Stage IV uterine cancer involves the bladder, bowel or distant locations in the body. Stage IVA cancer has invaded the bladder and/or bowel and IVB disease has spread to distant locations in the body.
Optimal treatment of patients with stage IV uterine cancer often requires more than one therapeutic approach. Thus, it is important for patients to be treated at a medical center that can offer multi-modality treatment involving gynecologic oncologists and radiation oncologists. For early stage uterine cancers, all visible cancer can be removed during surgery. Unfortunately, the removal of all cancer cannot typically be achieved in patients with stage IV disease. Treatment of stage IV uterine cancer is dictated by the site of metastatic cancer and symptoms related to the spread of cancer. The goal of treatment for women with stage IV uterine cancer is to reduce symptoms and prolong survival.
Uterine Cancer Mutations Targeted by Precision Cancer Medicines
Genetic Mutations: Not all uterine cancer cells are alike. They may differ from one another based on what genes have mutations. Molecular testing should be performed to test for genetic mutations or the proteins they produce on ALL patients. By testing an individual’s uterine cancer for specific unique genomic- biomarkers doctors can offer a personalized treatment approach utilizing precision medicines. Uterine cancer mutations are being identified and new precision cancer medicines are being developed to target these mutations on an ongoing basis.
Precision Cancer Medicine Treatment
Individuals with the following biomarkers may have their uterine cancer treated differently using targeted precision cancer medicines.
Microsatellite Instability High (MSI-H): MSI-H is a DNA abnormality found in about 20% of uterine cancers. It is most often found in tumors associated with genetic syndromes like Lynch syndrome but can also occur sporadically. MSI-High uterine cancer can be more effectively treated with the precision cancer immunotherapy drugs called “checkpoint inhibitors.” Keytruda, and Opdivo have both been demonstrated to improve treatment of individuals with MSI-High disease.
“Debulking” Surgery for Inoperable Uterine Cancer
When the cancer cannot be completely removed, an appropriate question to ask is whether surgical removal of as much cancer as possible is beneficial. This is referred to as a “debulking surgery,” and is often performed so that radiation therapy and/or chemotherapy will have fewer cancer cells to kill. This, however, is major surgery and has many potential complications. The value of debulking surgery has not been clearly demonstrated in controlled clinical studies; however, researchers have evaluated the outcomes of women with advanced uterine cancer who underwent debulking surgery. Patients with less than 2 centimeters of cancer remaining after debulking surgery were compared to patients who had more than 2 centimeters of cancer remaining after debulking surgery and to patients who did not undergo debulking surgery. The average survival for optimal surgical debulking was 32 months, compared to 12 and 13 months for women with inadequate or no debulking. Thus, there may be a role for surgically removing as much cancer as possible in women with widespread uterine cancer.
For bulky pelvic disease, radiation therapy consisting of a combination of brachytherapy (intracavitary placement of a radioactive isotope) and external-beam radiation therapy is frequently used. Radiation therapy can decrease symptoms and improve survival for patients with inoperable uterine cancer.
Primary Hormone Therapy
Cancers that have estrogen or progesterone receptors (small proteins on the surface of the cells) can be treated with hormonal therapy, which can delay cancer progression and prolong survival, especially in patients with small amounts of cancer not involving the lung or liver. Estrogen and progesterone are female hormones produced mainly by the ovaries and are found circulating in the blood. Many organs in the body are composed of cells that respond to or are regulated by exposure to these hormones. Cells in the breast, uterus and other female organs have estrogen and progesterone receptors and when exposed to these hormones, are stimulated to grow. When cells that have these receptors become cancerous, the growth of these cancer cells can be increased by exposure to the female hormones.
The basis of hormonal therapy as a treatment for uterine cancer is to block or prevent the cancer cells from being exposed to estrogen and progesterone hormones. Removal of the ovaries, the organ chiefly responsible for producing these hormones, is one effective approach to eliminating hormone production and is commonly used in many countries. Another approach is to utilize drugs that can accomplish a similar effect without removing the ovaries.
Progestational agents have long been used in the treatment of advanced or recurrent uterine cancer because of the presence of receptors for these agents on the cancer cells. Well-differentiated cancers respond better to progestational agents than undifferentiated cancers. Progestational agents that have been used include hydroxyprogesterone, medroxyprogesterone and megestrol. These agents produce a partial or complete disappearance of cancer in 20-29% of women with advanced or recurrent uterine cancer. The combination of a progestional agent (megestrol) and Nolvadex® (an anti-estrogen) may be better treatment than megestrol alone.
Chemotherapy is the use of chemicals (drugs or medications) to kill cancer cells. Numerous chemicals have been developed for this purpose and most act to injure the DNA of cells. When the DNA is injured, the cells cannot grow or survive. Successful chemotherapy depends on the cancer cells being at least somewhat more sensitive to the chemicals than the normal cells. Because the cells of the bone marrow, the intestinal tract, the skin and hair follicles are also very sensitive to these chemicals, injury to these organs are common side effects of chemotherapy (i.e., mouth sores, diarrhea, rashes and hair loss). Several chemotherapy medications used alone or in combination can effectively induce remissions in ~ 30% to 70% of women with recurrent uterine cancer.
Chemotherapy and Hormonal Therapy
Chemotherapy and hormonal therapy prevent cancer cells from growing by different methods. Combining chemotherapy with hormonal therapy may reduce cancer cell growth more than either treatment administered alone. Researchers in Greece have evaluated a four-drug combination of Paraplatin®, methotrexate, fluorouracil and medroxyprogesterone. These physicians treated 23 patients with advanced or recurrent uterine cancer. None of the patients had received prior chemotherapy or hormonal therapy and 10 had received prior radiation therapy. Responses were observed in 74% of women, with two long-lasting complete remissions. The average duration of response was over 10 months and the average survival was over 16 months. This regimen was administered on an outpatient basis and was well tolerated. These doctors concluded that this was an active treatment regimen for women with advanced or recurrent uterine cancer.
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