The Limited Evidence Base for Multilevel Lumbar Interbody Fusion and Its Consequences for Clinical Conclusions: A Systematic Review

<b>Background/Objectives</b>: Lumbar interbody fusion (LIF) is widely utilized to treat multilevel degenerative lumbar spine pathologies. This systematic review aimed to comprehensively review lateral and posterior multilevel LIF procedures and their clinical and radiographic outcomes. <b>Methods</b>: Following the PRISMA guidelines, a search of PubMed, Embase, Web of Science, and Cochrane identified eligible studies. Patient demographics, as well as clinical and radiographic outcomes were collected. Risk of bias was assessed using the MINORS criteria, while randomized trials were evaluated using the RoB-2 tool. An extensive subgroup analysis was completed when that was possible. <b>Results</b>: A total of 45 studies were included consisting of 5623 patients. The pooled outcomes indicated that TLIF demonstrated the lowest operative duration (198.7 ± 77.83 min) and LOS (5.09 ± 2.5 days), alongside favorable ODI (33.68 ± 6.43), VAS leg pain (5.39 ± 0.66), and VAS back pain (4.67 ± 0.79) score gains. Comparative evidence found that LLIF and OLIF provided advantageous radiographic improvement to the posterior approaches. Comparative evidence on techniques challenged the use of autogenous bone within PLIF, PEEK over HA/PA66 cages, and found no advantages in unilateral decompression within TLIF. There was minimal clinical difference in evidence assessing MIS (minimally invasive) vs. open-TLIF or unilateral vs. bilateral pedicle screw fixation (PSF). <b>Conclusions</b>: This is the first systematic review of the multilevel LIF literature, revealing that while pooled data favored TLIF, a publication bias was detected, and comparative evidence reported advantages for lateral and oblique approaches. Given the lack of conclusive evidence, robust study designs are needed to guide clinical decision-making for multilevel lumbar pathology.