Sentinel-Lymph-Node Biopsy Alone or With Lymphadenectomy in Cervical Cancer

Primary treatment for early-stage cervical cancer is surgery, usually a form of hysterectomy and nodal assessment. Historically, pelvic lymphadenectomy, which refers to the complete removal of lymphoid tissue near the iliac vessels, has been performed. There are, however, limitations to this method, including risk of vascular and neural injury, lymphedema, lymphocyst, venous thromboembolism, and mortality. In cases of early-stage disease, this treatment may pose more risk than benefit, as the surgery removes nodes that are not metastatic. An alternative method for nodal assessment is sentinel-lymph-node biopsy, which is targeted at precise removal of the “sentinel” node that manifests the highest risk for metastasis. This procedure reduces surgical complications while achieving similar outcomes in terms of disease treatment. This study, the PHENIX study (Lymph-Node Dissection in Cancer of the Cervix), was a randomized trial aiming to assess oncologic outcomes of these 2 methods for the treatment of cervical cancer. This was a phase 3, open-label, randomized trial conducted across 11 hospitals in China. The hypothesis for this trial was that sentinel-lymph-node biopsy is noninferior to pelvic lymphadenectomy. Inclusion criteria were women between the ages of 18 and 65 who were diagnosed with histologically confirmed squamous-cell carcinoma, adenocarcinoma, or adenosquamous carcinoma classified as stage IA1, IA2, IB1, or IIA1, tumor diameter of 3cm or less, no radiologic evidence or lymph-node or distant metastasis, and Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1, and no desire for fertility preservation. Exclusion criteria were complete cervix involvement precluding tracer injection, previous chemotherapy or radiotherapy, history of severe cardiac disease, deep-vein thrombosis, or other concurrent or previous cancer, pregnancy, and postpartum status. The primary outcome for this study was 3-year disease-free survival, and secondary outcomes were retroperitoneal nodal recurrence and cancer-specific survival, as well as surgical outcomes and adverse events. Final enrollment for the study included 838 patients, with 420 in the biopsy-only group and 418 in the lymphadenectomy group. The biopsy group had shorter mean operative duration, less blood loss, lower incidence or intraoperative complications, shorter duration of antibiotic use, and shorter hospital length of stay. Median follow-up was 62.8 months, and recurrences were observed in 16 cases in the biopsy group and 26 cases in the lymphadenectomy group. Disease-free survival at 3 years was 94.6% in the lymphadenectomy group (95% CI: 91.9%-96.4%) compared with 96.9% (95% CI: 94.7%-98.2%) in the biopsy group. This clearly demonstrated noninferiority ( P < 0.001). A total of 6 cancer-related deaths were reported in the biopsy group compared with 16 in the lymphadenectomy group. Cancer-specific survival at 3 years was 99.2% in the biopsy group and 97.8% in the lymphadenectomy group. Sensitivity and subgroup analyses supported these findings. In addition, sentinel-lymph-node biopsy was associated with fewer postoperative adverse events compared with pelvic lymphadenectomy (58.1% vs 71.3%, P < 0.001). These results provide evidence that both cancer-specific and disease-free survival were noninferior when comparing sentinel-lymph-node biopsy to pelvic lymphadenectomy for early-stage cervical cancer. In addition, the biopsy group showed lower retroperitoneal nodal recurrence than the lymphadenectomy group, with no instances within the study period. This supports the use of sentinel-lymph-node biopsy as a new standard treatment for the management of these cases. (Abstracted from N Engl J Med. 2025 Oct 16;393(15):1463-1474. doi: 10.1056/NEJMoa2506267.)