One-stage Synovectomy Does Not Lead to Worse Outcomes in D-TGCT of the Knee

R. Lor Randall, MD, FACS

One-stage synovectomy was associated with a similar range of motion, fewer complications, and shorter hospital stays compared with 2-stage synovectomy in patients with diffuse-type tenosynovial giant cell tumor (D-TGCT) of the knee, and the 1-stage procedure should be considered when feasible, according to results from a retrospective study published in Cancers.

The retrospective, global cohort analysis included 191 patients with D-TGCT of the knee from 9 sarcoma centers globally and compared the short-term postoperative outcomes of 1- vs 2-stage synovectomy. Findings showed that the maximum range of motion achieved within 1 year of surgery was similar between 1- and 2-stage synovectomy (flexion, 123° vs 120°; P = .109; extension, 0°; P = .093). Additionally, 2-stage synovectomies were associated with longer hospital stays (6 vs 4 days; P < .0001).

The rates of complications were 36% for 2-stage synovectomies compared with 24% for 1-stage synovectomies, although these differences were not considered statistically significant (P = .095). Notably, more radiological progression (52% vs 37%; P = 0.036) and requirement for subsequent treatments (54% vs 34%; P = .007)were observed more in patients who underwent 2-stage synovectomies vs those treated with 1-stage synovectomies.

“If [synovectomy] can be done in 1 setting, it’s better to do it in 1 setting rather than 2. Again, there is potential selection bias in the patients [in the study], meaning those patients who had more advanced disease [may have] needed that 2-stage operation,” co-study author R. Lor Randall, MD, FACS, explained. Randall is the David Linn Endowed chair for Orthopedic Surgery, the chair of the Department of Orthopedic Surgery, and a professor at UC Davis Comprehensive Cancer Center in Sacramento, California.

In an interview with OncLive^®, Randall detailed the standard treatment approach for patients with D-TGCT, the results of the retrospective cohort study evaluating 1- vs 2-stage synovectomies in these patients, and the importance of having additional treatment options for this patient population.

OncLive: What is the current standard of care for patients with TGCT?

Randall: TGCT is an entity that has gotten a lot of attention lately because there are some new pharmacological agents—CSF1 inhibitors, specifically—that have been used to manage some of these conditions. To be clear, TGCT is a benign condition, but locally, it can behave aggressively. It can cause a lot of morbidity to patients and usually involves a large joint. The knee is the most common, but it can effectively arise in any joint. Sometimes, it may also arise in tendon sheaths, particularly around the hand.

While surgery has historically been the mainstay of treatment, there are high recurrence rates and high complication rates associated with it. There are 2 types of TGCT: a solitary, nodular, or focal type, and then a more diffuse type. Unfortunately, the diffuse type is much more common.

Could you expand on the methods utilized in this retrospective study on 1- vs 2-stage synovectomy for patients with D-TGCT of the knee?

We recently published a study from 9 sarcoma centers globally. I use the term sarcoma because sarcoma centers are generally the referral place for [patients with TGCTs]. Many orthopedic surgeons may manage some of [these patients], particularly sports medicine doctors or knee specialists who will see this condition and treat it arthroscopically or even with an open procedure. However, invariably, if the disease is locally recurrent, patients are sent to a sarcoma specialist, because we deal with some of these locally aggressive, locally malignant conditions.

These 9 sarcoma centers from around the world pooled data, looking at open and arthroscopic management of knee D-TGCT requiring either 1- or 2-stage synovectomy, which means removing all of the lining of the knee joint. [Synovectomy] can be done in 2 ways: arthroscopically or in an open fashion. Anatomically, it is important [to remember] the front of the knee and the tissues that the typical orthopedic surgeon will see: the joint that involves the patella, the femur, and the tibia articulation. Then there is also the pouch in the back of the knee, where the TGCT can also [reside].

Getting at the tumor from the front into the back can be a technical challenge from a surgical perspective. Therefore, some surgeons will do a 1-stage complete synovectomy, where they go in from the front with the patient supine on the operating table, then finish that up by lying the patient prone to then go in the back, or vice versa. That would be considered a 1-stage synovectomy where they manage both [sides] in the same setting.

Some surgeons will treat patients in 2 stages, where they complete 1 part first, let the patient recover, and then bring them back for a second procedure. We pleasantly argue amongst ourselves if it is better to do [synovectomy] all at once or to do it in stages. We wanted to get some empirical data around this.

What were the key findings derived from this study?

This paper that we published in Cancers is not a randomized trial. [This was a study of] our experience from some of the bigger centers around the world looking at outcomes [of 1- vs 2-stage synovectomy]. What we found was that 1-stage synovectomy had equal or better results than 2-stage synovectomy. There can be some selection bias here. Perhaps the cases that were less advanced underwent a 1-stage synovectomy, whereas those who were more advanced underwent a 2-stage synovectomy.

What is nice to see is that patients ultimately do just as well in terms of range of motion and have less complications with a 1-stage [synovectomy] compared with a 2-stage. The conclusion of the [study], which had 191 patients, was that 1-stage synovectomy had optimal results.

The other part of this paper is that it's a nice platform from which to say that surgery is often not going to be a conclusive treatment for patients, and they are going to need something more.

Did the study detail the frequency of open vs arthroscopic surgery?

Interestingly, the majority of patients were treated open. That is because these patients have already had treatments at other centers where arthroscopic treatments have failed. Arthroscopic surgery is minimally invasive, and we do generally believe that if the surgeon is comfortable with arthroscopic techniques, they should try to employ this. You may be able to get durable control rates with an arthroscopic procedure. However, in this [study], the majority were open.

What are the currently available, FDA-approved treatment options for patients with D-TGCT?

D-TGCT has a high predominance of recurrence, and it can be disfiguring, painful, and sometimes can ultimately lead to an amputation for benign disease. We don't like to see amputations in general, but particularly for benign disease, it is a poor outcome.

Therefore, there has been some work, and there is now a commercially available and FDA-approved agent, pexidartinib [Turalio], which is a CSF1 inhibitor, that has been shown to improve symptoms in some patients. We don't have the optimal treatment algorithm for pexidartinib [yet]. Pexidartinib and other agents that are being studied are utilized when surgery has failed.

There are questions now being raised in the sarcoma world, especially in the sarcoma surgery world, about the concept of a neoadjuvant treatment for [TGCT], where you can potentially stun the tumor, treating them up-front with pexidartinib or a similar agent, and then go in surgically. We would love to know if that helps improve local control. Unfortunately, that study hasn't come to fruition yet, but we are pushing for something like that.

Are there concerns that the use of neoadjuvant pexidartinib may delay surgery?

Usually, the adverse effects of pexidartinib are a bit of acute elevation liver function tests [LFTs], fatigue, or hair color changes. There is very close monitoring for the LFT bump, and usually it can be corrected with dose reduction or cessation of the drug. There haven't been any concerns about wound healing or anything of that sort. Therefore, in concept, if patients were to undergo neoadjuvant [pexidartinib] and were to get good local control, it wouldn’t delay the surgery. It does beg the question: If patients get symptomatic relief, should they have surgery at all?

Regarding 1-stage vs 2-stage synovectomy, do you see that high-volume centers vs low-volume centers may take a different interpretation of these results?

I believe that low volume centers will take note of the fact that these recurrence rates are pretty high no matter how they're treated, even when they're treated at high-volume centers. Maybe these [low-volume] centers will refer them to the high-volume centers to begin with so that the treatment journey is started sooner rather than later.

Reference

Spierenburg G, Verspoor FGM, Wunder JS, et al. One-stage synovectomies result in improved short-term outcomes compared to two-stage synovectomies of diffuse-type tenosynovial giant cell tumor (D-TGCT) of the knee: a multicenter, retrospective, cohort study. Cancers (Basel). 2023;15(3):941. doi:10.3390/cancers15030941