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10.1245/ASO.2005.03.097
Annals of Surgical Oncology 12:10-17 (2005)
© 2005 Society of Surgical Oncology
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Original Article

The Indications for and the Prognostic Significance of Amputation as the Primary Surgical Procedure for Localized Soft Tissue Sarcoma of the Extremity

Michelle A. Ghert, MD, FRCSC1, Adesegun Abudu, MSc, FRCSC1, Natasha Driver1, Aileen M. Davis, PhD2, Anthony M. Griffin, BSc1, Dawn Pearce, MD, FRCPC3, Lawrence White, MD, FRCPC3, Brian O’Sullivan, MD, FRCPC4,5, Charles N. Catton, MD, FRCPC4,5, Robert S. Bell, MD, MSc, FRCSC1,5 and Jay S. Wunder, MD, MSc, FRCSC1,5

1 University Musculoskeletal Oncology Unit, Mount Sinai Hospital, 600 University Avenue, Suite 476E, Toronto, Ontario M5G 1X5, Canada
2 Research, Toronto Rehabilitation Institute, 550 University Avenue, Toronto, Ontario M5G 2A2, Canada
3 Department of Diagnostic Imaging, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada
4 Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada
5 Sarcoma Site Group, Princess Margaret Hospital, University of Toronto, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada

Correspondence: Address correspondence and reprint requests to: Jay S. Wunder, MD, MSc, FRCSC; E-mail: wunder{at}mshri.on.ca


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: The indications for primary amputation of a localized soft tissue sarcoma (STS) of the extremity are not well defined in the literature. However, it has been suggested that patients who require an amputation to treat an STS are at increased risk for developing metastases. We categorized the main indications for primary amputation in our patient population and compared their oncological outcome with the outcome of patients who underwent limb-sparing surgery.

Methods: 413 consecutive patients treated surgically at a single center for primary, non-metastatic, deep, intermediate-, or high-grade STS of the extremity were reviewed. Indications for primary amputation were identified. Demographics and outcomes were compared between the amputation and limb-salvage groups. Multivariate Cox model analysis was used to identify independent risk factors for systemic relapse.

Results: Twenty-five (6%) of 413 patients with STS underwent primary amputation: they were older (P = .05), had larger tumors (P = .001), and had a significantly greater risk of developing metastatic disease than patients who underwent limb-sparing procedures (P = .008). However, multivariate analysis demonstrated that the only independent predictors of systemic relapse were tumor size (P = .0001) and tumor grade (P = .0001). Primary amputation was not an independent risk factor for metastatic disease.

Conclusions: The decision to perform a primary amputation for an STS of the extremity is based on the location and local extent of the tumor, and the expected function of the extremity after tumor resection. The higher risk of metastases for patients who require primary amputation is accounted for by independent risk factors associated with their tumors—predominantly large tumor size.

Key Words: Amputation • Soft-tissue sarcoma • Indications • Prognosis • Metastasis


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The aim of local management for patients with extremity soft tissue sarcoma (STS) is complete tumor resection without local tumor relapse. Historically, amputation was the preferred surgical treatment for achieving this objective.1–3 However, there has been a considerable shift in surgical strategy from amputation toward conservative limb-sparing surgery because of improved imaging techniques, surgical expertise at specialist treatment centers, and the use of adjuvant radiotherapy. Current multidisciplinary management involving surgery and adjuvant radiotherapy allows many patients who would have been treated with amputation in the past to undergo limb-sparing procedures.1–4

Despite these advances in local management of STS, a small group of patients remain unsuitable for limb-preserving surgery and require amputation. The indications for amputation have not been well defined in the literature. Recent studies have focused on amputation for locally recurrent disease but not as primary surgical management at initial presentation.5–7 Our aims were to identify the indications for amputation at initial presentation for patients with extremity STS and to determine whether patients who require a primary amputation have a worse prognosis than those who undergo limb-sparing surgery as the initial surgical management.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
We reviewed the records of 532 patients who presented with a deep, intermediate-, or high-grade STS of the extremity and underwent surgical treatment at our center between January 1986 and March 2000. Sixty-six patients presented with metastatic disease and were excluded. Fifty-three patients presented to our institution with recurrent disease after resection elsewhere and were also excluded. Patients who underwent unplanned excision at another institution before referral were included in this study. Therefore, 413 patients remained to serve as the focus of this investigation. All patients underwent staging studies that included computed tomographic scan of the chest and magnetic resonance imaging and/or computed tomographic scan of the involved limb. Histological confirmation of sarcoma was obtained in all patients before definitive surgical management. After review at our multidisciplinary tumor board, a treatment strategy involving surgery with or without adjuvant radiation was devised for each patient. No patient received chemotherapy. The clinical charts, prospectively collected database records, radiological investigations, and pathologic records were reviewed. Documented reasons for amputation were identified and categorized. The patients were divided into two groups according to their primary tumor management: limb salvage or primary amputation.

Descriptive analysis of the demographic characteristics and oncological outcomes of the amputation and limb salvage groups were compared by using the independent t-test for continuous variables and Fisher’s exact test or {chi}2 analysis for dichotomous variables. Metastasis-free survival (defined as the time from surgery to the time of systemic relapse) for the two groups was compared by using the Kaplan-Meier method.8 Survival was censored at the time of last follow-up. The Cox proportional hazards model9 was used to determine whether amputation was an independent predictor of metastasis-free survival compared with limb preservation surgery after controlling for known prognostic factors in the model.10,11


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Twenty-five (6%) of the 413 patients underwent primary amputation as initial surgical management. We identified three major indications to perform a primary amputation (Table 1Go). The rates of amputation in patients with upper extremity and lower extremity sarcomas were similar. Three (3%) of the 99 patients who presented with an upper extremity sarcoma had an amputation, compared with 22 (7%) of the 314 patients who presented with a sarcoma of the lower extremity.


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  		TABLE 1. Indications for a primary amputation
 
In the lower extremity, 12 patients had primary amputation because complete local excision of the tumor would have resulted in grossly inadequate function of the limb (type 1 indication for a primary amputation; Fig. 1Go). Seven patients with large tumors involving multiple compartments that would require composite tissue resections including muscle compartments, major blood vessels, nerves, and bone underwent primary amputation (type 2 indication; Fig. 2Go). One patient in this group had multifocal disease. In three patients, amputation was required because excessive soft tissue and joint contamination had resulted during unplanned surgery before referral (type 3 indication).



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  		FIG. 1. Type 1 indication: severe functional impairment expected. A 40-year-old man presented with a synovial sarcoma on the plantar aspect of the right foot. A sagittal T2-weighted (TR, 3500 msec; TE, 90 msec) fast-spin echo image of the foot with fat suppression (A) demonstrated a high-signal heterogenous mass on the plantar aspect of the foot extending from the hindfoot to the proximal forefoot. A corresponding coronal T2-weighted (TR, 3500 msec; TE, 90 msec) fast-spin echo image with fat suppression (B) verified that the mass involved the talocalcaneal joint. Wide resection would have involved excision of the major functional joints and structural supports of the foot. As a result, the patient underwent below-knee amputation.

 


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  		FIG. 2. Type 2 indication: composite tissue involvement. A 76-year-old man presented with a dedifferentiated liposarcoma of the right thigh. An axial T1-weighted (TR, 800 msec; TE, 10 msec) image (A) through the right thigh demonstrated a large multilobulated mass encasing the sciatic nerve and femoral neurovascular bundle. The posterior component of the mass was predominantly composed of fat signal (white arrows) and involved the posterior compartment of the thigh. The more anterior and higher-grade component (*) lay predominantly within the vastus medialis muscle and was of intermediate signal. A corresponding sagittal T1-weighted (TR, 800 msec; TE, 10 msec) image (B) demonstrated encasement of the femoral neurovascular bundle (black arrow) by the dedifferentiated component of the tumor (*). The patient underwent primary above-knee amputation because of multicompartment and composite tissue involvement.

 
In the upper extremity, three patients had a tumor with complex neurovascular structure involvement that would require resection of multiple major peripheral nerves and vessels. Limb salvage in these patients was therefore expected to result in a functionally impaired limb (type 1 indication). Two patients underwent forequarter amputation for gross invasion of the brachial plexus and axillary vessel, and one underwent above-elbow amputation for gross involvement of both the median and ulnar nerves and the brachial vessels (Fig. 3Go).



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  		FIG. 3. Type 1 indication in the upper extremity involving complex neurovascular structure involvement. A 48-year-old woman presented with a neurosarcoma of the right arm and elbow. An axial T1-weighted (TR, 800 msec; TE, 10 msec) image of the arm (A) and a corresponding axial T2-weighted (TR, 3500 msec; TE, 90 msec) fast-spin echo image with fat suppression (B) demonstrated a large heterogeneous mass in the anterior aspect of the distal arm arising along the neurovascular bundle. The patient underwent primary above-elbow amputation because of extensive involvement of the neurovascular structures and the expectation of severe functional impairment with limb salvage (type 1 indication).

 
Table 2Go compares the demographics and outcomes of the two patient groups. The patients who underwent amputation were significantly older at presentation compared with those who underwent limb salvage (61 vs. 54 years; P = .05). The tumors in the amputation group were also significantly larger (maximum diameter, 13 vs. 9.3 cm; P = .001). With the numbers available in the study group, we did not find a statistically significant difference between the two groups with respect to sex, tumor location, previous unplanned excision, tumor grade (2 vs. 3), or American Joint Committee on Cancer/International Union Against Cancer staging.12 Even though negative margins were more common in the amputation group (100% vs. 81%; P = .05), there was no significant difference in local recurrence between the two groups (P = .25). However, with relatively small numbers in the study group, this result may reflect a type II error.


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  		TABLE 2. Univariate comparison of patient demographics and outcomes
 
Figure 4Go illustrates the metastasis-free survival curves for both surgical groups. The estimated 5-year metastasis-free survival rate of 32% for patients treated by primary amputation was significantly worse than 62% for the limb-salvage group (P = .008; log rank). To control for additional factors that may affect the risk of developing metastatic disease, a multivariate time-dependent analysis was performed with the Cox regression model (Table 3Go). Factors initially entered into the model were chosen because they are known or suspected to be prognostic for metastasis-free survival (i.e., tumor size, tumor grade, and primary amputation).2,13,14 In this group of 413 patients, univariate analysis confirmed that besides primary amputation, only large tumor size (P = .001) and high histological grade (P = .001) predicted worse systemic outcome. The only factors that were identified as independent predictors of systemic relapse by multivariate analysis were tumor size (P = .0001) and tumor grade (P = .0001). The performance of a primary amputation was not an independent risk factor for metastases.



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  		FIG. 4. Kaplan-Meier curves showing metastasis-free survival for patients treated with limb-salvage surgery and primary amputation. Survival was censored at the time of last follow-up for patients who remained free of systemic disease and is indicated by vertical lines on the graph. The risk of metastasis was significantly higher in the amputation group compared with the limb-salvage group (P = .008).

 

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  		TABLE 3. Multivariate analysis of independent risk factors for metastasis
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Most patients with an STS of the extremity can be treated with limb-sparing surgery with or without adjuvant radiotherapy, without increasing their risk for local tumor relapse or metastatic disease.1,4,15–17 Amputation is rarely required to treat these patients.5–7 Extensive locally recurrent disease is a common indication for amputation.5–7 We sought to characterize the factors that lead to primary amputation and to investigate whether patients undergoing primary amputation can expect an inferior oncological outcome.

The factors that led to a primary amputation in this series differed on the basis of the anatomical location of the lesion. In the lower extremity, the expectation that inadequate function of the limb would result from complete tumor clearance (type 1) or composite tissue involvement (type 2) was the most frequent indication for amputation. In the upper extremity, invasion of major neurovascular structures was the most common reason to expect severe functional impairment with limb salvage and, therefore, to perform a primary amputation.

One reason for this difference between the upper and lower extremity has been the successful use of vascular reconstruction for lower extremity sarcomas that encircle the major vessels. When vascular resection and reconstruction are performed in the lower extremity, the major nerves can frequently be preserved for adequate limb function.18–23 However, even resection of a major nerve in this setting, including the sciatic nerve, can be tolerated quite well by the patient, with the expectation of an acceptable functional result compared with amputation.24 In comparison, vascular involvement in the upper extremity was generally accompanied by gross encasement of multiple major nerves by tumor, thus precluding limb salvage procedures. All 16 patients with vascular reconstructions who were included in this study had lower extremity tumors, whereas concomitant involvement of the brachial plexus or both the median and ulnar nerves together with the axillary or brachial vessels precluded vascular reconstruction in patients with upper extremity sarcomas.

Patients with prior unplanned resection of an STS present a challenge to the musculoskeletal oncologist. When possible, further surgery to re-excise the contaminated tumor bed, with or without radiation, is recommended.25–27 Approximately half of such cases will demonstrate residual tumor after re-excision of the tumour bed, and failure to completely remove residual disease will frequently lead to local recurrence even when radiotherapy is used.26–28 These patients generally required more extensive surgery than would have been necessary if they had undergone an appropriately planned oncological resection initially. Three patients in this series underwent primary amputation as a result of extensive contamination of important structures and major joints at the time of prior unplanned surgery (type 3 indication).

Although the patients in this study who underwent amputation were older than those treated by limb salvage, age alone did not mandate amputation for any patient. Many elderly patients afflicted by sarcoma have medical comorbidities, which may themselves preclude the very complex and extensive operative procedures frequently required for limb preservation. This was not the case in our study. However, the combination of older age and major medical conditions may together define another indication for amputation in select patients with sarcoma.

Although several studies have shown that the survival of patients who require amputation for STS may be worse than that of those treated with limb salvage, 29,30 other investigations have identified no survival differences between the two patient groups.1,15,17,31,32 In this study, we show that patients who require primary amputation for local management of extremity STS have a prognosis similar to that of those who are candidates for limb-salvage surgery when one controls for the adverse features of tumor grade and size. We excluded patients who presented with a tumor located superficial to the investing extremity fascia and those with low-grade tumors, because these rarely metastasize or require treatment by amputation. Previous studies comparing oncological outcomes for patients undergoing amputation or limb salvage included both superficial and low-grade tumors, and this potentially biased the results against the amputation group.29,30 We also excluded patients with locally recurrent disease, who are known to require amputation more frequently because of extensive soft tissue involvement.5–7 Inclusion of patients with local disease recurrence in previous studies may have further biased the results toward a higher risk of metastasis in the amputation group.33

The results of univariate survival analysis in this study show a significantly higher risk of systemic relapse in patients treated by primary amputation. However, multivariate analysis revealed that the apparent prognostic effect of amputation was actually due to the influence of histological grade and tumor size, which were the only independent predictors of outcome. Patients treated by amputation had a greater proportion of high-grade sarcomas, as well as significantly larger tumors, than patients who were candidates for limb-salvage procedures. Although anatomical tumor extent, as described in this article (Table 1Go), is an important consideration in determining the need for amputation as local sarcoma management, large tumor size has an important influence on both local treatment and metastatic risk.

In summary, primary amputation is rarely necessary to treat patients with a localized STS of the extremity; however, it is the appropriate initial management in a select group of patients. The decision to perform a primary amputation is a difficult one based on a small number of clinical indications, as well as the wishes of the patient. Patients who require a primary amputation for extremity STS are at a greater risk for metastatic disease than patients managed by limb salvage only because they tend to have tumors with worse prognostic features. Primary amputation is not an independent risk factor for systemic relapse.


   ACKNOWLEDGMENTS
 
A.M.D. is supported by a Health Career Award from the Canadian Institutes of Health Research. This study was supported by the Canadian Institutes of Health Research.

Received for publication March 29, 2004. Accepted for publication August 19, 2004.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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