Reassessing the 8 cm Cutoff: Continuous Tumor Size-Mortality Risk Supports Three-Tier Staging in High Grade...

Primary tumor size is a key prognostic factor in osteosarcoma, but quantitative risk estimates and optimal thresholds remain undefined. We quantified the size-survival relationship in high-grade osteosarcoma.

We analyzed 1,807 high-grade osteosarcoma patients from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2021) using Cox regression, systematic threshold testing (40-150 mm with multiple testing corrections), and propensity score matching at the AJCC 80 mm threshold.

Each 10 mm increase in tumor size was associated with a 6.6% increased hazard of death after adjusting for age, sex, tumor site, surgery, radiation, and chemotherapy (Hazard ratio [HR] = 1.066, p < 0.001; adjusted C-index = 0.694). Binary AJCC staging demonstrated limited mortality discrimination (34.4% vs 44.4%, 10-percentage-point spread), while three-tier soft tissue sarcoma (STS)-adapted staging revealed a 21-percentage-point mortality gradient (26.6% to 47.7%) with superior adjusted discrimination (C-index = 0.695 vs 0.680, p < 0.001). All tested thresholds demonstrated significant associations, with no single optimal cutpoint identified. Polynomial testing indicated a linear relationship (p = 0.334). Propensity score matching at the AJCC 8 cm threshold of 666 patient pairs confirmed the effect (HR = 1.443, 95%-confidence interval: 1.214-1.715, p < 0.001). Polynomial testing indicated a linear relationship (p = 0.253).

Tumor size demonstrates a continuous dose-response relationship with survival. Three-tier STS staging outperforms binary AJCC classification for risk stratification.