Time to treatment initiation and overall survival in osteosarcoma: a national cancer database analysis

Patients with rare diseases, such as osteosarcoma, often experience diagnostic delays, and clinicians have limited evidence-based guidelines to inform care. Time to treatment initiation (TTI), the interval between a definitive diagnosis and the start of a definitive treatment, has emerged as a prognostic factor for various cancer types. However, the relationship between TTI and survival outcomes has not been established in patients with high-grade, localized osteosarcoma. The aim of this study was to evaluate the impact of TTI on overall survival in patients with this aggressive bone sarcoma.

The National Cancer Database was queried from January 2004 to December 2021 to identify all patients with histologically confirmed high-grade, localized osteosarcoma. Survival analysis was conducted using Kaplan-Meier curves and Cox regression modelling controlling for clinically pertinent covariates.

A total of 3,750 patients were included. Overall survival was significantly higher in the cohort that experienced TTI of less than four weeks in Kaplan-Meier analysis (p < 0.001, log-rank test). Univariable Cox regression conveyed a significant association between prolonged TTI and overall survival (hazard ratio (HR) 1.03 per week of delay; 95% CI 1.02 to 1.04; p < 0.001). However, there was no statistically significant relationship following multivariable Cox regression (HR 1.01; 95% CI 0.99 to 1.02; p = 0.284).

Prolonged TTI was associated with increased mortality, although not independently. Multicollinearity between covariates and TTI complicates the interpretation, making it unclear whether TTI itself or related factors primarily influence survival. Nevertheless, prompt treatment initiation remains a reasonable clinical goal to help minimize avoidable delays and support coordinated, timely care.