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What is Uterine Sarcoma?

Summary to be written

The Basics

Diagnosis and Prognosis

The Basics

Uterine sarcoma is a rare type of cancer that originates in the muscle tissue of the uterus. The
uterus is a small, pear-shaped organ in a female's pelvis, and is where a fetus develops and
grows. Uterine sarcoma accounts for about 1% of all female genital malignancies and <10% of
uterine tumors.[see References: 1] Uterine sarcomas include several different subtypes, such as leiomyosarcoma,
endometrial stromal sarcoma, undifferentiated sarcoma, adenosarcoma, and rhabdomyosarcoma.
Among these, leiomyosarcoma and endometrial stromal sarcoma are the most common types of
uterine cancer, accounting for 2-5% of all uterine cancers.[see References: 2] Consequently, most of the available
research and clinical data focus on these two subtypes. Uterine sarcomas generally have a
less-favorable prognosis for long-term survival compared to endometrioid adenocarcinoma, the
most common form of uterine cancer. Despite their rarity, evidence suggests that the incidence is
increasing.[see References: 3] Because of their rarity and many subtypes, there is no agreed-upon best treatment.

Surgical management remains the cornerstone of treatment for most types of uterine sarcoma, as
these tumors generally show poor response to systemic treatment such as chemotherapy and
immunotherapy.[see References: 1, 4] For advanced-stage diagnoses with spread throughout the abdomen,
cytoreductive surgery (CRS) may be a viable treatment option. Even more promising, some
recent studies also indicate that adding hyperthermic intraperitoneal chemotherapy (HIPEC) to
CRS may offer a survival benefit in select patients.[see References: 5]

Risk Factors

Due to the rarity of the disease, risk factors are difficult to estimate, but can include:

Increasing age: the majority occur in patients over 40, with a mean age at diagnosis of approximately 60 years
African American women are more frequently diagnosed
History of tamoxifen use >5 years
History of pelvic radiation therapy
Certain inherited syndromes and conditions (renal cell carcinoma, hereditary leiomyomatosis, retinoblastoma)

Signs & Symptoms

Symptoms can be similar to other gynecologic conditions and are often non-specific:

Abnormal uterine bleeding
Postmenopausal bleeding
Abdominal/pelvic pain
Abdominal distension
Urinary symptoms, such as frequent urination, painful urination, difficulty urinating

Evaluation

Physical exam
Imaging studies: ultrasound, PET/CT scans, CT scan, MRI scan
Blood work to include tumor markers
Biopsy (endometrial biopsy, D&C, transabdominal or transvaginal biopsy of mass)

Key Facts

_title_

Uterine sarcomas are very rare and aggressive tumors, and there is limited information on
the most effective treatment options.

_title_
Surgery is the primary treatment, with the best outcomes seen when the entire tumor is
successfully removed. Thus, an experienced surgeon is essential.

_title_
Additional treatments, including radiation, chemotherapy, targeted therapy,
immunotherapy, and hormone therapy, show mixed results. Many clinical trials are
focused on improving and exploring these options further. A medical oncologist and
specialized gynecologic oncologist can help determine which option is best for your case.

_title_
While evidence is limited, recent studies suggest that adding HIPEC to cytoreductive
surgery (CRS) may improve progression-free and overall survival in select patients.

Treatment

A standard of care treatment for uterine sarcomas has not yet been established. Surgery is the
primary treatment and may be combined with additional therapies, including radiation therapy,
chemotherapy, and/or hormone therapy, depending on the stage and their histology (how
abnormal the cells look under a microscope) of the disease. The treatment plan is tailored to each
patient based on these factors and will most often require multi-disciplinary collaboration, or
team-based care between multiple clinicians.

Surgery:

Surgery for uterine sarcoma typically involves at least a total hysterectomy (removal of the
uterus and cervix). The extent of the surgery depends on the size of the tumor and how much it
has spread within the abdomen. If the disease is confined to the uterus, a total hysterectomy
(removal of the uterus and the cervix) is usually sufficient. In many cases, a bilateral
salpingo-oophorectomy (BSO) (removal of the both fallopian tubes and ovaries) is also
performed during the hysterectomy, particularly in postmenopausal women and those with
endometrial stromal sarcomas or undifferentiated sarcomas (a type of histologic subtype).[see References: 4]

If the cancer has spread beyond the uterus, more extensive surgery beyond the hysterectomy and
BSO may be required to remove all visible tumors within the abdomen. This may involve the
removal of pelvic and/or para-aortic lymph nodes if they appear suspicious on imaging or
examination during a surgical procedure.[see References: 4, 6, 7] Surgery is considered most successful and is
associated with the biggest survival increase when all visible tumors are completely removed.[see References: 8-12]
It is important that patients be treated by an experienced care team to help identify treatment
options that take into account several important factors, such as feasibility of removing the
tumor, the patient’s ability to undergo extensive surgery, and the timing of the metastases.[see References:13-15] To
reduce the risk of recurrence after complete removal of all visible tumors, surgery may be
followed by radiation, chemotherapy, and/or hormone therapy.

In many cases, uterine sarcoma (particularly leiomyosarcoma) is diagnosed after surgical
procedures to remove the uterus (called a hysterectomy) or uterine fibroids (called a
myomectomy) that were initially performed for what was thought to be benign leiomyomas
(fibroids).[see References: 8, 16] As a result, surgical procedures to remove other organs and tissues (including the
uterus, cervix, fallopian tubes, ovaries, and any residual tumors) may be necessary. During the
initial surgery, morcellation (the process of grinding fibroids or the uterus into small pieces for
easier removal) may have been used. Unfortunately, morcellation can spread tumor cells
throughout the abdominal cavity.[see References: 17] Therefore, a secondary surgery or re-exploration surgery is
often recommended, as many patients develop secondary uterine disease or extrauterine
disease.[see References: 18, 19] Morcellation should be avoided even in benign cases.

For patients who are not surgical candidates or in whom a complete cytoreduction is not feasible,
surgery offers no survival benefit and it may delay the start of systemic treatment like
chemotherapy.[see References: 20] In such cases, surgery should only be considered for palliative purposes to
alleviate significant symptoms such as pain or bleeding.

Chemotherapy:

Uterine sarcomas generally show mixed responses to chemotherapy, with effectiveness varying
depending on the specific subtype and molecular changes in the tumor.[see References: 24] The effectiveness of
adjuvant (postoperative) chemotherapy, especially in early stage disease, remains uncertain.[see References: 7, 15]
Although no definitive clinical trials have proven that chemotherapy improves progression-free
or overall survival, it is commonly recommended for high-risk sage I and II uterine sarcomas,
including cases following morcellation, as well as in stage III disease due to the higher risk of
recurrence.[see References: 25-27] Common chemotherapy drugs that may be considered for use include
doxorubicin, docetaxel, gemcitabine, ifosfamide, docarbazine, trabectedin, and eribulin.[see References: 28] These
may be given as single agents or in combination. In some cases, chemotherapy may be used
before surgery to shrink the tumor, making it easier to remove, and then after surgery to prevent
delay or recurrence. For patients with advanced, unresectable disease who are not candidates for
surgery, chemotherapy is typically the preferred treatment. This may be combined with radiation
therapy for palliative purposes.[see References: 15]

The role of chemotherapy, including the optimal regimen and drug choice, are still being
investigated in clinical trials.[see References: 7] It is essential to work with an experienced medical oncologist who
collaborates with your surgeon to determine the best treatment approach tailored to your
individual case.

Radiation:

Radiation therapy may be administered after surgery (called adjuvant radiation) to reduce the risk
of local recurrence.[see References: 21] There are two main types of radiation therapy: external beam radiation
therapy (EBRT) and vaginal brachytherapy (VBT). EBRT is the more commonly used for uterine
sarcoma and targets a broader area, typically including the pelvis and nearby lymph nodes,
whereas VBT specifically targets the vaginal cuff. These therapies can be used alone or in
combination depending on the individual case. The choice of radiation technique and the area to
be treated depend on the extent of the disease, but this remains a topic of ongoing debate. Data
on the benefits of adjuvant radiation is limited and mixed, and there is no strong evidence
supporting its use in all cases. Available research is primarily focused on leiomyosarcoma or
include multiple subtypes of uterine sarcoma, making it difficult to know the benefit in other
subtypes like endometrial stromal sarcoma or adenosarcoma.[see References: 7] While adjuvant radiation has not
been shown to improve survival for early stage disease (stage I & II), it may help prevent or
delay local recurrence in some high-risk stage II-IV patients (ie. those with positive surgical
margins, potential residual disease, or other aggressive features).[see References: 21, 22]

For patients with unresectable tumors who are not surgical candidates, radiation can be used
alone or in combination with chemotherapy (chemoradiation). In this scenario, it is intended to
manage symptoms such as pain or bleeding caused by tumor growth. However, it is not curative
and aims to improve the patient’s quality of life.[see References: 23] A specialized radiation oncologist will be
consulted to determine the appropriate administration for your specific case.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC):

When uterine sarcoma spreads throughout the abdominal cavity, it is referred to as peritoneal
sarcomatosis and is associated with a poor prognosis, with median survival ranging from 6-15
months.[see References: 1] Treatment options are limited in this setting, usually relying on systemic chemotherapy
with poor results, indicating the need for alternative treatments.[see References: 7, 15] Recent studies have shown
that combining extensive cytoreductive surgery (CRS) with hyperthermic intraperitoneal
chemotherapy (HIPEC) significantly improves survival.[see References: 5] CRS refers to the aggressive surgical
removal or destruction of cancer with the goal to remove all visible disease. It is performed
through an incision down the midline of the abdomen and may include removal of parts of or the
entirety of organs such as: the spleen, gallbladder, liver, peritoneum (lining of the abdominal
cavity), uterus, fallopian tubes/ovaries, and bowel. Following CRS, heated chemotherapy
(HIPEC) is circulated directly into the abdominal cavity to kill any remaining microscopic
cancer cells.

The largest multi-institutional study on this approach, involving 36 patients with uterine
sarcoma, reported a median overall survival of 37 months and a 5-year survival rate of 32%, with
a median progression-free survival of 19 months.[see References: 29] Another study comparing CRS alone to
CRS/HIPEC found that the HIPEC group had longer overall (43.8 vs 35.9 months) and
progression-free survival (11.3 vs 5.3 months), although the sample size was small.[see References: 30] Other
studies suggest that CRS/HIPEC may be beneficial after morcellation or in recurrent cases,
offering the potential for long-term survival, especially when complete cytoreduction is achieved
in select patients.[see References: 31-36] However, since data is still limited, HIPEC is generally recommended only
in clinical trials. A skilled surgeon specializing in peritoneal surface malignancies can help
determine if CRS/HIPEC is a suitable option for your situation.

Hormone Therapy:

Hormone therapy is sometimes used to treat low-grade endometrial stromal sarcoma, though it
has not been proven effective for other types of uterine sarcoma.[see References: 37] To determine if hormone
therapy might be effective, the pathologic evaluation of your tumor will include testing for
estrogen (ER) and progesterone receptors (PR). If your tumor is positive for these receptors,
hormone therapy may be beneficial. Hormone therapy is usually reserved for cases where the
cancer has spread beyond the uterus (advanced stage or metastatic) or has recurred after previous
treatment. There are no formal guidelines for the duration of hormone therapy, but it is
commonly administered for 5 years.[see References: 38] The most frequently used drugs are progestins (such as
Provera and Megace), which mimic the action of the hormone progesterone. Some studies have
shown that adjuvant therapy with Megace and Provera may improve recurrence rates.[see References: 39, 40] Other
hormone therapies, including aromatase inhibitors and gonadotropin-releasing hormone (GnRH)
analogs, are also being explored.[see References: 41, 42] Clinical trials are ongoing to evaluate the effectiveness of
other hormonal treatments for endometrial stromal sarcomas. Your medical oncologist and
gynecologic oncologist can help determine if hormone therapy is appropriate for you.

Targeted & Immunotherapy

Targeted and immunotherapies are relatively new approaches for treating uterine sarcoma and
are usually used for advanced disease, often after chemotherapy has been tried. One such
treatment is kinase inhibitors, like pazopanib, which was approved in the United States for
metastatic soft tissue sarcomas that have progressed after chemotherapy. A randomized trial
showed that pazopanib significantly improved progression-free survival (median: 5 months vs 2
months), although overall survival was similar to the placebo (13 months vs 11 months).[see References: 43]
Recent studies have also identified a genetic rearrangement in the NTRK genes in some uterine
sarcomas. TRK inhibitors, such as larotrectinib and entrectinib, target these abnormal proteins
and may offer treatment options for tumors with this specific molecular alteration.[see References: 44] In addition,
PARP inhibitors can target uterine sarcomas with BRCA mutations, and there is growing interest
in combining these with chemotherapy to potentially improve survival.[see References: 45] This could be a
promising option for the roughly 10% of uterine leiomyosarcoma patients who have a BRCA
mutation.[see References: 46] Immunotherapy, particularly PD-1 inhibitors like pembrolizumab, may also be used
for advanced uterine sarcomas, especially when other treatments have failed and if the tumor has
a high tumor mutational burden (TMB).[see References: 47] As more targeted treatments become available,
sequencing your tumor is increasingly important to identify specific molecular alterations,
allowing for more personalized and effective treatment strategies.

Diagnosis and Prognosis

The evolving classification and rarity of uterine sarcomas makes it challenging to compare
prognoses. However, in addition to the ability to achieve complete removal of all visible tumor,
tumor grade and stage are still the main factors contributing to prognosis. Low-grade (grades 1 &
2) endometrial stromal sarcoma have a 5-year disease free survival of over 90%,while high-grade
endometrial stromal sarcomas and undifferentiated uterine sarcomas (grade 3) have a 5-year
disease-free survival rate of only 42%.[see References: 54] Low-grade endometrial stromal sarcomas also tend to
have better overall survival, with 65-76% surviving for 10 years, compared to high-grade cases,
which have a median overall survival of just 11-24 months.[see References: 60] Leiomyosarcomas have a 5-year
survival of 66%, which varies by stage: 75% at stage 1 and decreasing to 29% at stage IV.61
However, all stages of leiomyosarcoma carry a high risk for relapse (up to 40%), particularly
within the first 5 years after treatment.[see References: 62, 63] Therefore, close surveillance and follow up, including
physical exams, tumor markers, and imaging (such as CT scans) with your gynecologic
oncologist are essential.

Research

Clinical Trials

There are many clinical trials registered for advanced and high-risk colorectal cancer. Below is a sample of a few of the clinical trials listed on www.ClinicalTrials.gov. Your oncologists can also help you review clinical trial options and recommendations.

In addition to the trials listed below, see this table that summarizes key research regarding CRS/HIPEC as a treatment for colorectal cancer:

Colorectal Cancer and HIPEC

Phase IV Multicentric Clinical Trial to Evaluate the Efficacy of HIPEC with Mitomycin-C after Complete Surgical Cytoreduction in Patients with Colon Cancer Peritoneal Metastases (GECOP-MMC) (NCT05250648)

Status: Enrolling
Prospective phase IV randomized trial comparing peritoneal recurrence rates in patients with colon cancer peritoneal metastases treated with complete CRS and systemic chemotherapy with or without HIPEC with mitomycin-C
Inclusion criteria: patients with colorectal cancer with peritoneal metastases (PCI≤20) that have not been previously treated, are surgical candidates and able to receive perioperative systemic chemotherapy, and a complete CRS is deemed feasible

ctDNA as a Assisted Diagnosis, Early Intervention and Prognostic Marker for Peritoneal Metastases from Colorectal Cancer (NCT04752930)

Status: Enrolling
Prospective randomized trial aiming to elucidate the correlation between postoperative ctDNA serum level status and the assisted diagnosis, early intervention, and prognosis for colorectal cancers with peritoneal metastases
Inclusion criteria: patients with colorectal cancer who are at high risk for peritoneal metastases and have previously undergone surgical resection of the primary tumor and completed adjuvant chemotherapy within 6-12 months

A Phase 1 Trial of Intraperitoneal LSTA1 in Patients Undergoing CRS/HIPEC for Peritoneal Surface Malignancy (NCT06216561)

Status: Enrolling
Prospective phase I randomized trial comparing patients who undergo CRS/HIPEC alone or CRS/HIPEC + LSTA1, an investigational drug designed to improve the delivery of chemotherapy
Inclusion criteria: non-mucinous colorectal cancer with peritoneal metastases who are eligible to undergo CRS/HIPEC

Adjuvant Pressurized Intraperitoneal Aerosol Chemotherapy to Prevent Colorectal Peritoneal Metastases (ProphyPIPAC) (NCT06091683)

Status: Enrolling
Single arm clinical trial aimed to assess the feasibility and safety of PIPAC for the prevention of peritoneal metastases after curative surgery for high-risk colorectal cancer
Inclusion criteria: diagnosis of high-risk colorectal cancer patients who previously underwent curative surgery with complete resection and are willing to start adjuvant systemic chemotherapy and postoperative follow up

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Quiénes somos

What is Uterine Sarcoma?

The Basics

Risk Factors

Signs & Symptoms

Evaluation

Key Facts

Diagnosis and Prognosis

Facing cancer is hard. But you are not alone - we’re right here with you.

Patient and Caregiver Network

Stories of hope

References

Unir a nuestra lista de correos. Oír todo lo relacionado con PFCCAP durante todo el año.

Facing cancer is hard.
But you are not alone - we’re right here with you.

Unir a nuestra lista de correos.
Oír todo lo relacionado con PFCCAP durante todo el año.