Landscape of ultra-rare sarcomas: a nationwide study for epidemiology and prognosis

The concept of 'ultra-rare sarcoma' was established to raise awareness of the clinical challenges resulting from its rarity. Given the novelty of this classification and the consequent paucity of data, this study aimed to investigate the epidemiology and prognosis of ultra-rare sarcomas.

We analyzed data from the Bone and Soft Tissue Tumor Registry in Japan from 2001 to 2019, comparing ultra-rare and non-ultra-rare sarcomas. To assess the prognostic impact of ultra-rare sarcomas, we used Kaplan-Meier survival analysis with propensity score matching, multivariate analysis, and a machine learning technique known as random survival forest.

Among the 22 821 patients analyzed, ultra-rare sarcomas accounted for 18.9% of the cases. Ultra-rare bone sarcomas were older than non-ultra-rare bone sarcomas (mean age: 57.6 versus 39.2 years, P < 0.001), while ultra-rare soft tissue sarcomas appeared in younger patients (mean age: 49.4 versus 62.2 years, P < 0.001). For patients >80 years old with bone sarcomas and those <20 years old with soft tissue sarcomas, ultra-rare sarcomas constituted approximately half of the cases. Survival analysis indicated that ultra-rare bone sarcomas were associated with longer survival (P = 0.022), whereas ultra-rare soft tissue sarcomas showed no significant difference in overall survival (P = 0.052). When stratified by age, however, patients <40 years old with ultra-rare soft tissue sarcomas had shorter survival (P < 0.001). Multivariate analysis indicated hazard ratios of 0.73 for ultra-rare bone and 1.25 for ultra-rare soft tissue sarcomas. Random survival forest showed that the importance of ultra-rare sarcomas was relatively low compared with other parameters.

Ultra-rare sarcomas are more common among older bone sarcoma patients and younger soft tissue sarcoma patients. Young patients with ultra-rare soft tissue sarcomas have a significantly worse prognosis. Overall, while ultra-rare sarcomas have a generally minor impact on prognosis, their effects are more pronounced in specific age groups.