The NCCN Clinical Practice Guidelines in Oncology, a non-profit academic consortium of 21 of the world’s top cancer centers, develop guidelines that are the standard for clinical decision making in the field of oncology in the United States and are the most widely used guidelines in clinical practice in oncology worldwide. The following is a cursory interpretation of last year’s guidelines for endometrial cancer to enlighten the treatment of patients. Jiang Jie, Gynecologic Oncology, Qilu Hospital, Shandong University
1. Surgical treatment of endometrial cancer
Early stage patients are still recommended for full staging surgery, including extra-fascial hysterectomy + double adnexal resection + pelvic and para-aortic lymph node dissection. Postoperative treatment is chosen with or without adjuvant therapy depending on the stage and the presence of high-risk factors. While ascitic fluid cytology is no longer used as a basis for staging, it is inconclusive whether finding cancer cells in ascites and peritoneal washings implies a risk of recurrence. The new guidelines still require cytology of ascites and peritoneal rinses in all patients. Suspected or visualized cervical invasion requires cervical biopsy or MRI, if negative: treatment is the same as if the lesion was confined to the uterus, if positive extensive hysterectomy with bilateral adnexa + pelvic and para-aortic lymph node dissection, or optionally radiotherapy (75-80 Gy at point A) followed by extrafascial hysterectomy + bilateral adnexa + para-aortic lymph node dissection; patients who cannot tolerate surgery Patients who cannot tolerate surgery can be treated with tumor-targeted radiotherapy. Full staging surgery can be performed either open or laparoscopically. Para-aortic lymph node dissection is recommended to reach the renal vascular level.
Advanced patients should undergo tumor cytoreduction. Estimated lesion spread outside the uterus limited to the abdominal cavity (including positive ascites, greater omentum, lymph nodes, ovaries, peritoneal metastases) is feasible with extrafascial uterus + bilateral adnexa + abdominal cytology + mass excision ± pelvic and para-aortic lymph node dissection; lesions limited to the pelvic cavity (uterus, vagina, bladder, bowel/rectum/parametrium) may be preceded by external pelvic irradiation followed by surgery + vaginal brachytherapy ± chemotherapy Palliative hysterectomy + bilateral adnexal resection ± radiotherapy ± hormonal therapy ± chemotherapy may be chosen for lesions beyond the abdominal cavity or metastases to the liver. The new guidelines emphasize tumor cytoreductive surgery to reach lesions without measurable lesions when possible.
2. Adjuvant therapy after completion of staging surgery for endometrial cancer
High risk factors
G1
G2
G3
IA
None
Observation
Observation or vaginal brachytherapy
Observation or vaginal brachytherapy
Yes
Observation or vaginal brachytherapy
Observation or vaginal brachytherapy or pelvic radiotherapy
Observation or vaginal brachytherapy or pelvic radiotherapy
IB
No
Observation or vaginal brachytherapy
Observation or vaginal brachytherapy
Observation or vaginal brachytherapy or pelvic radiotherapy
Yes
Observation or vaginal brachytherapy or pelvic radiotherapy
Observation or vaginal brachytherapy or pelvic radiotherapy
Observation or vaginal brachytherapy or pelvic radiotherapy ± chemotherapy
Adjuvant therapy after surgical staging of stage I endometrial cancer: chemotherapy±radiotherapy is selected according to the presence or absence of high-risk factors.
High-risk factors include: 1) age > 60 years; 2) lymphovascular interstitial infiltration; 3) large tumor; 4) invasion of the lower uterine segment or cervical glands. Patients with one of these factors are considered high-risk.
Adjuvant therapy after full staging in stage II G1 patients includes external pelvic irradiation + vaginal brachytherapy; G2 external pelvic irradiation ± vaginal brachytherapy; G3 external pelvic irradiation + vaginal brachytherapy ± chemotherapy.
Adjuvant therapy after stage IIIA surgery staging includes radiotherapy ± chemotherapy, tumor-targeted radiotherapy ± chemotherapy and external pelvic irradiation ± vaginal brachytherapy.
IIIB, IIIC1, IIIC2 chemotherapy and/or tumor-targeted radiotherapy. adjuvant therapy after stage IV surgical staging includes chemotherapy and/or tumor-targeted radiotherapy. Chemotherapy ± radiotherapy in advanced patients with no naked eye residual lesions or microscopic abdominal lesions after tumor cytoreductive surgery. 3. Treatment after endometrioid adenocarcinoma without full surgical staging If the patient does not undergo full surgical staging, the general principle is that those with no postoperative myxoid infiltration and G1 to 2 grade (high to medium differentiation) can be observed. In other cases, re-staging surgery is recommended. The new guidelines state that for those with myxoid infiltration <50% and G1 to 2 grade, imaging first: negative: observation or complementary vaginal brachytherapy ± pelvic radiotherapy; positive: re-surgical staging followed by reference to adjuvant therapy after full surgical staging has been performed. Grade IA, G3 (hypofractionated), IB, Stage II: re-surgical staging followed by adjuvant therapy after full surgical staging has been performed. Or imaging first: negative: pelvic radiotherapy + vaginal brachytherapy ± abdominal para-aortic radiotherapy, including for G3, radiotherapy ± chemotherapy; positive: re-surgical staging, followed by adjuvant therapy with reference to the full surgical staging already performed. 4. Treatment of patients with recurrence The treatment plan for patients with recurrence depends on the site and extent of recurrence and previous treatment. If the recurrence is after surgery or vaginal brachytherapy and the lesion is confined to the vagina or regional lymph nodes, tumor-targeted radiotherapy ± vaginal brachytherapy ± chemotherapy may be used. If the recurrence is beyond the pelvis and the lesion is small, chemotherapy ± tumor-targeted radiotherapy may be used. For local recurrence after external pelvic irradiation therapy, surgery ± intraoperative radiotherapy or hormonal therapy or chemotherapy is recommended, and for isolated distant recurrence, surgical resection ± targeted radiotherapy is recommended. Patients with disseminated lesions (extensive metastases) are asymptomatic or G1: hormonal therapy, with chemotherapy if the patient continues to progress despite hormones, and supportive therapy or clinical trials for further progression after chemotherapy; symptomatic or grade G2-3 or giant lesions: chemotherapy and/or palliative radiotherapy. Re-progression then supportive therapy or clinical trial. 5. Treatment of special types of endometrial cancer.
Special pathological types mainly include plasmacytoid papillary adenocarcinoma, clear cell carcinoma, and carcinosarcoma. The surgical staging for early-stage patients is the same as that for ovarian cancer: including extrafascial hysterectomy + bilateral adnexa, pelvic and para-aortic lymph node dissection, abdominal cytology, greater omentum resection, and peritoneal surface biopsy (including subdiaphragm); tumor cytoreductive surgery is performed in advanced stages. Postoperative stage IA without myofibrotic infiltration: observation or chemotherapy or tumor-targeted radiotherapy; stage IA with myofibrotic infiltration, stage IB, stage II and stage III and IV after satisfactory reduction: chemotherapy ± tumor-targeted radiotherapy or total pelvic abdominal radiotherapy ± vaginal brachytherapy. Stage III and IV after unsatisfactory reduction: chemotherapy. 6. systemic therapy for patients with recurrence, metastasis or high risk Patients with endometrioid carcinoma may choose hormonal therapy: aromatase inhibitors, progesterone analogs, tamoxifen, etc. Other types of endometrial carcinoma are given supportive therapy or clinical trials.
7. Follow-up Follow-up is emphasized for at least 3 years, recommended every 3-6 months for 2 years and every 6 months or 1 year thereafter]. Follow-up visits include detailed consultation, physical examination, vaginal cytology and chest X-ray, and imaging such as CT or MRI and CA125 test if necessary.
New guidelines for chemotherapy regimens recommend multi-drug combination regimens, mainly including cisplatin + adriamycin, cisplatin + adriamycin + paclitaxel, carboplatin + paclitaxel, repeated every 3 weeks for 4 to 6 courses. Liposomal adriamycin may also be recommended.