Patterns and prognostic significance of extrapulmonary metastasis at initial diagnosis in primary bone sarcomas: a nationwide registry-based study

Abstract Background Extrapulmonary metastases in primary bone sarcomas remain poorly characterized, particularly across histological subtypes. We aimed to elucidate their incidence, associated clinicopathological factors, and prognostic impact at initial diagnosis using a nationwide registry. Methods We retrospectively analyzed 5,399 patients with primary bone sarcomas registered in the Bone and Soft Tissue Tumor Registry in Japan between 2006 and 2019. The incidence and distribution of extrapulmonary metastases were assessed by histological subtype, and associated factors were evaluated using logistic regression. Overall survival by metastatic pattern (lung-only, extrapulmonary-only, or both) was estimated using Kaplan–Meier analysis and compared using log-rank tests with adjustment for multiple comparisons. Results At diagnosis, 686 patients (12.7%) had distant metastases and 256 (4.7%) had extrapulmonary metastases, predominantly to bone (87.5%). Extrapulmonary metastases accounted for more than half of metastatic cases in Ewing sarcoma, undifferentiated pleomorphic sarcoma, and leiomyosarcoma of bone. In multivariable analysis, extracompartmental extension, skip metastasis, regional lymph node metastasis, and concomitant lung metastasis were independently associated with extrapulmonary metastasis in the analysis of the entire cohort. Skip metastasis was consistently associated with extrapulmonary metastasis in osteosarcoma, Ewing sarcoma, and undifferentiated pleomorphic sarcoma. Metastatic pattern significantly affected survival in the overall cohort, osteosarcoma, and Ewing sarcoma, but not in conventional chondrosarcoma or undifferentiated pleomorphic sarcoma. Conclusions The clinical features of extrapulmonary metastases in primary bone sarcomas differed substantially across histological subtypes. Their risk factors and prognostic impact vary by subtype, which may support histology-specific and risk-adapted systemic staging.