BackgroundTo compare the efficacy of ipsilateral lower neck sparing irradiation (ILNSI) versus ipsilateral lower neck prophylactic irradiation (ILNPI) for unilateral or bilateral neck node-negative nasopharyngeal cancer (NPC).MethodsA comprehensive literature search of PubMed, EMBASE, the Cochrane Library and other public databases was conducted in October, 2017. The outcomes were 3-year overall/regional recurrence-free/disease-free/distant metastasis-free survival (OS/RRFS/DFS/DMFS) and ipsilateral lower neck (ILN) recurrence. We performed subgroup analysis of ILNSI versus ILNPI for different radiotherapy techniques. Sensitivity analysis was performed to examine the stability of the results.ResultsNine head-to-head comparative studies (2, 521 patients) were included in the meta-analysis. For the comparison of ILNSI versus ILNPI, there was no significant difference in 3-year OS (HR = 1.16, 95% confidence interval [CI] = 0.85–1.58, P = 0.36), RRFS (HR = 1.37, 95% CI = 0.76–2.47, P = 0.30), DFS (HR = 1.08, 95% CI = 0.80–1.44, P = 0.62) and DMFS (HR = 1.00, 95% CI = 0.69–1.44, P = 0.99). ILNSI and ILNPI also led to equivalent ILN recurrence rates (OR = 0.98, 95% CI = 0.47–2.03, P = 0.96). No significant heterogeneity was observed for any outcome. Subgroup analysis confirmed no significant differences between ILNSI and ILNPI for any outcome, regardless of radiotherapy technique. Sensitivity analysis indicated all outcomes were highly stable in favor of the original conclusions.ConclusionsILNSI provided equivalent survival outcomes and regional control compared to ILNPI; ILNSI represents an appropriate alternative strategy for patients with unilateral or bilateral neck node-negative NPC.