Uterine cancer is a type of cancer that occurs in the endometrium, the inner lining of the uterus. The uterus is a hollow, pear-shaped pelvic organ where fetal development takes place. Uterine cancer is the sixth most common cancer among women and the fifteenth most common cancer in general.

In 2020, more than 417,000 new cases of uterine cancer were registered worldwide [1]. Most patients diagnosed with uterine cancer are post-menopausal, with an average age of 60 years at diagnosis.

Risk factors for uterine cancer include a history of breast or ovarian cancer. Other risk factors associated with uterine cancer include obesity, age over 50 years and factors that affect the balance of female hormone levels. Uterine cancer mainly occurs sporadically due to random mutations in genes throughout an individual's lifetime. However, approximately 5% of cases are due to the hereditary condition Lynch syndrome, also known as hereditary non-polyposis colorectal cancer. People with Lynch syndrome are at high risk of developing uterine cancer [2].

Uterine cancer is divided into different types based on the characteristics of tissue samples from the tumor. The majority of cases of uterine cancer have either endometrioid (70-80% of cases) or serous (10% of cases) characteristics. There are also other less common types of endometrial cancer, including clear cell carcinoma and carcinosarcoma (formerly known as malignant mixed Müllerian tumors (MMMTs)). Serous carcinoma, clear cell carcinoma and carcinosarcoma are considered high-risk tumors and generally show aggressive behavior and poor prognosis [4].

Furthermore, uterine cancer is categorized into four stages (1-4) depending on the extent of the disease. The stages describe where the cancer is located and whether it has spread to other parts of the body.

Stage 1: The cancer is found only in the uterus.

Stage 2: The tumor has spread outside the uterus but is still in the pelvis.

Stage 3: The cancer is in the abdominal cavity and possibly in nearby lymph nodes.

Stage 4: The cancer has spread to the rectum, bladder, lungs or bones [5].

Approximately 70% of patients are diagnosed with stage 1 uterine cancer due to obvious symptoms. In patients with tumors confined to the uterus, the 5-year survival rate is ≥ 95%, but this rate drops dramatically once the disease has spread outside the uterus, with survival rates of 69% in patients with regional metastasis and 17% in those with distant metastases [4]. Uterine cancer can also be divided into three different grades. The grades describe the extent to which the cancer cells resemble healthy cells under a microscope. If the cancer cells look like healthy tissue, it is called "well-differentiated" or a "low-grade tumor". When the cancer cells look very different from healthy tissue, the tumor is called "poorly differentiated" or a "high-grade tumor" [4, 6].

The treatment of uterine cancer can vary depending on the patient's general health, age, as well as the type, stage and grade of the disease. Surgery is the primary method of treatment for patients with uterine cancer at all stages, unless there are contraindications to performing it.

Standard surgery involves total hysterectomy, bilateral salpingo-oophorectomy and lymph node evaluation.

Total hysterectomy removes the uterus and cervix, while bilateral salpingo-oophorectomy removes the fallopian tubes and ovaries.

Patients with stage 1 cancer are recommended surgery only. However, some patients at this stage may be recommended radiation therapy after surgery to reduce the risk of cancer recurrence.

The choice of treatment after surgery depends on various factors such as age, cancer grade, how deeply the tumor has grown into the muscle layer of the uterus (if at all), and whether there are cancer cells in blood vessels or lymphatic vessels outside the tumor.

Vaginal brachytherapy and external beam radiation therapy are two common types of radiation therapy for the treatment of uterine cancer. In vaginal brachytherapy, a small applicator is inserted into the vagina that delivers radiation directly to the targeted area. External beam radiation therapy delivers carefully directed radiation from outside the body to the tumor site.

Most patients with stage 2 endometrioid cancer are recommended surgery followed by radiation therapy. Patients with stage 3 and 4 are mainly treated with a combination of surgery, radiation therapy and systemic therapy.

Systemic therapy is a treatment method that travels through the bloodstream and acts on the entire body. Either chemotherapy or hormone therapy can be used as systemic treatment for such patients. However, hormone therapy is only considered for patients with slow-growing tumors.

Uterine cancer can sometimes develop in young women of childbearing age. In such cases, surgery is still the recommended treatment. However, hormone therapy may be considered as an option if patients are low risk and choose fertility preservation after thorough counseling.

If the cancer recurs after the first treatment, the choice of treatment depends on the location of the tumor and previous treatment. Patients who experience a local recurrence of their cancer, i.e. in the vagina, pelvis and abdominal cavity, will receive radiation therapy if they have not received it in their first treatment. Patients with previous radiotherapy, on the other hand, are recommended to receive systemic therapy, either with or without radiotherapy. Radiation therapy in this context has no curative role, but is only used to relieve symptoms.

There is also a possibility of the cancer spreading to other parts of the body, which is called metastasis. Surgery of the tumor in metastatic areas, radiotherapy and systemic therapy are the recommended options. Furthermore, there are some new systemic treatment options, such as targeted therapy and immunotherapy (e.g. checkpoint inhibitors), for patients with uterine cancer who express certain biomarkers of recurrence or metastasis during chemotherapy [2, 5].