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Presurgical Chemotherapy Compared With Immediate Surgery and Adjuvant Chemotherapy for Nonmetastatic Osteosarcoma: Pediatric Oncology Group Study POG-8651

Allen M. Goorin, Douglas J. Schwartzentruber, Meenakshi Devidas, Mark C. Gebhardt, Alberto G. Ayala, Michael B. Harris, Lee J. Helman, Holcombe E. Grier, Michael P. Link

From the Department of Pediatrics, Dana-Farber Cancer Institute; Division of Medicine, Children’s Hospital Boston; Department of Pediatrics, Department of Orthopedic Surgery, Harvard Medical School; and Massachusetts General Hospital, Boston, MA; Surgical Oncology Branch and Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Statistics, University of Florida, and Pediatric Oncology Group Statistical Office, Gainesville, FL; Department of Surgical Pathology, University of Texas, and M.D. Anderson Cancer Center, Houston, TX; Tomorrows Children’s Institute, Hackensack, and University Medical Center and University of Medicine and Dentistry of New Jersey, Newark, NJ; and Department of Pediatrics, Stanford University School of Medicine, Stanford, CA.

Address reprint requests to Allen M. Goorin, MD, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; email: allen_goorin{at}dfci.harvard.edu.

Purpose: Successful therapeutic interventions to prevent disease progression in patients with nonmetastatic osteosarcoma have included surgery with adjuvant chemotherapy. Presurgical chemotherapy has been advocated for these patients because of putative improvement in event-free survival (EFS). The advantages of presurgical chemotherapy include early administration of systemic chemotherapy, shrinkage of primary tumor, and pathologic identification of risk groups. The theoretic disadvantage is that it exposes a large tumor burden to marginally effective chemotherapy. The contribution of chemotherapy and surgery timing has not been tested rigorously.

Patients and Methods: Between 1986 and 1993, we conducted a prospective trial in patients with nonmetastatic osteosarcoma who were assigned randomly to immediate surgery or presurgical chemotherapy. Except for the timing of surgery (week 0 or 10), patients received 44 weeks of identical combination chemotherapy that included high-dose methotrexate with leucovorin rescue, doxorubicin, cisplatin, bleomycin, cyclophosphamide, and dactinomycin.

Results: One hundred six patients were enrolled onto this study. Six were excluded from analysis. Of the remaining 100 patients, 45 were randomly assigned to immediate chemotherapy, and 55 were randomly assigned to immediate surgery. Sixty-seven patients remain disease-free. At 5 years, the projected EFS ± SE is 65% ± 6% (69% ± 8% for immediate surgery and 61% ± 8% for presurgical chemotherapy; P = .8). The treatment arms had similar incidence of limb salvage (55% for immediate surgery and 50% for presurgical chemotherapy).

Conclusion: Chemotherapy was effective in both treatment groups. There was no advantage in EFS for patients given presurgical chemotherapy.

Supported in part by grant nos. CA-03161, CA-05587, CA-11233, CA-15525, CA-15898, CA-20549, CA-25408, CA-28383, CA-28439, CA-28476, CA-29139, CA-29293, CA-30969, CA-32053, CA-33587, CA-33603, CA-33625, CA-41573, CA-69177, and CA-69428 from the National Institutes of Health, Bethesda, MD.

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Related Correspondence

• Preoperative Therapy Versus Immediate Surgery in Nonmetastatic Osteosarcoma
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• Surgical Expertise and Outcome in Osteosarcoma Trials
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