Does involvement of the lower uterine segment in carcinoma endometrium (endometrial cancer) change the decision for adjuvant treatment in a postmenopausal woman?

Lower Uterine Segment Involvement in Endometrial Cancer and Adjuvant Treatment Decisions

Yes, lower uterine segment (LUS) involvement is recognized as an adverse risk factor that influences adjuvant treatment decisions in endometrial cancer, though it does not independently change staging—it increases recurrence risk and should prompt consideration of more aggressive adjuvant therapy, particularly external beam pelvic radiotherapy in combination with other high-risk features. 1

Risk Stratification Framework

LUS involvement is explicitly listed as one of the adverse intrauterine pathologic risk factors used to stratify patients with stage I endometrial cancer after thorough surgical staging, alongside age, positive lymphovascular space invasion (LVSI), tumor size, grade, and depth of myometrial invasion. 1

The NCCN guidelines emphasize that risk exists on a continuum, with the trend toward selecting more aggressive adjuvant therapy as tumor grade, myometrial invasion, and other adverse factors worsen. 1 In surgical stage I and II endometrial cancer, LUS involvement is specifically identified as a pathologic factor that may influence the decision regarding adjuvant therapy. 1

Clinical Impact on Recurrence Risk

The evidence demonstrates that LUS involvement carries significant prognostic implications:

• In stage IB grade 2-3 endometrial cancer treated with vaginal brachytherapy alone, LUS involvement was independently associated with reduced disease-free survival (p=0.031) on multivariable analysis. 2 Pelvic recurrence occurred in 11% of patients overall, and was significantly more likely with LUS involvement, most often presenting with synchronous distant disease. 2

• In stage IB-IIA endometrioid adenocarcinoma with LVSI, LUS invasion was significantly associated with relapses (p=0.035) and correlated with overall survival (p=0.008) in multivariate analysis. 3 Overall recurrence rates in this population were high at 23%, with LUS involvement emerging as a critical adverse factor. 3

• While one study suggested LUS involvement was not an independent prognostic factor for poor survival, it was strongly associated with other poor prognostic factors including deep myometrial invasion, uterine serosal involvement, LVSI, lymph node metastasis, and higher FIGO grade. 4

Adjuvant Treatment Algorithm When LUS Involvement is Present

For Stage IA Disease:

• Grade 1-2 with LUS involvement: Consider observation or vaginal brachytherapy; if additional adverse risk factors present, consider vaginal brachytherapy and/or pelvic RT. 1
• Grade 3 with LUS involvement: Observation or vaginal brachytherapy and/or pelvic RT recommended. 1

For Stage IB Disease:

• Grade 1-2 with LUS involvement and other adverse factors: Observation or vaginal brachytherapy with or without pelvic RT (category 2B for pelvic RT). 1
• Grade 3 with LUS involvement and other adverse factors: Observation or vaginal brachytherapy and/or pelvic RT, with or without chemotherapy (category 2B for chemotherapy). 1

The presence of LUS involvement in conjunction with established risk factors (high grade, ≥50% myometrial invasion, LVSI, and larger tumor size >4 cm) may identify a group of high-risk patients who might benefit from pelvic radiotherapy rather than vaginal brachytherapy alone. 2

Evidence on Radiation Therapy Modality Selection

Modern external beam radiotherapy (EBRT) significantly improved recurrence-free survival and overall survival in stage IB patients, particularly those with grade 3 disease, bulky tumors, or LVSI. 5 In stage IB grade 1/2 patients, those with age >60 years, myometrial invasion beyond the outer third, or LVSI benefited most from EBRT. 5

While adjuvant radiation therapy improves pelvic control in patients with selected risk factors, it did not improve overall survival in major trials, largely due to distant failure rates. 1 This highlights that patients with multiple adverse factors including LUS involvement may require consideration of systemic therapy in addition to radiotherapy. 3

Critical Clinical Pitfalls

• Do not dismiss LUS involvement as clinically insignificant—it consistently emerges as an adverse factor associated with increased recurrence risk, particularly when combined with other high-risk features. 2, 3

• Vaginal brachytherapy alone may be insufficient for patients with LUS involvement plus other adverse factors (grade 3, deep myometrial invasion, LVSI, large tumor size), as these patients experience high rates of pelvic and distant recurrence. 2, 3

• Consider systemic therapy in addition to radiation for patients with LUS involvement combined with high-grade tumors or LVSI, given the high distant failure rates (84% of recurrences in radiated patients were distant). 3

• Ensure adequate surgical staging with ≥10 lymph nodes removed, as <10 lymph nodes removed was independently associated with reduced disease-free survival (p=0.032). 2