In this article, we have compiled detailed notes on endometrial cancer, and we hope you will criticize and correct us.
Overview
1. Endometrial cancer, also known as uterine body cancer, mostly occurs in postmenopausal women and accounts for 20%-30% of gynecologic malignancies in China, second only to cervical cancer.
2. The causes of endometrial cancer are unknown, but the risk factors for its development include
(1) long-term estrogen stimulation.
(2) obesity, hypertension, diabetes mellitus (endometrial cancer syndrome)
(3) early menarche, late menopause, infertility and menstrual disorders
(4) Genetic factors.
(5) Long-term use of tamoxifen.
The main pathological type of endometrial cancer is adenocarcinoma, among which endometrioid adenocarcinoma is the most common (60%~65%), also known as type I endometrial cancer.
4. Endometrial cancer symptoms: (1) vaginal bleeding: a. postmenopausal vaginal bleeding (main symptom); b. perimenopausal menstrual disorder or irregular menstruation; c. usually non-contact bleeding; (2) abnormal vaginal discharge; (3) lower abdominal pain and other symptoms.
Diagnosis and treatment of endometrial cancer
1. Endometrial histological examination is the basis for the confirmation of endometrial cancer diagnosis and oncological grading. CA125 may be elevated in endometrial cancer patients, which has certain reference value for diagnosis and postoperative disease monitoring.
2. The FIGO 2009 surgical pathological staging is used as the standard for endometrial cancer, but only for cases treated with initial surgery. For cases inoperable with radiotherapy or preoperative radiotherapy, the 1971 clinical staging is still used.
3. The prognostic high-risk factors of endometrial cancer include: (1) G3 grade tumor (poorly differentiated); (2) myometrial infiltration >50%; (3) lymphovascular interstitial infiltration; (4) non-endometrioid cancer tissue type (plasmacytosis, clear cell, undifferentiated, small cell, interstitial, etc.); (5) cervical interstitial infiltration.
4. Stage I patients with or without resected lymph nodes, low-risk patients (stage I, G1 or G2, no myxomatous infiltration or infiltration of superficial myxomatous layer) and patients with only one high-risk factor do not need adjuvant radiotherapy.
5. Stage I intermediate-risk patients (at least 2 high-risk factors: age >60 years, deep myxoid infiltration, G3, plasmacytoid or clear cell carcinoma, lymphovascular interstitial infiltration) have an advantage over EBRT with vaginal brachytherapy alone.
6. There is no definite conclusion on adjuvant chemotherapy with or without EBRT for stage I high-risk patients (with 3 or more high-risk factors), stage II or stage III patients.
7. Routine postoperative addition of progestin therapy in stage I patients has no significant effect on improving survival.
8. For stage I endometrial cancer patients, lymph node dissection has no effect on their overall survival and recurrence-free survival.
9. In patients with stage I endometrial cancer, postoperative adjuvant radiotherapy can reduce pelvic recurrence regardless of the presence of low-, intermediate- or high-risk factors, but does not affect the survival rate.
10. Vaginal brachytherapy is effective in reducing vaginal recurrence in patients with high-risk factors.
Table 1 Postoperative management of patients with stage I endometrioid adenocarcinoma
11. Radical hysterectomy with bilateral pelvic lymphadenectomy and selective para-aortic lymph node dissection is recommended for stage II patients with significant cervical infiltration (lack of evidence to support this).
There are no randomized controlled studies of postoperative adjuvant radiotherapy in stage II patients.
Table 2 Postoperative management of patients with stage II endometrioid adenocarcinoma
Most of the stage III patients can be treated surgically with complete resection of all metastatic lesions and postoperative external pelvic irradiation and/or chemotherapy.
The GOG-184 trial included patients with stage III and residual lesions larger than 2 cm with endometrial cancer and was designed to evaluate the efficacy of postoperative total pelvic radiotherapy followed by 6×AP (adriamycin + cisplatin) or 6×TAP (paclitaxel + adriamycin + cisplatin). The results showed that the three-drug combination regimen did not improve PFS but increased toxicity (there was a difference in PFS between the GOG-184 trial and the GOG-177 trial, which requires further analysis).
Stage III patients with inoperable vaginal or parametrial infiltrative involvement are best treated with external pelvic radiation as initial therapy.
Table 3 Postoperative management of patients with stage III endometrioid adenocarcinoma
Stage IV patients with predominantly abdominal dissemination may benefit from ablative surgery to achieve no residual lesions, and patients with evidence of extra-abdominal metastases are usually treated with platinum-based systemic chemotherapy, or hormonal therapy if they are G1 and/or estrogen receptor positive.
17. The GOG-177 trial comparing the efficacy of 8×TAP (paclitaxel + adriamycin + cisplatin) and 8×AP (adriamycin + cisplatin) showed that the TAP regimen significantly improved RR, PFS and median OS, but required routine application of G-CSF on day 4 of chemotherapy because the TAP regimen was too toxic (treatment-related death occurred despite the use of growth factors).
18. The GOG-0209 trial was designed to evaluate the efficacy of TC regimen (carboplatin + paclitaxel) and TAP regimen (paclitaxel + adriamycin + cisplatin), and the results showed that TC was non-inferior to TAP and had lower side effects, and TC chemotherapy regimen has become the standard adjuvant chemotherapy regimen for stage III/IV endometrial cancer.
19. Tumors larger than 1 mm3 in size must rely on the generation of new blood vessels, and studies have found that VEGF overexpression is associated with poor prognosis in most gynecologic malignancies, including endometrial cancer.
20. The current use of bevacizumab for endometrial cancer is all in phase II clinical studies.
(1) Bevacizumab monotherapy in recurrent or persistent endometrial cancer showed that 13.5% achieved clinical remission and 40.4% had stable disease for 6 months;
(2) Bevacizumab + TC (paclitaxel and carboplatin) regimen for advanced or recurrent endometrial cancer with measurable lesions showed no disease progression at 6 months in 14 out of 15 patients.
21. Intracavitary brachytherapy can achieve a cure rate of more than 70% in patients who cannot undergo surgery; it can be combined with external pelvic irradiation in the presence of high-risk factors such as lymph node involvement. Radiotherapy can better control stage I and II endometrial cancer and reduce the recurrence rate.
22. Endometrial cancer under 35 years of age is rare, and G1 endometrial cancer can be easily confused with severe endometrial atypical hyperplasia, so women of childbearing age should be cautious in diagnosing endometrial cancer.
For patients with stage III and residual abdominal lesions less than 2 cm in diameter, chemotherapy is preferable to total pelvic radiotherapy.
24. Preservation of reproductive function is only applicable to endometrioid adenocarcinoma, provided that
(1) Pathological type of endometrioid adenocarcinoma, grade G1, in the segmental scraping specimen.
(2) MRI examination (preferred) or transvaginal ultrasonography reveals a lesion confined to the endometrium.
(3) No suspicious metastatic lesions on imaging.
(4) No contraindications to drug therapy or pregnancy.
(5) Adequate consultation to understand that preservation of reproductive function is not the standard of care for endometrial cancer and that patients need to consult with a fertility specialist prior to treatment.
(6) Genetic counseling or genetic testing for appropriate patients.
(7) The options of megestrol, medroxyprogesterone acetate and levonorgestrel intrauterine delayed release system.
(8) Perform endometrial scraping or endometrial biopsy every 3-6 months during treatment. If endometrial cancer persists for 6-9 months, perform total hysterectomy + bilateral adnexal resection + surgical staging; if the lesion is in complete remission after 6 months, encourage the patient to conceive, and continue endometrial sampling every 3-6 months before conception.
(9) Total hysterectomy + bilateral adnexal resection after completion of childbirth or if endometrial sampling reveals disease progression.
(10) All nine conditions must be met in order to preserve reproductive function.
25. Patients with endometrial cancer are followed up every 3-6 months for the first 2-3 years and every 6-12 months thereafter; for stage I patients, asymptomatic vaginal recurrence is only 2.6%, and the 2016 edition of the NCCN guidelines no longer recommend vaginal cytology for postoperative asymptomatic patients.
26. The postoperative recurrence rate in stage I and II patients is approximately 15%, with 50% to 70% of recurrences being symptomatic, and isolated vaginal recurrences have a 5-year survival rate of 50% to 70% after radiotherapy. The prognosis for recurrence beyond the vagina or pelvic lymph nodes is poor.
27. Systemic therapy includes hormonal therapy and chemotherapy, mainly for patients with recurrence, metastasis or high risk. Hormonal therapy includes megestrol/tamoxifen (both can be used alternately), progestins, aromatase inhibitors, tamoxifen, etc. It is only suitable for well differentiated, ER/PR positive endometrioid adenocarcinoma.