Comparing the Outcomes of Neoadjuvant Versus Adjuvant Chemotherapy for Osteosarcoma Patients

<i>Background</i>: Neoadjuvant chemotherapy followed by surgery and subsequent adjuvant chemotherapy has been a mainstay of many osteosarcoma treatment protocols. However, the overall survival (OS) benefit over surgery and adjuvant chemotherapy is unclear. <i>Aims</i>: This study therefore directly compares the outcomes among these treatment groups using a large population in the National Cancer Database (NCDB). <i>Methods</i>: In a retrospective cross-sectional study, osteosarcoma patients in the NCDB (2004-2019) were stratified based on chemotherapy and surgery timing (neoadjuvant and adjuvant vs adjuvant-only chemotherapy). We used Kaplan-Meier curves to compare OS in the unmatched population and in a propensity score matched cohort that controlled for demographics, treatment, and tumor characteristic differences. Univariate and multivariate analyses were also used to predict the likelihood of positive margins among the population. Chi-square tests were used to compare 30- and 90-day mortality among treatment groups. P-values <0.05 were considered significant. <i>Results</i>: The study population included 4,659 patients: 3,733 neoadjuvant and 926 adjuvant-only chemotherapy regimens. Patients who underwent neoadjuvant therapy had significantly longer survival in the unmatched analysis (p<0.001), but this difference narrowed when controlling for covariates in the matched cohort (p=0.67). Mortality at 30 and 90 days was insignificant between treatment groups in both the full and matched cohorts (p=0.3 and p=0.9 respectively). Neoadjuvant chemotherapy regimens predominated with over 75% utilization, but this rate remained constant during the 15-year study period. Three- and five-year survival rates were relatively unchanged during this period at 75% and 62.5% respectively. Factors significantly associated with positive margins in the multivariate analysis included adjuvant-only chemotherapy (OR=1.6, p<0.001), older age (OR=1.01, p<0.001), female sex (OR=1.27, p=0.04), adjuvant radiation (OR=4.96, p<0.001), and stage IVB tumors (OR=2.11, p<0.001). <i>Conclusions</i>: These results indicate that neoadjuvant chemotherapy did not increase overall or short-term survival compared to adjuvant chemotherapy alone in our study. However, neoadjuvant therapy was associated with fewer positive margins at the time of surgery. These insights offer information to help clinicians evaluate osteosarcoma treatment regimens to maximize outcomes and limit treatment morbidity.