Introduction
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma accounting for ⅔ of all sarcomas and approximately 7-8% of all solid malignant tumors in children.1 The genitourinary tract is the second most common primary tumor location.2Tumors at this site are conventionally classified as bladder-prostate RMS (BPRMS) and genitourinary non-bladder prostate RMS. Although perineal and perianal rhabdomyosarcoma have a close anatomical relationship in the lower pelvis, they are considered separately. Therefore, genitourinary non-bladder prostate RMS include tumors located at the paratesticular site or in the female genital tract (vulva, vagina and / or uterus, (FGU-RMS) which is the focus of this consensus statement).
Tumors of the female genital tract account for 4% of all RMS cases and 10% of all cases in females.3, 4 Histology of most tumors is FOXO1 fusion negative embryonal RMS.5 The prognosis for FGU-RMS is favorable, with 5-year overall survival rates of more than 90%.4, 6-8 In addition, tumors located at this site seem to respond extremely well to chemotherapy.7 There has been a paradigm shift in treatment from aggressive local control, with radical surgery and external beam radiotherapy (EBRT), towards more conservative approaches with chemotherapy alone in patients with complete response or organ-sparing surgery in combination with intracavitary brachytherapy (BT) or EBRT. This strategy has been introduced by the Malignant Mesenchymal Tumor Group (MMT) trials of the International Society of Pediatric Oncology (SIOP)4, 7 and is currently used as the standard approach for patients treated within the European pediatric Soft Tissue Sarcoma Group (EpSSG).4 The Children’s Oncology Group (COG) previously investigated an even more conservative strategy, employing lower doses of cyclophosphamide and omitting RT in complete responders. Due to increased rates of local recurrence on D9602 and ARST0331 for vaginal primary tumors, the COG now recommends both treatment with more intensive chemotherapy and the use of RT or brachytherapy for incompletely resected RMS of the vagina.8
Analysis of pooled data from four cooperative groups, including SIOP MMT, EpSSG, COG, and the Italian Soft Tissue Sarcoma Committee (STSC) examined the optimal treatment for patients with FGU-RMS.4 Two-hundred and thirty-seven patients were included in the analysis, with a 10-year event free survival rate (ESF) of 74% and a 10-year overall survival rate of 92%. Patients in whom RT was initially omitted had inferior EFS but no difference in OS. The local control rate with BT is excellent.7 The pooled analysis concluded that half of the patients could be cured without external beam RT or radical surgery.4
A collaboration of the American and European pediatric oncology cooperative groups (COG, EpSSG and CWS) was initiated recently. The resulting International Soft Tissue Sarcoma Consortium (INSTRuCT) has several goals, one of which is to develop consensus positions regarding best practice treatment that would be broadly applicable. This consensus for patients with FGU-RMS provides treatment recommendations for the local treatment as well as long term follow up of these tumors.