Local recurrence of soft tissue sarcoma. A Scandinavian Sarcoma Group Project.

The aim of this project was to investigate the diagnosis, treatment and consequences of local recurrence of soft tissue sarcoma (STS). It is based on patients reported to the Karolinska Hospital Sarcoma Register and the Scandinavian Sarcoma Group Register. Demographic and treatment data, based on 1613 adult patients reported to the Scandinavian Sarcoma Group Register by sarcoma centers in Norway, Sweden and Finland are presented. They all had STS of the extremities or trunk wall, and were diagnosed between 1986 and 1995. One third of the tumors were subcutaneous and two thirds deep-seated. The median size was 7 (1-35) cm and 75% were high grade. Metastases at presentation were diagnosed in 8% of the patients. Two thirds of the patients were referred to a sarcoma center before surgery. The preoperative morphologic diagnosis was made by fine-needle aspiration cytology in 72%. Among patients with final treatment for primary tumor at a sarcoma center (n = 1331), the surgical margins were wide or better in 76% of subcutaneous lesions, and in 58% of deep-seated lesions. Adjuvant radiotherapy has not generally been considered indicated after wide or compartmental excisions in Scandinavia. Overall, 23% of patients managed by surgery had adjuvant radiotherapy. Among patients with an intralesional or marginal excision, 44% had postoperative radiotherapy. Patients treated outside of sarcoma centers were seldom referred for radiotherapy. The crude local recurrence rate was 225/1331 (17%) among the patients with final treatment for primary tumor at a sarcoma center. The local recurrence rate after local surgery for high-malignant deep-seated STS was 103/391 (26%). The rate was 25/64 (39%) after an intralesional/marginal margin without postoperative radiotherapy versus 28/119 (24%) when radiotherapy was given. Fine-needle aspiration cytology (FNAC) was used to diagnose suspected local recurrences. 95 FNAC were performed in 86 patients from Karolinska Hospital. There were 47 local recurrences, of which 44 were diagnosed correctly by FNAC; one biopsy was inconclusive, and two lesions were incorrectly assessed as benign. 39 patients proved to have benign lesions in the scar examined cytologically on 50 occasions. None of the specimens was regarded as malignant, but in 4 cases FNAC was inconclusive. The inconclusive or false cytological diagnoses had no serious clinical consequences. Among 205 patients with local recurrence identified in the SSG Register 1987-1995, 169 patients were surgically treated. An intralesional or marginal margin was achieved in 110 of these patients, 59 of whom were also given radiotherapy. 54 of the 169 patients had a second local recurrence. The second local recurrence rate was 0.50 if the first local recurrence was treated using surgery with a marginal margin alone, compared to 0.28 if treated using either surgery with a marginal margin and radiotherapy, or a wide margin (p = 0.0008). In extremity STS, the amputation rate for local recurrences was 0.22, compared to 0.09 for primary tumors. The overall 5-year MFS was 0.72 (95% CI 0.68-0.76). High histopathological malignancy grade (Relative Risk 3.0; 95% CI 1.5-6.3) and an inadequate surgical margin (2.9; 95% CI 1.8-4.6) were independent risk factors for local recurrence. High histopathological malignancy grade and large tumor size (> 7 cm) were the most important risk factors for metastasis. Local recurrence was associated with an increased risk of metastasis (4.4; 95% CI 2.9-6.8), but an inadequate surgical margin was not a risk factor for metastasis (1.1; 95% CI 0.8-1.7). In conclusion, it is unlikely that local recurrence of STS is a major source of metastases. It nevertheless represents a costly, complicated and emotionally difficult problem. More radical surgical margins would improve the local recurrence rate, but this can hardly be achieved for center-operated patients without increasing the amputation rate. Instead, local control will improve by giving radiotherapy to all patients after marginal surgery, and to selected patients with wide margins. Radiotherapy is indicated especially after a previous open biopsy or when a local recurrence might lead to an amputation. Furthermore, radiotherapy seems indicated after local recurrence, regardless of margin or grade. The most effective way of reducing costs and detriment associated with local recurrence is to increase referral to sarcoma centers before biopsy or surgery as primary surgical margins would then improve.

Monitoring referral and treatment in soft tissue sarcoma: study based on 1,851 patients from the Scandinavian Sarcoma Group Register.

This report is based on 1.851 adult patients with soft tissue sarcoma (STS) of the extremities or trunk wall diagnosed between 1986 and 1997 and reported from all tertiary referral centers in Norway and Sweden. The median age at diagnosis was 65 years and the male-to-female ratio was 1.1:1. One third of the tumors were subcutaneous, one third deep, intramuscular and one third deep, extramuscular. The median size was 7 (1-35) cm and 75% were high grade (III-IV). Metastases at presentation were diagnosed in 8% of the patients. Two thirds of STS patients were referred before surgery and the referral practices have improved during the study. The preoperative morphologic diagnosis was made with fine-needle aspiration cytology in 81%, core-needle biopsy in 9% and incisional biopsy in 10%. The frequency of amputations has decreased from 15% in 198688 to 9% in 1995-1997. A wide surgical margin was achieved in 77% of subcutaneous and 60% of deep-seated lesions. Overall, 24% of operated STS patients had adjuvant radiotherapy. The use of such therapy at sarcoma centers increased from 20% 1986-88 to 30% in 1995-97. Follow-up has been reported in 96% of the patients. The cumulative local recurrence rate was 0.20 at 5 years and 0.24 at 10 years. The 5-year metastasis-free survival rate was 0.70.

Local recurrence of deep-seated, high-grade, soft tissue sarcoma: 459 patients from the Scandinavian Sarcoma Group Register.

This study was based on 459 adult patients with deep, high-grade, soft tissue sarcoma of extremities or trunk wall reported to the Scandinavian Sarcoma Group Register (1986-1993). All patients had their definitive surgery for primary tumor at a sarcoma center. The median follow-up was 7.5 (3-12) years. 204 patients are still alive. 68 patients had amputations and 391 underwent limb-sparing surgery. Among 183 patients with intralesional or marginal margins after limb-sparing surgery, 65% had postoperative radiotherapy and 9% of the 198 patients with wide margins. The local recurrence rate after limb-sparing surgery was 26%. The rate with an intralesional or marginal margin was 39% without postoperative radiotherapy versus 24% when radiotherapy was given. It was 25% after a wide margin, and no recurrences were noted among the 10 patients with a compartmental surgical margin. Among patients with a wide margin, a subset fulfilling criteria for a myectomy was defined. The local recurrence rate was 26% among these 62 and there was no advantage of myectomy over other wide margins. More radical surgical margins would improve the local recurrence rate, but this can hardly be achieved in center-operated patients without increasing the amputation rate. Instead, increased use of radiotherapy in all patients with inadequate margins, and to a larger extent in those with wide margins will improve local control.

Surgical margins, local recurrence and metastasis in soft tissue sarcomas: 559 surgically-treated patients from the Scandinavian Sarcoma Group Register.

The prognostic importance of surgical margins on local recurrence rates and metastasis-free survival (MFS) was studied in 559 patients with soft tissue sarcoma of the extremities and trunk wall. The patients were all surgically treated, but received no adjuvant treatment. The median follow-up for the survivors was 7.4 (range: 0.1 - 12.5) years. Independent prognostic factors for MFS were analysed by Cox models. The overall 5-year MFS was 0.72 (95% confidence intervals (CI) 0.68 - 0.76). High histopathological malignancy grade (relative risk (RR) 3.0; 95% CI 1.5 - 6.3) and an inadequate surgical margin (RR 2.9; 95% CI 1.8 - 4.6) were independent risk factors for local recurrence. High histopathological malignancy grade and large tumour size (> 7 cm) were the most important risk factors for metastasis. Local recurrence was associated with an increased risk of metastasis (RR 4. 4; 95% CI 2.9-6.8), but an inadequate surgical margin was not a risk factor for metastasis (RR 1.1; 95% CI 0.8-1.7). This study confirms that, as regards metastasis, tumour-related risk factors (malignancy grade and tumour size) are more important risk factors than treatment-related factors. Local recurrence was associated with an increased metastasis rate, whereas inadequate surgical margin was a risk factor for local recurrence but not for metastasis. Hence, the proposed causal association between local recurrence and metastasis is doubtful, and if it exists is a weak association.

Consequences of local recurrence of soft tissue sarcoma: 205 patients from the Scandinavian Sarcoma Group Register.

From the Scandinavian Sarcoma Group Register, information on 1,224 surgically-treated patients with soft tissue sarcoma (STS) of the extremity or trunk wall, diagnosed between 1987 and 1995, was collected. 205 patients, one third of whom were referred to a center with a local recurrence, had a total of 284 local recurrences. This analysis describes the treatment for these local recurrences, complications and risk of further recurrences. 169 patients were surgically treated for their first local recurrence. An intralesional or marginal margin was achieved in 110 of these patients, 59 of whom were also given radiotherapy. 54 of the 169 patients had a second local recurrence. The second local recurrence rate was 0.50 if the first local recurrence had been treated with only surgery with a marginal margin, compared to 0.28 if treated with surgery with a marginal margin and radiotherapy or with a wide margin (p = 0.0008). In extremity STS, the crude amputation rate for local recurrences was 0.22 (31 of 142)-i.e., higher than for primary tumors 0.09 (96 of 1065) (p < 0.0001). A high local recurrence rate after treatment outside of sarcoma centers has earlier been shown. We conclude that the consequences of local recurrence in terms of morbidity and costs justifies referral of STS patients for multidisciplinary evaluation and multimodality treatment.

Clinical course in synovial sarcoma: a Scandinavian sarcoma group study of 104 patients.

We analyzed treatment and outcome in 104 Scandinavian patients with synovial sarcoma in the extremities or trunk wall, diagnosed between 1986 and 1994. Only surgically treated patients without metastases at diagnosis were included. Median follow-up of survivors was 6 (3-11) years. 34 patients developed metastases. The overall 5- and 7-year survival rates were 0.76 (95% CI 0.66-0.83) and 0.69 (0.58-0.78), respectively. Large tumor size and amputation were significantly associated with impaired metastasis-free survival. Patients with local recurrence had a higher risk of metastases following the local event. Local excision with inadequate margin was associated with a higher risk of local recurrence.

Fine needle aspiration (FNA) cytology in the diagnosis of recurrent soft tissue sarcoma.

We have used FNA cytology to diagnose suspected local recurrences of soft tissue sarcoma. Since 1991, a total of 95 FNA cytologies were performed on 86 patients. There were 47 local recurrences, of which 44 were diagnosed correctly by FNA cytology; one biopsy was inconclusive, and two lesions were incorrectly assessed as benign. Thirty-nine patients proved to have benign lesions in the scar area examined cytologically on 50 occasions. None of the specimens was regarded as malignant, but in four cases FNA cytology was inconclusive. Overall, there were 5% inconclusive cytological biopsies, 0% falsely malignant and 5% falsely benign. The inconclusive and false-negative cytological diagnoses had no important clinical consequences. FNA biopsy provides a simple means of diagnosing local recurrence of soft tissue sarcoma.

Fibrosarcoma in children--a rare tumour with long-term survival even with advanced disease--a report of 3 cases.

Fibrosarcoma is a rare tumour in children. The potential of malignancy has been questioned. We present three cases of fibrosarcoma in children . The follow-up periods range from 10 to 37 years. The first patient had pulmonary metastases at the time of diagnosis in 1958. The primary tumour in fossa ischio-rectalis was resected in 1960. Lung metastases were resected in 1960 and 1989. Radiotherapy was given in 1992. He is still alive with metastases 37 years after the first manifestation of disease. The second patient had a primary tumour and several local recurrences in the mandible. He is alive without evidence of disease 4 years after resection of pulmonary metastases and 21 years after resection of the primary tumour. The third patient has no signs of recurrence or metastatic spread 10 years after a wide excision of subcutaneous tumours of the left upper arm. The cases demonstrate a special tumour-entity of low-grade malignancy, which show a good prognosis and a wide spectrum of biological behaviour.

Local recurrence of soft tissue sarcoma a risk factor for late metastases. 379 patients followed for 0.5-20 years.

We performed a retrospective analysis of 379 adult patients treated for soft tissue sarcoma. None had metastasis at the time of diagnosis and all were treated surgically. Patients who developed metastatic disease before the local recurrence were excluded. The 8-year metastasis-free survival rate in the group of 261 patients with local tumor control was 0.72, compared to 0.67 in the 118 patients with local recurrence (P 0.2). Multiple regression analysis showed that high-grade malignancy and large tumor size were risk factors for metastases. Local recurrence was not a risk factor. However, when patients with small and/or low-grade tumors were analyzed separately, local recurrence emerged as a risk factor. In this group of patients, the 8-year survival rate was 0.87 for those with local control and 0.64 for those with local recurrence (P 0.004). Local recurrence appears to be a risk factor for the development of late metastases in patients who otherwise have a low risk of metastases.