The Expanding Concern Surrounding Abdominal Metastases in Osteosarcoma

Early detection and quick intervention of abdominal metastases in patients with osteosarcoma could be a tactic to improve patient outcomes as well as palliative care, according to R. Lor Randall, MD.

In a case report published in Case Reports in Oncology, investigators assessed the presentation and survival outcomes of patients with osteosarcoma and abdominal metastases. The report followed 2 cases of primary distal femur osteosarcoma with subsequent metastases to the abdomen that the study authors had treated.

Through their query to determine the incidence of this patient subgroup, 42 patients with primary osteosarcoma of the bone with subsequent abdominal metastases were reviewed. Twenty-one patients were male and the mean age was 22.1 years; 78.5% of patients had primary osteosarcoma about the knee, 52.4% in the distal femur, and 26.2% in the proximal tibia. All patients received neoadjuvant chemotherapy expect one, and when the abdominal metastases presented, 10 patients (23.8%) had intussusception.

Incomplete survival data were reported for 10 patients, and 8 did not have survival outcome data noted at all. One patient each was alive at 62 months, 32, 31, and 24 months, respectively. Of the 24 patients with known time to death, 18 (75%) had died within 6 months of abdominal metastases; 7 of these (29.2%) had succumbed to their disease within the month of onset of their abdominal symptoms.

With the available data, the 5-year overall survival rate was 10.9%. Therefore, the authors concluded that metastasis often presents at later stages and is a poor prognostic factor.

“The question will become: ‘Does this sort of relatively uncommon event in osteosarcoma warrant doing more advanced imaging regularly through the [National Comprehensive Cancer Network] guidelines?’ I think the answer is ‘no’,” said Randall, an author on the study. “It’s good for the medical oncologist to think if someone is having abdominal discomfort, or they should ask about in the review of systems about abdominal conditions, concerns, or symptoms, and then do an abdominal exam. If they have any concerning findings, then get advanced imaging of the abdomen.”

In an interview with OncLive, Randall, the David Linn Endowed Chair for Orthopedic Surgery, as well as professor and chair of the Department of Orthopedic Surgery at University of California Davis Comprehensive Cancer Center, shed light on the case review and the importance of early detection of abdominal metastasis in patients with osteosarcoma.

OncLive: Please discuss the case review of these patients with osteosarcoma and abdominal metastasis.

Randall:Abdominal metastases in patients with osteosarcoma is pretty unusual, and we did a search and looked at it. It [involved] a couple of patients of ours with osteosarcoma who developed abdominal metastasis. However, more importantly, the review of the literature demonstrated to us that it is still a pretty rare event to develop abdominal metastases.

As you well know, lung metastases are in at least 90% of patients; it is the most common site [in osteosarcoma]. Then sometimes, you get osseous metastases. Beyond lung and bone [metastases], there are not many reports of other sites, including the abdomen, the liver, the retroperitoneum, etc. We did a pretty exhaustive literature search—we used a search engine [for terms like] extra-extraosseous, and non–extra-pulmonary osteosarcoma metastases, etc. and came up with a total of 40 patients, if you included [our 2 from before, then it is] 42 patients.

When you look at the autopsy specimens, up to one-third of patients with osteosarcoma have some sort of extra-pulmonary metastasis that isn't detected, because we're not looking for them. If you look at other studies, you'll see even higher numbers of [these extra-pulmonary metastases].

That is basically telling us that we don't think that these patients have clinically relevant metastasis outside the lungs and the bones in most cases, but they are, and it is happening—and when [the abdominal metastases] do happen, it's pretty much the kiss of death. This is because they don't respond nearly so well as those with pulmonary metastases.

If abdominal metastases are detected, what are the appropriate next steps?

People have tried all sorts of things; they've tried peritoneal lavage with cytotoxic therapies, they've done metastectomies, and conventional systemic chemotherapy, and most of these patients have not done well. The take-home message for this is, while it's a very uncommon event, and there has been no controlled study to look at it, it is a harbinger for poor outcome more so than lung [metastases].

What about early detection for abdominal metastases? Can that be built into routine clinical practice?

It’s a good question. The provocative question is: Should we build this into guidelines, to be doing surveillance of the abdomen, do PET/CT or abdominal CT to look for disease? I would think the answer to that is definitively ‘no’, unless clinically indicated. But it does bring up the fact that a careful review of systems is very important, and that you need to do an abdominal exam and see if they have any signs or symptoms that are concerning and then potentially do an imaging study is needed.

Potentially, if people are asking about an abdominal exam, if they have abdominal symptoms and [we are] picking it up, then maybe it wouldn't be as bad prognostically. I think these patients probably get their symptoms deferred because they're not asked specifically about whether they have any abdominal discomfort, for example, or they don't think to bring it up because they're never told to mention any of these other symptoms.

If you’re following someone for osteosarcoma with surveillance or even with ongoing therapy, just ask about the review of systems of the abdominal contents in the abdominal exam. Hopefully, you can pick it up early if it does manifest that way.

Now, by picking it up early, though, it doesn't mean the patients are going to do better, right? There is no evidence to say that it's better, and they may do just as poorly. Having said that, most of these cases in the literature cases picked up in an advanced state. There is not enough of an incidence of this to do any sort of trial or observational study, because it's uncommon. However, if we do start to find that we're picking up [these metastases] earlier, we may see some survivors.

Reference

Serpico R, Brown J, Blank A, Jones K, Randall RL, Groundland J. Metastasis of osteosarcoma to the abdomen: a report of two cases and a review of the literature. Case Rep Oncol. 2021;14:647-658. doi:10.1159/000515195