Management of soft tissue sarcoma of the limbs depends on the location of the primary disease within the limb as well as the presence of distant metastasis.
Localised disease (Stage I-III)
There are several decisions to be made with regards to management:
- Is surgery possible?
- If possible, is limb sparing surgery possible or appropriate?
- If surgery is not possible is radiotherapy alone a worthwhile option?
- Is radiotherapy necessary?
- In most cases radiotherapy is administered pre-operatively or post-operatively
- Is chemotherapy necessary?
Most patients should be assessed in a multi-disclipinary team to assess their potential treatment pathways. The most important decision is to determine whether surgical resection is possible, and if possible whether limb-sparing surgery or amputation should be used.
- For Stage I tumours (ie, < 5 cm), surgery alone can be considered if there is no breach of fascial compartments and clear margins (1 cm) can be obtained. If clear margins are not obtained, post-operative radiotherapy is indicated.
- Stage II and above tumours usually require a combination of surgery with radiation and/or chemotherapy
Radiotherapy
Radiotherapy has been shown in adjuvant studies to improve local control in extremity sarcomas.
- The first major trial - Rosenberg et al (1982) - found that the use of limb sparing surgery followed by adjuvant radiotherapy had equivalent survival to patients undergoing amputation. Radiotherapy did not compensate for positive margins in this trial.
- Yang et al (1992) showed significantly reduced local failure in patients with high grade sarcoma. Although there was also reduction for low grade lesions, the results were not significant.
- Pisters et al (1996), which utilised brachytherapy instead of external beam therapy, also found reduced local failure in patients with high grade sarcoma. Low grade lesions received no benefit.
There is minimal controversy that radiotherapy is useful for extremity, high grade soft tissue sarcomas, allowing patients to avoid amputation. Ongoing discussion continues whether adjuvant or neo-adjuvant radiotherapy is best. In general, neo-adjuvant therapy is associated with higher rates of wound complications (25-35% instead of 5-15%) but lower rates of long term fibrosis (35% instead of 50%). Neoadjuvant radiotherapy is often easier to deliver, as the tumour is visible on the planning scan and the scar does not require treatment.
Recommendation: Most patients should receive neo-adjuvant radiotherapy despite a higher risk of wound complications, as late effects are less common in this group and both approaches provide local control rates of 90%. The dose is 50.4 Gy in 28 fractions. If positive margins occur after surgery, a boost of 16 Gy can be delivered to the site of positive margin. Adjuvant radiotherapy (60-66 Gy) should be given if surgery was undertaken prior to referral to a radiation oncologist.
Chemotherapy
Chemotherapy generally utilises doxorubicin and/or iphosphamide. These have been the subject of two meta-analyses:
- SMAC (2000), suggesting an improvement in disease free surival and overall survival when doxorubicin was used.
- Pervaiz //et al// (2008), demonstrating that the combination of doxorubicin with ifosfamide in the adjvant setting led to significantly improved disease free survival and overall survival (absolute risk reduction of 6%).
The evidence for chemotherapy in the adjuvant setting is that ifosfamide and doxorubin combined improve overall survival compared to those that did not. Studies that did not use chemotherapy at all were not included (eg. where patients had stage I tumours that were surgically excised). The absolute risk reduction of 6% is unlikely to carry over to the stage I patients were outcomes after surgery alone are very good.
Stage IV Disease
Metastatic soft tissue sarcoma generally has a terrible prognosis.
