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EDITORIAL |
From the Memorial Sloan-Kettering Cancer Center, New York, New York.
Correspondence: Address correspondence to: Dr. Murray F. Brennan, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; Fax: 212-794-5845; E-mail: brennanm{at}mskcc.org
In this edition of the Annals of Surgical Oncology, Dr. Malawer and his colleagues1 provide an important and thought-provoking article. Although there is a great deal of material contained within this article, there are three central issues:
An important observation is that with the use of their method, which includes intra-arterial cisplatin, higher tumor necrosis rates approximating that seen in osteogenic sarcoma can be achieved. Although most studies of intra-arterial administration of doxorubicin (Adriamycin) have shown no benefit over intravenous administration of doxorubicin, this may not be so for cisplatin—but that still remains unproven. Such results from cisplatin would be an important finding, because attempts to reproduce the increased degree of tumor necrosis seen in osteogenic sarcoma with chemotherapy have been replicated only rarely in sarcomas of the soft tissues. Conversely, because of the added potential complication of intra-arterial injection, this approach is confined mainly to centers with considerable experience.
I have some concerns about this article. As the authors carefully point out, only 33 patients were selected from a larger number, some of whom did receive radiotherapy. As described in the text, 17 of 33 (52%) had tumors greater than or equal to 10 cm—certainly a high-risk group. Examination of the table, however, suggests that in only 12 of 33 (36%) were the tumors actually greater than 10 cm. A very fine distinction! This then becomes a very aggressive regimen for over 50% of the patients. The authors suggest that as the follow-up exceeded 2 years, the majority of patients who were going to develop recurrences would have done so. However true this may be for the "majority," only 66% of all patients who will experience recurrences do so within 2 years, and late recurrence of lower risk lesions also is common.
The authors raise the important issue of the value of a second local therapy, i.e. radiotherapy after a "good margin" resection. In prospective randomized trials, the benefit to local control by the addition of radiotherapy is about 25%; however, it may be considerably less in lesions 10 cm or less. In multiple retrospective studies, local recurrence is associated with a bad prognosis; however, the prevention of local recurrence by either amputation or radiotherapy has not translated into a survival benefit.2
It is reasonable to consider not treating patients with wide negative margins with radiotherapy, although radiotherapy does appear to have a benefit in local recurrence in other studies, independent of margin status.2 Patients with positive margins were benefited, but so too were patients with negative margins, emphasizing again the difficulty in characterizing margin status, despite our best efforts.
The central issue, however, is the one problem that beleaguers the management of soft-tissue sarcoma. It is possible to identify a high-risk group, i.e., patients with large, deep, high-grade tumors, who have a very significant risk of metastatic disease, but can treatment improve survival in that group? Local recurrence in the extremity rarely is a cause of death, whereas the development of metastatic disease usually is synonymous with ultimate death from disease.
This is the important issue in high-grade sarcoma: "the ability of preoperative systemic treatment to improve metastasis-free and long-term disease-specific survival." Attempts at developing this approach, to be led by orthopaedic oncologists, given their confidence and experience with preoperative chemotherapy for osteogenic sarcoma, would be a real advance. Such a trial has been proposed before the American College of Surgeons Oncology Group, but awaits approval and implementation as the opponents and proponents argue about the appropriateness of the study. What greater opportunity do we have to ask a meaningful question that would clearly prove, as has been done in osteogenic sarcoma, that preoperative chemotherapy is (or is not) of benefit in the survival of patients with high-risk sarcoma? The added potential benefit of limiting local recurrence and obviating the need for amputation or additional radiotherapy would be of great secondary benefit to the patient and his or her physician.
We are left with the frustrating situation that although we can minimize local recurrence in high-risk patients, we have no proven option for improving disease-specific survival in such patients.
Received for publication April 9, 2001. Accepted for publication April 17, 2001.
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