Determinants of metastatic phenotypes at diagnosis in prostate cancer: A population-based analysis of organotropism, disparities, and clinical implications.

Abstract

e17113 Background: Metastatic prostate cancer is biologically heterogeneous, yet metastatic sites are often grouped together in clinical decision-making. Methods: Using the National Cancer Database (2016–2022), 56,112 patients with metastatic prostate cancer at diagnosis were identified. Patients were classified into four mutually exclusive metastatic phenotypes: bone-only, distant lymph node (LN)-only, visceral organ-only (liver, lung, or brain), and multi-site disease. Multinomial logistic regression was used to estimate adjusted odds ratios (ORs) for each metastatic phenotype relative to bone-only disease. Results: Bone-only metastasis was the most common phenotype (64.5%), followed by multi-site (26.4%), distant LN-only (6.0%), and visceral organ-only disease (3.1%). Small cell/neuroendocrine carcinoma was strongly associated with visceral organ-only metastasis (OR 13.7, 95% CI 10.5–17.9) and multi-site disease (OR 6.4, 95% CI 5.3–7.8) compared with acinar adenocarcinoma. Each additional year of age was associated with lower odds of distant LN-only disease (OR 0.98 per year) but higher odds of visceral organ-only metastasis (OR 1.01 per year). Black race (OR 1.20, 95% CI 1.13–1.26) and Medicaid insurance (OR 1.18, 95% CI 1.09–1.27) were independently associated with higher odds of multi-site disease. Hispanic ethnicity was associated with increased odds of visceral organ-only (OR 1.22, 95% CI 1.01–1.48) and multi-site metastases (OR 1.20, 95% CI 1.11–1.30). Conclusions: Distinct metastatic phenotypes at prostate cancer diagnosis are strongly associated with tumor histology, age, and sociodemographic factors. These findings highlight biologic organotropism in aggressive histologic subtypes and persistent disparities in metastatic burden. Adjusted odds ratios for metastatic phenotypes relative to bone-only disease. Predictor Distant LN-only OR (95% CI) Visceral organ-only OR (95% CI) Multi-site OR (95% CI) Age (per year) 0.98 (0.98–0.98)* 1.01 (1.00–1.02)* 0.99 (0.98–0.99)* Black vs White 1.05 (0.95–1.16) 1.10 (0.96–1.26) 1.20 (1.13–1.26)* Hispanic vs Non-Hispanic 1.04 (0.90–1.20) 1.22 (1.01–1.48)* 1.20 (1.11–1.30)* Medicaid vs Private 0.67 (0.57–0.78)* 1.02 (0.83–1.26) 1.18 (1.09–1.27)* Charlson ≥3 vs 0 0.87 (0.74–1.02) 1.20 (1.00–1.44)* 1.11 (1.03–1.20)* Small cell / neuroendocrine 2.83 (2.00–4.01)* 13.69 (10.50–17.85)* 6.40 (5.29–7.75)* Adenocarcinoma w/ NE differentiation 2.70 (1.62–4.48)* 3.37 (1.78–6.36)* 3.20 (2.35–4.36)* Undifferentiated / anaplastic ------ 98.88 (21.35–457.86)* 10.96 (2.36–50.82)* Odds ratios derived from multivariable multinomial logistic regression. Bone-only metastasis served as the reference outcome. Models adjusted for demographics, insurance status, comorbidity burden, tumor grade, histology, facility type, and year of diagnosis. *p<0.05.