When do you recommend preop RT for retroperitoneal sarcomas?

I imagine I'm not alone in feeling a tad frustrated with the STRASS trial results, not because of the negative primary endpoint in regards to radiotherapy, but because it failed to clearly answer the question it was supposed to.

In brief, the STRASS trial was a 2-arm randomized controlled trial of surgical resection with or without radiotherapy for primary retroperitoneal sarcoma. Patients were over age 18, had good performance status, and were deemed suitable for both an operation and radiotherapy. After stratification by hospital and performance status, patients were randomized to receive surgical resection alone or preoperative radiotherapy of 50.4 Gy in 28 fractions (3D-CRT or IMRT) followed by surgical resection. The primary endpoint wa...

The STRASS study of surgery versus RT + surgery had obvious impact on our field. I think it is good, however, to keep in mind the limitations of the study and the reported outcome at this time (ACRO meeting 2020 - Sarcoma session, DeLaney et al., PMID 33387499). I look forward to the continued outcomes of this trial and that of STRASS II to assess the role of chemo in controlling disease beyond the local site. This information will be helpful in determining the best management of these patients going forward. In the meantime, I continue to evaluate my patients on a case-by-case situation and seek to enroll in clinical trials such as the NRG trials of MDM2 AMG-232 with neoadjuvant RT or the NRG/Civatech trial of local brachytherapy.

STRASS did not show "no benefit" from preop RT. On the contrary, every piece of data we have--including STRASS--suggests about a 50% reduction in local recurrence rates with preop RT for STS. That number is remarkably consistent across studies.

These studies include:

1. STRASS itself, appendix p6 and as noted in DeLaney et al letter in reply to STRASS, PMID 33387499.

2. Gronchi et al., PMID 26727100. (This was updated in Haas et al., PMID 30602058 and the CI widened beyond significance after adjustment for cofounders, but the HR point estimate of 0.5 remained exactly the same.)

3. Albertsmeier et al., PMID 28895107

4. Kelly et al., PMID 26061213

So the questions I ask are:

1. Is this patient likely to benefit from a 50% reduction in LR? (The de...