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© 2003 American Society for Clinical Oncology
Preoperative Therapy Versus Immediate Surgery in Nonmetastatic OsteosarcomaDepartment of Musculoskeletal Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy To the Editor: The study by Goorin et al1 is an important tool for the definition of associated treatment of nonmetastatic osteosarcoma of the extremities. The rationale for preferring neoadjuvant to adjuvant treatment, as stated by Rosen in 1979,2 is not valid anymore; in fact, according to Rosen, the advantages of neoadjuvant chemotherapy in comparison with adjuvant chemotherapy were: (a) offering the surgeon the time necessary to have a custom-made prosthesis, therefore the possibility to make a reconstruction and thereby avoid amputation, (b) immediate treatment of micrometastases, (c) the opportunity to choose the most appropriate postoperative treatment according to the rate of necrosis observed in the resected specimen, and (d) reduction of tumor mass, making a limb salvage operation easier. These "advantages" are not valid anymore, because today new prostheses and other biologic techniques used for reconstruction are immediately available, and chemotherapy is usually restarted 3 to 5 days after surgery. Moreover, because postoperative salvage chemotherapy with drugs different from those used before surgery was proven not to improve the prognosis of poor responder osteosarcoma patients, today, at Rizzoli, as well as at other institutions, all four active drugs in osteosarcoma (high-dose methotrexate, cisplatin, doxorubicin, and ifosfamide) are used regardless of the histologic response; neither type of surgery is dependent on the histologic response. So the use of a preoperative treatment actually represents a risk of metastasis-dissemination for approximately 30% of patients with poor response to chemotherapy. For these reasons, we agree with Goorin et al1 that the choice of performing adjuvant or neoadjuvant treatment should be made on an individual basis. However, our concern about Goorin’s paper is the high number of amputations performed (50% in both groups treated with adjuvant and neoadjuvant chemotherapy). This is a general problem with multi-institutional osteosarcoma studies that show rates of limb salvage much lower than those of mono-institutional protocols. In a recent review of the literature,3 we observed that the number of amputations performed in multicentric studies was almost double that of monoinstitutional studies, without significant differences in local recurrences. Similar rates were observed for patients treated in other monoinstitutional studies at Debré Hospital (10%),4 at the University of Vienna (15%),5 at G. Roussy Hospital (20%),6 at the University of Muenster (20%),7 and at Memorial Sloan-Kettering Cancer Center (20%),8 whereas multicentric trials had rates similar to those of the Goorin et al trial: COSS-86: 60%,9 Children’s Cancer Group: 57%,10 and SSG-VIII: 65%.11,12 This is not surprising; in fact, in the Goorin et al study, 100 patients were treated over the course of 7 years in 37 different institutions, meaning that the mean number of patients treated by each institution participating in the study was one patient every 3 years. The same happened in other multicentric studies. In the COSS studies, according to Bielack et al,13 480 patients were treated over an 18-year period in 133 institutions—approximately one case every 5 years. In a lesser proportion, this was also the case for SSG-VIII (one case per year in every center) and for the Children’s Cancer Group study (two cases per year per center). In other words, although in monoinstitutional studies, surgery is performed by teams that treat 30 to 50 osteosarcoma patients per year, in multicentric trials, many patients are operated on in institutions that treat very few osteosarcoma cases. Unfortunately, papers on multicentric trials do not report types of surgery performed according to center and number of patients treated per year. Our opinion is that orthopedic surgeons and medical oncologists having the opportunity to treat one osteosarcoma patients every 3 to 5 years or more may not have enough experience to offer them the best treatment possible. For this reason, we think that in rare tumors, such as osteosarcomas, effort should be made toward centralization of treatment in highly specialized institutions, at least for surgery. If numbers are important for the solution of medical questions, we believe that the patient’s right to receive the best care is even more important. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The authors indicated no potential conflicts of interest. REFERENCES
1. Goorin AM, Schwartzentruber DJ, Devidas M, et al: Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric Oncology Group Study POG-8651. J Clin Oncol 21:1574–1580, 2003 2. Rosen G, Marcove RC, Caparros B, et al: Primary osteogenic sarcoma: The rationale for preoperative chemotherapy and delayed surgery. Cancer 43:2163–2177, 1979[CrossRef][Medline] 3. Bacci G, Ferrari S, Longhi A, et al: Neoadjuvant chemotherapy for osteosarcoma of the extremity: A comparison of the results of single institution vs multicentric trials. Oncol Rep (in press). 4. Delepine N, Delepine G, Desbois JC: A monocentric therapy study: An approach to optimize the results of the treatment of osteosarcoma by protocols based upon HDMTX, associated with systematic conservative surgery, in Humphrey GB (ed): Osteosarcoma in Adolescent and Young Adults. Boston, MA, Kluver Academic Publisher, 1993 5. Sluga M, Windhager R, Lang S, et al: Local and systemic control after ablative and limb sparing surgery in patients with osteosarcoma. Clin Orthop 358:120–127, 1999 6. Kalifa C, Razafindrakoto H, Vassal G, et al: Chemotherapy in osteogenic sarcoma: The experience of the pediatric department of the Gustave Roussy Institute, in Humphrey GB (ed): Osteosarcoma in Adolescent and Young Adults. Boston, MA, Kluver Academic Publisher, 1993 7. Lindner NJ, Ramm O, Hillmann A, et al: Limb salvage and outcome of osteosarcoma: The University of Muenster experience. Clin Orthop 358:83–89, 1999 8. Meyers PA, Heller G, Healey J, et al: Chemotherapy for nonmetastatic osteogenic sarcoma: The Memorial Sloan-Kettering experience. J Clin Oncol 10:5–15, 1992[Abstract]
9. Fuchs N, Bielack SS, Epler D, et al: Long-term results of the co-operative German-Austrian-Swiss Osteosarcoma Study Group’s protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs. Ann Oncol 9:893–899, 1998
10. Provisor AJ, Ettinger LJ, Nachman JB, etal: Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy: A report from the Children’s Cancer Group. J Clin Oncol 15:76–84, 1997
11. S 12. Smeland S, Muller C, Alvegard TA, et al: Scandinavian Sarcoma Group Osteosarcoma Study SSG VIII: Prognostic factors for outcome and the role of replacement salvage chemotherapy for poor histological responder. Eur J Cancer 39:488–494, 2003[CrossRef][Medline]
13. Bielack SS, Kempf-Bielack B, Delling G, et al: Prognostic factors in high-grade osteosarcoma of the extremities or trunk: An analysis of 1702 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol 20:776–790, 2002
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Copyright © 2003 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ter G, Wiebe T, Wiklund T, et al: Chemotherapy in osteosarcoma: The Scandinavian Sarcoma Group experience. Acta Orthop Scand 285:74–82, 1999 (Suppl)
