What is the best course of treatment for a 40-year-old female with abnormal uterine bleeding (AUB), diagnosed with endometrioid adenocarcinoma on endometrial biopsy, showing endometrial thickening without myometrial invasion on magnetic resonance imaging (MRI) and no evidence of metastasis on computed tomography (CT) chest scan?

Management of Grade 1 Endometrioid Adenocarcinoma in a 40-Year-Old Woman

This 40-year-old woman requires immediate discussion of two distinct pathways: standard surgical treatment with total hysterectomy and bilateral salpingo-oophorectomy, or fertility-sparing treatment with high-dose progestins if she desires future childbearing. 1, 2

Critical First Step: Fertility Desires Assessment

Before proceeding with any treatment, you must explicitly determine whether this patient wishes to preserve fertility. 1 This single factor fundamentally alters the entire treatment algorithm, as the standard curative approach permanently eliminates reproductive potential. 1

If Fertility Preservation is NOT Desired (Standard Treatment)

Proceed directly to total hysterectomy with bilateral salpingo-oophorectomy, preferably via minimally invasive approach (laparoscopic or robotic). 1, 2, 3

Surgical Staging Considerations

• Lymphadenectomy can be considered for staging but is optional in this low-risk scenario (Grade 1, no myometrial invasion, no enlarged nodes on imaging). 1, 3
• Sentinel lymph node dissection (SLND) is an acceptable alternative to full lymphadenectomy if staging is pursued. 1, 3
• Given the imaging shows no myometrial invasion and no enlarged retroperitoneal lymph nodes, this patient appears to have Stage IA disease, which carries approximately 10.4% recurrence risk. 4

Post-Operative Management

No adjuvant therapy is required after surgery for this low-risk presentation (Stage IA, Grade 1, no myometrial invasion, no lymphovascular space invasion). 2, 4, 3 The 5-year survival rate for this stage is 93%. 1

If Fertility Preservation IS Desired (Non-Standard Treatment)

This patient meets criteria for fertility-sparing treatment: age 40, Grade 1 endometrioid adenocarcinoma, no myometrial invasion on MRI, and no metastatic disease. 1, 2

Mandatory Pre-Treatment Requirements

Before initiating fertility-sparing therapy, complete these steps:

• Refer immediately to a specialized center with expertise in fertility-preserving endometrial cancer management. 1
• Obtain expert gynaecopathologist review of the endometrial biopsy to confirm Grade 1 endometrioid adenocarcinoma. 1 Standard pathology review has significant inter-observer variability; 11 of 22 patients in one series had their diagnosis changed from well-differentiated adenocarcinoma to atypical hyperplasia upon expert review. 1
• Perform dilatation and curettage (D&C) rather than relying solely on the initial endometrial biopsy, as D&C is superior for accurate tumor grading. 1
• Confirm MRI findings show no myometrial invasion and no adnexal involvement. 1 The MRI has already been done and shows appropriate findings.

Fertility-Sparing Treatment Protocol

Initiate high-dose progestin therapy with either medroxyprogesterone acetate (MPA) 400-600 mg/day or megestrol acetate (MA) 160-320 mg/day. 1 Alternatively, levonorgestrel-releasing intrauterine device (LNG-IUD) with or without GnRH analogues can be considered. 1

Critical Patient Counseling Points

You must inform the patient of the following:

• This is a non-standard treatment approach. 1
• Response rate is approximately 75%, but recurrence rate is 30-40% even among responders. 1
• Close surveillance is mandatory during and after treatment. 1
• Hysterectomy will be required if treatment fails or after completion of childbearing. 1
• Even if treatment succeeds, hysterectomy with bilateral salpingo-oophorectomy is recommended after pregnancies are completed. 1

Response Assessment and Follow-Up

• Perform repeat D&C and imaging at 6 months to assess response. 1
• If complete response is achieved, immediately refer to fertility clinic and encourage conception. 1 Pregnancy is associated with reduced recurrence risk. 1
• If no response at 6 months, proceed immediately to standard surgical treatment (hysterectomy with bilateral salpingo-oophorectomy). 1
• If partial response, consider maintenance treatment for an additional 6 months in patients wishing to delay pregnancy. 1

Common Pitfalls to Avoid

• Do not rely on the initial endometrial biopsy alone—expert pathologist review and D&C are essential, as misdiagnosis rates are substantial. 1
• Do not assume all 40-year-old women want fertility preservation—explicitly ask, as many may prefer definitive treatment. 1
• Do not check progesterone receptor status routinely before initiating progestin therapy—50% of PgR-negative patients still respond to treatment. 1
• Do not forget to examine the ovaries carefully at surgery if proceeding with hysterectomy—19% of young women with endometrial cancer have coexisting ovarian neoplasms. 5
• Do not perform lymphadenectomy routinely in this low-risk scenario—it does not improve survival and adds morbidity. 4, 3

Age-Specific Considerations

At age 40, this patient is at the upper limit for fertility-sparing treatment consideration. 1 Only 4% of endometrial cancers occur in women under 40 years of age. 1 Younger women with endometrial cancer have better prognosis with increased rates of early-stage and low-grade disease. 1