The treatment of endometrial cancer has fundamentally changed over the past decade with the introduction of new staging systems and surgical and adjuvant modalities. Surgery is the mainstay of treatment, but its effectiveness and the extent of lymph node dissection have changed, with two randomized controlled trials demonstrating no survival benefit from lymph node dissection. The role of radiotherapy has changed, and chemotherapy, either alone or in combination with radiotherapy, has been increasingly used to treat extra-pelvic and lower abdominal tumor lesions. Novel agents and targeted therapeutic agents are being developed. Research on genetic susceptibility and potential mutations in endometrial cancer may lead to a change in treatment modalities.
Endometrial cancer is the leading cause of morbidity and mortality in women worldwide, with close to 200,000 new cases each year. It is the seventh most common malignancy in the world, with incidence rates varying by region, and it is the most common female reproductive system tumor, second only to breast, lung, and colorectal tumors in North America and Europe.
The vast majority of patients with endometrial cancer are diagnosed at an early stage when it is confined to the uterine body, as it is often associated with vaginal bleeding. Overall, the prognosis of endometrial cancer is good, but it is not good for specific pathological types such as high stage, deep invasion, and clear cell carcinoma. The main factors of prognosis are age, race, stage, grade, depth of invasion, tumor size, receptor status and cell type.
Endometrial cancer is most common in postmenopausal women, and the most important risk factor is elevated endogenous estrogen, with obesity being another important factor, in addition to the use of tamoxifen being associated. Family members with transmissible nonpolyposis colorectal cancer (HNPCC) also known as Lynch syndrome are prone to endometrial cancer at a young age, mainly due to genetic mutations in DNA mismatch repair proteins (MLH1,PMS2,MSH2,MSH6). This review focuses on type I endometrial cancer in which proliferative changes occur in the endometrium under the long-term effect of estrogen without progesterone antagonism, eventually leading to carcinogenesis.
Pathological factors and staging
Whether lymph node dissemination is an important factor in the prognosis of patients with endometrial cancer, and a series of studies have demonstrated that surgical pathological staging for tumor staging, depth of invasion, whether lymphatic vessels are infiltrated, and whether cervical invasion and lymph node metastasis are closely related to survival rates.
Surgical treatment
Surgical treatment of endometrial cancer is controversial because of the necessity and extent of lymph node dissection and the need to preserve the ovaries in patients with endometrial cancer. Because many patients with endometrial cancer are older and have more comorbidities, treatment must be tailored to the individual patient.
Although the most common mode of dissemination of endometrial cancer is through lymphatic dissemination, the role of lymph node dissection in patients with early-stage endometrial cancer has been controversial, with some gynecologic oncologists recommending selective lymph node dissection, primarily for high-risk patients (patients with high stage and deep invasion), and others recommending routine lymph node dissection. The main reason for the difficulty of using elective lymph node dissection in clinical practice is that it is often difficult to determine the depth of invasion and the stage of the tumor. However, there is no doubt that lymph node dissection provides important information for postoperative adjuvant therapy.
Several studies have confirmed the potential therapeutic role of lymph node dissection and its impact on survival, but the extent of lymph node dissection is controversial. Fotopoulou and his colleagues illustrated the high incidence of metastasis in the para-aortic lymph nodes and even above. Two randomized controlled trials demonstrated that lymph node dissection did not result in a survival benefit.
Bilateral hysterectomy is the main treatment modality for endometrial cancer and has demonstrated its feasibility over the past decade through laparoscopic and robotic procedures.
Although the vast majority of patients with endometrial cancer are postmenopausal, 20% of patients still occur in premenopausal women and it has been shown that fertility can be preserved with the right treatment options for endometrial cancer.
Adjuvant therapy for low to intermediate risk endometrial cancer
Low to intermediate risk endometrial cancer is the most controversial of the gynecologic tumor treatments. G1 and G2 tumors confined to the endometrium have a better prognosis and are considered low risk. Their 10-year recurrence rate was found to be only 3% in a retrospective study, and given their good prognosis, adjuvant therapy is usually not required.
In the intermediate-risk group there is no evidence of any survival benefit from adjuvant therapy, and radiotherapy was the most commonly used treatment, although two studies demonstrated the effectiveness of either chemotherapy alone or combined radiotherapy in the intermediate-risk group. Radiotherapy reduced the risk of local pelvic recurrence, but did not improve survival in stages I and II.
The failure of pelvic radiotherapy to improve survival may be partly explained by the fact that the majority of recurrences were in the vaginal stump, but nonetheless, this result needs to be interpreted with caution because a significant proportion of the patients included in the study were at low risk. Given this limitation, the investigators sought to clarify the benefit of radiotherapy for endometrial cancer by subgroup analysis, and the final study demonstrated that radiotherapy improves survival in stage IC G3.
In the past, endometrial cancer has been thought to spread primarily through lymphatic dissemination, but clinicians often find that tumors confined to the body of the uterus still have the potential to metastasize distantly. One study found that nearly one-third of patients with highly differentiated, deeply invasive endometrial cancer who received pelvic radiotherapy developed distant metastases, and a growing number of trials are underway to investigate the role of chemotherapy in the intermediate-risk group of endometrial cancer patients.
Adjuvant therapy for advanced endometrial cancer
Chemotherapy is considered the primary treatment modality for III and IV endometrial cancers. A study comparing the efficacy of total abdominal radiotherapy and cisplatin adriamycin combined with chemotherapy demonstrated the benefits of chemotherapy. The five-year survival rate was 53% versus 42%, and in light of this, chemotherapy is increasingly being used in patients with advanced endometrial cancer.
Recurrent endometrial cancer
Patients with recurrent endometrial cancer are a mixed population and treatment must be individualized, with surgery, radiation, chemotherapy, and hormonal therapy all available for treatment.
Radiotherapy is a treatment modality for recurrence of vaginal stump after endometrial cancer surgery. Surgery or radiotherapy may be considered for recurrent pelvic mass type lesions.
Progestin and tamoxifen are the most commonly used hormonal treatment modalities for recurrent endometrial cancer, and studies have demonstrated that low-dose and high-dose treatments are similarly effective but do not have the same toxic response. AP chemotherapy regimens are considered to be the most effective treatment modality. Research has focused on paclitaxel analogs, and a series of studies have confirmed the effectiveness of paclitaxel plus platinum-based chemotherapy in the treatment of recurrent endometrial cancer.
Vascular regeneration and endothelial growth are considered key factors in the progression of endometrial cancer, and the efficacy of bevacizumab is yet to be confirmed by trial results.