Management of clinically node-negative early-stage oral cancer: network meta-analysis of randomized clinical trials

The best treatments for the clinically node-negative (cN0) neck in early-stage oral squamous cell carcinoma (OSCC) patients are a subject of ongoing debate and there is no consensus. A network meta-analysis (NMA) of randomized clinical trials (RCTs) was conducted to determine the most effective treatment and to rank treatments based on their effectiveness. A systematic search was performed in accordance with the PRISMA guidelines to retrieve RCTs that compared therapeutic neck dissection (TND), sentinel lymph node biopsy (SLNB), and elective neck dissection (END). The outcomes analysed were overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and nodal recurrence. Hazard ratios and risk ratios were calculated by direct meta-analysis and NMA. Ten RCTs with a total of 1858 patients were eligible for inclusion. Direct meta-analysis showed END to be superior to TND and comparable to SLNB. The NMA revealed no statistically significant difference between END and SLNB (very low quality evidence) regarding OS, DSS, DFS, and nodal recurrence. However, END was found to significantly improve OS and DFS, and reduce nodal recurrence when compared to TND (moderate quality evidence). END ranked as probably the top treatment option for maximizing OS and DSS, and reducing nodal recurrence in early-stage OSCC, followed by SLNB and TND. There was very low quality evidence supporting SLNB as non-inferior to END for patients with early-stage OSCC. This NMA yielded favourable results for the use of END (with moderate quality evidence) in early-stage OSCC patients, although excellent results have also been obtained with SLNB. However, data in the literature for SLNB are scarce, as this technique has not yet been formalized in many countries. There is a need to further explore SLNB for early-stage OSCC patients, as well as its value in detecting occult lymph node metastases on the contralateral side. More studies comparing morbidity, quality of life, and costs between the different management strategies for the clinically negative neck in early-stage OSCC patients are needed.