Beyond albumin: a systematic review, meta-analysis, and GRADE assessment of seven preoperative nutritional and inflammatory biomarkers in metastatic spine surgery.

Abstract

To evaluate the prognostic value of preoperative nutritional and inflammatory biomarkers-including serum albumin, prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), modified Glasgow Prognostic Score (mGPS), systemic immune-inflammation index (SII), and C-reactive protein/albumin ratio (CAR)-for clinical outcomes following open surgery for spinal metastases. A comprehensive literature search of PubMed/MEDLINE, Embase, Cochrane CENTRAL, Scopus, and Web of Science (January 2010-April 2026) identified studies of adult patients who underwent open surgery for histologically or radiologically confirmed spinal metastases and had at least one preoperative biomarker measurement. Percutaneous-only procedures were ineligible. Paired reviewers independently extracted data and appraised methodological quality (QUIPS tool). Effect estimates were pooled in DerSimonian-Laird random-effects models where at least two studies reported comparable metrics, and the certainty of evidence was graded with the GRADE framework. Fifteen studies (N = 6,253 patients; 14 retrospective cohorts, 1 prospective multicenter) met eligibility criteria. Serum albumin was consistently associated with overall survival (pooled HR = 1.88 per 1 g/dL decrease, 95%CI 1.60-2.20; I²=0%; p < 0.001; GRADE: LOW). PLR elevation was associated with worse survival (pooled HR = 1.50, 95%CI 1.22-1.85; I²=55%; p < 0.001). NLR showed a significant but substantially heterogeneous association (pooled HR = 2.40, 95%CI 1.12-5.12; I²=86%). PNI demonstrated a consistent protective association across three studies (OR range 0.86-0.93 per unit increase), though disparate effect measures (OR vs. HR) and endpoints (90-day mortality, wound complications, overall survival) precluded quantitative pooling. In the only prospective multicenter study (JASA; n = 336, 35 centres), mGPS was the sole independent nutritional predictor of 3-month mortality (OR = 1.99, 95%CI 1.21-3.48; AUC = 0.716). Hypoalbuminemia (< 3.5 g/dL) was associated with a 5-fold increase in 30-day mortality in 1,498 NSQIP patients (OR = 5.20, 95%CI 3.36-8.04). Preoperative nutritional and inflammatory biomarkers-particularly serum albumin, PNI, and mGPS-are consistently associated with outcomes following metastatic spine surgery. Although the certainty of evidence is predominantly LOW-to-VERY-LOW-reflecting observational study designs rather than inconsistent findings-the large effect magnitudes, biological plausibility, and cross-cohort consistency suggest that albumin and PNI may warrant consideration for incorporation into preoperative risk stratification. A tiered preoperative nutritional risk stratification pathway is hypothesised for future prospective validation. This pathway uses only routinely available laboratory values and can be readily implemented alongside existing prognostic scoring systems.