HALP score outperforms systemic inflammatory biomarkers for prognosis in locally advanced rectal cancer

The prognostic value of systemic inflammatory and nutritional biomarkers in patients with locally advanced rectal cancer (LARC) remains inadequately defined. This multicenter retrospective study comprehensively assessed the prognostic performance of twelve inflammation-based indices, aiming to identify the most informative biomarker for patients undergoing neoadjuvant chemoradiotherapy followed by surgery. We analyzed data from 427 patients with stage II-III LARC treated at three medical centers between 2010 and 2021. Twelve biomarkers, derived from routine pretreatment blood parameters-including hemoglobin, albumin, neutrophils, lymphocytes, monocytes, and platelets-were evaluated for their association with overall survival (OS) and disease-free survival (DFS). The prognostic performance was measured using the concordance index (C-index), time-dependent area under the receiver operating characteristic curve (time-AUC), and Brier score. Among the evaluated biomarkers, the hemoglobin-albumin-lymphocyte-platelet (HALP) score exhibited robust and consistent prognostic performance. For OS, HALP achieved a C-index of 0.687 and a time-AUC of 0.668, along with the lowest Brier score (0.134); similar results were observed for DFS (C-index 0.675, time-AUC 0.665). Patients with low HALP scores had significantly worse OS and DFS compared to those with high HALP scores. Multivariate Cox regression analysis confirmed low HALP as an independent risk factor for OS (HR = 3.937, 95% CI: 2.445-6.329; p < 0.001) and DFS (HR = 2.212, 95% CI: 1.577-3.096; p < 0.001). Nomograms integrating HALP with key clinicopathological variables provided incremental prognostic value, demonstrating good discrimination and calibration at 12, 36, and 60 months. These findings indicate that HALP is a simple and cost-effective biomarker for prognostic stratification in LARC.