Among individuals diagnosed with bone or soft tissue sarcoma, approximately 10% will have metastatic disease at the time of presentation,1-6 and an estimated 40% will develop metastatic disease during long-term follow-up.7,8 One of the historical challenges associated with managing patients with metastatic bone and soft tissue sarcoma has been the relative rarity of this disease: bone and soft tissue sarcoma represent only 1.1% of adult and 11.8% of pediatric malignancies in the developed world.9 Moreover, bone and soft tissue sarcomas do not behave as a single clinical entity, but actually comprise a heterogeneous group of over 50 distinct malignancies,10 each with important distinguishing features.
Management of patients with metastatic sarcoma is consequently best undertaken as a multidisciplinary effort, with input from pathology, radiology, radiation oncology, and medical and surgical subspecialties. Studies have routinely showed that these patients are best managed within a sarcoma specialty center.11,12 Although most patients with metastatic sarcoma are not treated with curative intent, selected patients with favorable histologies and clinical circumstances may experience long-term durable remissions with aggressive multidisciplinary management.
It is important for the practicing oncologist to be familiar with the natural history and the spectrum of management strategies for patients with metastatic disease.
Risk Factors for Metastatic Disease
Among patients with localized sarcoma, factors associated with risk of metastasis and disease-specific mortality in large registry studies are patient age, anatomic site of primary tumor, tumor size, tumor depth (superficial or deep to fascia), and histologic grade.13,14 The risk of metastasis appears most strongly correlated with tumor grade, with low-grade soft tissue sarcoma associated with a 10% to 20% risk of metastatic disease, compared to 40% to 50% for high-grade soft tissue sarcoma.15-17 The 7th edition of the American Joint Committee on Cancer (AJCC) Staging Manual for soft tissue sarcoma incorporates several of these factors, including tumor size (≤5 vs. >5 cm), depth (superficial or deep to fascia), regional nodal involvement, and FNCLCC histologic grade, as key components in the staging of patients with soft tissue sarcoma. Staging for bone sarcomas is similar, incorporating tumor size (≤8 vs. >8 cm), regional nodal involvement, and histologic grade.18 The general utility of the AJCC TNM staging system for predicting risk of disease-specific survival has been largely validated.13
However, tumor size, depth, and grade alone cannot fully describe a patient's risk of metastasis. In particular, tumor histology has long been known to be important in determining risk and pattern of metastases: for example, large (>10 cm), well-differentiated liposarcomas of the extremities rarely metastasize, whereas large (>10 cm), pure myxoid liposarcomas of the trunk or extremities can metastasize in up to 30% of cases.19-22 In an attempt to address the importance of histologic subtype, Kattan et al included fibrosarcoma, ...