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.