Natural History of Subclinical Lower Limb Lymphedema After Gynecologic Cancer Surgery Using Indocyanine Green...

Subclinical lymphedema is characterized by abnormal lymphatic findings in the absence of clinical symptoms or edema. However, the natural history of subclinical lymphedema after gynecologic cancer surgery remains unclear.

In this observational cohort study, the asymptomatic lower limbs of patients treated for gynecologic malignancies were evaluated using indocyanine green (ICG) lymphography between April 2021 and June 2024. Subclinical lymphedema was defined as asymptomatic limbs with abnormal ICG findings (stage ≥ 1). Patients were followed up at approximately 6-month intervals without therapeutic intervention until objective edema developed. Time-to-event outcomes were analyzed using the Kaplan-Meier method and Cox regression. Longitudinal changes in the lower extremity lymphedema index were assessed using a mixed-effects model.

Eighty asymptomatic lower limbs were included, of which 26 were classified as subclinical. During a median follow-up of 24 months, objective edema developed more frequently in the subclinical group than in the nonsubclinical group (50% versus 5.6%, P < 0.001). Subclinical lymphedema was independently associated with objective edema development (hazard ratio, 8.57; 95% confidence interval, 2.36-31.2; P = 0.0011). Subjective symptoms also occurred earlier in the subclinical group (P = 0.021). Mixed-effects modeling demonstrated significantly greater longitudinal increases in the lower extremity lymphedema index in the subclinical group (P = 0.023).

Asymptomatic abnormalities detected using ICG lymphography are associated with an increased risk of subsequent lower limb lymphedema after gynecologic cancer surgery. However, not all subclinical cases progress, which supports the need for risk-based surveillance.