Evidence
The surgical approach for patients with FGU-RMS changed dramatically
from the North American IRS-I trial, in which the primary surgery was
commonly pelvic exenteration, hysterectomy or vaginectomy, towards
preservation of these organs in IRS-III & -IV. With these less radical
procedures the excellent survival rates of IRS-I were preserved with
much lower morbidity.6 Arndt et al. further outlined
the evolution of treatment from IRS I-IV to determine the optimal
management strategy for FGU-RMS, demonstrating 5-year failure-free and
overall survival of 72% and 87%, respectively, in those with
nonmetastatic tumors.9 Importantly, aggressive initial
surgical resection was performed in IRS-I but was discouraged by IRS-III
and -IV to decrease morbidity. Rate of organ removal (vagina +/- uterus
+/- bladder) decreased from 66% in IRS-I/II to 41% in IRS-III/IV, yet
cure rates were preserved at 82% and 84%, respectively. Of 27 patients
with recurrence, 23 (85%) were local/regional, and most did not receive
any or had inadequate RT. Eighteen (67%) were salvaged with additional
multimodal treatments. As such, conservative initial surgery followed by
primary chemotherapy approach with selective RT was recommended to
decrease morbidity and late effects. This treatment paradigm was
utilized in the subsequent series of COG trials D9602 and ARST0331. The
majority of patients therefore had unresected disease at enrollment in
both of these trials, however there was a significantly increased local
recurrence rate between D9602 (26%) study and the subsequent ARST0331
(43%) likely due to decreasing the cumulative dose or eliminating
cyclophosphamide and delaying or eliminating RT.8Although high salvage rates allowed 3-year OS to remain excellent (95%)
on ARST0331, this was at the expense of intensified second-line therapy
for patients who developed recurrence, with inherent long-term
complications.
Further support for a conservative primary surgery paradigm came from a
pooled, multinational analysis including data from 237 patients treated
within trials of COG, SIOP MMT, STSC, and EpSSG in which approximately
50% of the patients achieved CR with chemotherapy alone and some were
cured without systematic RT or radical surgery.4 In
this large patient cohort only 31% (72/231) underwent upfront gross
resection (IRS group I or II) and the remaining 69% (159/231) had gross
residual disease or biopsy only (Group III) before the initiation of
chemotherapy. The 10-year EFS and OS for these patients were similar
(Group I, II, III EFS was 79%, 72%, 72%, and OS was 97%, 85% and
92% respectively, p=0.62).
In summary, the evidence would suggest that a conservative approach to
the primary surgical intervention in these tumors, when used in
conjunction with adequate chemotherapy and possible RT, provides
excellent local control and outcomes. This does not imply that upfront
resection is unreasonable in very select instances, such as small,
localized and well circumscribed tumors that can be grossly excised with
minimal compromise to normal local structures. However, the possibility
of a complete resection is often difficult to judge so the majority of
patients are better served with conservative organ preserving surgical
procedures limited to obtaining tissue for diagnosis.