Clinical Question 3: Does delayed surgical resection of the primary tumour impact on outcome for pelvic Ewing sarcoma?

  • Population: Localises pelvic Ewing Sarcoma (all age group)
  • Intervention: Delayed surgical resection of the primary tumour
  • Comparison: Surgery at time point of recommended local control in protocol
  • Outcomes: Survival

Authors: Natacha Omer, Julie Cayrol, and Sarcoma Guidelines Working Party

The definitive treatment of localised Ewing sarcoma involves chemotherapy followed by local therapy, and post-operative chemotherapy. Local therapy consists of RT or surgery, or a combination of both. However, the optimal timing of local therapy after the initiation of chemotherapy remains unclear. Despite advances in systemic therapy, Ewing sarcoma of the pelvis remains an anatomic site with poor prognosis due to its relative inaccessibility, complex anatomy, and limited reconstructive options available. Surgery may involve potential severe complications including delayed wound healing and secondary infection, which can impact ongoing post-operative chemotherapy delays, therefore impacting prognosis. In this context, oncologists and orthopaedic surgeons may elect for certain patients to continue and complete chemotherapy before initiation of local control. The delay in surgery to the end of chemotherapy can also allow more time for surgical planning and further possible tumour volume reduction.

Systematic review only identified four retrospective studies analysing the impact of delayed local control in the management of pelvic Ewing sarcoma. The four studies included all primary sites and the number of patients with pelvic location is generally unknown and not specifically nor separately analysed  (72-75). Delays in local control (surgery and/or radiation therapy) beyond 16 weeks or 4 months were associated with reduced overall survival compared to no delay (Hazard ratio 1.41 to 16.1; p<0.01), however these studies had relatively small numbers. The largest study was from the US NCDB and included 1318 patients (74). The 5-year overall survival was significantly better in patients who started local therapy (surgery and/or RT) 6 to 15 weeks after initiation of chemotherapy compared to those who started after 16 weeks (78.7% vs 70.4%, p=0.002).  For those who had surgery alone, a trend in worse 5-year overall survival when delayed beyond 16 weeks was observed (81.6% vs 79.4%; p=0.092). In the multivariable cox proportional hazards regression model, time to first definitive local therapy beyond 16 weeks was associated with reduced overall survival with a HR of 1.41 (95% CI 1.11-1.8, p=0.005).

 

Evidence summary

  Level

  References

Delays in surgery (alone or with postoperative radiotherapy) for localised pelvic Ewing sarcoma beyond 4 months from the start of chemotherapy is associated with reduced overall survival.

  III-3

  (72-75)

Evidence-based recommendation

  Grade*

Delays in surgery (alone or with postoperative radiation therapy) for localised pelvic Ewing sarcoma beyond the recommended timepoint by treatment protocol should be avoided.

  C

 

 

Practice point

Patients with pelvic Ewing sarcoma should be managed within a multidisciplinary team who should work closely during the initial chemotherapy period to coordinate the optimal time for disease response evaluation, restaging imaging, and local therapy as per treatment protocol.

*National Health and Medical Research Council. NHMRC levels of evidence and grades for recommendations for developers of guidelines. Canberra: NHMRC; 2009. (https://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/developers/nhmrc_levels_grades_evidence_120423.pdf)

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