Age-related differences in outcomes and tumor characteristics of ultra-rare sarcomas: A Nation-wide Study

BACKGROUND: Ultra-rare sarcomas (URSs) are subtypes of sarcomas with an extremely low incidence (≤1 per 1,000,000), resulting in limited clinical understanding. This study aimed to investigate the clinical characteristics, overall survival (OS) outcomes, and prognostic factors of URS by using a national cancer registry database. METHODS: Patients in the Taiwan Cancer Registry, diagnosed between January 2002 and December 2019, were included. Based on ICD-O-3 histologic codes and their incidence, patients were categorized into URS, non-ultra-rare sarcoma (NURS), or non-sarcoma solid tumors (NSST). Annual percentage change (APC) and factors associated with OS were analyzed. RESULTS: Among 1,578,049 patients, 0.23% (n = 3,690) were URS, 1.93% (n = 30,503) NURS, and 97.83% (n = 1,543,856) NSST. The most common URS histologies were conventional chordoma and extraskeletal Ewing sarcoma. The incidence of URS demonstrated an increase from 2002 to 2019 (APC = 2.0), without an improvement in OS (2011-2019 vs 2002-2009 URS: HR, 1.12, 95% CI, 1.02-1.20). After multivariable adjustment, OS remained worse in URS compared with NURS (HR: 1.86, 95% CI: 1.77-1.96). Across all age groups except 0-18 years, URS patients had inferior OS to those with NURS. Notably, within individual URS histologies, age was independently associated with OS. CONCLUSIONS: Despite a rising incidence, outcomes for URSs remain poor. Age emerges as a major determinant of heterogeneity and prognosis, underscoring the need for age-stratified approaches in future research and clinical management. IMPACT: Our findings underscore the urgent need for increased awareness of URS and characterize the impact of age on these patients.