Metabolic abnormality and advanced AJCC stage at prostate cancer diagnosis: a single-center retrospective cross-sectional study

Background Metabolic status and body mass index (BMI) capture related but distinct host characteristics. We examined whether metabolic abnormality was associated with American Joint Committee on Cancer (AJCC) stages III–IV at prostate cancer diagnosis after accounting for BMI category. Methods This retrospective cross-sectional study included 324 consecutive patients newly diagnosed at one center from July 2015 to March 2026. The AJCC eighth-edition clinical prognostic stage was reconstructed from pretreatment clinical tumor, nodal, and metastatic (TNM) categories; total prostate-specific antigen (PSA); and Grade Group. Metabolic abnormality was defined as the presence of at least two of the following: hypertension, a fasting glucose level of ≥5.6 mmol/L or diabetes, a triglyceride level of ≥1.7 mmol/L, and a high-density lipoprotein cholesterol (HDL-C) level of <1.04 mmol/L. Metabolic status and a BMI of <25 or ≥25 kg/m 2 were used to classify patients into four groups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically abnormal non-obese (MANO), and metabolically abnormal obese (MAO). Logistic models were adjusted for age, current smoking, current alcohol consumption, and non-metabolic comorbidity count. An exploratory classification analysis used 100 repeats of stratified 5-fold cross-validation. Results Among the 324 patients, 214 (66.0%) had AJCC stages III–IV, and 211 (65.1%) had metabolic abnormalities. Compared with MHNO, adjusted odds ratios (ORs) for stages III–IV were 0.50 (95% CI 0.18–1.37) for MHO, 5.72 (3.10–10.58) for MANO, and 3.44 (1.58–7.50) for MAO. In an independent-terms model, estimates were 5.97 (3.46–10.30) for metabolic abnormality and 0.56 (0.31–1.03) for BMI ≥ 25 kg/m 2 . MANO and MAO estimates showed the same direction of association in separate stage analyses and at BMI cutoffs of 24 and 28 kg/m 2 . Adding phenotype changed the mean repeated cross-validated area under the curve (AUC) from 0.582 to 0.725 (paired difference: 0.143, 95% empirical interval: 0.126–0.162) and the mean Brier score from 0.222 to 0.195. Complementary NHANES and TCGA-PRAD analyses examined related PSA-based and tumor-molecular outcomes. Conclusion Metabolic abnormality was associated with AJCC stages III–IV at prostate cancer diagnosis after adjusting for BMI category and other covariates. Prospective studies with prediagnostic metabolic measurements are needed to establish temporality and clinical relevance.