Randall Shares How Postoperative Radiotherapy Retains a Role in Soft Tissue Sarcoma

Preoperative radiotherapy has become a standard of care for patients with soft tissue sarcoma of the extremeties, according to R. Lor Randall, MD, FACS; however, postoperative radiation still plays a role in the paradigm, especially when wound risks are considered to be precarious.

“For 2 decades now, I have been treating a patient with metastatic soft tissue sarcoma; the cancer has spread all over his body. After careful thought, I decided to use postoperative radiation therapy in this patient. This immediately set off alarm bells amidst the rest of my team; they didn’t understand why I was doing this,” Randall said. “Many benefits exist with preoperative therapy, which is why it has become a standard. However, it’s paramount to remember that, in certain cases, postoperative radiation has its own list of advantages. In this particular case, the advantages outweighed those of preoperative therapy.”

In an interview with OncLive, Randall, David Linn Endowed Chair for Orthopaedic Surgery, as well as professor and chair of the Department of Orthopaedic Surgery at the University of California, Davis Health, weighed the pros and cons of using preoperative versus postoperative radiotherapy in patients with soft tissue sarcoma of the extremities.

OncLive: Could you shed light on the difference between preoperative and postoperative radiotherapy?

Randall: Many years ago, several prospective randomized trials were conducted at Princess Margaret Cancer Centre, in Toronto, Canada, in which investigators examined preoperative versus postoperative radiotherapy. The data were convincing in showing the advantages of preoperative radiation therapy. [With this approach, we] could give more controlled doses to more controlled areas while decreasing the complications of lymphedema, arthrofibrosis of joints, etc. We believed there were just as good, if not better, local control and survivorship [with preoperative radiotherapy], although the studies weren't designed to prove that latter point.

As such, many started approaching extremity sarcomas with preoperative radiotherapy. For example, if a patient came in with a large, deep soft tissue sarcoma that needed to be resected, more often than not, they would get preoperative radiotherapy and resection. The downside of preoperative radiation therapy is the marked increase in wound complications. You treat the skin, and even though you're trying to minimize the skin damage, there is a risk of wound complications. This is a real concern for sarcoma surgeons; the risk is much higher with preoperative radiation.

However, again, the lymphedema, the stiffness of the joints, all these things are much better managed by giving preoperative radiotherapy. That being said, in some cases where there is either recurrence of disease or the patient has other comorbidities, such as diabetes, the wound risks are so precarious that we'll do postoperative radiotherapy.

Do any disadvantages exist with postoperative radiation therapy?

The disadvantage with postoperative radiation is, while the wound will heal, you now have to give a larger field. When giving a larger field, patients will most likely have swelling, lymphedema, and stiffness in the limb because you're now including a knee joint. When we take out a sarcoma in the midst of the distal thigh and the skin incision comes down over the knee, the radiation therapist needs to extend the field of coverage, at least by a couple of centimeters, to treat any risk of contamination. Many of these patients have a hard time with getting their limbs back to a functional standpoint, but they have much less of a problem with wound healing.

Would you say that the field has shifted to using more preoperative radiotherapy rather than a postoperative approach? If so, why do you think that is?

I believe so, because the science has shown us that despite womb problems, you're able to limit the extent of treatment and have less complications in other areas. Howver, in the case of one of my patients, it just so happened that the metastatic site was very close to where his prior treatments had been. For over 2 decades, he has been showing lesions in a variety of places. My concern was that the skin incision would be going into an area that had already been irradiated before. By irradiating again, I was worried that he was going to have a real problem with wound healing. In this particular location, he would have needed free flap coverage to get this under control. Because he had metastatic diseas already in other sites, we didn't want to make his treatment worse than the problem itself by needing to do all this tissue rearrangement and microsurgery to cover an area that would otherwise be very low risk if he underwent postoperative radiation.

How is this patient doing after you used the postoperative approach? Do you have any advice for your colleagues who may be treating patients with similar conditions?

This patient is doing very well. His wound healed beautifully. I'm sure he's going to have ongoing oncologic issues with his initial sarcoma which, again, was found almost 2 decades ago. The message from this is, in 2020, in select cases, there's a role for postoperative radiotherapy definitely still exists. [The decision] should be made in the setting of a multidisciplinary tumor board. That way, if a surgeon is making the call, he or she can argue their point to ensure the rationale is sound. In cases such as this, where the wound problems are very precarious, postoperative radiotherapy should definitely be considered.

Are approaches with chemotherapy and radiation therapy, either in combination or sequentially, being utilized in soft tissue sarcoma?

Doxorubicin is a radiosensitizer that can cause wound issues. I want to be very careful with saying this because I'm not a radiation therapist, nor am I a chemotherapist; I'm a surgeon. I don't want to make any recommendations, although in some cases, they will use a radiosensitizing chemotherapeutic agent to facilitate either an immune response or some other response in the tumor to facilitate necrosis. However, whether to use that approach should always be determined by a multidisciplinary sarcoma tumor board.

Is there anything else that you would like to add?

While the norm has really become preoperative radiation therapy in extremity soft tissue sarcoma, there are select cases [that call] for postoperative therapy. However, as previously stated, this should be at the discretion of the surgeon and the multidisciplinary team of radiation therapists, medical and pediatric oncologists. It’s truly a team decision.