Understanding RECIST Responses to Radiation in Retroperitoneal Sarcoma

Retroperitoneal sarcoma (RPS) presents a unique challenge for oncology teams due to its infrequent diagnosis and the size of tumors at the time of discovery. Although neoadjuvant radiation has traditionally been considered a tool to downsize tumors and facilitate organ-sparing surgery, its clinical utility remains a subject of intense debate within the multidisciplinary community.

In a recent study published in the Journal of Surgical Research, Emily Papai, MD, a PGY-3 surgery resident at Fox Chase Cancer Center, and colleagues examined how these tumors radiographically respond to radiation using RECIST criteria.¹ Their findings revealed that 18.2% of patients experienced progressive disease during the neoadjuvant period. Notably, no changes in organ involvement were observed among patients whose tumors encased adjacent organs prior to treatment.

The study assessed 22 patients, with 4.5% having a RECIST response, 77.3% having stable disease, 63.6% having tumors that decreased in size, and 36.4% having tumors that remained unchanged or increased in size. After a mean relative tumor increase of 38.0%, 18.2% of patients met the criteria for progressive disease.

In this discussion with CancerNetwork®, Papai explored the implications of these findings; the shift toward utilizing less neoadjuvant radiation in institutional practice; and the importance of translating large-scale trial data, such as the phase 3 EORTC-62092 (STRASS) trial (NCT01344018), into individualized surgical decision-making for patients with RPS.²

CancerNetwork: What is the background of your study?

Papai: Generally, patients with RPS are presenting with vague abdominal symptoms or even incidentally discovered [features] on other cross-sectional imaging. Maybe they come in for something else and get a CT scan, or they’re a patient [with trauma], and then they end up finding that they have this large mass in their retroperitoneum. Sarcoma in general is pretty uncommon, so there’s no common education thread for people who are, for example, surgeons in the community who aren’t often seeing this problem. It’s something that we manage a lot more frequently at a cancer center like where I did this work, at Fox Chase Cancer Center in Philadelphia.

What RECIST responses were observed, and how are these findings clinically relevant?

RECIST is a way of classifying the radiologic difference. When someone gets a CT scan or an MRI, for example, you can measure the approximate size of a mass on that imaging. RECIST is a way to categorize how much that mass has increased or decreased in size, and there’s a cut off point for what we would call someone who has progressive disease, stable disease, or improving disease.

Given that 18.2% of patients in your study experienced progressive disease with a mean size increase of 38%, do you recommend a maximum waiting period for surgery after radiation to avoid losing the window for curative resection?

Ultimately, that would be a great question to answer, but I don’t think that our study was designed appropriately to answer that question; it was retrospective in nature. I do think that looking at the larger studies that I referenced [in the paper], like STRASS and the upcoming STRASS2, will probably be the most effective data to look at and make a decision. Ultimately, while neoadjuvant radiation is a waiting period, it does take time for people to get coordinated and see the radiation oncologist and get the treatment beforehand. All those clerical things that patients have to go through outside of just simply getting the treatment can delay things, but it’s still not significantly long.

I did want to make the point that waiting can lead to things, and there’s no treatment that is a free lunch. For example, if someone does get a complication from their radiation, that can set them back a few days or 1 or 2 weeks before they’re ready for surgery again. Although I can’t give you a specific time estimate, I would say that time is money and cancer in general can be impactful for people, let alone the emotional challenge of having to go through treatment in more than one modality and not knowing if it’s going to do anything for you before going to surgery.

Among patients whose tumors were radiographically touched or encased in adjuvant organs, none showed changes in organ involvement after treatment. Should neoadjuvant radiation still be considered as a tool to facilitate organ-sparing surgery in RPS?

It is up to the clinician. I can’t tell everyone what to do, and that’s what the NCCN guidelines are there for. Our practice at Fox Chase has been slowly leaning towards utilizing less neoadjuvant radiation, which is demonstrated in our data. We found that over half of the patients that we’ve treated in our inclusion type criteria did not receive neoadjuvant radiation, so we weren't even able to comment on their response for this study. While our practice is leading away from it, it’s not something that I would tell a patient who received it that it was the wrong thing. Ultimately, people are trying to help in any way they can, especially when someone comes in with a very large tumor that may be involving other organs. There’s always this hope that maybe giving it some extra treatment will spare that person a nephrectomy, an oophorectomy, or something along those lines. If we could spare an entire organ, why not take the chance? That is a clinical discussion with the patient and with the multidisciplinary team that’s taking care of them. That does highlight the importance of having [patients] with something like RPS getting treated by a multidisciplinary team, which is often most effectively coordinated at somewhere like a cancer center.

Those with progressive disease had an increased wait time and blood loss compared with those who had stable disease. What are some potential causes for those results?

I looked into those variables because I wanted to know if radiation—although not changing the size of the tumor or the organ abutment—made the case a little less difficult or maybe a little more difficult, as radiated tissues can be a little more friable when you’re going into the operation. I don’t think that the study was large enough to make an actual statement on that. That’s why we didn’t do any sort of parametric testing to say this was directly caused by or correlated with the fact that they had radiation responses or not; the study was so small. What I was trying to imply by the results and looking at those questions in general is that, as clinicians, it makes sense for us to look at these patients and say, “Okay, this person got radiation. How is their body going to behave when I cut into it?” Intuitively, those patients didn’t respond to radiation. Their tumors got too large, and we had to take them out. Maybe it was a more intensive resection, or maybe the tissues in general were more friable.

Do you believe your findings combined with STRASS provide enough data for the routine use of neoadjuvant radiation in primary resectable RPS? Or is there still a role for specific high-risk histologies?

I’m going to be diplomatic here and defer to the more rigorous statistical analysis that’s provided by STRASS. Looking at STRASS is going to be a helpful way to further delineate that because everyone in the sarcoma field is questioning the right thing to do. We still use radiation for other entities of sarcoma. Because it’s not necessarily demonstrating a huge benefit in patients in the retroperitoneum, there’s still this clinical question of [whether] there’s a better way to do it. Are we delivering it effectively? Is there a different way we can provide it for patients that will give them a benefit? It’s hard to write it off completely as a clinical practice. When patients have cancer, we’re trying to do everything we can to help them. It’s not a part of our practice, necessarily, but it’s not something that we would look down upon if someone were to choose to provide that for their patient.

What do you hope your colleagues take away from this conversation or from the study you published?

It’s important to discuss if a patient is going to get anything out of this radiation. Maybe there’s someone who’s already teetering on being too frail for surgery. Maybe they’re too frail for treatment; if there’s time to get them in right away, that might do something for them. Maybe they’re anxious, and they just want the tumor out of their body. We can more comfortably say, “Okay, let’s just go for it. Let’s go and take the surgery. This is the best thing I can do for you, and I know that.” I would emphasize the importance of [conducting] these big clinical trials. [Considering] the fact that we do all this work in the scientific literature to improve patient care, it’s exciting to translate that work into clinical decisions. Empowering surgeons and other clinicians to develop research that re-informs your clinical decision-making is an exciting thing, and the study re-demonstrates how those randomized clinical trial results can translate to the patients that you’re taking care of.

References

1. Papai E, Crear B, Kim A, et al. RECIST responses to radiation in retroperitoneal soft tissue sarcoma: when and how often do they occur? J Surg Res. Published online December 15, 2025. doi:10.1016/j.jss.2025.11.057
2. Bonvalot S, Gronchi A, Le Péchoux C, et al. Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020;21(10):1366-1377. doi:10.1016/S1470-2045(20)30446-0