Associations between preoperative biomarkers and patient-reported outcomes after single-level lumbar discectomy: a systematic review.

Background: Single-level discectomy is among the most frequently performed spine procedures for radiculopathy due to disc herniation. Although most patients improve, a subset experiences suboptimal recovery, disability, or reoperation. Current preoperative risk stratification remains limited, highlighting the need for objective biomarkers that can improve the prediction of postoperative outcomes. The objective of this study is to review the effect of biomarkers on standard patient outcomes, identify consistencies and gaps in the literature, and outline priorities for biomarker panel standardization to support clinically meaningful prediction in discectomy. Methods: We conducted a systematic review in accordance with PRISMA guidelines. PubMed, Embase, and the Cochrane Library were searched from inception to August 27, 2025, using terms for discectomy procedures, serum/tissue biomarkers, and PROs. Eligible studies enrolled adults undergoing single-level discectomy, measured biomarkers pre- or intra-operatively, and reported associations with PROs such as Visual Analog Scale (VAS), Oswestry disability Index (ODI), or EuroQol 5-Dimension Questionnaire (EQ-5D). Three authors independently performed screening, data extraction, and risk-of-bias assessment. Risk of bias was assessed using the Newcastle-Ottawa scale for observational studies. Results: Eight studies met inclusion criteria. Given heterogeneity in biomarkers, assays, and outcome reporting, findings were synthesized narratively by biomarker class; quantitative meta-analysis was not feasible. Across cohorts, pro-inflammatory cytokines consistently predicted worse outcomes: higher preoperative interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) were associated with higher postoperative VAS and ODI scores, and higher preoperative IL-1β was associated with higher postoperative VAS scores. The acute phase reactant C-reactive protein (CRP) was associated with increased VAS scores. In addition, regulatory cytokine transforming growth factor beta 1 (TGF-β1) corresponded to worse postoperative VAS. In contrast, anti-inflammatory/type-2 signaling with higher IL-4 correlated with greater VAS improvement. Brain-derived neurotrophic factor (BDNF) was also inversely correlated with worse VAS scores in specific studies. Conclusions: Preoperative biomarker profiles provide prognostic value for patient outcomes following single-level discectomy. Standardized, prospective studies using multivariable biomarker panels are warranted to validate current findings and establish quantitative prognosis.