Up-Front Osteosarcoma Resection: An Approach Worth Exploring?

Neoadjuvant chemotherapy may be the standard approach for patients who present with osteosarcoma, but recent discussions have resurfaced the prospect of, and potential with, up-front resection as an alternative approach, explained R. Lor Randall, MD, FACS.

The topic was broached by the Osteosarcoma Collaborative, an organization that unites data, researchers, patients, and families to find new cures for osteosarcoma and supports new therapeutic options for this patient population. According to Randall, next steps will be to get more experts involved and conduct a national survey to gauge interest in the topic.

“We definitely look [forward] to seeing what other thought leaders around the country think about this,” said Randall. “Would it be something that we would be willing to do in a patient population with advanced metastatic disease? We'll need to [see] if there's enough interest to move forward with it.”

In an interview with OncLive, Randall, the David Linn Endowed Chair for Orthopedic Surgery, as well as professor and chair of the Department of Orthopedic Surgery at University of California Davis Comprehensive Cancer Center, discussed the concept and prospect of up-front resection in osteosarcoma from the Osteosarcoma Collaborative. 

OncLive: How are you currently approaching treatment for your patients with osteosarcoma? 

Randall: The standard of care for patients with osteosarcoma, generally, is they will get a work-up, which includes staging studies in a biopsy, their case will be presented in a multidisciplinary tumor board, and [the oncologists will] go over the whole treatment algorithm. 

Then, they will start neoadjuvant chemotherapy, they will go get restaged, and go to local control where they get the tumor resected. We look at response, and then they will be treated with more chemotherapy. It is about a 1-year course [of treatment overall].

There was a study by Allen M Goorin, MD, et al published in the Journal of Clinical Oncology in 2003, where they randomized patients to up-front resection vs chemotherapy. They found that while it wasn't statistically significant, there was a slight improvement in event-free survival in the patients who underwent immediate surgery compared with those who got chemotherapy first. 

Again, this wasn't statistically significant, but it was an interesting finding. Basically, it's still entrenched that patients generally get the treatment that I've outlined: Up-front chemotherapy, resection, and more chemotherapy.

However, recently, a group of sarcoma experts have come together to revisit this question. Several years ago, the Children's Oncology Group looked at it; there wasn't much support for it. Then, recently, there was a meeting by thought leaders around the country looking at this question. It was run by the Children's Hospital at Montefiore in New York, but [there was representation of] Johns Hopkins Medicine and The University of Texas MD Anderson Cancer Center, Vanderbilt-Ingram Cancer Center, Cleveland Clinic, the Broad Institute, and UC Davis Comprehensive Cancer Center, to pitch the idea to an audience to look at whether or not we would entertain a study where we would potentially do up-front resection.

There are a lot of arguments against up-front resection, despite the 2003 study that I referenced earlier, because there are these ideas that getting the chemotherapy up front is attacking the tumor systemically.

Also, families need to make decisions about what sort of limb salvage surgery they want to have for their child—whether that's a conventional endoprosthesis or rotationplasty, or some other form of surgery. The decision making on that is, if you do the surgery later, you can spend more time with a family, counsel them and coach them, and advise them about the pros and cons of either procedure. 

Right now, most patients don't undergo up-front resection for osteosarcoma. There are certain cases where there might be a compromise of the skin or there might be a super-imposed infection or something like that. The vast majority don't do it.

However, at this recent virtual meeting, that was held by the aforementioned institutions, [there was a discussion] that there might be enough interest to consider doing this in a certain subset of patients. What emerged from that was perhaps [it would work] in patients who present with oligometastatic disease to the lungs, where we know the prognosis is so poor.

There, they might be a role for up-front resection to diminish the tumor burden—what they call the augmented first strike on the tumor—and get the vast majority of the tumor out of the primary site. Then, you would give chemotherapy, watch the lungs, and how they respond. Then, at the local control window, take out the lung metastases to look at how they're responding, and then do adjuvant chemotherapy.

This is a completely hypothetical proposal. Next steps are going to be that the group that supported this retreat, the Osteosarcoma Collaborative, are going to look into next steps to pull thought leaders around the country, even beyond the panel that was at this virtual meeting, to look at whether or not there might be enough interest in doing something like this.

How often are you seeing patients who actually present with the disease that can be resected up front?

Well, it's not a question of "can," I would say the majority can be resected up front. But most, if not all, don't get resected up front for the aforementioned reasons that they want to get the systemic therapy going, and then look at the response to the chemotherapy when they do resection. It's just that, again, the dogma is that they don't get enough [results] from resection.

Are there any other approaches in the up-front setting that you wanted to spotlight?

There was a discussion about patients other than those with metastatic disease that might be eligible for this, but there was a lot of thought leaders from around the country at this first retreat. Most of them were against the idea of up-front resection, but we will try to tease that out a bit more when we do a national survey.

Is there anything else about this topic that you would like to add?

I want to thank the Osteosarcoma Collaborative for having that meeting earlier this month. I thought it was very informative.