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.