Moving the Needle in Undifferentiated Pleomorphic Sarcoma: Impact of Immunotherapy on Surgical Planning

In this episode of OncChats: Moving the Needle in Undifferentiated Pleomorphic Sarcoma, the following experts discuss the impact of neoadjuvant radiation and immunotherapy on surgical planning, highlighting the importance of specialized sarcoma centers to minimize complications and improve outcomes for patients with soft tissue sarcomas:

• J. Dominic Femino, MD, an orthopaedic surgeon with Keck Medicine of USC and chief of the USC Musculoskeletal Oncology Center
• Lee Zuckerman, MD, an orthopaedic surgeon with Keck Medicine of USC
• Mark Agulnik, MD, a medical oncologist with the USC Norris Comprehensive Cancer Center, part of Keck Medicine of USC
• Andrew Lim, MD, a radiation oncologist with Keck Medicine of USC

Femino: So, what are the implications of this study, and having the immunotherapy and radiation therapy? How does that impact your surgical planning?

Zuckerman: It can impact the surgeon in different ways. Partially, let’s talk just about the radiation. Some institutions will do neoadjuvant radiation, as was performed in the study, which is radiation prior to surgery. There are some reasons why they may do surgery intraoperatively or postoperatively. So, there are different options with radiation. With this particular study, we’re going to be doing neoadjuvant [radiation], or prior to surgery. That can take some planning on part of the surgeon if they are not familiar with doing that type of surgery, which we routinely will do here, at University of Southern California, particularly with the importance of getting the patient healed quickly enough so that they don’t have a complication but also can get back on the adjuvant pembrolizumab [Keytruda]. So, it is important to understand, as a surgeon, how to get this patient healed—[for instance,] you may need a plastic surgeon to provide soft tissue coverage, particularly for tumors that you may be resecting a significant amount of skin—and working with those other teams to get the patient on track to get back on their adjuvant therapy afterward. The other difference can be the timing, and based on this study, surgery was performed somewhere between 5 and 9 weeks after radiation was completed. Many institutions and surgeons will perform surgery 4 to 6 weeks after radiation, so adjusting your timing based on this study may be inherent in using this medication.

Femino: For patients who have an unplanned surgery and then come to you as a sarcoma expert, how does that affect the treatment plan, and how does it affect the outcome for the patient?

Zuckerman: Yeah, so that’s the difficulty with sarcoma, because it is so rare. Again, this goes back to the importance of being treated by someone who specializes in sarcoma and going to a center that has that multidisciplinary treatment, because when a surgery is performed on a tumor that is not identified by biopsy to be a sarcoma prior to that resection, there can be contamination of the surrounding tissues. If the area is not resected with a margin of normal tissue around the tumor, or the tumor is cut into, then there is likely tumor left behind in the body. This can then be spread locally, typically, but can spread because now you’ve disrupted the normal capsule around that tumor.

What that does for us is it makes our surgery more extensive, so I have to usually, based on preoperative MRI or CAT scan or something, as well as discussion with the surgeon who performed the surgery, decide where the tumor was and what they did during surgery. And now, I have to resect—not just where the tumor was, but I have to take out the area where the surgeon operated, which may be much more extensive than what we would normally need to do if I saw this patient primarily. That, again, can impact both the radiation treatment, whether you need a plastic surgeon, etc. Ultimately, there are multiple studies that show that if a biopsy were performed in certain ways that we would be concerned about, we may not be able to perform that limb salvage surgery. The importance of having the surgery initially done at a sarcoma center is vital for these patients.

The good thing about this study, and this does not preclude a proper surgery done initially, is that we have another treatment so these patients who may have had an excisional biopsy, where the tumor was taken out, or taken out in pieces at another institution, ideally, this medication now helps decrease the risk of local recurrence as well as metastatic spread in these patients.

Check back tomorrow for the next episode in this series.