Clinical Trial Could Change Surgical Management of Metastatic Osteosarcoma

R. Lor Randall, MD, FACS

An exciting trial poised to come out of the Children's Oncology Group (COG) will randomize adult and pediatric patients with osteosarcoma that has metastasized to the lungs to thoracotomy versus video assisted thoracic surgery (VATS) for resection to determine the optimal way to manage this patient population, said R. Lor Randall, MD, FACS.

“The [trial] will evaluate thoracic event-free survival (EFS) in patients with resectable oligometastatic pulmonary osteosarcoma. It will be one of the first trials of its kind in the world,” said Randall.

The results have the potential to change the historical paradigm of applying a minimally invasive approach to adult patients and an open approach to pediatric patients, explained Randall.

In an interview with OncLive, Randall, professor and The David Linn Endowed Chair for Orthopaedic Surgery and professor and chair of the Department of Orthopaedic Surgery, University of California, Davis Health, discussed current approaches in the surgical management of patients with osteosarcoma that has metastasized to the lungs.

OncLive: Could you discuss the management of patients with osteosarcoma who have lung metastases?

Randall: We know that the lungs are the most common site of metastasis in sarcoma. There are a lot of data in osteosarcoma, as well other sarcoma types, in terms of the management of patients with metastatic disease.

Patients with osteosarcoma tend to be treated by pediatric oncologists. However, medical oncologists do [treat these patients] as well, especially at some of the big centers. Historically, if patients develop metastatic disease, they will frequently go on to have thoracotomies to reduce their tumor burden. About 20% of patients with metastatic osteosarcoma can have improved survival based upon aggressive surgical management of lung disease. Historically, that's been done through thoracotomy, which is basically an open approach. As technology has evolved, there's now VATS.

In adult surgical oncology, there are many thoracic surgical oncologists that are exceptionally adroit at using the thoroscope to do a digital metastasectomy. If a patient with osteosarcoma is treated at a children's hospital, chances are they will undergo an open thoracotomy to remove their chest disease. If they're treated at an adult center, they will get a thoracoscopic approach to manage their metastatic disease.

We don’t know which is better. There are theoretical pros and cons to both. With the open approach, the surgeon feels that they can palpate the lung and kick out micronodules that they would not know about with a thoracoscopic approach. Many of these nodules are so small that they're hard to pick up on CT. [Surgeons may feel that] they get can better resect metastases with an open approach [via] thoracotomy than thoracoscopically.

Thoracoscopic surgeons feel that they can do a very good job of cleaning out any relevant disease, and the morbidity associated with the approach is far less. Therefore, it’s really at the surgeon’s discretion [to decide] how the disease is managed. Most children's hospitals will tend to be [perform] open approach, whereas most adult hospitals will tend to [perform] thoracoscopic procedures. However, there are a few [surgeons] within each group that may take a different approach.

Could the COG trial help personalize surgical approaches?

Yes. Patients up to the age of 50 years would be eligible for enrollment. Patients with just a few nodules per lung field would be eligible for the trial. The goal of the trial when it opens is to determine which [approach] will lead to better thoracic EFS. We don't want to say [these approaches] will cure every patient, but in terms of the cancer burden in the lung fields, hopefully we will be able to say whether the patient needs an open approach or if they can get by with a thoracoscopic approach.

Hopefully, the trial will be open at every adult and pediatric sarcoma center in the country, which is most academic medical centers. We will definitely make an announcement through the National Cancer Institute and other venues to make sure that these trials are [made accessible] to medical oncologists, so they can enroll their patients. It will be really critical to do that.

How do the safety and recovery time for each of these approaches compare?

Thoracotomy is an open surgical procedure where you open up the chest, go through the ribs, and deflate the lung and resect portions of the lung. That takes weeks to months of recovery. It’s a big surgery. Typically, these patients have already had an extremity sarcoma, or some other functional impairing sarcoma. Now, you take out 1 lung field for a period of time while they recover, and it can be a big deal.

With a thoracoscopic approach which leaves tiny incisions, patients stay 1 maybe 2 nights in the hospital. The recovery is much shorter. If the goal is to improve thoracic EFS, any loving family member would be willing to have their other family member, and hopefully the patient themselves, go through an open approach if it proved to be better. If it doesn't prove to be better, then maybe the thoracoscopic approach is fine.

Are there similar controversies regarding the management of other sites of metastatic disease in osteosarcoma?

Over 90%, if not 95%, of osteosarcoma metastases are in the lung. A [small percentage of lung metastases] will develop in the bone, and an even smaller percentage will go to the liver and other sites. The predominant site—–the chest––is the only place where we have really good data on how patients do.

Is there any insight into why the lungs are such a common site of metastases?

The most common site [of metastatic disease] are the lungs in all sarcomas. People have various hypotheses. It could be somewhat physiologic and somewhat mechanical. There is good oxygen tension in the lung, and there's also a very fine capillary network. There could be a variety of influences that make the lungs the most common site.

Are there any studies you would like to see performed in osteosarcoma?

As in any cancer, metastases are the endgame of curing patients of their sarcoma. The metastases are the threat in most cases. Other sites, such as the primary is the real issue. In sarcoma, [the predominant site of metastatic disease] is the lung. You could potentially do this with other types of sarcomas depending on how [the COG trial] goes. However, because most of the other sarcomas are treated in adult centers, and get most of their disease treated thoracoscopically, it’s going to be hard to get a study like that off the ground.

Have either of these surgical approaches been impacted by the coronavirus disease 2019 (COVID-19)?

With COVID-19, most medical centers are only doing essential surgery: cancer surgery, trauma surgery, and a variety of other things. The issue is that with cancer surgery on the lung, you could potentially need ventilators, especially if they have the open approach. You don't want to compromise patients from a pulmonary standpoint in the era of COVID-19.

Those discussions are being had with patients about those concerns. During the surges [of COVID-19], I’m sure all of these surgeries were deferred. When the surges started to flatten out, I'm sure many of these patients that were waiting for one of these procedures were one of the first in a queue to get it done. We're probably seeing an uptick [of these procedures] around the country.

Is there anything else you would like to share?

I’d like to give a shout out to John J. Doski, MD, FACS. He is a pediatric surgeon at UT Health San Antonio, and he's been the driving force with [the COG trial]. If anyone has further questions around this, they're more than welcome to reach out to me, but the brain trust is Dr. Doski.