Long-term lymphedema and quality of life following lymph node staging in early cervical cancer: 3-year follow-up in the prospective multicenter SENTIREC CERVIX study

Background: Pelvic lymphadenectomy is the gold standard in nodal staging in cervical cancer but increases the risk of leg lymphedema. Sentinel lymph node mapping is a less invasive technique that enables accurate detection of nodal metastases, although evidence confirming its oncologic safety has yet to be established. Knowledge of chronic leg lymphedema and quality of life following pelvic lymphadenectomy or sentinel lymph node mapping is essential for informing treatment and survivorship strategies in women with cervical cancer, but current evidence is limited. 

Objective: This study aimed to evaluate long-term leg lymphedema after sentinel lymph node mapping alone and sentinel lymph node mapping with pelvic lymphadenectomy in women with cervical cancer, and to examine risk factors for leg lymphedema and condition-specific quality of life among patients with leg lymphedema at 12-month follow-up. 

Study Design: This national prospective cohort study included patients with early-stage cervical cancer who underwent radical surgery, including sentinel lymph node mapping (2017–2021). In case of tumors >20 mm, backup pelvic lymphadenectomy was performed. Patients completed validated patient-reported outcome questionnaires before surgery and at 3, 12, 24, and 36 months postoperatively. Leg lymphedema was assessed using the European Organisation for Research and Treatment of Cancer cervix cancer module (QLQ-CX24), supplemented by 8 single items from the European Organisation for Research and Treatment of Cancer item library addressing lymphedema of the legs, genitals, and groin. Quality of life was reported according to the LYMQOL (Lymphoedema Quality of Life) tool and the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-CX24 modules. Mean difference scores from baseline to each follow-up were estimated with 95% confidence intervals, defining a change of ≥8 points as clinically important. Linear regression models were used to examine predictors of leg lymphedema 12 months postoperatively. We evaluated quality of life within LYMQOL domains in patients with lymphedema and analyzed domain trends using multiple linear regression. We compared quality of life between patients with and without leg lymphedema using guidelines for interpretation of clinically important differences. 

Results: Among 109 women who underwent sentinel lymph node mapping alone, the leg lymphedema mean score differences from baseline to 3, 12, and 36 months were 6 (95% confidence interval, 2–10), 10 (95% confidence interval, 5–15), and 15 (95% confidence interval, 7–22), respectively. At similar time points, 77 women reported substantial leg lymphedema after sentinel lymph node mapping with pelvic lymphadenectomy, with mean score differences of 18 (95% confidence interval, 11–25), 29 (95% confidence interval, 21–37), and 21 (95% confidence interval, 11–32). Three-month leg lymphedema scores were positively associated with leg lymphedema scores at 12 months regardless of the extent of lymph node removal. Body mass index predicted leg lymphedema after sentinel lymph node mapping alone, whereas chemoradiotherapy was associated with lymphedema following backup pelvic lymphadenectomy. Reporting lymphedema at 12-month follow-up was associated with impairment in several quality of life aspects, including fatigue, pain, and physical, cognitive, social, and sexual functioning. 

Conclusion: Patients with cervical cancer reported long-term leg lymphedema, most pronounced after sentinel lymph node mapping with pelvic lymphadenectomy, and to a lesser extent after sentinel lymph node mapping alone. Three-month leg lymphedema score predicted persistent lymphedema, which was significantly associated with deterioration in several quality of life symptoms and functioning. Our findings support less invasive surgical approaches and may inform shared decision-making and survivorship intervention.