Risk factors for the development of local recurrence in extremity soft-tissue sarcoma

ABSTRACT

Introduction

Local recurrence (LR) is one of the main pitfalls in surgery for extremities soft tissue sarcoma (eSTS). Achieving clear histopathological margins is the most important factor to reduce the risk of LR, but the ability to do so depends on not only surgical technique but also the interplay between tumor biology, anatomical location and surgical approach. The balance between postoperative morbidity and oncological benefits in reducing the risk of LR needs to be considered.

Areas covered

This review will cover which etiological factors for the development of eSTS lead to an increased risk of LR and discuss histological subtypes that have a high risk of LR and which surgical and neoadjuvant therapeutic strategies can minimize the risk of LR.

Expert opinion

The traditional view that surgical radicality always results in low rates of LR, while marginality alone always leads to high rates of relapse, is outdated. In the modern era of surgical oncology, limb salvage and high-level function after resectional surgery are the key surgical goals. The best results are achieved by combining effective neoadjuvant treatments with planned bespoke oncological operations that consider the biological and anatomical factors of each individual sarcoma.

KEYWORDS:

• Extremity soft tissue sarcoma
• isolated limb perfusion
• local recurrence
• radiotherapy
• prognosis
• surgical oncology

Article highlights

• Limb sparing surgery is the mainstay treatment for extremity soft tissue sarcoma. Adjuvant and neoadjuvant treatment (radio- and chemotherapy, systemic or regional) are integral components of the multimodal therapy for primary localized sarcoma, especially when the tumor is close to a critical anatomical structure, meaning wide clearance cannot be achieved.

• Radiotherapy decreases the risk of developing local recurrence and is highly recommended in high-risk patients. It is usually preferable for neoadjuvant treatment as it can be administered with a lower radiation dose and therefore lower toxic effects. It also determines tumor shrinkage, making limb sparing surgery feasible.

• Histotype, tumor size, anatomical location, and margin status after surgery are the most important prognostic factors for the development of local recurrence. High-grade tumors are associated with a greater risk of distant metastases, but not of local recurrence.

• In patients with extremity soft tissue sarcoma, local recurrence does not affect overall survival.

• Unplanned excisions are surgical resections that occur without the initial aim of achieving negative margins, and without adequate preoperative diagnostic investigation. Up to 60% of patients with an eventual diagnosis of extremity soft tissue sarcoma are referred to a specialist sarcoma center only after an unplanned excision. Patients who experience an unplanned excision prior to referral have a risk of local recurrence twice as high as those primarily resected at a specialist sarcoma center.

• Neoadjuvant chemotherapy, whether delivered systemically or regionally by Isolated Limb Perfusion, is the main therapeutic approach that could further reduce local recurrence rates. However, the limitations to the efficacy of traditional cytotoxic drugs, including as a result of toxicity, mean there remains a significant unmet need for drugs that are effective against sarcoma.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.