Endometrial cancer is a common gynecologic tumor, which is easy to be diagnosed early and treated mainly by surgery with a better prognosis. However, there are some controversial issues in the treatment of endometrial cancer in clinical practice. For example, the scope of hysterectomy, the necessity of retroperitoneal lymph node dissection, the indications and clinical significance of endocrine therapy, and the issue of preserving the uterus or ovaries in endometrial cancer patients should be brought to the attention of obstetricians and gynecologists, especially gynecologic oncologists.
I. Scope of hysterectomy for endometrial cancer
When endometrial cancer patients have their uterus surgically removed, should it be total hysterectomy or extra-fascia or extensive hysterectomy? According to domestic textbooks, extra-fascia hysterectomy should be performed for stage I endometrial cancer, and for stage II endometrial cancer, extensive hysterectomy is recommended, which has been the accepted standard in China for many years.
However, the guidelines of the National Cancer Institute of Health (NCI) for diagnosis and treatment of endometrial cancer in stage I suggest that total hysterectomy + bilateral adnexal resection as well as selective pelvic lymph node and para-aortic lymph node dissection with hysterectomy is feasible for stage I endometrial cancer. At present, there is no unified surgical scope and standardized surgical steps about extra-fascial hysterectomy at home and abroad, which is difficult to implement in clinical practice. Regarding stage II endometrial cancer, NCI in the United States deals with stage II endometrial cancer, the tumor invades into the interstitial cervical canal, and total hysterectomy with both adnexa + biopsy of retroperitoneal lymph nodes can be performed to assist postoperative radiotherapy; extensive hysterectomy + retroperitoneal lymph node dissection is also feasible.
Let us analyze that in clinical work endometrial cancer, even for those with cervical mesenchymal invasion, paracervical metastasis rarely occurs, and the incidence of metastasis to the main ligament, sacral ligament or vagina is also very low. Since the metastatic route of endometrial cancer is rarely paracervical or vaginal, there is no need to remove too much paracervical tissue and vagina. The main routes of endometrial cancer metastasis are pelvic lymph nodes and para-aortic lymph nodes, but not paracervical and vaginal. Therefore, extensive hysterectomy for stage II endometrial cancer deserves careful consideration.
According to relevant literature, it is suggested that the scope of hysterectomy for stage I endometrial cancer can be total hysterectomy or extra-fascia hysterectomy, but standardized extra-fascia hysterectomy should be performed to avoid damaging the ureter. Regarding stage II endometrial cancer, it is recommended that the extent of hysterectomy should be subextensive hysterectomy, and there is no need to remove too much parametrial tissue.
II. Necessity of removing pelvic lymph nodes and para-aortic lymph nodes in patients with early-stage endometrial cancer
It has been long debated whether pelvic and retroperitoneal lymph nodes must be removed for endometrial cancer. There is a view that early endometrial cancer that is moderately to highly differentiated, invades <1/2 of the muscle and has few lymph node metastases. And it is found that lymph node dissection does not improve the five-year survival rate; therefore, it is considered unnecessary to remove lymph nodes in stage endometrial cancer. However, there is another view that pelvic lymph node dissection can reduce the recurrence of endometrial cancer in the pelvis, and that lymph node dissection can clarify the stage and formulate post-surgical adjuvant treatment plan, thus helping to improve the prognosis, so lymph node dissection is advocated. So, should we remove pelvic and para-aortic lymph nodes in clinical practice?
A recent Italian study reported 514 patients with preoperative stage I endometrial cancer over a 10-year period from 1996 to 2006, with 264 pelvic lymph node resections and 250 lymph node resections not performed in a randomized group. The results showed that the 5-year disease-free survival rates were 81.7% and 81% in patients who did not undergo lymph node dissection and those who underwent lymph node dissection, and the overall survival rates were 90% and 85.9%, respectively. There were 34 (12.9%) recurrences in the lymph node dissection group F with a mean time to recurrence of 14 months, compared with 33 (13.2%) recurrences without lymph node dissection with a mean time to recurrence of 13 months, and the sites of recurrence were almost identical in both groups. Also comparing the operative time and hospital stay, the operative time and hospital stay were longer for lymph node dissection. The study concluded that there is no evidence of benefit of pelvic lymph node dissection in early-stage women with endometrial cancer, either in terms of overall survival or recurrence-free survival, and that pelvic lymph node dissection cannot be recommended for routine treatment of patients with early-stage endometrial cancer for curative purposes, except for use in clinical trials.
The results of this study should have a very significant impact on the treatment of endometrial cancer and should be considered as such. Although lymph node dissection has no therapeutic benefit, that is, it has no therapeutic benefit, lymph node dissection has a predictive value in that it can more accurately identify the extent of metastases and the stage of the disease, and help in disease assessment and determination of prognosis.
Is it safe to assume that lymph node dissection is not necessary for early stage endometrial cancer? In fact, there is still a high rate of lymph node metastasis for patients with combined high-risk factors for lymph node metastasis. In the literature, the rate of lymph node metastasis increases to 10-15% if the lesion is larger than 2 cm, and 30% if the lesion is present in both uterine cavities. In addition, the degree of tumor differentiation and the depth of myometrial invasion are also closely related to lymph node metastasis. Therefore, it is recommended that retroperitoneal lymph node dissection be advocated in the presence of any of the following.
1. preoperative or intraoperative assessment of deep myxomatous invasion.
2, the tumor is hypofractionated.
3, clinical stage II and above.
4, suspicious metastasis of lymph nodes probed during surgery or biopsy taken to confirm the presence of lymph node metastasis; adnexal invasion.
5.Special types (plasma breast cancer and clear cell carcinoma, migratory cell carcinoma).
III. Necessity and clinical significance of endocrine therapy for endometrial cancer
In breast cancer, endocrine therapy plays a very important role, while endometrial cancer is also a hormone-related tumor, and the significance of endocrine therapy has not been confirmed. There is no uniform opinion at home and abroad on the indications for endocrine therapy for endometrial cancer. It is generally believed that endocrine therapy can be performed for patients with advanced inoperable, recurrent and metastatic endometrial cancer.
What are the drugs available for endocrine therapy of endometrial cancer? At present, the drugs commonly used in clinical practice include medroxyprogesterone, megestrol and progesterone caproate. There is also the estrogen receptor antagonist triamcinolone, which is mainly used for patients with negative progesterone receptors. In principle, the dose of progestin should not be less than 200 mg. It has been reported that the effect of progestin is the same for both 1000 mg and 200 mg. Regarding the duration of medication, more than one year is recommended. Do I need to use it for such a long time? As we all know that triamcinolone acetonide for breast cancer is five years, which indicates that endocrine treatment of tumors requires a long lasting effect. There is a research basis for the application of endocrine therapy for endometrial cancer for more than one year. In China, Wang Zhiqi et al. found that endocrine therapy was given to 178 cases of endometrial cancer, applying 250mg/d of medroxyprogesterone. 11 cases of recurrence (13.4%) were found in the treatment group, while 21 cases (24.6%) were found in the control group, but there was no statistically significant difference. Deaths due to cancer were 10 in the endocrine treatment group and 18 in the control group, and there was also no statistically significant difference in the statistical treatment. When the time of treatment was grouped again, if the time of treatment was within one year, recurrent metastasis was 7 cases, and if the time of treatment was more than one year, recurrent metastasis was 4 cases, and the control group that was without endocrine treatment was 21 cases, and the statistical results showed that recurrent metastasis was significantly lower in those who were treated for more than one year (P=0.02).
Whether all patients can apply endocrine therapy, because high-dose progestin therapy has certain adverse effects, therefore endocrine therapy is prohibited or used with caution in the following cases.
1, hepatic and renal insufficiency: why endocrine therapy for hepatic and renal insufficiency cannot be used? Hormonal drug therapy makes the liver metabolize and the kidneys excrete, and hepatic and renal insufficiency are prohibited.
2, severe cardiac insufficiency.
3, a history of thrombosis: hormonal drugs are likely to cause thrombosis, after a heart attack, cerebral infarction, etc. can not be used.
4, people with unstable diabetes.
5.Persons with mental depression.
6, those who are sensitive to progestin-like drugs.
The above 6 conditions are best not to undergo endocrine therapy.
What are the side effects of endocrine therapy? American GOG study: thrombophlebitis 5%, pulmonary embolism 1%. Mild fluid retention, reaction of the digestive tract and mental depression are common. Domestic studies have found that the main side effects of endocrine therapy for endometrial cancer are liver damage and weight gain, and less frequently thromboembolic disease and other side effects.
In conclusion, for endometrial patients without contraindications, it is recommended to apply high-dose progestin therapy for more than 12 months, which can improve appetite, improve quality of life, reduce recurrence and increase disease-free survival.
IV. Whether endometrial cancer patients can retain their reproductive function or retain their ovaries
The incidence of endometrial cancer is trending younger, and for young patients, it is strongly requested whether it is possible to preserve reproductive function. It is generally believed that the following 7 conditions must be met.
1, young <40 years old with no other fertility problems
2, Stage IA G1.
3, negative abdominal irrigation fluid.
4, absence of lymph node metastases assessed before and during the procedure.
5, positive estrogen and progesterone receptors based on scraping pathology.
6, the tissue type is endometrioid adenocarcinoma.
7. the patient urgently requires it and has a good follow-up.
Preservation of reproductive function can be considered only when 7 conditions are met.
The effect of preserving reproductive function has been reported both at home and abroad. 6 cases of endometrial cancer under 40 years of age were reported in China to have progestin therapy with methoprene 160 mg/day for 3 months. 4 cases were evaluated to be effective and 2 cases were ineffective. 2 of the 4 effective cases recurred after 10 and 12 months of treatment, respectively, and the other 2 cases were not pregnant at the time of the article. Another article reported 8 cases of endometrial cancer and 17 cases of severe SARS treated conservatively. 7 of the 8 cases of endometrial cancer were evaluable, 6 were effective, 1 case recurred 30 months after treatment, and none of the patients with endometrial cancer conceived. 17 cases of severe SARS treated endocrinologically were effective, 3 cases recurred, and the time of recurrence was 6, 11, and 16 months. 4 cases became pregnant, 3 delivered at full term, 1 miscarried, and 3 had normal postpartum follow-up. It indicates that it is less likely for conservative treatment of endometrial cancer to eventually achieve conception, while it is possible for severe SARS to achieve conception. Therefore, for patients with severe SARS, preservation of fertility can be considered, while caution must be exercised for endometrial cancer.
Finally, regarding the treatment of endometrial cancer, there are corresponding diagnosis and treatment guidelines both at home and abroad, and clinical diagnosis and treatment should be carefully standardized. However, it should be thought that endometrial cancer treatment is not without problems, and in clinical work, we should be good at observation, good at thinking, and diligent at research to truly individualize treatment.