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Metastatic Patterns Vary Substantially Between Subtypes of Soft Tissue Sarcoma

Key findings

  • This study sought to provide a comprehensive overview of the metastatic patterns of soft tissue sarcomas (STS) and their clinical course, using data from the SEER database on 2,553 patients who had metastases at diagnosis of STS
  • Extensive heterogeneity in rates of metastatic disease at presentation and organ involvement patterns was detected between different STS histologies
  • Most metastases (77%) involved the lung, but metastatic alveolar rhabdomyosarcoma most commonly affected the bones (85%) and lymph nodes (62%), and 30% of patients with leiomyosarcoma had liver metastasis
  • Disease-specific survival remained poor for patients with metastatic disease at presentation regardless of (neo)-adjuvant radiotherapy or chemotherapy
  • Histology-specific staging and surveillance guidelines are needed that account for the variable behavior of different STS subtypes

People with high-risk soft-tissue sarcoma (STS) have a 50% lifetime risk of developing metastases. Some potential sites of metastasis, including bone, liver, brain, and distant lymph nodes, are not often screened at diagnosis.

Researchers at Massachusetts General Hospital recently used the Surveillance, Epidemiology and End Results (SEER) database maintained by the National Cancer Institute to evaluate metastatic patterns of STS, treatments, and survival.

Marcos R. Gonzalez, MD, orthopaedic oncology research fellow, Santiago Lozano-Calderon, MD, PhD, orthopaedic oncology surgeon in the Department of Orthopaedic Surgery, and colleagues present their findings in the Journal of Cancer Metastasis and Treatment.


Specifically, the team analyzed SEER Research Plus Data, an extension of the SEER database that includes information on treatment strategy and outcomes. They retrieved records on 22,683 patients, including 2,553 (11%) who had metastatic disease at diagnosis. The database does not include patients who developed metastasis during the course of the disease.


By histology, the six most common STS presenting with metastasis at diagnosis were leiomyosarcoma, undifferentiated pleomorphic sarcoma, liposarcoma, synovial sarcoma, spindle cell sarcoma and alveolar rhabdomyosarcoma (A-RMS). As a percentage of cases, alveolar soft part sarcoma (44%) and A-RMS (35%) were the most common.

Metastatic Patterns

Overall, lung was the most common metastatic site (77%), followed by bone (30%), distant lymph nodes (18%), and liver (15%). However, in A-RMS, only 46% of patients had lung metastasis; instead, bone and lymph node metastases predominated (85% and 62%, respectively). In leiomyosarcoma, 30% of patients showed liver metastasis. The incidence of brain metastases was <5% across all histologies.

Treatment and Outcomes

Treatment data were available for 1,503 patients with metastasis and 27,240 without (all differences P<0.001):

  • Surgery at the primary site—42% of patients with metastases vs. 89% without
  • Amputation—14% vs. 6%
  • Chemotherapy—60% vs. 20%
  • Radiation therapy—42% vs. 47%


On multivariate analysis, receiving adjuvant or (neo)-adjuvant radiation or chemotherapy in addition to surgery was associated with improved disease-specific survival (DSS) (Hazards ratios [HR] = 0.79 and 0.76, respectively).

Patients treated with surgery, radiation, and chemotherapy had better DSS than those treated with only surgery and chemotherapy (P<0.001), but only after 12 and 24 months of follow-up. DSS at five or 10 years did not differ significantly between groups.

Patients with undifferentiated pleomorphic sarcoma had the worst DSS of the six most common STS subtypes and those with A-RMS had the best. Still, the five-year DSS for all subtypes was <20%.

One Approach Does Not Fit All

Current guidelines may not capture the unique metastatic patterns of rarer subtypes of STS. Imaging studies tailored to each tumor's specific metastatic behavior should be considered after a histopathological diagnosis is made.

of patients with soft tissue sarcomas had metastatic disease at diagnosis

of patients with soft tissue sarcomas who had metastatic disease at diagnosis underwent surgery

less risk of disease-specific mortality in patients with soft tissue sarcomas who had metastatic disease at diagnosis and underwent surgery plus (neo)-adjuvant radiation

less risk of disease-specific mortality in patients with soft tissue sarcomas who had metastatic disease at diagnosis and underwent surgery plus (neo)-adjuvant chemotherapy

Learn more about the Orthopaedic Oncology Program at Mass General

Learn more about the Orthopaedic Oncology Fellowship at Mass General

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