Primary transcrotal excision for paratesticular rhabdomyosarcoma
Is hemiscrotectomy really mandatory?
To evaluate the role of primary reexcision (PRE) with scrotal resection in patients with paratesticular rhabdomyosarcoma enrolled in the German-Italian Cooperative Studies. The authors compared patients who underwent this procedure, according to the protocol guidelines, with those who did not.
In 32 of 198 patients with localized disease, the primary surgery was performed through a noncorrect scrotal approach. Twenty-four patients underwent PRE as recommended by the protocol guidelines (Group A) and 8 did not receive this treatment (Group B). The Group B patients were treated with the same chemotherapeutic regimens as the Group A patients and no radiotherapy was given to either group.
After PRE, residual tumor was not detected in 21 of the 24 Group A patients. Twenty patients are alive in first complete remission 26–250 months after diagnosis (median, 40 months), 2 are alive in second complete remission at 3 and 9 months from diagnosis of lymph node and lung recurrence, and 2 died of disease after lymph node and distant metastases at 16 and 13 months from diagnosis. Three-fourths of these patients were older than 10 years old and the tumor was larger than 5 cm. The eight Group B patients are all alive in first complete remission 24–250 months since diagnosis.
The data on the eight patients who obtained local control without PRE or radiotherapy warrant further investigation. Because of the supposed high risk of contamination with subsequent microscopic residual tumor after a transcrotal approach, we emphasize the utility of PRE with hemiscrotectomy. Cancer 2003;97:1981–4. © 2003 American Cancer Society.
Paratesticular rhabdomyosarcomas (P-RMS) account for about 7% of childhood RMS and 12% of childhood scrotal tumors.1, 2 They arise from the mesenchymal tissues of the spermatic cord, epidydimis, testis and testicular tunics, generally producing a painless scrotal mass. The children affected have a good prognosis, due to the superficial location, which allows for an early diagnosis and the possibility of a complete resection.3 Radical orchiectomy via an inguinal incision with a high section of the spermatic cord is the recommended first therapeutic step.2, 4
The scrotal approach is considered to be inadequate because it carries the risk of scrotal contamination. Therefore, when the operation has been carried out with this approach, a primary reexcision (PRE) is recommended. PRE a nonmutilating, wider, local excision is performed before any other treatment in order to achieve a complete tumor resection. As a result, less intensive chemotherapeutic treatment is needed and irradiation can be avoided.5–7 PRE consists of a hemiscrotectomy with a high resection of the spermatic cord, which is the recommended approach.
This study comprises patients with P-RMS enrolled in the German Cooperative Soft Tissue Sarcoma Group (CWS), the Italian Cooperative Group (ICG), and the Istituto Nazionale Tumori (INT) of Milan, who underwent a primary resection of the tumor through a transcrotal approach. We evaluate the role of PRE with scrotal resection and compare patients who received PRE according to the protocol guidelines after transcrotal resection (Group A) with those who did not (Group B).
MATERIALS AND METHODS
Between September 1978 and June 1999, 198 patients with nonmetastatic P-RMS were enrolled in the German and Italian Studies on soft tissue sarcomas. The TNM staging system was used to classify the clinical status of the tumor: T1, tumor confined to the organ or tissue of origin (a, ≤ 5 cm; b, > 5 cm); T2, tumor involving contiguous organs or structures (a, ≤ 5 cm; b, > 5 cm); N1, clinical involvement of regional lymph nodes; N0, no clinical involvement; M0, no metastases.
Patients were also classified using the surgical Intergroup Rhabdomyosarcoma Study (IRS)8 staging system: Group I, complete microscopic excision (pT1, pT2); Group II, excision with microscopic residual (IIa) (pT3a) or regional lymph node involvement (IIb) (pT3b); and Group III, initial biopsy or excision with macroscopic residual involvement (pT3b,c).
The chemotherapy regimens used in the different protocols have been described.9 The German group used vincristine, dactinomycin, cyclophosphamide, and doxorubicin (VACA regimen) in the CWS-81 protocol,10 replacing cyclophosphamide with ifosfamide in the VAIA regimen adopted in the subsequent CWS-86 and CWS-91 studies. The INT protocols11 used the VACA regimen for 6, 9, or 12 months depending on the initial extent and the degree of the primary surgery. The Italian group switched from vincristine, dactinomycin, cyclophosphamide (VAC regimen)/cyclophosphamide, doxorubicin, and vincristine (CAV regimen) adopted in the RMS-79 study12, 13 to the VAIA, IVA, and VA regimens (depending on the IRS group involved) in the RMS-88 protocol. Finally, VA was adopted in the CWS-96 and RMS-96 protocols for low-risk patients. No radiotherapy was recommended after an initial complete resection. The results of this study was previously reported.9
In 32 of 198 patients with localized P-RMS, despite the protocol guidelines, the primary surgery was performed using a transcrotal approach. These patients were supposed to be considered as IRS Group IIa because of suspicious microscopic residual disease due to transcrotal contamination. In case of microscopic residual disease after initial surgery, the therapeutic guidelines advocated the use of local radiotherapy. However, this treatment was omitted if a complete surgical removal of the suspected disease was obtained with PRE. Patients who were restaged as Group I after a successful PRE received only chemotherapy. Twenty-four of 32 patients underwent PRE (Group A), as recommended, whereas the remaining 8 did not receive this treatment because of center decision (Group B).
In the 24 Group A patients, the median age at diagnosis was 10 years, the TNM distribution was 14 T1a, 4 T1b, 3 T2a, and 3 T2b, and the histologic subtypes were embryonal in 21 and alveolar in 3. In the eight Group B patients, the age range was 2–5 years, the TNM distribution was 7 T1a and 1 T1b, and the histologic subtypes were embryonal in 7 and alveolar in 1.
All patients in Groups A and B received different regimens of chemotherapy according to the different German and Italian protocols. The Group B patients were treated with the same regimens as the Group A patients, despite the inadequate surgical approach. None of the patients received radiotherapy (Table 1).
Table 1. Clinical Features and Outcomes
|Age (yrs)|| || |
| < 10||10 (1 DOD)||8|
| > 10||14 (2 II CR, 1 DOD)|| |
|T status|| || |
| T1a||14 (1 DOD)||7|
| T1b|| 4 (1 IICR)||1|
| T2a|| 3|| |
| T2b|| 3 (1 IICR,1 DOD)|| |
|Histology|| || |
| Embryonal||21 (1 II CR, 2 DOD)||7|
| Alveolar|| 3 (1 IICR)||1|
|Chemotherapy|| || |
| VACA/VAC||11 (2 DOD)||5|
| VAIA/IVA + CAVAIE||2/4 + 1 (2 II CR)||1|
| VA|| 6||2|
At the histologic evaluation of the specimen from PRE, residual tumor was not detected in 21 of 24 patients. Residual tumor was found in the remaining three patients and was completely resected. The chemotherapeutic regimens adopted were VACA in 11, IVA in 4, VA in 6, VAIA in 2, and CEVAIE in 1. Twenty patients are alive in first complete remission at 26–250 months (median, 140 months) from diagnosis. Two are alive in second complete remission at 3 and 9 years from diagnosis, after lymph node and lung recurrence. Two patients, initially treated with VACA and VA regimens, presented with lymph node and distant recurrence at 16 and 13 months from diagnosis and died of disease. Three of the four patients who had disease recurrence were older than 10 years and the tumor was larger than 5 cm. In three cases, the histologic type was embryonal and in one alveolar.
The eight patients who were not treated with PRE received chemotherapy alone (VACA in 5, VAIA in 1, and VA in 2) and are all alive in first complete remission at 24–250 months (median, 170 months) from diagnosis.
Paratesticular rhabdomyosarcoma represents a favorable subgroup of RMS, the overall survival rate being 80–94%. Several reports confirm the excellent outcome of patients with localized disease.9, 14–16
The superficial location of the tumor usually allows for a complete resection at diagnosis, which accounts for the favorable outcome in these patients. In addition, the histology plays an important role on survival because these tumors are mostly represented by the embryonal subtype.4, 11, 15
Orchiectomy with high section of the spermatic cord through an inguinal approach should be the initial surgical procedure.5, 7, 17 In some cases, the first surgical approach is performed in a nononcologic setting using a transcrotal approach, because of a clinical diagnosis of a nonmalignant lesion. This type of resection may cause scrotal contamination, and microscopic residual disease may be left on the tumor bed, increasing the risk of local recurrence.14, 15, 18 In this situation, PRE has been demonstrated to be effective in completing the surgical removal of the tumor, improving local control, and avoiding a more aggressive treatment.
In our experience, eight patients had a scrotal approach without PRE but did not show any disease recurrence. Two main considerations may be derived from the evaluation of this small group of patients. First, the transcrotal approach may not cause scrotal dissemination. Second, the chemotherapy regimen adopted was effective in sterilizing the scrotal dissemination.
Regarding the transcrotal approach, microscopic disease has been identified in hemiscrotectomy specimens obtained in some series.18 In our experience, 3 of the 24 Group A patients had residual disease in the specimens resected with PRE. Historically, scrotal contamination has been believed to be the consequence of a nononcologic surgical approach, but controversy still exists in the adult literature regarding hemiscrotectomy for all patients. A “wait and see” strategy seems to be reasonable in patients with Stage I testicular carcinoma.19
Regarding the chemotherapy effect, the current chemotherapy regimens have lowered disease recurrence and improved survival.20 In our subset of patients, various regimens have been adopted over the years according to the different protocols. In the 1980s, a VACA regimen was used. In more recent years, cyclophosphamide has been replaced by ifosfamide (VAIA). More importantly, a subgroup of patients with favorable features (i.e., young children, embryonal histotype, small and noninvasive tumors, completely resected tumor at diagnosis) has been identified. This group of patients, including Stage I P-RMS patients, can be cured with an alkylating and anthracycline-free regimen with vincristine and dactinomycin alone (VA). None of the Group B patients were treated with a more aggressive chemotherapy compared to that utilized in Group A patients (in corresponding protocols).
A final consideration regards the prognostic characteristics of the patients. As seen in other series, in which the majority of patients in IRS Group I and II are prepubertal and those in IRS group III and IV are postpubertal, age is emerging as an important prognostic factor for P-RMS.15, 21 In the Group B patients, the age ranged between 2 and 5 years, confirming the data reported. These patients also had small tumors and no local invasiveness, which may explain their better outcome. Conversely, alveolar histology did not show a prognostic significance.
In conclusion, our data on the eight patients who had local control without PRE or radiotherapy question the role of PRE in these cases. Due to the small number of cases and the supposed high risk of contamination with subsequent microscopic residual tumor after a transcrotal approach,7, 14 we prefer not to reconsider the role of hemiscrotectomy and still emphasize PRE after a noncorrect surgical approach. Primary reexcision is particularly useful in these sites, given the easier surgical approach and considering that the patients who obtain a radical surgery are treated with a less intensive chemotherapy in the ongoing protocols.