Improving the management of soft tissue sarcoma

Musculoskeletal sarcomas comprise 1% of all malignancies and have traditionally been associated with a poor prognosis. However, the past two decades have shown a dramatic improvement in prognosis for osteosarcoma and Ewing′s sarcoma when treated by teams of pathologists, radiologists, oncologists, and surgeons who can provide the necessary combination of chemotherapy, surgery, and radiotherapy. A similar evolution has also occurred in some places in the treatment of soft tissue sarcoma. However, whereas no one questions that patients with bone sarcomas should be treated at specialist tumour centres, many patients with soft tissue sarcoma (which is at least twice as common) are treated outside such centres, often with a poor outcome.

Last December Clasby et al reported recent treatment outcomes for soft tissue sarcoma in the South East Thames region of England.¹ The first surgical procedure was a marginal excision (shelling out) in two thirds of cases. Less than half of these patients were given radiotherapy or had a re-excision with wider margins. This means that almost half of the patients had inadequate treatment. Consequently, the local recurrence rate was high and, with longer follow up, recurrence will probably occur in at least a third of the patients. This poor treatment is not unique: most reports from specialist centres all over the world include a substantial proportion of patients first referred after local recurrence because of earlier inappropriate treatment.^2–4 How many patients who are not referred at all is not known. In a Swedish study the local recurrence rate was three times higher in patients treated outside a tumour centre.⁵ Local recurrence may be detrimental to the patient and is expensive. In a recent Scandinavian investigation the median cost of operation for local recurrence was £7000 (US$11 000) and a fifth of the patients needed an amputation (C Trovik, personal communication).

Soft tissue sarcomas are commoner with increasing age but do occur in younger people. Two thirds of the tumours are situated in the extremities and often present as a lump incidentally noticed by a patient in good general health with no pain or loss of function despite a tumour that may be large: the median size of deep seated extremity sarcomas is 9 cm.⁶ This presentation makes soft tissue sarcomas easy to misdiagnose as benign tumours, such as lipomas, or muscle ruptures. Optimal treatment requires preoperative staging, including magnetic resonance imaging of the tumour, chest radiographs, and biopsy (incisional or needle). For a correct diagnosis of the over 50 histological types of soft tissue sarcoma conventional light microscopy often has to be supplemented by immunohistochemistry, electron microscopy, DNA cytometry, and cytogenetics or molecular genetics.

Limb sparing procedures—often with the help of plastic surgery—can be performed in nine tenths of patients and are often combined with radiotherapy. This treatment requires referral before surgery: anatomical staging is impossible after shelling out, and the risk of local recurrence is high even after re-excision with a wider margin.⁷ Also open biopsy before referral is dangerous: outside a specialist centre wrong diagnoses are common because of inexperienced surgeons (who do not sample representative tissue) or pathologists (who do not seek second opinions).⁸ Patients managed in specialist centres are regularly followed for early detection of recurrence, either local (in 10-15% of patients) or distant (in more than a third, the commonest being pulmonary metastases). Chemotherapy and metastatectomy are increasingly used. With this treatment programme, morbidity and mortality from soft tissue sarcoma have decreased substantially.

How can we ensure that more patients get the benefit of optimal treatment? Twenty five years ago we faced the same problem as Clasby et al and started a sarcoma centre in the southern region of Sweden. We soon realised that the mere existence of a centre was not sufficient: during the first five years of our tumour service data from the Swedish national cancer registry showed that only a third of patients with soft tissue sarcoma were referred before surgery and a third were not referred at all. Most of the patients referred before surgery had been seen by orthopaedic surgeons, whereas general surgeons usually shelled out all lumps for diagnosis—Clasby et al found the same. We lacked clearcut guidelines on which tumours to select for referral from among the overwhelming numbers of benign lesions that were 200 times more common.

Based on epidemiological data we formulated the following simple guidelines: refer to our centre before surgery all patients with soft tissue lesions that are (a) larger than 5 cm or (b) deep seated (muscular) or (c) otherwise suspected of malignancy. We repeatedly lectured at local hospitals explaining the advantage of following these guidelines. We gave the same information to all medical students during their course in pathology and again during general surgery and orthopaedics. Doctors who referred patients with sarcoma before surgery were sent personal letters outlining the specific advantages for their patients. The outcome was remarkable: over the past 10 years over four fifths of all patients in our region with a deep seated soft tissue sarcoma of the extremity or trunk wall have been referred before surgery.⁹ This experience exemplifies one strategy for achieving the necessary centralisation of soft tissue sarcoma.