Chondroblastic Subtype Is Associated with Higher Rates of Local Recurrence in Skeletal Osteosarcoma

<b>Background/Objectives:</b> Locally recurrent osteosarcoma is associated with high patient morbidity and mortality, yet the risk factors for local recurrence remain incompletely understood. Therefore, the objective of this study was to comprehensively assess the impact of tumor histology, patient demographics, surgical resection, and chemotherapy delivery on the risk of local recurrence, development of metastases, and overall patient survival in osteosarcoma. <b>Methods:</b> This single-center retrospective review included 102 patients with skeletal osteosarcoma who underwent primary surgical resection between August 2001 and August 2021. Primary outcomes included the development and timing of local recurrence following primary resection. Data was abstracted from the electronic medical record, and statistical analyses were performed to identify demographic, tumor, or management (surgical and chemotherapy) related factors associated with an increased risk of local recurrence. <b>Results:</b> Locally recurrent osteosarcoma developed in 13.7% (<i>n</i> = 14) of patients after primary resection. Patients with local recurrence were more likely to have the chondroblastic subtype (57.1% versus 19.3% in those without local recurrence, <i>p</i> = 0.005). The chondroblastic subtype was associated with shorter local recurrence-free survival and overall survival than other histologic subtypes (<i>p</i> < 0.001). Resection approach, surgical margin status, histologically assessed response to neoadjuvant chemotherapy, and type and dose intensity of chemotherapy delivered were not statistically associated with risk of local recurrence. <b>Conclusions:</b> Chondroblastic histology is a risk factor for local recurrence in osteosarcoma and is associated with poor overall survival in our patient cohort.