Endometrial Cancer Xử trí

Đánh giá

The staging of endometrial cancer is based on imaging studies, histological results, and surgery. These determine the extent of cancer upon diagnosis. This is an important factor in the choice of treatment and can also predict prognosis.

American Joint Committee on Cancer (AJCC) TNM and International Federation of Gynecology and Obstetrics (FIGO) Surgical Staging Systems for Endometrial Cancer

The staging systems for endometrial cancer were developed in 2023 by the International Federation of Gynecology and Obstetrics (FIGO) and the American Joint Committee on Cancer (AJCC).

¹No longer included in FIGO staging
²Endocervical glandular involvement only to be considered as Stage I
³IIIC1: Pelvic nodes positive for metastasis; IIIC2: Para-aortic nodes positive for metastasis with or without pelvic LN involvement
⁴Suffix (sn) added in metastasis identified only by sentinel LN biopsy  

Histologic Grade

• GX: Grade cannot be assessed
• G1: Well differentiated
• G2: Moderately differentiated
• G3: Poorly differentiated or undifferentiated

International Federation of Gynecology and Obstetrics (FIGO) Endometrial Cancer Stage based on Molecular Classification

• Stage IAm_POLEmut: POLE mutation confined to the uterine corpus or with cervical extension regardless of the degree of lymphovascular space invasion or histological type
• Stage IICmp_53abn: p53-abnormal (p53abn) endometrial carcinoma confined to the uterine corpus with any myometrial invasion, with or without cervical invasion regardless of the degree of lymphovascular space invasion or histological type

Prognostic Groups  

The prognostic groups are developed by the American Joint Committee on Cancer (AJCC) in 2017.

The Cancer Genome Atlas (TCGA) Prognostic Subtypes

• POLEmut endometrial cancer: A rare subtype characterized by a high number of single nucleotide variants, a specific mutation spectrum, and an excellent prognosis across all disease stages. These are usually high-grade tumors with deep myometrial invasion and lymphovascular space invasion. 
• Micro-satellite instability (MSI) endometrial cancer: Characterized by mismatch repair deficiency, high mutation stress and moderate prognosis
• Copy number (CN) low endometrial cancer (wild-type p53): Endometrioid subtype with intermediate good prognosis, including all remaining tumors that do not meet the criteria of the other endometrial cancer subgroups
• CN-high endometrial cancer (abnormal p53): Includes all serous endometrial cancer individuals, characterized by high levels of somatic copy number alterations and a poor prognosis

Risk Groups  

Risk groups are defined based on International Federation of Gynecology and Obstetrics (FIGO) staging and molecular subtype used as a guide for the decision to prescribe adjuvant therapy.

Nguyên tắc điều trị

The management of endometrial cancer should be divided based on risk, disease stage, and the patient's desire for fertility. Cytoreduction therapy, which includes debulking with surgery and chemotherapy or radiation therapy, improves survival rate and helps reduce recurrence in patients with intra-abdominal disease. The surgical approach should include total (extrafascial) hysterectomy-bilateral salpingo-oophorectomy (TH-BSO), lymphadenectomy, and pelvic washing cytology. Enrollment in a clinical trial is recommended in patients with POLE-mutated, MSI-H, p53 aberrant, or NSMP tumors.

Adjuvant Therapy

Adjuvant therapy may be considered depending on the extent, risk group and staging. This is not recommended in patients with POLE-ultramutated endometrial cancer.

Low Risk

Observation is preferred for patients without any risk factors, both for surgically and nonsurgically staged disease. In patients with any risk factors eg ≥60 years of age, depth of invasion, lymphovascular space invasion, or adjuvant vaginal brachytherapy may be considered. Vaginal brachytherapy is strongly suggested if a patient has ≥2 risk factors.

Intermediate Risk

Adjuvant vaginal brachytherapy is preferred. Observation may be considered if without myoinvasion and lymphovascular space invasion.

High-Intermediate Risk

Adjuvant vaginal brachytherapy is preferred. For patients who did not undergo surgical nodal staging, adjuvant external beam radiotherapy is recommended. Consider adjuvant brachytherapy for those patients with grade 3 tumors but negative for lymphovascular space invasion. An addition of chemotherapy may be considered in patients with grade 3 tumors with lymphovascular space invasion. Participation in clinical studies should be encouraged.

High Risk

Adjuvant vaginal brachytherapy and/or external beam radiotherapy with limited fields should be considered for high-risk stage I endometrial cancer patients with grade 3 tumors if surgical nodal staging was performed and confirmed negative for node involvement. For patients ≥60 years of age, with extensive lymphovascular space invasion or with >50% myoinvasion, the addition of systemic therapy to radiotherapy is recommended.

For high-risk stage I endometrial cancer patients with grade 1-2 tumors who underwent surgical staging, adjuvant vaginal brachytherapy is preferred and may consider observation for patients negative for risk factors. For high-risk stage I endometrial cancer patients who did not undergo surgical nodal staging, adjuvant external beam radiotherapy is recommended, and sequential adjuvant chemotherapy may be considered.

For high-risk patients with stage II endometrial cancer who underwent simple hysterectomy, surgical nodal staging and confirmed node-negative, vaginal brachytherapy and/or external beam radiotherapy is recommended for patients with grade 1-2 tumor. Observation or adjuvant vaginal brachytherapy is a management option for patients who had radical hysterectomy with negative surgical margins and no extrauterine disease. Limited field external beam radiotherapy is recommended for grade 3 patients or those positive for lymphovascular space invasion; may also consider additional vaginal brachytherapy and/or chemotherapy. For patients ≥60 years of age, with extensive lymphovascular space invasion or with >50% myoinvasion, an addition of systemic therapy to radiotherapy is recommended. For high-risk patients with stage II endometrial cancer who underwent simple hysterectomy but did not undergo surgical nodal staging, external beam radiotherapy is recommended, and brachytherapy is recommended. Sequential adjuvant chemotherapy should be considered in patients with a grade 3 tumor.

External beam radiotherapy, vaginal brachytherapy, and chemotherapy are recommended for patients with surgically staged high-risk stage III-IV endometrial cancer. Combination external beam radiotherapy with or without vaginal brachytherapy with or without chemotherapy is recommended in patients with stage IIIA-IVA FIGO classes. The alternative regimen includes chemotherapy with or without vaginal brachytherapy. Chemotherapy with or without extended field external beam radiotherapy with or without vaginal brachytherapy is recommended in patients with stage IVB FIGO classification.

For patients with high-risk non-endometrioid cancer with serous and clear cell types based on staging, chemotherapy should be given. Vaginal brachytherapy may be considered in patients with stage IA LVSI-negative disease. Chemotherapy plus external beam radiotherapy may be considered in patients with stage ≥IB, especially in patients positive for node invasion. For patients with high-risk non-endometrioid cancer and undifferentiated tumors based on staging, chemotherapy is recommended, and external beam radiotherapy and participation in clinical trials are encouraged.

Neoadjuvant Therapy

Neoadjuvant therapy may benefit patients expected to have residual disease after primary debulking surgery.

Uterine Cavity-limited Disease

After surgical confirmation, endometrial cancers confined within the uterine walls are best managed by surgery. It is recommended that surgery include total hysterectomy-bilateral salpingo-oophorectomy and lymphadenectomy with pelvic washing cytology. Sentinel node mapping may also be considered. For patients with uterine-confined disease with contraindications to surgery, external beam radiotherapy and/or brachytherapy is preferred, and may consider systemic therapy in patients with high-risk disease.

Cervical Involvement Suspected or Confirmed

For operable patients with cervical involvement, total hysterectomy or radical hysterectomy with bilateral salpingo-oophorectomy, pelvic washing cytology, lymphadenectomy is recommended. Radical or modified radical hysterectomy is an option to total hysterectomy-bilateral salpingo-oophorectomy. External beam radiotherapy with brachytherapy prior to TH/BSO and surgical staging is also recommended for initial management. For patients with gross cervical involvement with contraindications to surgery, external beam radiotherapy and brachytherapy are preferred. Consider the addition of systemic therapy to radiotherapy for patients with high-risk disease. Systemic therapy alone may also be considered, followed by adjuvant external beam radiotherapy and brachytherapy if still not suitable for surgery.

Suspected Extrauterine Disease

For suspected extrauterine disease, neoadjuvant systemic therapy may be considered. The goal of surgical treatment is to eradicate all residual disease; thus, debulking is recommended for patients with abdomen- or pelvis-confined endometrial carcinoma. For patients with extrauterine disease who are not suitable for primary surgery, external beam radiotherapy with or without brachytherapy and systemic therapy is recommended. Systemic therapy alone may be considered in those with distant metastases. For patients suitable for primary surgery and with distant visceral metastasis, systemic therapy and/or external beam radiotherapy and/or stereotactic body radiotherapy are recommended. Palliative total hysterectomy-bilateral salpingo-oophorectomy may also be considered.

Fertility-preserving Treatments

Conservative treatments may be considered for young women of childbearing age and those considering pregnancy in the future. The criteria for inclusion: Pathologically-confirmed well-differentiated grade 1 endometrioid adenocarcinoma on dilatation and curettage; disease limited to the endometrium as confirmed in MRI (preferred) or TVUS; no metastasis or extrauterine involvement on imaging studies; no contraindications to medical therapy or pregnancy; and patients should have been informed that fertility-sparing therapies are not standard treatment for endometrial cancer and that close follow-up is required. A continuous progestin-based therapy with either Megestrol, Medroxyprogesterone or IUD-containing Progestin is the preferred primary treatment regimen for patients who choose to preserve their childbearing potential. Patient counselling on weight management and healthy lifestyle changes is recommended. Strict monitoring with endometrial evaluation every 3-6 months is recommended until conception or disease progression. After completion of childbearing, treatment failure after 6-12 months of progestin-based therapy, or disease progression, total hysterectomy-bilateral salpingo-oophorectomy with surgical staging is recommended.

Pharmacological therapy

Systemic Therapy

Combination regimens are recommended for high-risk disease, and recurrent or metastatic endometrial cancer. Single-agent therapy is used when multi-agent regimens are contraindicated. The recommended option for patients with high-risk endometrial histology (serous carcinoma, clear cell carcinoma, undifferentiated/dedifferentiated carcinoma or carcinosarcoma) who are not suitable for primary surgery. Post-operative platinum-based chemotherapy may benefit patients with high-risk endometrioid disease (eg increased progression-free survival, or overall survival).

Preferred Regimens

Cisplatin plus radiotherapy followed by Carboplatin/Paclitaxel is the preferred primary or adjuvant chemoradiation therapy option for patients with stage I-IV endometrial cancer. Carboplatin/Paclitaxel is the preferred first-line combination regimen and adjuvant treatment for uterine-confined disease and for recurrent or metastatic disease. This is preferred only for patients with recurrent disease who have not received any prior systemic therapy. Carboplatin/Paclitaxel/Bevacizumab is preferred for patients with advanced measurable tumors. Carboplatin/Paclitaxel/Pembrolizumab is preferred for patients with advanced or recurrent tumors except carcinosarcoma. Carboplatin/Paclitaxel/Dostarlimab-gxly is preferred for patients with advanced or recurrent tumors. For stage IIIA, IIIB, or IIIC1 with measurable disease, and stage IIIC1 with carcinosarcoma, clear-cell, serous or mixed histology, stage IIIC2 or stage IV regardless of the presence of measurable disease. Carboplatin/Paclitaxel/Durvalumab is preferred for patients with dMMR advanced or recurrent tumors and for stage III with measurable disease post-surgery and stage IV with or without measurable disease. Carboplatin/Paclitaxel/Pembrolizumab is preferred for patients with advanced or recurrent tumors except carcinosarcoma and for stage III or IVA with measurable disease post-surgery or stage IVB with or without measurable disease. Carboplatin/Paclitaxel/Trastuzumab is preferred for patients with HER2-positive advanced or recurrent uterine serous carcinoma and carcinosarcoma and for patients without previous Trastuzumab therapy. All triple combination regimens mentioned may be continued as maintenance therapy.

Other Recommended Regimens - Combination Therapy

Capecitabine/Mitomycin is for patients with stage I-IV disease if Cisplatin and Carboplatin are unavailable. Carboplatin/Docetaxel is the first-line therapy for recurrent disease that may be considered in patients with contraindications to Paclitaxel therapy. Carboplatin/Paclitaxel/Bevacizumab is the first-line therapy for recurrent disease. Cisplatin/Doxorubicin is the second-line or subsequent therapy for recurrent disease. Cisplatin/Doxorubicin/Paclitaxel is the second-line or subsequent therapy for recurrent disease. Cisplatin/Gemcitabine is the second-line or subsequent therapy for recurrent disease. Cisplatin/Ifosfamide is the second-line or subsequent therapy for patients with carcinosarcoma. Ifosfamide/Paclitaxel is the second-line or subsequent therapy for patients with carcinosarcoma.

Other Recommended Regimens - Monotherapy

The primary or adjuvant therapies for stage I-IV tumors are Gemcitabine and Paclitaxel. The second-line or subsequent therapy for recurrent disease include: Albumin-bound Paclitaxel, for patients with hypersensitivity to Paclitaxel but negative for skin testing; Bevacizumab may be considered in patients unresponsive to cytotoxic chemotherapeutic agents; Cabozantinib; Carboplatin; Cisplatin; Docetaxel; Doxorubicin; Gemcitabine; Ifosfamide, for patients with carcinosarcoma; Lenvatinib; Liposomal Doxorubicin; Paclitaxel; Topotecan; and Temsirolimus.

Biomarker-directed Systemic Therapy

Lenvatinib/Pembrolizumab is used for patients with proficient MMR (pMMR) recurrent endometrial cancer whose disease has progressed following previous systemic therapy including neoadjuvant and adjuvant therapy and are not candidates for curative surgery or radiation. Pembrolizumab may be used in patients with tumor mutational burden-high (TMB-H) (≥10 mutations/megabase [mut/Mb]), or MSI-H/dMMR tumors whose disease has progressed following prior treatment and who have no satisfactory alternative treatment options. Avelumab is a second-line or subsequent therapy for patients with MSI-H/dMMR recurrent disease. Dostarlimab-gxly is for patients with MSI-H/dMMR tumor recurrent or advanced endometrial carcinoma that has progressed on or following prior treatment with a platinum-containing regimen. Fam-trastuzumab deruxtecan-nxki is a second-line or subsequent therapy for HER2-positive recurrent disease (IHC 3+ or 2+). Larotrectinib, Entrectinib or Repotrectinib is a second-line or subsequent therapies for patients with NTRK gene fusion-positive tumors. Repotrectinib is indicated as second-line or subsequent therapy for patients with NTRK-positive tumors which are naïve to previous NTRK-targeted treatment or have progressed on previous NTRK therapy. Nivolumab is a second-line or subsequent therapy for patients with MSI-H/dMMR recurrent disease.

Hormone Therapy

Hormone therapy is a treatment option for patients with metastatic, recurrent, or high-risk endometrial cancer. This may also be considered in patients with lower grade endometrioid histology only with small or slow-growing tumors. This is also used in patients with p53 wild-type-positive NSMP endometrial cancer. This is indicated for advanced (grade 1 or 2) endometrioid-type endometrial cancer. This is a preferred first-line systemic treatment for hormone-positive grade 1-2 tumors negative with rapid disease progression. Close monitoring with endometrial biopsy every 3-6 months is required if to undergo this management option.

Fertility-sparing Agents

Progestin-based agents include Megestrol acetate, Medroxyprogesterone acetate, and Levonorgestrel intrauterine device (IUD). This is the preferred conservative treatment in select patients with non-invasive disease, or young patients with endometrial hyperplasia, who wish to preserve their fertility or whose disease is not suitable for primary surgery. This is contraindicated in patients with increased risk for breast cancer, stroke, myocardial infarction, pulmonary embolism, and/or deep vein thrombosis.

Agents for Recurrent or Metastatic Endometrial Cancer

Endometrial Cancer_Management 1

Nonpharmacological

Observation

The recommended follow-up intervals for surveillance of signs and symptoms suggestive of recurrence after surgery are as follows: Physical examination is recommended every 3-6 months for 2-3 years, then every 6 months up to year 5, and then annually thereafter and testing for CA-125 if initially elevated; for low-risk patients, history and physical examination and follow up is every 6 months for 1 year, then every 6-12 months 1-2 years post-treatment, and yearly thereafter; for high-risk patients, history and physical examination should be every 3 months for 1 year, then every 3 months 1-2 years post-treatment, every 6 months after >2 years, and yearly after >5 years post-treatment; and if recurrence is highly likely, may consider CT scan or PET/CT scan with or without CA-125 testing.

The recommended follow-up intervals for surveillance of signs and symptoms for patients who did not undergo surgical treatment and opted for fertility-sparing regimens (eg progestin-based therapy) are as follows: Endometrial sampling every 3-6 months; and if a complete response to therapy is seen at 6 months after initiation of therapy, continue surveillance every 3-6 months until pregnancy occurs.

Phẫu thuật

Surgery is considered the primary treatment for patients whose disease is confined to the endometrium (endometrioid type, grade 1 or 2). The initial surgical approach should include comprehensive surgical staging and peritoneal cytology. The recommended surgical technique depends on the anatomical involvement of the disease and desire for fertility. Complete surgical staging involves extrafascial hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy and para-aortic lymphadenectomy. Surgical staging via open laparotomy is preferred for comprehensive surgical staging in patients with BMI >40. Surgical staging via laparoscopy produces lesser post-op adverse effects and a higher quality of life during the recovery period compared to laparotomy. Extrafascial hysterectomy and bilateral salpingo-oophorectomy (EH-BSO) is the preferred surgical procedure for staging and management of medically operable endometrial carcinoma. Extrafascial hysterectomy and bilateral salpingo-oophorectomy with cytology of peritoneal lavage, lymphadenectomy, and surgical debulking is recommended especially for patients with intra-abdominal involvement.

An open, laparoscopic, or vaginal approach may be utilized. Vaginal hysterectomy is preferred in women with benign disease or early-stage endometrioid endometrial cancer at high surgical morbidity risk and is an option for low-risk patients not requiring LN dissection. Minimally-invasive surgical technique eg laparoscopy (traditional and robotic-assisted) is an alternative for patients opposed to open laparotomy and recommended for patients with low to intermediate risk. This is reported to have fewer postoperative adverse events and shorter operative time. For patients with incomplete surgical staging, imaging is recommended, especially for patients with higher grade and deeply invasive disease.

Recommended Surgical Technique Based on Cancer Stage

Stage I Endometrial Cancer

Total hysterectomy-bilateral salpingo-oophorectomy with surgical staging and LN assessment is recommended. Fertility-preserving techniques may be considered in patients with stage I G1-G2 tumors. Vaginal hysterectomy with salpingo-oophorectomy may be considered in patients with contraindications to open surgery. Sentinel lymphadenectomy may be considered for nodal assessment in patients with stage I G3 tumors. For patients with non-endometrioid type, extrafascial hysterectomy and bilateral salpingo-oophorectomy with lymphadenectomy are recommended. Omentectomy + random peritoneal biopsy should also be considered in patients with papillary serous carcinoma or carcinosarcoma.

Stage II Endometrial Cancer

Total hysterectomy-bilateral salpingo-oophorectomy or radical hysterectomy with surgical staging and LN assessment is recommended. Radical hysterectomy is the preferred surgical technique. Type A or B (modified) radical hysterectomy may be used. Lymphadenectomy should also be done.

Stage III-IV Endometrial Cancer

Total hysterectomy-bilateral salpingo-oophorectomy, complete cytoreductive surgery, and comprehensive staging are recommended for patients whose disease is confined within the abdomen or pelvis. These are also recommended for non-endometrioid type endometrial cancer. Multidisciplinary methods should be applied in managing advanced endometrial cancer.

Salpingectomy

Endometrial Cancer_Management 2

Salpingectomy is a surgical option for patients not willing to undergo or who are not candidates for salpingo-oophorectomy. Bilateral salpingo-oophorectomy may be excluded in patients <45 years old with grade 1 endometrioid-type endometrial cancer, <50% myometrial invasion and without metastatic disease. This is not recommended for patients at high risk for ovarian cancer.

Cytoreductive Surgery

Cytoreductive surgery may improve progression-free and overall survival rates in patients with advanced-stage or recurrent disease.

Lymphadenectomy

Lymphadenectomy is used for cancer staging, and serves as a guide for appropriate adjuvant therapy for better survival rates and lesser adverse events. This is recommended for high-risk patients (eg patients with serous carcinoma, clear cell carcinoma, carcinosarcoma, or tumors that are deeply invasive or with high-grade histology). This may be considered in intermediate-risk patients for staging purposes, but it is not necessary in low-risk patients. Lymphadenectomy includes dissection of the pelvic and/or para-aortic LNs. This may serve as a guide for appropriate adjuvant therapy for better survival rates and lesser adverse events. Pre-/intra-operative findings that excludes the need for lymphadenectomy: <50% myometrial invasion; tumor size <2 cm; and well or moderately differentiated histology. This should not be performed in patients with uterine sarcoma. Sentinel LN dissection (SLND) may be considered to improve the detection of small metastases and isolated tumor cells in LNs in patients with low-risk/intermediate-risk endometrial cancer (eg stage IA, G1-G3, stage IB, G1-G2).

Sentinel Lymph Node (SLN) Mapping 

Endometrial Cancer_Management 3

Sentinel LN mapping is a strategy in staging endometrial cancer, and used to help detect LN metastasis with promising potential as an alternative to complete lymphadenectomy. SLN mapping with ultrastaging is preferred instead of lymphadenectomy in a patient with uterine-confined malignancy that is negative for metastasis in imaging studies or during exploration but may need further assessment for pelvic LN involvement, especially those with low to intermediate risk for metastases and those intolerant of standard lymphadenectomy. Components include serial sectioning with review of multiple hematoxylin and eosin (H and E)-stained slides with or without cytokeratin immunohistochemistry staining. This involves injection of a dye (ie indocyanine green, Tc-99 radiocolloid, isosulfan blue 1%, methylene blue 1%, or patent blue 2.5% sodium) into the cervix, which travels to the sentinel nodes. Identification of the sentinel LN must be done before hysterectomy unless in the presence of a bulky uterus where access to iliac LNs is hindered. This is contraindicated in patients with uterine sarcoma.

Palliative Treatment

Palliative Surgery

Palliative TH/BSO may be considered in patients with distant metastases suitable for primary surgery. Minimally invasive surgery is the preferred approach when technically feasible.

Radiation Therapy

Radiotherapy may be considered in patients not qualified for surgery and those at moderate-high risk for recurrence. This is used as adjuvant therapy, together with chemotherapy, for patients with extrauterine disease. This is also used in patients with dMMR, NSMP and p53abn endometrial cancer. The confirmation of tumor extent and absence of distant metastases using imaging techniques is required prior to initiation of radiotherapy.

Tumor-Directed Radiotherapy

Tumor-directed radiotherapies include external beam radiotherapy and/or vaginal brachytherapy. These are radiotherapy directed at known or suspected tumor sites.

External Beam Radiotherapy

Endometrial Cancer_Management 4

The recommended doses include: For microscopic disease, the dose is 45-50 Gy; gross nodal disease boost dose is 60-65 Gy with normal tissue constraints; post-operative boost dose is a total dose of 60-70 Gy low-dose rate equivalent; and the dose for neoadjuvant radiation is 45-50 Gy with 1-2 high-dose rate insertions to a total of 75-80 Gy low-dose rate equivalent may be considered.

Vaginal Brachytherapy (Internal Radiotherapy)

Vaginal brachytherapy is an adjuvant treatment of choice over whole pelvic radiotherapy in patients with intermediate-risk, and high-intermediate-risk patients for recurrence prevention. This is a treatment option for patients with grade 1 or 2 tumors with ≤50% myometrial invasion, no l lymphovascular space invasion, and microscopic cervical invasion or grade 3 tumors with <50% myometrial invasion. This may be considered as an alternative treatment in high-risk patients. This should be considered for patients after extrafascial hysterectomy and bilateral salpingo-oophorectomy if with high-intermediate patients or low-risk patients but with signs of higher-risk disease. This may be considered as additional therapy to external beam radiotherapy in patients with serous carcinoma, clear cell carcinoma or carcinosarcoma or as additional therapy to systemic therapy for patients with undifferentiated/dedifferentiated carcinoma, who are not suitable for primary surgery.

Vaginal brachytherapy may provide locoregional control with competitive overall survival rates in the following patients: Those >60 years old with intermediate- to high-intermediate-risk; endocervical glandular involvement present but disease confined to the uterus; and patients with high-intermediate-risk for recurrent endometrial cancer. This should be initiated once vaginal cuff has healed, 6-8 weeks or <12 weeks post-surgery. The recommended post-operative high-dose rates include: 6 Gy x 5 fractions to the vaginal surface; and 7 Gy x 3 fractions or 5.5 Gy x 4 fractions 5 mm below the vaginal surface. The recommended dose to boost external beam radiotherapy is 4-6 Gy x 2-3 fractions to the vaginal mucosa and 15-25 Gy for macroscopic residual disease. For patients not suitable for primary surgery, the dose should be individualized based on the patient's clinical status. Studies revealed lesser gastric toxic effects and better quality of life with vaginal compared to whole pelvic irradiation.

Palliative Therapy

Palliative Radiotherapy

External beam radiotherapy may be considered for the palliation of symptoms in patients with painful node recurrences, bleeding, or bone metastasis.