Cervical cancer remains a significant health challenge, with its incidence and mortality rates being a concern, particularly in advanced stages where lymph node metastasis (LNM) is a common predictor of poor prognosis. Accurate assessment of lymph node involvement is essential for effective staging and guiding subsequent treatment decisions, including adjuvant radiation and chemotherapy.
Historically, systematic lymphadenectomy has been a standard part of staging for gynecologic cancers, as recommended by the International Federation of Gynecology and Obstetrics (FIGO). However, this extensive procedure is well-known to be associated with various complications. These include systemic morbidity (such as chest infections, thrombo-embolic events, and cardiac events) and specific complications like lymphedema and lymphocyst formation. One study revealed an overall complication rate of 42.4% for lymphadenectomy, with intra-operative complications at 26.1%, acute post-operative at 11.0%, and long-term at 14.0%. Factors like laparotomy, positive lymph nodes, and operative time exceeding 240 minutes were identified as significant predictors of overall complications. Symptomatic lymphocele and lymphedema, specifically linked to lymphadenectomy, were reported in 6.0% and 2.0% of patients, respectively. Despite these risks, the authors of that study concluded that lymphadenectomy can be performed safely.
Given the morbidity associated with systematic LND, sentinel lymph node (SLN) biopsy has emerged as a less invasive and highly accurate alternative, proving more sensitive in detecting nodal disease, including micrometastases and isolated tumor cells, compared to traditional full lymphadenectomy. However, even SLN mapping techniques carry risks such as peri-operative complications, mapping failures (occurring in 20-25% of cases, and up to 20% for surgeons early in their learning curve), and “empty node packets” where no lymph node tissue is found (up to 8% in obese patients). Furthermore, while modern imaging like PET/CT is used for evaluating LNM, it still has a false-negative rate of 6%–15% for para-aortic lymph nodes. For LACC patients, where radiotherapy is the primary treatment, there is concern that standard radiation doses may not be sufficient to eradicate enlarged lymph nodes, raising questions about whether surgical removal of these nodes could improve outcomes. This meta-analysis aimed to systematically evaluate the impact of pre-treatment LND on oncological outcomes and postoperative complications in LACC to provide clarity on this controversy.
Methodology The study utilized a systematic literature review and meta-analysis approach, adhering to the PRISMA guidelines and registered with PROSPERO. The search spanned major scientific databases (PubMed, Embase, Science Direct, Cochrane Database of Systematic Reviews) up to December 2023. Inclusion criteria focused on studies of LACC patients (FIGO 2009 stage IB2, IIA2–IVA) where LND was performed as initial treatment, compared to control groups receiving radiotherapy or chemotherapy only. Detailed patient, treatment, and outcome data were extracted, and the quality of included cohort studies was rigorously assessed using the Newcastle–Ottawa Scale. Statistical analysis involved fixed-effects models to synthesize hazard ratios (HR) for survival outcomes, with heterogeneity and publication bias (via Egger’s test) also evaluated.
Key Findings From an initial pool of 1,025 articles, the systematic review ultimately included four studies, encompassing a total of 838 women with LACC. These studies, published between 2012 and 2022, were conducted in various countries, including Spain, The Netherlands, Germany, and Taiwan. All selected studies demonstrated a low risk of bias according to the Newcastle–Ottawa scale.
The central finding of the meta-analysis indicated that pre-treatment lymph node dissection did not significantly affect overall survival (OS) in patients with locally advanced cervical cancer (HR = 1.11, 95% CI = 0.91–1.36, P = 0.30) when compared to patients receiving concurrent radiotherapy. This suggests no direct survival benefit from performing LND as an initial step for LACC.
Crucially, the study also found that pre-treatment LND did not increase the incidence of postoperative complications or cause delays in subsequent radiotherapy. This is an important finding given the known complications of lymphadenectomy discussed in other sources, particularly those associated with open surgery, which can have complication rates as high as 34% compared to 1.6%–7% for laparoscopic approaches. The meta-analysis detected no significant publication bias.
Discussion and Clinical Implications Despite the absence of a direct OS benefit, the authors emphasize the critical roles and advantages of pre-treatment LND in LACC management.
Enhanced Staging and Diagnostic Precision: Performing LND before primary treatment facilitates a precise pathological evaluation of lymph nodes, which can improve diagnostic accuracy by approximately 20%–40% compared to imaging modalities like PET-CT. This provides invaluable, concrete information for accurate surgical staging, leading to more tailored and precise treatment planning for individual patients.
Optimized Radiotherapy Planning: For patients with LNM, particularly those with enlarged positive lymph nodes (e.g., >10 mm or >2 cm), surgical removal can be therapeutically beneficial. Such large nodes are challenging to eradicate with conventional radiotherapy doses and may not be adequately covered by the radiation field. LND allows for better local control and enables surgeons to accurately delineate the radiation field, thereby minimizing potential radiation-related complications and preventing overtreatment in patients without nodal involvement.
Surgical Approach Considerations: The choice of surgical approach for LND also influences outcomes. While the study indicates no increase in overall complications from pre-treatment LND, other sources highlight the benefits of minimally invasive surgery (MIS) techniques. Robotic-assisted surgery (RAS) for pelvic lymph node dissection (PLND) may result in a greater number of resected lymph nodes, especially for cervical cancer, compared to conventional laparoscopic surgery (CLS), although RAS might involve slightly longer operative times and greater blood loss. Novel approaches like vaginal natural orifice transluminal endoscopic surgery (vNOTES) offer additional advantages such as no abdominal incisions, reduced postoperative pain, shorter hospital stays, and avoiding the Trendelenburg position which aids in ventilation for obese patients. However, vNOTES is a relatively new technique with a learning curve, and an initial cohort experienced a bladder injury rate of 5%, higher than rates typically reported for laparoscopic hysterectomies.
Prognostic Value of Lymph Node Burden: Beyond the presence of positive nodes, the lymph node ratio (LNR)—the ratio of positive to total resected lymph nodes—is recognized as a powerful prognostic tool. A higher LNR consistently correlates with worse OS, PFS, and DFS across various gynecologic cancers, including cervical cancer. This emphasizes that even if pre-treatment LND doesn’t directly improve OS, the detailed information it provides about the extent of nodal disease is profoundly significant for prognosis and for guiding adjuvant therapy choices.
Limitations and Future Directions: The authors acknowledge that the retrospective nature of most included studies and the limited sample size are significant limitations, potentially affecting the generalizability and robustness of the findings. Variability in patient characteristics and surgical techniques across studies also contributes to heterogeneity. Nevertheless, the study highlights the initiation of new prospective randomized controlled trials (e.g., Casper, NCT04555226) that are expected to provide more definitive evidence.
Conclusion In conclusion, this meta-analysis suggests that while pre-treatment lymph node dissection for locally advanced cervical cancer may not offer a clear, direct survival advantage, its diagnostic and guiding roles are invaluable. It enables accurate pathological staging and precise radiotherapy planning, potentially preventing both undertreatment of macroscopic disease and overtreatment in patients without nodal involvement, thereby reducing treatment-related complications. Furthermore, the study confirms that this LND can be performed without increasing overall postoperative complications or delaying subsequent treatment. The authors recommend that gynecologic oncologists consider tailored treatment strategies, emphasizing accurate pre-treatment lymphatic assessment to identify patients who would most benefit from LND. Further randomized controlled studies are necessary to conclusively validate the full impact of pelvic lymph node dissection in this specific patient population.