R. Lor Randall, MD, FACS, discusses novel precision surgery techniques that are making progress in sarcoma care.
Bridging the gaps between extensive preoperative imaging, operating room procedures, and more precise surgeries represent some of the benefits of novel precision surgery techniques that are developing in sarcoma care, according to R. Lor Randall, MD, FACS.
“One can imagine the entire revolution: MRI and CT tells us where the tumor is before surgery, navigation tells us where our instruments are relative to that tumor, three-dimensional guides may help us produce the planned resection, and fluorescence may eventually tell us where viable tumor actually ends,” Randall said in an interview with OncLive®.
Three-dimensional cutting guides, robotic-guided surgery, near-infrared imaging, artificial intelligence [AI]–driven workflows, and early data for these approaches were all topics that Randall explored in the interview.
Randall is the David Linn Endowed Chair for Orthopedic Surgery, chair of the Department of Orthopedic Surgery, and a professor at the University of California Davis Comprehensive Cancer Center in Sacramento.
Randall: One of the fundamental challenges in orthopedic oncology is that we can see the tumor extraordinarily well before surgery. But, once we start operating, much of that information disappears. If we think about pelvic surgery before surgery, I can sit down at a workstation with an MRI and CT scan and define the tumor in exquisite detail. I can see [the tumor’s] relationships to the acetabulum, sacrum, neurovascular structures, and surrounding soft tissues, but then I walk into the operating room, and I have to translate all of that imaging onto the patient’s anatomy using anatomic landmarks, experience, and surgical judgment.
One of the most interesting developments in orthopedic oncology recently is image-guided sarcoma surgery. [Image-guided surgery] is essentially bringing what we see on the scans into the operating room theater. The first step or iteration has been computer-assisted navigation and three-dimensional surgical planning. This is particularly relevant for pelvic and sacral tumors, where the anatomy is complex and the difference between an intralesional resection and sacrificing normal tissue may literally be millimeters. There are now clinical data suggesting that navigation can improve our ability to reproduce the resection that we’ve planned out. [Specifically, data reported] computer-assisted navigation in pelvic and sacral tumors with registration errors under 1 mm and clear bony margins in their primary tumor resections.1 [Another study] subsequently compared navigated and non-navigated pelvic or sacral sarcoma resections and found improved bony margin control with the navigation.2 Patient-specific three-dimensional cutting guides are another expression of the same concept: plan the osteotomy virtually, then physically transfer that plan to the patient in surgery.
There’s an important limitation to all these technologies. They tell us where the tumor was on the preoperative scans, but they don’t actually show us the tumor in surgery. That brings us to what is the really fascinating next frontier of fluorescence-guided sarcoma surgery. One approach uses indocyanine green [ICG], which can be visualized intraoperatively with near-infrared imaging because of tumor vascularity and permeability; many sarcomas demonstrate fluorescence. The idea is straightforward: instead of relying on the surgeon’s mental reconstruction of the MRI, we may be able to visualize tumor-associated signal during the operation.
There are early human data suggesting that this may be clinically useful. [Previously reported data] demonstrated the feasibility of ICG fluorescence in bone and soft-tissue sarcomas [STS].3 [Another trial] included 115 patients, and 37 of 39 tumors in the fluorescent-guided group fluoresced.4 More provocatively, the unexpected positive margin rate was 5.1% with fluorescence guidance vs 25.0% with conventional surgery. This is an intriguing concept, but it needs to be interpreted cautiously because this was not a randomized trial. The groups were heterogeneous, and ICG is not necessarily tumor specific. Fluorescence can occur in non-malignant tissues, and a lack of fluorescence certainly does not prove absence of tumor. [Therefore,] this is not a replacement for oncologic judgment or pathologic margin assessment, but conceptually it changes the question. Instead of asking where the tumor should be based on MRI, we are ultimately now asking where it would be visible. Where would viable tumor be right now, in my surgery, based upon this fluorescent signal.
What You Need to Know About Evolving Precision Surgery in Sarcoma
ICG may only be an intermediate step. The next generation is molecularly targeted fluorescence agents designed to bind to a tumor-associated target and illuminate malignant tissue. A first-in-human study published in 2025 evaluated ABY-029, an EGFR-targeted fluorescent peptide, in patients with STS, and demonstrated the feasibility of tumor-targeted fluorescence in the operating room.5
The future will probably integrate all of these approaches in varying degrees, advancing the imaging and three-dimensional planning, navigation, and biologically targeted, more specific visualization of tumor cells. The point is not technology for technology’s sake; the fundamental objective of sarcoma surgery has not changed even with all of this technology. We still want to remove the tumor completely and preserve as much normal anatomy and function as is oncologically appropriate.
Historically, when we have worried about the margin, we have often compensated by taking more tissue. Precision surgery potentially changes that equation. The goal is not necessarily a bigger margin; the goal is a better defined and more reliable margin. That is why one of the most interesting questions in orthopedic oncology today is whether we are moving from an era in which surgeons have to mentally reconstruct the tumor [location] to an era where we can actually see the tumor, and ultimately the margin, in real time. If we can do that reliably, it could represent a fundamental advance in precision sarcoma surgery.
AI is going to influence all of health care surgery and society in general. It’s here, and we need to stay on the front end of it; it’s really an exciting time. It’s fair to say that AI will help us with some of our preoperative planning, so that when we’re making these cutting jigs, we will use AI to help us with our planned cuts as we’re going through them with human minds.
Intraoperatively, there are probably [AI applications] for image-guided fluorescence. [In contrast with] sarcoma surgery, urologic surgery is mostly robot driven right now. When you have a robot, AI can augment into that and become the brain of the arms of the robot. Currently, much of sarcoma surgery, particularly extremity surgery, is non-robotic driven, but, for example, in conventional total knee arthroplasties, we use robots all the time. AI will be coming online very quickly in the application of conventional joint arthroplasty, but we have to get some of the extremity robotics up to speed compared with fields like urology and intra-abdominal surgery.
When patients are blinded, and they engage with current-generation AI vs a human being, but they don’t know [which they are engaging with], their empathetic response and satisfaction to that response is approximately 50/50. From the human experience, AI empathetic algorithms are getting very good, and their depth of knowledge about the patient is also [getting better] because of the access to all sorts of information about their patient that they will be able to use to customize the interface with the patient a bit more. Lastly, a human physician has to have a 15- or 30-minute encounter with patients, then they [often need to] move on to the next patient. When you interface with an algorithmic provider, patients don’t have that kind of constraint. [AI] can talk to patients at 3:00 in the morning. There’s more depth to this discussion than the human component.
Only humans will understand at this point what it means to be a human, and there will still be that necessity for that human physical and mental touch. But we do need to realize for any of us that have interfaced with AI, there really is a joy with that as well. We need to be creative in thinking about integration.
Anyone who is involved in sarcoma care should be engaging with their surgeons and asking the question: Are you using some of these custom techniques? It’s fair to say that many of us are already [using custom techniques], but medical and community oncologists should be having conversations with their surgeons about these technologies and making sure that that they are starting to use them because it will become standard practice to use these technologies. The community physician or the non-surgical oncologist should be having these conversations at their multidisciplinary tumor boards.
