Advanced soft-tissue sarcoma: a disease that is potentially curable for a subset of patients treated with chemotherapy

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Abstract

Adult patients with metastatic or locally advanced irresectable soft-tissue sarcoma (ASTS) are generally considered as incurable. Whether some of these patients achieve long-term survival after first-line treatment with chemotherapy is not known. Patients with ASTS still alive 5 years after initial treatment with a doxorubicin-containing regimen, i.e. long-term survivors, were analysed among the 2187 patients included in first-line chemotherapy protocols between 1976 and 1990 in seven trials of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC STBSG) group. 1888 patients were followed for at least 5 years. The initial clinical characteristics and the outcome of the long-term survivors were investigated. 66 of the 1888 patients were alive at 5 years and the projected 5-year survival was 8% in this series. Age or histological subtypes were similar in the long-term survivors compared with the other patients. The percentages of females (69%), of grade 1 tumours (35%), of patients with an initial performance status (PS) of 0 (63%) were significantly higher in the long-term survivors while liver metastasis (6% versus 21%) were significantly less frequent. Long-term survivors were observed in all subgroups of patients. 31, 31, 31 and 6% of the long-term survivors were in complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), respectively, after the first-line regimen. A CR to a doxorubicin-containing regimen was the major parameter correlated to 5-year survival. In multivariate analysis using a logistic model, independent parameters correlated to 5-year survival were PS, female gender, grade I tumours, and the achievement of a CR after first-line treatment, which was retained as the most powerful predictor for 5-year survival. 10 of the 66 patients died after 5 years in this series, including 8 patients in PD or SD after first-line treatment versus 2 patients in PR or CR (P=0.01). 8% of patients with ASTS are alive 5 years after first-line chemotherapy with a doxorubicin-containing regimen. Long-term survivors are observed in all prognostic subgroups of patients, in particular those achieving a CR to first-line chemotherapy.

Introduction

The prognosis of patients with irresectable or advanced metastatic soft-tissue sarcoma (ASTS) remains poor with response rates to chemotherapy ranging from 20–35% in most series and a median survival of at best 12 months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11. The treatment of ASTS is therefore generally considered as palliative. However, long-term survival can be achieved in patients with metastatic sarcoma in whom complete remission is achieved after complete resection of all metastases 12, 13, as well as in patients with locally advanced disease when adequate surgery is rendered possible by preoperative chemotherapy [14]. However, whether long-term survival can be achieved in patients with irresectable metastatic or advanced sarcoma treated with chemotherapy has seldom been addressed in a large prospective series of ASTS [15]. If long-term survival can be achieved in some patients with ASTS treated with chemotherapy, the therapeutic strategy may be significantly modified for subsets of patients.

The objectives of this study were to evaluate the frequency and the clinical characteristics of long-term survivors in patients with ASTS. With this aim, we performed a retrospective study of long-term survivors in a database of 2187 patients treated with a doxorubicin-containing regimen between 1976 and 1990 in trials carried out by the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC STBSG) 2, 3, 4, 5, 6, 7, 8.

Section snippets

Database

This study was performed retrospectively using a database involving 2187 patients ASTS, treated with a doxorubicin-containing regimen as first-line chemotherapy, within 7 prospective EORTC STBSG studies between 1976 and 1990 1, 2, 3, 4, 5, 6, 7, 8 (Table 1). Of these 2187 patients, 1888 (86%) had a minimum follow-up of 5 years since the initiation of chemotherapy: 66 were alive at 5 years, and 1822 had died within the first 5 years. The chemotherapy regimens used in these studies were:

Results

The median overall survival of the series of 2187 patients was 354 days (11.7 months). 355 patients were still alive in October 2000. The survival estimate was 8% at 5 years, 7.6% at 6 years, 6.8% at 7 years and 5.6% at 8 years (standard error <1%). No deaths were recorded beyond 8 years; 9- and 10-year survival estimates were therefore also 5.6%. Among the 66 patients alive at 5 years, 10 died beyond 5 years after inclusion. The 6-, 7- and 8-year survival estimates for 5-year survivors were

Discussion

These results show that ASTS is not an incurable disease: 8% of these patients are alive 5 years after initial diagnosis, and the majority of them experience long-term survival afterwards. Several clinical parameters, such as gender, PS, tumour grade and liver metastasis were found to be correlated to 5-year survival in univariate and multivariate analysis, and independent prognostic factors for 5-year survival were actually similar to those correlated to overall survival since the inclusion in

Acknowledgements

This work was supported by the Prix Pierre Bardoux.

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    on behalf of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG), EORTC, 1200 Brussels, Belgium.

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