ESGO || Clinical advice for patients with endometrial cancer to retain reproductive function

Endometrial cancer is a common gynaecological tumor, and the incidence rate in developed countries is increasing year by year.
1 patients are mainly post-menoanthic women, with an average age of 61 years, of whom about 5 per cent are under 40 years of age.
1,2 many women who did not have children before menomosis were diagnosed with EC because modern women delayed the age of childbearing.
genetic predispositions (e.g. Lynch syndrome), obesity, polycystic ovary syndrome, and no ovulation cycle are all major causes of the body's high estrogen status.
As a result of irregular vaginal bleeding at an early stage, 90% of patients were found to be early highly differentiated endometrial-like adenocarcinoma (IFGO phased IA - confined to the endometrium or immersed in the shallow layer of the uterine muscle).
3EC's standard treatment is hysterectomy, double-sided uterine attachment removal, pelvic or abdominal aorta bypass lymph node cleaning, which can achieve a total survival rate of 93% (OS) and a 99% disease-related survival rate.
4 but for young women, standard therapy can make them infertile and greatly affect their quality of life.
So for this particular patient, there are more high-dose oral contraceptive treatments, such as methadone (MPA), methyl progesterone (MA), and there have been recent reports of treatment with L-18 methyllenoid ICDs.
most of the current studies are retrospective studies and are small sample studies with different treatment methods and inclusion criteria.
so it's not easy to draw the applicable conclusions out of it.
Gallos et al.'s 2012 research project is the largest systematic review of the current 7, which includes 34 raw data and includes 408 patients with conservative treatment EC.
2013, a large series of studies from South Korea included 148 EC patients treated conservatively.
10 and more and more evidence that this is rare, we need more information to help these patients get the best treatment.
Before performing conservative treatment on EC patients, the attending physician should consider two questions: first, evaluating the clinical pathological and biological behavior of the tumor, such as histological credit type, gradation, degree of muscle immersion, pulse immersion, and second, determining the best drug, dosage, treatment time, and follow-up plan.
this article will try to address the issues mentioned above and develop guidelines for the treatment of EC patients who retain the requirements for reproductive function.
although the data are relatively scarce and the level of evidence is not high, there will be more and more EC patients with fertility requirements.
this article will summarize clinical treatment recommendations to help with the clinical recommendations and treatment of such EC patients.
this paper summarizes the recommendations by reviewing the raw data of EC patient conservative treatment studies, including published system reviews and laboratory studies that are not included in the system review, and reaching consensus with the ESGO Working Group.
1. Patient inclusion criteria: Phase 1A, G1 endometrial cancer patients almost all clinicians believe that only those who require the retention of reproductive function of Phase 1A (not immersed in the uterine muscle layer) G1 EC patients, can retain reproductive function of the treatment.
also require patients to be effective in progesterone therapy and less likely to develop advanced diseases.
this means that patients with persistent lesions and/or recurrence can still under perform simple hysterectomy treatment, conservative treatment can not affect their good prognosis.
but unless a hysterectomy is under way, there is currently no diagnostic tool to accurately estimate EC-graded phases, so we need to advise patients with moderate tumour differentiation and beyond stage 1A.
, doctors need to exclude terminally ill patients and tumor-low-differentiated patients as much as possible before starting progesterone therapy.
study by GOG in the 1980s found that the most important prognostic factors affecting lymph node metastasis in EC patients were the classification of tumors and the depth of immersion at the grass-roots level.
less than 1% risk of lymph nodes in patients with G1 and no muscle immersion, pelvic and/or abdominal aorta.
clearly, patients who met both had good prognosis, with a five-year disease-free survival rate of up to 95%.
3, 11, 12 however, it is not easy to accurately diagnose grading and stages without hysterectomy.
2. Determining grading: The degree of differentiation of the approgated vs endometrial harvesting (pipelle biopsies) EC is the most important indicator for predicting disease grading and progesterone efficacy response.
Duska et al. reviewed EC patients under the age of 40 and found that only G1 EC patients were able to predict stage I of the disease.
, Thigpen et al. found that G1 EC patients responded 37 percent to MPA, compared with 9 percent of G3 EC patients.
endometrial biopsy is the basic test for EC diagnosis.
recently obtained endometrial tissue for histological diagnosis through uterine scraping and endometrial harvesting.
the results of the initial diagnosis obtained by the two methods in the study, compared with the final histological diagnosis of the patient's post-hysterectomy sample, the non-conformity rate between the two results could reach 20%.
compared with 15 methods, the accuracy of uterine surgery was higher than that of endometrial harvesting.
Lei Tao et al. 15 studies found that for G1 EC, only 8.7% of tumor grading results diagnosed by scraping were upgraded in the final diagnosis, while 17.4% of endometrial harvesting results were statistically different (P-0.007).
addition, it is more likely that the tumor will be completely removed, reducing the tumor load and improving the efficacy of progesterone therapy, but there are no prospective studies to prove it.
16 recommendation: It is recommended to use scraping for histological diagnosis.
3.I-type EC difficulties in histological diagnosis and graded diagnosis In Kaku et al. 17 studies, tissue samples from endometrial growth or EC patients were rediagnosed by three pathologists, only 19 of the 39 cases were initially diagnosed correctly, and the remaining 20 were either upgraded or demoted.
addition, in the Phase 2 study from Japan, 7 of the 47 cases had inconsistent pre- and post-histological diagnoses, of which 5 were reduced from G1 to atypical growth and 2 were upgraded from G1 to G2.
18 further demonstrates the difficulty of comparing and interpreting the findings of conservative treatment EC, especially since most existing studies do not provide a centralized pathological review of the initial diagnosis.
, many of the cases analyzed contained false EC (which later proved to be only atypical proplation), so there can be a high rate of clinical remission.
it is necessary to review the initial pathological diagnosis by a number of experienced histological pathologists to improve the accuracy of histological diagnosis.
recommends that all samples be diagnosed by two pathologists.
if there is only one pathologist, consider digital image transmission of microscopic photographs for remote consultation.
4. Judgement phase: Judging the degree of uterine muscle immersion according to imaging is the second important prognostic factor in patients with late EC.
3,19 patients with shallow muscle immersion, the total survival rate of 5 years was 80% to 90%.
when the tumor is immersed in the deep muscle layer, the total survival rate of 5 years is reduced to 60%.
20, it is necessary to determine the degree of muscle immersion for conservative treatment.
sensitivity and specificity of vaginal ultrasound (TVUS), CT scans and MRI scans have been reported.
20,21 most studies have found that enhanced MRI scanning is the most accurate way to diagnose myocardial immersion before surgery, and relevant meta-analysis has been proven.
22 meta-analysis from the same group found that if the MRI was negative, less than 1% later proved to be GI.
TVUS can also be used by experienced physicians to more accurately determine the degree of muscle immersion.
in a prospective study, TVUS could achieve the same effectiveness as MRI, and for areas where MRI examination is more difficult, TVUS could be used as an alternative to MRI in determining muscle layer immersion.
, however, there is no way to accurately determine the image method of muscle layer immersion.
for EC patients who require reproductive function to remain, a small percentage of them have some degree of muscle immersion, but are not detected using existing imaging tools.
For example, Kaku et al.'s study found that 12 patients who received conservative treatment were initially found to have no muscle immersion, however, two cases were not responded to progesterone therapy, and after hysterectomy, histology was eventually diagnosed with early muscle immersion.
2 cases were only 1 month apart from the final diagnosis.
prospective study of the same group found that 19 out of 45 patients under performed hysterectomy due to relapse or poor conservative treatment, 7 of which were diagnosed with early muscle immersion after hysterectomy.
18 suggests that strengthening MRI is the best way to determine the degree of muscle immersion.
5. The choice of therapeutic drugs, dosages, treatment time, and the role of follow-up MPA/MA and LNG-IUD on EC's conservative treatment has been described in the literature for many different drug treatments.
most applications MPA or MA.
also used to release hormones such as oxycodone, oxyprogesterone, lysol, tamoxifen, oral contraceptives and LNG-IUD.
few reported treatments for progesterone drugs with laparoscopic tumor excision and oral surgery.
, however, there has been no prospective study comparing the efficacy of the above options.
the MPA and MA data is contradictory.
a meta-analysis, the risk of relapse with other medications, including MPA, is higher than with MA.
9 In contrast, this meta-analysis does not include the largest studies to date that show that patients treated with MPA and MA have similar rates of complete remission, but that the former is significantly associated with a reduced risk of recurrence.
a small number of initial reports indicating that EC patients using LNG-IUD can achieve the same effect on remission rates as oral progesterone.
Similarly, a prospective observational study found that 14 EC patients who received conservative treatment, using only ioestrogen remission devices and GnRH similars, were able to achieve the same effect as MPA or MA, with a full remission rate of 57% and a recurrence rate of 25%.
these valuable results, KGOG is conducting a forward-looking multi-center trial (KGOG2009) to analyze the therapeutic value of IUDs (LNG-IUDs) plus oral progesterone.
: Both MPA and MA can be used.
the effects of LNG-IUD need more experimental evidence.
results are encouraging.
6. Although progesterone use has been the main method of conservative treatment for young EC patients, the optimal dose for treatment has not yet been determined.
in several studies, the dose of the drug varied, with MPA of 100 to 1200 mg/d and MA of 40 to 600 mg/d.
most of the studies were small samples and retrospective studies, and because of the non-homogeneity inherent in these studies, it was difficult to draw clear conclusions about the dosage.
a GOG study that treated late EC and relapsed EC, oral high-dose MPA therapy (200 vs. 1000mg) did not significantly benefit.
14, a small sample study of 21 cases of MA, Eftekhar et al. may prove that an increase in MA dose can benefit patients.
treatment with oral MA 160 mg/d for 3 months, with an initial response rate of 28% and a 56% increase in response rate after 6 months of dose double therapy.
but the increased response rate was due to a double dose of the drug or an increase in treatment time, which is not clear.
29 studies did not report significant toxic reactions to high-dose progesterone therapy.
, however, in a study from Japan, three patients had a level 3 toxic reaction - two weight gain and one liver dysfunction.
no studies have reported treatment-related thrombosis or death.
: Based on most studies, MPA 400 to 600mg/d, or MA 160 to 320mg/d is recommended.
7. The optimal treatment time for progesterone has not yet been decided.
in a review of 231 cases, 47 percent were treated for no more than six months, 17 percent for seven to nine months, 13 percent for more than nine months, and the remaining 23 percent had no data on treatment time.
6 retrospective queue study from Korea, the medium treatment time for progesterone was 8 months (range 2 to 31 months), and the medium treatment time for complete remission was 18 weeks (range 8 to 55 weeks).
10 A prospective study in Japan showed that progesterone was treated for 26 weeks, and only 6 (50%) of the 12 patients who were completely in remission were treated at 8 weeks, and 11 (91%) at 16 weeks of treatment.
18 Koskas et al. 9 studies, 72.4% of patients were relieved within 6 months, and the extension of treatment time was of little significance (78% of patients were relieved within 12 months).
the heterogeneity of treatment options in different studies, it is not easy to agree on treatment time.
, however, most studies agree that treatment should last at least six months.
: Progesterone may be remission for at least 6 months.
evidence of "late remission" occurring after more than 6 months of treatment.
8. Follow-up during and after treatment is defined as no form of growth in the largest retrospective cohort studies and prospective cohort studies.
follow-up period for the 10,18 studies was two to six months.
, however, two studies showed that patients who did not progress in the first six months of treatment did not progress.
, an earlier follow-up is not necessary.
present, there is no standard programme for follow-up.
in order to prove complete remission, a uterus is necessary