Extremity soft tissue sarcoma: controversial management issues

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Abstract

Unlike common malignancies, such as breast and colorectal carcinoma, where treatment modalities can be investigated with large prospective randomized trials, such an endeavor has been hampered with soft tissue sarcomas (STS) due to its rarity. In absence of such randomized clinical trials, controversy exists with regards to numerous clinically relevant questions and clinicians are left with single institutional experiences gathered either in a retrospective or prospective fashion. Some of these frequently encountered issues in the management of STS include (1) whether poorly executed biopsies affect outcome? (2) Do all unplanned excisions require re-excisions? (3) Is MRI a superior imaging modality? (4) Whether radiation should be provided pre- or post-operatively? (5) Does extent of surgical margin influence local control? (6) Is adjuvant radiation therapy necessary for stage IIB STS? (7) Does adjuvant chemotherapy influence local control? (8) Does local recurrence influence survival? We will address these topics in this review.

Introduction

Soft tissue sarcomas (STS) represent a diverse histological group of rare tumors, but they share a common embryological origin, the mesoderm. Exceptions include neurosarcomas, Ewings sarcoma and peripheral neuroectodermal tumors (PNET) that arise from the ectoderm. Of particular note, though more than 75% of the human body weight consists of soft tissue and skeleton comprise, these tumors comprise only 1% of adult malignancies and 15% of all pediatric malignancies. In 2002, approximately 8300 new cases of soft tissue tumors are expected to occur in United States, with 3900 deaths underscoring the relatively high overall mortality associated with this malignancy.

Unlike common malignancies, such as breast and colorectal carcinoma, where treatment modalities can be investigated with large prospective randomized trials, such an endeavor has been hampered with STS due to its rarity. It has been estimated that, to detect differences of approximately 10% for a given end-point, such as recurrence free-survival or overall survival, it would require around 900 patients. [1] To accomplish such enrollment would necessitate a large-scale collaborative effort between national cancer cooperative groups. In absence of such randomized clinical trials, controversy exists with regards to numerous clinically relevant questions and clinicians are left with single institutional experiences gathered either in a retrospective or prospective fashion. Some of these frequently encountered vexing issues in the management of STS will be outlined in this review.

Section snippets

Poorly executed biopsies: does it affect outcome?

Whereas biopsy frequently demands relatively few technical skills, the decision related to the performance of the biopsy require considerable thought and experience. Without appropriate planning or execution, biopsies frequently lead to adverse effects on patient prognosis and on subsequent treatment options (Fig. 1). Poorly performed biopsies, poorly placed incisions and biopsy complications can considerably compromise the subsequent local management of soft tissue tumors (Fig. 2). Before

Hazards of unplanned excisions: do all require re-excisions?

An equally difficult scenario is when a patient has undergone an unplanned total excision of a lesion for diagnostic purposes or for treatment of a benign soft-tissue mass that on permanent sections reveal the presence of a STS. Guiliano et al. reviewed their experience of surgical management of patients referred to UCLA after an unplanned excision of a sarcoma [3]. Review of the operative report from the referring institution showed that a histologic diagnosis of malignancy was not mentioned

Radiologic evaluation: CT or MRI—which is superior?

For evaluation of an extremity mass either suspicious or proven to be a soft tissue tumor, there is a limited role for plain radiographs, ultrasonography or nuclear bone scintigraphy. The current imaging modalities of choice are either contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) and debate continues regarding which of the two is superior. Several authors have performed small comparative studies, where the tumor dimensions, relationships to the investing fascia

Preoperative vs. post-operative radiation: which is superior?

Radiation therapy can be administered prior to, during or following the surgical resection with estimated local recurrence rate of approximately 5–20%. Considerable controversy exists regarding the sequencing of radiation and surgery. The theoretical advantages with the use of post-operative radiation include the following:

  • 1.

    avoid the increased risk of wound complications;

  • 2.

    in certain cases, if wide resection has been obtained and negative histological margins achieved, adjuvant radiation is

Does extent of surgical margin influence local control?

Rosenberg et al. in their seminal prospective trial evaluating the role of limb sparing surgery plus radiation compared to amputation demonstrated that the only correlate of local recurrence was the final resection margin [13]. Patients with positive margins of resection had a higher likelihood of local recurrence compared with those with negative margins, even when post-operative radiotherapy was used. Such adverse impact of positive margins has also been confirmed other investigators [8], [14]

Does adjuvant chemotherapy influence local control?

In the clinical trial conducted at the Surgery Branch of the National Cancer Institute, patients with STS after amputation or limb-salvage surgery, were randomized to adjuvant post-operative chemotherapy [22]. In addition to demonstrating an overall improvement in the disease-free survival for the chemotherapy group, patients in the limb sparing-group who received chemotherapy had a significantly lower local recurrence rate (p=0.01). This suggests that adjuvant chemotherapy can affect the local

Small, superficial, high-grade tumors (stage IIB): is adjuvant radiation therapy necessary?

Small, superficial, high grade sarcoma have been demonstrated to have a favorable 5-year survival of 91%, and this was not consistent with the designation of this group of STS in the previous AJCC staging (stage III) with the projected 5-year survival of 30%. With the inclusion of the depth of the tumor, the new AJCC staging classifies these tumors as stage IIB. For these small soft tissue tumors, controversy exists as to the extent of resection and the need for adjuvant therapy. Rydholm et al.

Does local recurrence influence survival?

The effect of local recurrence on survival remains controversial. Evans stated that it is important to distinguish the two manifestations of locally recurrent disease based upon the extent of primary resection; local recurrence following radical surgery is a grave sign whereas that following limited surgery represents “local persistence” and is often an innocent event [30]. This notion was investigated by Ueda et al. in their review of 173 patient with STS of extremity and trunk where after

Conclusions

A number of issues in the management of soft tissue sarcomas remain an enigma, primarily due to the lack of prospective randomized trials. Most analyses are performed in a retrospective manner with the associated inherent limitations of these studies. Thus, concerted efforts are warranted to identify the optimal treatment approach for these tumors and the recently established American College of Surgeons Oncology Group will play a critical role in leading Intergroup clinical trials.

Vijay P. Khatri

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