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Primary Metastatic Osteosarcoma: Presentation and Outcome of Patients Treated on Neoadjuvant Cooperative Osteosarcoma Study Group Protocols

From the St Anna Children’s Hospital and Departments of Orthopaedics and Pathology, University Hospital of Vienna, Vienna, Austria; Centre for Pneumonology and Thoracic Surgery, Grosshansdorf; Department of Pediatrics, University Hospital of Hamburg, Hamburg; Charite, Campus Berlin-Buch, Robert Roessle Klinik, Berlin; Department of Orthopaedics, University Hospital of Muenster, and Department of Pediatric Hematology and Oncology, University Children’s Hospital Muenster, Germany; and Institute for Pathology, Kantonsspital Basel, Basel, Switzerland.

Address reprint requests to Leo Kager, MD, Cooperative German-Austrian-Swiss Osteosarcoma Study Center, Department of Pediatric Hematology and Oncology, University Children’s Hospital Muenster, Albert-Schweitzer Str 33, 48129 Muenster, Germany; email: coss{at}uni-muenster.de.

Purpose: To determine demographic data and define prognostic factors for long-term outcome in patients presenting with high-grade osteosarcoma of bone with clinically detectable metastases at initial presentation.

Patients and Methods: Of 1,765 patients with newly diagnosed, previously untreated high-grade osteosarcomas of bone registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies before 1999, 202 patients (11.4%) had proven metastases at diagnosis and therefore were enrolled onto an analysis of demographic-, tumor-, and treatment-related variables, response, and survival. The intended therapeutic strategy included pre- and postoperative multiagent chemotherapy as well as aggressive surgery of all resectable lesions.

Results: With a median follow-up of 1.9 years (5.5 years for survivors), 60 patients were alive, 37 of whom were in continuously complete surgical remission. Actuarial overall survival rates at 5 and 10 (same value for 15) years were 29% (SE = 3%) and 24% (SE = 4%), respectively. In univariate analysis, survival was significantly correlated with patient age, site of the primary tumor, number and location of metastases, number of involved organ systems, histologic response of the primary tumor to preoperative chemotherapy, and completeness and time point of surgical resection of all tumor sites. However, after multivariate Cox regression analysis, only multiple metastases at diagnosis (relative hazard rate [RHR] = 2.3) and macroscopically incomplete surgical resection (RHR = 2.4) remained significantly associated with inferior outcomes.

Conclusion: The number of metastases at diagnosis and the completeness of surgical resection of all clinically detected tumor sites are of independent prognostic value in patients with proven primary metastatic osteosarcoma.

Related Correspondence

• Metastatic Osteosarcoma: A Curable Advanced Malignancy
  Bruce E. Brockstein
  JCO 2004 22: 5017 [Full Text]

Related Reply

• In Reply:
  Leo Kager, Andreas Zoubek, and Stefan Bielack
  JCO 2004 22: 5017-5018 [Full Text]

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