What are the treatment options for endometrial cancer?

Treatment Options for Endometrial Cancer

The primary treatment for endometrial cancer is total hysterectomy with bilateral salpingo-oophorectomy (TH/BSO), with adjuvant therapy determined by stage, grade, and depth of myometrial invasion. 1

Surgical Management by Stage

Stage I Disease (Confined to Uterus)

Primary Surgery:

• Total hysterectomy with bilateral salpingo-oophorectomy is the standard surgical approach 2, 1
• Minimally invasive techniques (laparoscopy or robotic surgery) provide equivalent oncologic outcomes to laparotomy with shorter hospital stays, less pain, and fewer complications 2
• Systematic exploration, inspection, and palpation of the entire abdomen must be performed 1
• Peritoneal cytology should be obtained, though it no longer affects FIGO staging 1

Lymph Node Assessment:

• For intermediate-high risk disease (stage IA grade 3 and IB), complete surgical staging with pelvic lymphadenectomy should be considered for prognostic information and to tailor adjuvant therapy 2
• Para-aortic nodal evaluation is indicated for high-risk tumors including deeply invasive lesions, high-grade histology, serous adenocarcinoma, or clear cell carcinoma 1
• Sentinel lymph node mapping may be considered in selected patients 1

Important caveat: Two large randomized trials (Italian study and ASTEC trial) showed that systematic lymphadenectomy did not improve disease-free or overall survival in stage I disease, making routine lymphadenectomy controversial 2. However, lymphadenectomy remains valuable for prognostic stratification and treatment planning 1.

Adjuvant Treatment for Stage I:

• Grade 1-2, Stage IA: Follow-up alone is standard 2, 1
• Grade 3, Stage IA: Vaginal brachytherapy is an option 2, 1
• Grade 1-2, Stage IB: Vaginal brachytherapy or follow-up alone 2, 1
• Grade 3, Stage IB or Stage IC (any grade): External pelvic radiotherapy with or without vaginal brachytherapy boost, or vaginal brachytherapy alone 2, 1

Stage II Disease (Extension to Cervix)

When cervical involvement is confirmed preoperatively:

• Modified radical hysterectomy (Piver type II) is recommended for macroscopic cervical lesions 1
• Alternative: External radiotherapy with brachytherapy followed by surgery 2

When cervical involvement is not confirmed preoperatively:

• Primary surgery is recommended 2

Adjuvant Treatment for Stage II:

• Stage IIA (endocervical glandular involvement): Vaginal brachytherapy if myometrial invasion <50% and grade 1-2; external radiotherapy with brachytherapy boost if myometrial invasion >50% or grade 3 2
• Stage IIB (cervical stromal invasion): Postoperative external pelvic radiotherapy with brachytherapy boost is standard 2

Stage III Disease (Extension Beyond Uterus)

Surgical Approach:

• Debulking surgery is standard when performance status permits, as cytoreductive surgery improves overall survival 2
• Total hysterectomy with salpingo-oophorectomy 2
• Bowel resection if complete resection is possible or necessary to avoid obstruction 2
• Partial or total bladder resection if possible 2
• Para-aortic nodal clearance is an option 2
• Omentectomy if ovaries are involved 2

If radical surgery is not possible: Total hysterectomy plus BSO by abdominal approach is preferable to radiotherapy alone when performance status is poor 2

Adjuvant Treatment for Stage III:

• Stage IIIA (ovaries or positive cytology only): External pelvic radiotherapy or abdomino-pelvic radiotherapy are options 2
• Stage IIIA (multiple extrauterine sites): Abdomino-pelvic radiotherapy is standard 2
• Stage IIIB (vaginal involvement): Pelvic external beam irradiation with brachytherapy if possible 2
• Stage IIIC (pelvic nodes involved): Postoperative pelvic radiotherapy with brachytherapy boost is standard 2
• Stage IIIC (para-aortic nodes involved): Extended postoperative radiotherapy (pelvic and para-aortic) with brachytherapy 2
• High-risk Stage III: Combined chemoradiation has shown improved recurrence-free and overall survival 1

Stage IV Disease (Invasion of Neighboring Organs or Distant Metastasis)

Surgical Approach:

• Cytoreduction surgery with paramedial approach 2
• Total hysterectomy plus BSO 2
• Gut resection if complete resection is possible or necessary to avoid obstruction 2
• Partial or total bladder resection with urinary diversion 2
• Anterior or posterior pelvectomy depending on tumor location with pelvic clearance 2

Adjuvant Treatment:

• Postoperative pelvic radiotherapy with or without brachytherapy 2
• Clinical trial of hormone therapy or chemotherapy 2

Special Histologic Considerations

For serous adenocarcinoma, clear cell adenocarcinoma, or carcinosarcoma:

• Omentectomy is commonly performed 1
• Para-aortic nodal evaluation is indicated 1
• These Type II tumors carry worse prognosis and may benefit from more aggressive surgical staging 3

Common Pitfalls and Caveats

Preoperative Assessment Limitations:

• No preoperative imaging is sufficiently sensitive and specific to distinguish between stage I and stage II disease 1
• CA125 has no diagnostic value for endometrial cancer but may predict extra-uterine extension at levels >35 U/ml 1

Avoid Preoperative Radiotherapy for Stage I:

• Preoperative radiotherapy is not recommended for stage I disease because it cannot be planned according to specific histoprognostic factors or exact tumor extent, resulting in overtreatment for some patients 2

Fertility Preservation:

• Should only be considered in well-differentiated (grade 1) endometrioid adenocarcinoma limited to the endometrium in patients who wish to preserve fertility 1
• Ovarian preservation may be considered in young women (<50 years) with low-grade, early-stage endometrioid endometrial cancer as it has not been demonstrated to worsen overall survival 1