurrence represented the major cause of treatment failure. Sites of relapse were local in four patients, local and nodal in two patients, local and distant in one patient, retroperitoneal alone in seven patients, nodal and distant in one patient, and distant in three patients. Eleven of the relapsing patients were older than 10 years of age, and retroperitoneal nodal recurrence was observed in six. Ten of the 18 relapsing patients died of disease despite further therapy 9 to 34 months (median, 22 months) after diagnosis. Eight children achieved a second CR and were without evidence of disease at 9 to 140 months from recurrence. In seven of these eight patients, the site of recurrence was local and/or nodal. Only one of the five children who relapsed with distant metastases was in second CR. Among patients who died, six of 10 were adolescents. Low-risk patients. In our series, 106 patients had low-risk paratesticular rhabdomyosarcoma according to the definition adopted in the most recent CWS and ICG protocols, ie, favorable histology, T1N0M0, and complete resection at diagnosis (IRS group I). These patients were treated with chemotherapy using regimens that have been progressively reduced in intensity and duration over the years. The 5-year survival of this subset was 99.1%. Four patients relapsed and one (the only one with distant metastasis at recurrence) died of disease; two were under and two were over 10 years of age. No differences in outcome were observed in relation to the different regimens administered in subsequent studies. The relapsing patients were initially treated with VACA (two patients), VAIA (one patient), and VA (one patient). Among the 36 patients treated with VA, 11 were older than 10 years and only one recurrence was observed in a 13-year-old boy. Prognostic factors. Patients with locoregional disease were stratified according to the different factors influencing outcome. The estimated survival curves were compared in univariate analyses (Table 4, Fig 1). Statistically significant differences in survival and/or EFS were found in relation to tumor gross resectability, local invasiveness, and size, as well as nodal involvement and the patient’s age at diagnosis. Patients classified as T2B, with either local invasiveness or tumor size more than 5 cm, represented the worst risk group.
Alveolar Subtype Eighteen patients with alveolar histology were involved in the studies, a proportion (8%) significantly smaller than in the rhabdomyosarcoma population as a whole (20% to 30%). The clinical features of these patients were particularly favorable at presentation: 17 children were classified as IRS group I, 11 were T1A; only two had nodal involvement; and none presented with distant metastases. The median age was 5 years, with only four patients over 10 years old. The chemotherapy regimens adopted were VACA in six patients, VAIA in nine patients, IVA in two patients, and CEVAIE in one patient. Fourteen patients were alive in first CR and three were in second CR; one patient died of disease after nodal relapse. The 5-year survival rate was 93.3%, compared with 88.1% for the nonalveolar rhabdomyosarcomas in this series (P = .46).
Patients With Metastatic Disease The 5-year survival rate for the patients with metastases was 22.2%. Only four children were alive in first CR 122 to 262 months after diagnosis; the sites of metastases were the lung in two of the patients and the soft tissues in the other two. The other 14 patients died of disease at 3 to 25 months.
Our report on this large series of patients with paratesticular rhabdomyosarcomas confirms the excellent outcome of patients with localized disease.3-10,21 The prognosis of patients with distant metastases remains unsatisfactory, as in group IV patients with rhabdomyosarcomas at other sites.17 In patients with localized disease, the aim should be to reduce the morbidity of the treatment without jeopardizing the survival results obtained so far. Experience in consecutive protocols enabled us to identify a low-risk group of patients represented by completely resected, T1N0M0, embryonal paratesticular rhabdomyosarcomas who have been progressively treated over the years with less intensive chemotherapy, withholding of alkylating drugs and anthracyclines, and shortening of the treatment from the 52 weeks of the first protocols to the 22 weeks of the ongoing Italian-German cooperative study. These changes have not impaired patient outcome: the 5-year survival rate was 99.1% for the whole low-risk group, with only one recurrence in the subset of 36 children treated with VA for 22 weeks (median follow-up, 52 months; range, 19 to 146 months). In completely resected cases, the outcome was excellent, even in the event of a inadequate primary surgical approach. Inguinal incision is considered mandatory and re-excision is recommended in cases of prior trans-scrotal incision. In our series, 24 patients had primary re-excision with scrotal resection and were consequently downstaged to IRS group I. Despite these guidelines, hemiscrotectomy was not performed in eight patients who had previously undergone to trans-scrotal resection; no local relapses occurred in this small subgroup of patients, suggesting that chemotherapy was effective in sterilizing scrotal microdissemination or, alternatively, casting doubts on whether the trans-scrotal approach causes local contamination. Such a small number of patients does not entitle us to reconsider the role of hemiscrotectomy in such cases, however. As for the factors potentially affecting the prognosis, the roles of local invasiveness, tumor size, nodal involvement, surgical resection, and age were evaluated in the cohort of patients with localized disease. Given the small number of events, only univariate analysis was performed. Patients with T2B tumors had the worst results.21 The prognostic significance of retroperitoneal nodal involvement and gross surgical resection at diagnosis was also confirmed.4,5,8 As in other series,4,8,21,22 the patient’s age at diagnosis showed prognostic relevance: in our analysis, age more than 10 years correlated strongly with the presence of metastases at onset (17 of 18 metastatic patients were over 10 years old) as well as with retroperitoneal lymph node involvement (detected in 21% of older children with localized disease v 5% of the younger patients). The longer interval between onset of symptoms and diagnosis that we documented among older patients might have had a bearing on the higher incidence of nodal and distant spread. The low number of adolescents (11 patients) treated with the VA regimen does not allow us to unequivocally prove the adequacy of this less intensive chemotherapy in this subset of patients. Unlike rhabdomyosarcoma that occurs elsewhere, alveolar subtypes were not a prognostic factor in our patients. A major issue in the management of paratesticular rhabdomyosarcoma patients concerns how best to assess the retroperitoneal lymph nodes at diagnosis. Considering the high incidence of retroperitoneal nodal spread (26% to 40% in the oldest reports),3-6 and the unfavorable outcome in N1 patients, unilateral retroperitoneal lymphadenectomy was required in the IRS I, II, and III studies (1973 to 1991)3 in all patients in order to stage the disease and establish the need for adjuvant radiotherapy or intensified chemotherapy. In most European protocols, since 1980 to 1985, laparotomy has been reserved for patients with radiologically suspect retroperitoneal involvement.8-10,13 This approach aims to reduce the risk of side effects of lymphadenectomy, which is particularly high in the case of subsequent radiotherapy11,12 (bowel obstruction, ejaculating dysfunction, hydrocele, and lymphedema have been described in up to 40% of cases). The improved radiologic staging procedures (thin-cut CT scan) were found to be accurate, reducing the likelihood of missing disease in retroperitoneal nodes; chemotherapy was presumed to be effective in controlling microscopic disease in nodes that were not irradiated. A comparison between radiologic and pathologic node evaluation was performed in the IRS III study.4 Pathologically involved nodes were found in only 14% of cN0 patients, whereas 94% of enlarged nodes on CT scans were confirmed as positive by the pathologist. As a result, in the IRS IV study (1991 to 1997),23 neither nodal dissection nor biopsy was recommended in children with completely resected tumors and negative CT scan findings. Unlike the case in European studies, this approach reduced the N1 cases to 8%, so fewer children received radiotherapy; the decrement in incidence of node positivity was particularly evident in adolescents, where it fell from 47% to 13%. Consequently, an increase in nodal relapses was unfortunately recorded, especially in children over 10 years old,23 thus raising the issue of whether or not to return to a surgical staging, maybe only in the older patients.22,24 Our experience confirms previous European reports.8-10,13 Although the rate of nodal involvement in patients in groups I, II, and III was lower (10%) than the results reported elsewhere, the comparison between clinical and pathologic stages in 95 children prompted some important suggestions. Among 72 patients with negative radiologic findings, only one case of nodal involvement was detected by the pathologist, which suggests that CT accurately evaluates the retroperitoneum. In analyses of only those patients older than 10 years, results do not seem different, even if the number of cases decreases substantially (13 of 13 cN0 patients were pN0 too). Consequently, conclusions on the accuracy of CT in detecting nodal involvement in adolescents must be made with caution. In our series, switching from routine surgical procedures to radiologic evaluation of the retroperitoneum did not correlate over the years with any difference in positive node detection and outcome. Therefore, surgical assessments only seem necessary in cases of radiologically suspected nodal spread (enlarged nodes of 1.5 to 2.5 cm) to confirm the spread and prompt radiotherapy. In 35% of our patients, a suspected CT scan was not confirmed by pathology. The data failed to support a comparison between multiple samplings and dissection in the accuracy of nodal staging. However, although lymphadenectomy might be considered a therapeutic action, we regard surgical assessment as a staging procedure. Accurate multiple samplings should therefore be preferred to avoid complications, though recently introduced nerve-sparing lymphadenectomy techniques carry a lower morbidity than dissections of the past. No significant differences in nodal relapse rate were observed in N1 patients who did or did not receive radiotherapy, raising doubts as to whether irradiating positive nodes could be avoided, given this tumor’s high chemosensitivity. In conclusion, our report confirms the excellent outcome in children with localized paratesticular rhabdomyosarcoma despite a reduced intensity of chemotherapy over the years. A subset of low-risk patients was identified for whom an alkylating drug–free and anthracycline-free regimen proved adequate. However, caution is needed in reducing the treatment in patients over 10 years old or patients with large tumors (even if they are completely resected). The comparison between the clinical and surgical staging of retroperitoneal lymph nodes suggests that pathologic evaluation of the retroperitoneum should be reserved for patients with enlarged lymph nodes on CT scans. Radiologic assessment seems adequate in case of completely resected tumors with no suspected radiologic findings. Due to the higher incidence of nodal involvement in older patients, more caution in this conclusion could be suggested in adolescents, even if in our experience the accuracy of CT compared with surgical assessment seems the same in patients under and over 10 years old.
1. Wexler L, Helman LJ: Rhabdomyosarcoma and the undifferentiated sarcomas, in Pizzo PA, Poplack DC (eds): Principles and Practice of Pediatric Oncology, ed 3. Philadelphia PA, Lippincott-Raven, 1997, pp 799–829 2. de Vries JD: Paratesticular rhabdomyosarcoma. World J Urol 13: 219–225, 1995[Medline] 3. Raney RB, Tefft M, Lawrence W, et al: Paratesticular sarcoma in childhood and adolescence: A report from the Intergroup Rhabdomyosarcoma Studies I and II, 1973-1983. Cancer 60: 2337–2343, 1987[CrossRef][Medline] 4. Wiener ES, Lawrence W, Hays D, et al: Retroperitoneal node biopsy in paratesticular rhabdomyosarcoma. J Pediatr Surg 29: 171–178, 1994[CrossRef][Medline] 5. La Quaglia MP, Ghavimi F, Heller G, et al: Mortality in pediatric paratesticular rhabdomyosarcoma: A multivariate analysis. J Urol 142: 473–478, 1989 (part 2) 6. Blyth B, Mandell J, Bauer SB, et al: Paratesticular rhabdomyosarcoma: Results of therapy in 18 cases. J Urol 144: 1450–1453, 1990[Medline] 7. Leonard MP, Jeffs RD, Leventhal B, et al: Pediatric testicular tumors: The Johns Hopkins experience. J Urol 37: 253–256, 1991[CrossRef] 8. Ferrari A, Casanova M, Massimino M, et al: The management of paratesticular rhabdomyosarcoma: A single institutional experience with 44 consecutive children. J Urol 159: 1031–1034, 1998[CrossRef][Medline] 9. Gamba PG, Cecchetto G, Katende M, et al: Paratesticular rhabdomyosarcoma (RMS) and paraaortic lymphadenectomy. Eur J Pediatr Surg 4: 158–160, 1994[Medline] 10. Olive D, Flamant F, Zucker JM, et al: Paraaortic lymphadenectomy is not necessary in the treatment of localized paratesticular rhabdomyosarcoma. Cancer 54: 1283–1287, 1984[CrossRef][Medline]
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Heyn R, Raney RB Jr, Hays DM, et al: Late effects of therapy in patients with paratesticular rhabdomyosarcoma. J Clin Oncol 10: 614–623, 1992 12. Hughes LL, Baruzzi MJ, Ribeiro MC, et al: Paratesticular rhabdomyosarcoma: Delayed effects of multimodality therapy and implications for current management. Cancer 73: 476–482, 1994[CrossRef][Medline] 13. Cecchetto G, Grotto P, De Bernardi B, et al: Paratesticular rhabdomyosarcoma in childhood: Experience of the Italian Cooperative Study. Tumori 74: 645–647, 1988[Medline] 14. Harmer MH: TNM Classification of Pediatric Tumors. Geneva Switzerland, UICC International Union Against Cancer, 1982, pp 23–28 15. Maurer HM, Beltangady M, Gehan EA, et al: The Intergroup Rhabdomyosarcoma Study I: A final report. Cancer 61: 209–220, 1988[CrossRef][Medline] 16. Koscielniak E, Jurgens H, Winkler K, et al: Treatment of soft tissue sarcoma in childhood and adolescence: A report of the German Cooperative Soft Tissue Sarcoma Study. Cancer 70: 2557–2567, 1992[CrossRef][Medline]
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Carli M, Colombatti R, Oberlin O, et al: High-dose melphalan with autologous stem-cell rescue in metastatic rhabdomyosarcoma. J Clin Oncol 17: 2796–2803, 1999 18. Kaplan E, Meier P: Non-parametric estimation from incomplete observation. J Am Stat Assoc 53: 457–481, 1958[CrossRef] 19. Conover WJ: Practical Nonparametric Statistics. New York NY, Wiley, 1980, pp 153–169 20. Newton WA, Gehan EA, Webber BL, et al: Classification of rhabdomyosarcomas and related sarcomas: Pathologic aspects and proposal for a new classification—An Intergroup Rhabdomyosarcoma Study. Cancer 70: 1073–1085, 1995 21. Stewart RJ, Martelli H, Rey A, et al: Prognostic factors in non-metastatic paratesticular myosarcoma treated in the MMT 89 study: XXXII SIOP Meeting. Med Pediatr Oncol 35: 320, 2000 (P-399)
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Kattan J, Culine S, Terrier-Lacombe MJ, et al: Paratesticular rhabdomyosarcoma in adult patients: 16-year experience at Institut Gustave-Roussy. Ann Oncol 4: 871–875, 1993 23. Wiener E, Grier H, Breneman J, et al: Changing pattern of relapse with localized paratesticular rhabdomyosarcoma in the Intergroup Rhabdomyosarcoma Study (IRS) Group trials. Proc Am Soc Clin Oncol 16: 519, 1997 (abstr 1865) 24. Hermans BP, Foster RS, Bihrle B, et al: Is retroperitoneal lymph node dissection necessary for adult paratesticular rhabdomyosarcoma? J Urol 160: 2074–2077, 1998[CrossRef][Medline] Submitted April 24, 2001; accepted October 1, 2001.
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Copyright © 2002 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
5 cm or more than 5 cm, respectively. Regional lymph node involvement is defined as N1 (no node involvement is defined as N0); cN defines a clinical-radiologic evaluation of retroperitoneal lymph nodes, while pN is used in case of pathologic-surgical assessment. The presence of distant metastases at diagnosis is defined as M1 (no metastases is defined as M0).
