A cancer of smooth muscle
Obligatory—This is not medical advice
During my first visit with patients who have leiomyosarcoma, they often recount their history, including prior doctor visits. They tell me how they’ve been told they have a rare diagnosis. I often respond that it’s while it may be thought of as an uncommon cancer, it’s very common in our sarcoma center.
Part of what makes this diagnosis intimidating also for patients is that it’s difficult to pronounce. I’ve recorded my saying it here.
Feel free to use it for practice. In all honesty, it takes even us physicians a few attempts to get it right.
Let’s talk a little bit more about the ‘what’ of leiomyosarcoma. We know that it originates from smooth muscle cells, but how does someone actually make the diagnosis?
Most patients who present with soft tissue sarcoma have gotten some form of imaging first. Ideally this would be an MRI of the initial site with and without contrast. This can be reviewed by an expert radiologist. Typically, local imaging is accompanied by a CT scan of the chest, abdomen, and pelvis with contrast—but this can also appropriately follow tissue diagnosis in the absence of symptoms.
A biopsy of the site of diagnosis should be performed in a manner that has the highest yield of tissue. It is best if this is performed by core needle biopsy, as a fine needle aspirate may be insufficient for diagnosis. That said, occasional technical or medical factors may preclude this.
What’s seen is usually ‘spindle’ shaped cells with varying amounts of mitotic figures, and necrosis. Samples usually stain positive for smooth muscle actin (SMA), desmin, caldesmon, and MSA. Of course, cancer doesn’t always read the textbook, so these may be positive or negative in leiomyosarcoma. That’s why it’s so important to have an experienced pathologist—which is nearly uniformly recommended.
The differentiation (that is how much it looks like normal smooth muscle cells) is used in conjunction with the mitotic rate (visible number of cell divisions), and necrosis (percentage of dead tissue) to determine the grade. We will cover grading at a separate time. Let’s just call things high or low grade going forward. High indicates more aggressive, and low less aggressive.
When all these details come together—we have a diagnosis of leiomyosarcoma and a grade.
Staging involves knowing the diagnosis, grade and imaging of the rest of the body to rule out the presence of metastatic disease (cancer that’s spread to other organs or sites). Acceptable means of performing staging are CT Chest, Abdomen, Pelvis with contrast, PETCT. Depending on the clinical circumstances, other types of imaging may also be appropriate.
I generally talk about two separate categories of diagnoses (see below). Keep in mind that these apply at a single point in time.
Resectable: cancer that is present in one or a small number of locations that can be removed with an intent to cure
Advanced or Unresectable: this is cancer that would result in too much toxicity by attempting to remove up front and may benefit from chemotherapy, or radiation.
As one could imagine, there is big range within these groups. That’s why it’s so important that a patient with a new leiomyosarcoma diagnosis be seen at a reference center.It’s not uncommon that we talk about patients with our multidisciplinary tumor board so that we can engage the expertise of all specialists together in one place.
For disease that can be removed, typically radiation is administered either before or after surgery. While the rates of the disease coming back at the original location are the same, each has varied risks.
We talk about the role of neoadjuvant chemotherapy elsewhere in this substack, and not to cannibalize what I’ve written there, it is debated. This is reflected in a recent post relaying a Eur J Cancer article on controversies in management of sarcoma.
Treatment of Advanced Disease
For patients who do not have resectable disease, there is wide variation in what chemotherapy regimens might be recommended. Common examples are as follows:
Doxorubicin and Trabectedin
Doxorubicin and Ifosfamide
Gemcitabine and Docetaxel
Most of these incorporate various subtypes of sarcoma, not just leiomyosarcoma. See the figure below from the Judson paper which demonstrated that the combination of doxorubicin and ifosfamide together did not increase overall survival for patients on average. This has guided management of patients with metastatic sarcoma for the last decade and shaped care perhaps more than any other publication.
In July 2022, data regarding the combination of trabectedin and doxorubicin was published with an analysis of progression free survival. While we are still waiting to see if combining these medicines helps our patients live longer, given that this was specific to leiomyosarcoma, it may have large ramifications for the treatment of those patients. See the figure below which has been modified.
Given how pronounced these early data are, I will cover this in greater detail in a separate post. It’s important to point out that, in addition to these treatment regimens, and especially in later lines, there are also ongoing clinical trials for patients with leiomyosarcoma.
The combination of cabozantinib and temozolomide, for instance, offers an entirely oral regimen.At UCSF recruitment is ongoing for an antibody-drug conjugate, (CAB-AXL-ADC) in a population that includes leiomyosarcoma—which would be a first in sarcoma. These are just two examples amongst many that will continue to define the first and later line treatment landscape for our patients with this disease.
To sum it all up, the diagnosis of leiomyosarcoma should be done with the assistance of an experienced pathologist. Staging studies with at least a CT of the Chest, Abdomen, and Pelvis are performed after tissue diagnosis. Following staging, appropriate determination of whether a patient is a surgical candidate is performed in a multidisciplinary setting. Patients who are not surgical candidates are eligible for many types of treatment, including clinical trials.