Surgical Resection of Primary Soft Tissue Sarcoma of The Extremities - UpToDate

7/13/2018 Surgical resection of primary soft tissue sarcoma of the extremities - UpToDate
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Surgical resection of primary soft tissue sarcoma of the extremities
Author: Mark C Gebhardt, MD
Section Editors: Raphael E Pollock, MD, Robert Maki, MD, PhD
Deputy Editors: Kathryn A Collins, MD, PhD, FACS, Diane MF Savarese, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2018. | This topic last updated: Mar 15, 2018.
INTRODUCTION — Sarcomas are uncommon malignant tumors that arise from skeletal and extraskeletal
connective tissues, including the peripheral nervous system. They can arise from mesenchymal tissue at any
body site.
The surgical management of primary soft tissue sarcomas (STSs) of the extremities will be reviewed here.
The clinical features, diagnosis, classification, and staging of primary STS of the extremity and radiation
associated sarcomas, as well as an overview of multimodality therapy as used for STS of the extremities and
chest wall, are discussed separately. (See "Clinical presentation, histopathology, diagnostic evaluation, and
staging of soft tissue sarcoma" and "Radiationassociated sarcomas" and "Overview of multimodality
treatment for primary soft tissue sarcoma of the extremities and chest wall".)
Because of their rarity and the frequent need for multimodality treatment, surgical management of STS should
ideally be carried out in a center with expertise in the treatment of sarcomas. The surgical expertise of
dedicated subspecialists improves clinical outcomes. In one study that examined outcomes of 375 patients
with STS of the extremities, local recurrence rates were 1.3fold higher in those referred only after definitive
surgery and were 2.4fold higher for patients not referred at any time [1]. (See "Clinical presentation,
histopathology, diagnostic evaluation, and staging of soft tissue sarcoma" and "Overview of multimodality
treatment for primary soft tissue sarcoma of the extremities and chest wall" and "Systemic treatment of
metastatic soft tissue sarcoma".)
TREATMENT OVERVIEW — The goals of treating extremity soft tissue sarcomas (STSs) are to minimize
local recurrence, perioperative morbidity, and mortality and to maximize function and longterm survival. To
achieve these goals, radiation therapy (RT) combined with wide surgical resection is recommended for most
patients with highgrade primary extremity STS, with some exceptions [2]. The role of chemotherapy
continues to be studied and debated.
Adjuvant radiation is often used to aid with local control when it is predicted that adequate margins will be
difficult to achieve, usually around major nerves and blood vessels. The particular adjunctive therapy
(chemotherapy and/or RT) chosen is based upon the size and grade of the tumor but also upon institutional
expertise, experience, and preferences. (See 'Adjunctive medical therapies' below and "Overview of
multimodality treatment for primary soft tissue sarcoma of the extremities and chest wall", section on
'Radiation therapy' and "Overview of multimodality treatment for primary soft tissue sarcoma of the extremities
and chest wall", section on 'Initial chemoradiotherapy for large highgrade STS'.)
Wide local excision of STS involves excision of the sarcoma with an adequate margin of normal (uninvolved)
tissue, leaving the tumor pseudocapsule (if one exists) intact and as part of the en bloc resection specimen.
Following resection of small tumors, primary closure of the wound may be possible, but, for larger defects,
rotation flaps or free flap reconstruction may be necessary. (See 'Sarcoma resection and reconstruction'
below and 'Soft tissue reconstruction' below.)
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Although it is rarely needed, primary amputation may be indicated for patients with large locally advanced or
recurrent STS not amenable to resection or in those with severe medical comorbidities. If amputation is not
accepted, RT alone is an alternative treatment for STS [3]. This is also considered when there is widespread
metastatic disease and longterm survival is unlikely. Although some early data suggested that STSs were
relatively radioresistant [3,4], cell lines derived from sarcomas are no less radiosensitive compared with
epithelial cell lines [5]. Myxoid liposarcomas are a particularly radiosensitive subtype [6]. However, tumor size
matters. Although local control can be readily obtained in small tumors, high RT doses may be needed for
local control rates to exceed 90 percent for tumors of estimated volume that is 15 to 65 mL (approximately a
sphere of 3 to 5 cm in diameter), which require high RT doses (>75 Gy) [7]. As most treatment volumes are
relatively large, the late normal tissue changes resulting from these dose levels are clinically important in
nearly all patients and must be considered.
Where available, techniques such as systemic chemotherapy with regional hyperthermia or regional
chemotherapy (isolated limb perfusion, isolated limb infusion) may also be considered as a means of sparing
the limb. (See 'Primary amputation' below and "Treatment of locally recurrent and unresectable, locally
advanced soft tissue sarcoma of the extremities", section on 'Unresectable locally advanced disease'.)
PREOPERATIVE EVALUATION AND PREPARATION
Preoperative imaging — Magnetic resonance (MR) imaging is the most useful test for the initial local
assessment of a soft tissue sarcoma (STS). The main site of distant metastatic disease is within the chest for
most histologic tumor types, and assessment for distant disease is carried out with chest computed
tomography (CT). The added value of fluorodeoxyglucosepositron emission tomography (FDGPET) or
integrated PETCT over routine crosssectional imaging is uncertain, and PET scans are not routinely
recommended as a component of the initial staging workup of STS in consensusbased guidelines from the
National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO)
[2]. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma",
section on 'Role of PET scanning'.)
If neoadjuvant therapy is used for the primary tumor, such as preoperative radiation with or without
chemotherapy, MR imaging is usually repeated after the radiation treatment and before the resection to look
for response or other changes, including progression, and to help with planning of the surgical procedure.
Adjunctive medical therapies — Adjunctive medical therapies used in conjunction with surgery for the
treatment of STS include radiation therapy (RT; most commonly) and chemotherapy, which can be
administered preoperatively (neoadjuvant RT, neoadjuvant chemoradiotherapy) or postoperatively (adjuvant
RT, adjuvant chemotherapy):
● The combination of RT plus wide resection achieves better local control than either modality alone for the
majority of STSs for which adjuvant therapy is indicated. The use of adjuvant radiation lessens the
necessity for primary amputation or radical resection and results in reasonable functional outcomes and
acceptable cancer outcomes without the significant morbidity and cosmetic deformity of radical surgery or
amputation. Neoadjuvant RT is generally preferred over postoperative RT for most patients because of
significantly lower rates of late treatmentrelated toxicity. However, surgical resections are more
challenging in a previously irradiated field, and wound healing is challenging in this setting. (See
"Overview of multimodality treatment for primary soft tissue sarcoma of the extremities and chest wall",
section on 'Radiation therapy' and "Overview of multimodality treatment for primary soft tissue sarcoma of
the extremities and chest wall", section on 'Preoperative versus postoperative RT'.)
Although it has been difficult to identify the appropriate subset, some patients with lowgrade extremity
STS do not appear to require adjunctive medical therapy [813]. We reserve surgical excision without RT
for patients with superficial lowgrade tumors that are 5 cm or less in diameter, as well as for carefully
selected patients with small, purely intramuscular or subcutaneous tumors, even if highergrade, provided
that adequate surgical margins can be obtained [14,15]. Some patients with larger, lowgrade lesions that
can be resected with wide margins may be considered for surgery alone [14]. For all other patients,
including those with lowgrade histology, we advise RT in addition to surgery.
● Neoadjuvant therapy is most often considered in the setting of a large or recurrent highgrade tumor,
particularly if limb salvage is an issue. In these situations, RT is most commonly selected with or without
chemotherapy. The optimal neoadjuvant regimen and how best to integrate RT, chemotherapy, and
surgery are unknown. (See "Overview of multimodality treatment for primary soft tissue sarcoma of the
extremities and chest wall", section on 'Initial chemoradiotherapy for large highgrade STS'.)
● The benefit of adjuvant chemotherapy for common adult STS of the extremities continues to be debated,
and there is little consensus as to the indications or specific benefit. The appropriateness of adjuvant
chemotherapy should be addressed on a casebycase basis, taking into consideration the patient's
performance status, comorbid factors (including age), disease location, tumor size, and histologic
subtype. The potential for benefit must be discussed in the context of expected treatmentrelated
toxicities, including sterility in younger individuals, cardiomyopathy, renal damage, second cancers, and
overall impairment of quality of life. (See "Adjuvant and neoadjuvant chemotherapy for soft tissue
sarcoma of the extremities", section on 'Sarcomas more commonly seen in adults'.)
● In addition, for patients with large, locally advanced, or recurrent extremity STS, neoadjuvant
chemotherapy can be administered systemically in conjunction with regional hyperthermia or regionally
(intraarterially) using procedures such as isolated limb infusion and isolated limb perfusion. These
treatments are only available in a few centers in the United States, but, where available, they represent
potentially limbpreserving options. (See "Treatment of locally recurrent and unresectable, locally
advanced soft tissue sarcoma of the extremities", section on 'Chemotherapy with regional hyperthermia'
and "Treatment of locally recurrent and unresectable, locally advanced soft tissue sarcoma of the
extremities", section on 'Regional chemotherapy'.)
SARCOMA RESECTION AND RECONSTRUCTION
Wide local excision — Wide surgical excision of the primary tumor (total en bloc excision of the primary
tumor without cutting into tumor tissue and having an adequate margin of normal tissue completely
surrounding the tumor while preserving the major neurovascular structures, if possible) is the essential
component of treatment for virtually all patients with soft tissue sarcoma (STS). The resection should take
place through tissues outside of the tumor pseudocapsule, if one exists, through apparently normal
uninvolved tissue. Violation of the tumor (ie, intralesional surgery or a resection that results in gross or
microscopic residual tumor) is associated with a higher local failure rate even if radiation therapy (RT) is used.
In one report, for example, the local control rate in 95 patients with extremity STS treated with preoperative
RT followed by resection was 47 versus 87 percent in patients with and without tumor violation, respectively
[16].
Lower versus upper extremity — The general principles of resection of STS are similar in the upper and
lower extremities. The main difference is that amputation is avoided whenever possible in the upper extremity,
particularly for proximal tumors. No prosthesis comes close to replicating the function of a normal hand,
whereas for the lower extremity, modern prosthesis can offer reasonably good ambulatory function and, in
younger patients, can support vigorous sport activities. To this end, when a major nerve requires resection,
tendon transfers and (at times) nerve grafts are used in the upper extremity. While this is also possible in the
lower extremity, in general, the results are not as favorable.
Resection margins — The status of the surgical margins is the most important surgical variable that
influences local control [7,8,1622]. Although a positive margin by itself is not associated with a survival
detriment, a positive surgical margin increases the risk of a local recurrence, which in turn is a risk factor for
distant metastasis and inferior longterm survival [21,23]. Even in patients treated with combined surgery and
RT, the status of the surgical margins influences the rate of local recurrence [19,22,2426].
However, the exact width (thickness) of the negative margin that is optimal for local control is not known. The
postoperative assessment of the margin width is difficult once the specimen is removed due to the retraction
of the tissues, especially skeletal muscle, when the specimen is passed off the surgical field. It is essential
that the surgeon and pathologist work closely together to assess the true margin. Inking of the specimen may
help, but the surgeon's assessment of how to orient and mark the specimen adds to the ability of the
pathologist to determine a correct statement regarding margin. What may seem like a very wide margin
through muscle to the surgeon may look very different to the pathologist when the muscle retracts. There is
no perfect way to definitively assess margins, but the optimal result happens when there is direct
communication between the surgeon and the pathologist.
Most clinicians recommend that if surgery is used as the sole modality of treatment, the margin should be at
least 1 cm in all directions or include a fascial barrier [27]. Onecentimeter margins seldom occur in reality,
especially around neurovascular structures, and it is generally accepted that the type of tissue is important:
thinner (1 to 2mm) margins of fascia are likely adequate, whereas wider margins that consist of fat or
muscle are suggested.
If surgery is combined with RT, the thickness of the surgical margin can be safely reduced without
compromising local control [19]. In one study of patients treated with preoperative RT followed by surgery for
an extremity STS, local control rates were similar among patients with a negative margin of ≤1 or >1 mm (96
versus 97 percent) [19]. In a later study, no local failures were seen among 56 patients treated with
preoperative computed tomography (CT)planned RT if the surgical margins were ≥1 mm [28].
Strategies to reduce wound complications — The following strategies may help to reduce wound
morbidity in patients being treated with preoperative RT or perioperative brachytherapy for STS, although
highlevel evidence to support these recommendations is lacking:
● Gentle handling of tissue during surgery.
● The use of contemporary prospectively planned reconstructive efforts with vascularized tissue flaps,
which have reduced the incidence of serious wound healing issues to 3 to 5 percent in most (but not all
[29,30]) series.
● Meticulous attention to achieving hemostasis before wound closure.
● Avoidance of closure under tension.
● Minimizing wound dead space, using rotational or free tissue muscle transfers if necessary.
● Wound drainage with tubes remaining in place until drainage is decreasing is usually advised, although
there are few studies that document benefit [31,32].
● Use of bulky, cotton compression dressings may be helpful.
● Immobilization of the affected extremity until it is clear that there are no significant wound healing issues.
● Use of imageguided preoperative intensitymodulated radiation therapy (IMRT) may spare the proposed
surgical flap and reduce acute wound healing complications [33]. (See 'Adjunctive medical therapies'
above.)
Handling the bone — Since the majority of STSs do not invade bone, it is seldom necessary to resect
adjacent bone to achieve a negative margin [34,35]. In the absence of frank bone invasion, resection up to
and possibly including the periosteum is an adequate surgical margin for STSs that are treated with wide
excision and radiation. Resection of the periosteum should be limited to those cases where the tumor is
abutting the periosteum. Periosteal stripping should be avoided unless necessary to achieve a negative
margin because it may increase the risk of a later radiationrelated pathologic fracture, particularly of the
femur, although the evidence to relate fractures to periosteal stripping is weak [3638]. A fracture through
irradiated bone does not heal normally and may be quite prolonged.
Large, deep tumors often do require periosteal stripping to obtain a margin. If radiation will be part of the
treatment, some surgeons advocate prophylactic stabilization with a rod or a plate at the time of the resection,
particularly when the femur is involved [39]. However, the evidence to support prophylactic fixation is weak
[36,37]. The incidence of these fractures is fortunately low, but it is highest in the femur and directly related to
radiation dose [40]. Because of poor fracture healing in irradiated bone, treatment may sometimes be
augmented with the use of a vascularized fibular graft to assist in bony union [41].
Nerve resection — It is rarely necessary to resect a major nerve unless the tumor is a neurogenic STS.
Surgical resection of the tumor can be accomplished in most patients without sacrificing a major nerve.
Major nerves can often be preserved if they are carefully resected from the tumor, leaving the nerve sheath as
a margin, as it is rare that a nerve is actually invaded by a tumor. But if this is the case, such as with
neurogenic tumors arising in the nerve itself, it is necessary to resect the nerve in continuity with the tumor.
Ambulatory function is still possible with complete resection of the sciatic nerve [42]. The patient will need to
use an anklefoot orthosis and extreme care in protecting the plantar skin to avoid pressure ulcers since
protective sensation will be lost.
In the upper extremity, one tends to try to preserve the major nerves if at all possible, but if one of the nerves
(median, ulnar, or radial) requires resection, at times, nerve grafts may be useful, and tendon transfers can be
used to restore some function. Nerve grafts are seldom useful in the lower extremity in adults, particularly in a
radiated field, but may be successful in children or, at times, in the upper extremity.
Vascular resection — Major arteries such as the superficial femoral artery can be excised if necessary to
achieve negative margins and reconstructed with reverse saphenous vein grafts or prosthetic graft material
[43].
Reconstructing the vein does not appear to be essential but has been accomplished successfully and may
reduce the severity of postoperative edema and late sequelae of chronic venous insufficiency [44]. (See
'Extremity edema' below.)
Handling the specimen — At the completion of the surgical resection, the specimen should be oriented
for the pathologist with sutures denoting proximaldistal, deepsuperficial, and mediallateral orientations. With
the specimen removed, we usually place vascular clips in the wound to mark the tumor bed for the radiation
therapist to guide any necessary postoperative RT.
Ideally, the specimen will be reviewed by the pathologist and surgeon either in the operating room or the
cutting room. The surgeon should point out areas of the resected specimen where the margin is concerning
and discuss retraction of muscle from the specimen with the pathologist. If there is a question of a positive
margin, additional tissue can be taken at the time of resection for frozen section study (and, later, permanent
pathology) to look for residual tumor. Orientation of the additional tissue for the pathologist may be difficult in
these situations, but communication with the pathologist regarding the "new" margin is critical.
If a positive margin is recognized at the time of the resection, further resection should be attempted to obtain
final negative margins. Preoperative RT may make close margins more acceptable but can also make
intraoperative assessment of margins more difficult because of radiation changes in the surrounding normal
but irradiated tissues.
If a positive margin is detected postoperatively on the final specimen, then the treatment team needs to weigh
the pros and cons of reresection compared with adding more radiation. (see 'Inadequate initial resection'
below). Sometimes, it is possible to resect more tissue if it is known where the area of concern is, and at other
times, this may add too much morbidity. It may not be possible to determine exactly where the positive margin
is, or it might be near a vital structure, in which case another operation will not be helpful.
Where the margins are questionable and the defect is deemed appropriate for flap closure, some surgeons
have preferred to use negative pressure wound therapy in the interim. Formal wound closure is delayed until
the surgical margins are certain, and if they are positive, more tissue can be resected before definitive flap
closure. (See 'Soft tissue reconstruction' below and 'Use of negative pressure wound therapy' below.)
Lymphadenectomy — Most adulttype STSs have a ≤5 percent risk of lymph node metastases. Exceptions
are synovial sarcoma, the vascular sarcomas, rhabdomyosarcoma (RMS), and the epithelioid and clear cell
subtypes, which have a higher risk of nodal metastases (9 to 44 percent). (See "Clinical presentation,
histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Pattern of spread'.)
In most cases, regardless of the histologic tumor type, regional lymph node dissection is recommended only if
there is clinical or radiologic evidence of regional nodal disease. In most (but not all [45]) series, isolated
nodal metastases do not carry the same dire prognosis as distant metastases [4648]. Some series report
four to fiveyear survival rates of 46 to 71 percent following lymphadenectomy [4749]. In the 8th edition
(2017) of the TNM staging system, regional nodal metastases have been reclassified as stage IV disease
(table 1) [50]. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue
sarcoma", section on 'Staging'.)
Sentinel lymph node biopsy — Sentinel lymph node biopsy (SLNB) has emerged as a reliable method of
detecting occult nodal metastases in a variety of malignancies (eg, melanoma, breast, penile cancer). For
these cancers, the status of the sentinel lymph node (SLN) reflects the status of the nodal basin with 95 to 97
percent accuracy.
For STSs, particularly those types with a higher frequency of nodal involvement, it is unknown if earlier
identification and treatment of occult nodal metastases using SLNB (followed by completion
lymphadenectomy if the SLN is positive) would result in improved survival compared with lymphadenectomy
only for clinically evident nodal metastases found by physical examination or radiologic imaging. The role of
SLNB in patients with highrisk STS subtypes has been addressed in a few retrospective reports [5157]. The
two largest are described in detail:
● In a series of 62 consecutive patients with clear cell sarcoma, synovial sarcoma, epithelioid sarcoma, or
RMS who underwent SLNB, positive sentinel nodes were identified in 2 of 42 patients with synovial
sarcoma and in 6 of 12 with clear cell sarcoma [57]. Only two patients with clear cell sarcoma had
additional metastatic nodes after regional dissection, both of whom developed later distant metastases
and died of disease. The other four were without evidence of disease on followup. One patient with
synovial sarcoma and another with epithelioid sarcoma developed regional nodal disease following a
negative SLNB, while a further patient with RMS developed distant, local, and regional metastases
following a negative SLNB.
● In another report, 29 patients with a nonmetastatic extremity STS associated with a high rate of nodal
metastases (synovial, clear cell, angiosarcoma, RMS, epithelioid sarcoma) underwent SLNB along with
resection of the primary tumor [51]. Among the 20 who had it, the preoperative staging positron emission
tomography (PET) scan was interpreted as negative in 16, indeterminate in 3, and suspicious in 1. At
least one SLN was found in 28 patients (97 percent). Only one patient (who had a suspicious PET scan)
had a positive SLN with micrometastatic disease on pathologic evaluation. He refused completion
lymphadenectomy and, despite regional nodal irradiation, developed lung metastases. Two other patients
had only immunohistochemical evidence of SLN involvement, and neither relapsed despite not having a
completion lymphadenectomy. An additional patient with a negative SLNB later developed a nodal
metastasis, and five other patients with a negative SLNB developed distant metastatic disease.
The results of other smaller series and singlecase reports are mixed [5256]. In many but not all cases,
patients with positive SLNB have developed distant metastases despite therapeutic lymphadenectomy, and
several SLNnegative patients have developed later metastatic disease.
Taken together, these sparse data suggest that a positive SLNB does not necessarily imply future metastatic
disease, nor does the removal of involved nodes by completion lymphadenectomy prevent later distant
metastatic spread. Furthermore, a negative SLNB does not imply the absence of disease spread. The rarity of
lymph node positivity makes the role of SLNB a difficult question to answer prospectively; this would require
proof that patients with a positive SLN have inferior outcomes compared with those with a negative sentinel
node in a population of patients, all of whom have had SLNB. Thus, the role of SLNB in this disease, even for
histologies with a high rate of nodal spread, remains unclear.
Inadequate initial resection — If a positive margin is detected postoperatively on the final specimen, the
treatment team needs to weigh the pros and cons of reresection compared with additional radiation.
Sometimes, it is possible to resect more tissue if it is known where the area of concern is, and at other times,
this may add too much morbidity. It may not be possible to determine exactly where the positive margin is, or
it might be near a vital structure, in which case another operation will not be helpful. If the resection has been
performed elsewhere prior to referral to the tumor center, it may not be possible to know whether the margins
were adequate from the pathology reports or even from the histologic slides since this requires careful
analysis. Many times, these are "shellout" or "oops procedures" where the surgeon thought he or she was
excising a benign neoplasm.
Because local control is still worse with positive as compared with negative margins, it is generally considered
prudent to reresect the tumor bed, but this can be challenging with regard to knowing what to resect and in
achieving wound healing. However, it is important to note that only a minority of marginpositive (R1)
resections ever result in a local recurrence (approximately 30 percent in most series), whereas not all
complete (R0) resections avoid recurrence (5 to 10 percent in most series) [5862]. Reresection to negative
margins is performed in conjunction with RT given either before or after reresection. Approximately 37 to 68
percent of such patients will have residual tumor in the reresection specimen.
Reexcision must take into account the size of the reexcised field and the potential for damage or exposure
of critical neurovascular structures necessitating reconstructive surgical procedures. In major sarcoma
centers, positive margins in patients with extremity lesions usually reflect tumor on the neurovascular bundle,
and further surgery to achieve negative margins would usually entail an amputation; most patients in this
setting are treated with higher doses of adjuvant RT (in the range of 66 to 68 Gy), with amputation reserved
for salvage.
Partial excision of the tumor before referral to a tertiary center also does not appear to compromise limb
preservation, local control, or, in most series, survival [58,6265]. However, a higher incidence of distant
metastatic disease has been reported in such patients [66], and reresection may entail a larger procedure
than a de novo procedure and impact upon the functional result. These data underscore the importance of
transferring patients with soft tissue masses of uncertain diagnosis to centers that specialize in treating
sarcomas so that they can undergo adequate initial resection.
Some patients are not candidates for reresection because of either a medical contraindication or the desire
to preserve extremity function. The use of RT as an alternative to reresection can help secure local control in
a substantial proportion of these patients, although there may be dose limitations because of prior radiation to
the site.
Brachytherapy — Brachytherapy is a wellestablished modality for treatment, but it may extend
hospitalization and may not be covered by insurance. Because of these issues and the increasing use of
outpatient IMRT, brachytherapy is less often chosen.
For patients who are selected to undergo brachytherapy, afterloading catheters are placed in a target area of
the tumor operative bed, defined by the surgeon, and spaced at 1cm intervals to cover the entire area of risk.
Brachytherapy minimizes the radiation dose to surrounding normal tissues, maximizes the dose delivered to
the tumor, and shortens treatment times [67]. In the usual schedule, treatment is completed within six days
and requires only one hospitalization. (See "Radiation therapy techniques in cancer treatment", section on
'Brachytherapy'.)
There are no randomized comparisons of the relative efficacy or morbidity of external beam radiation therapy
(EBRT) compared with brachytherapy. Although it is unclear if brachytherapy is associated with a higher risk
of wound complications, the rate of wound reoperation may be higher [68].
Brachytherapy has been combined with free flap construction as a means of enhancing primary healing in
difficult anatomic situations without an increase in the incidence of wound breakdown [69].
Soft tissue reconstruction — Rotational flaps or free tissue transfers may be necessary to achieve wound
closure [70].
The determination of the need for free or rotational flaps is beyond the scope of this review, but it emphasizes
the team approach to treatment of these patients. A plastic surgeon is an essential part of this team.
Discussion preoperatively about the resection plan, including how much skin and other soft tissue will be
removed, and an estimation of the resulting "dead space" and the quality of the remaining soft tissues,
especially in older adult patients who have had radiation, will affect the decision for the use or not of rotational
or free flaps. More proximal sarcomas around the thigh and pelvic area are more likely to develop soft tissue
healing problems and require special attention from the surgical team.
PRIMARY AMPUTATION — At times, primary amputation may be the only reasonable alternative or may be
necessary if there is a major complication. The current indications for primary amputation for soft tissue
sarcoma (STS) include distal disease where the limit of resection encompasses an entire digit or significant
portion of the hand/foot; for massive disease such that a functional limb following resection is not achievable;
the need for resection of certain major nerves (eg, brachial plexus); or severely compromised tissue perfusion
due to age, peripheral artery disease, or other comorbidities.
If required, standard amputations are used:
● For upper extremity lesions, a ray amputation of the index, middle, ring, or little finger can be performed
with relatively little loss of function and acceptable cosmesis. A thumb amputation is more devastating
from a functional point of view, but a pollicization of the index finger or a toetothumb free tissue transfer
can be used depending on the location of the tumor. Other amputation levels, depending on the location
of the tumor and prior treatments such as radiation therapy, include below and aboveelbow amputation,
shoulder disarticulation, and, on rare occasions, forequarter amputation. Prosthetics that mimic hand
function are lacking, but this is an area of active research. Prototypes of myoelectric hand prostheses
have been developed, and this field continues to evolve.
● For lower extremity lesions, standard amputations include belowknee for foot lesions, aboveknee for
large calf lesions, and hip disarticulation for large proximal thigh lesions. For major amputations, many
patients can usually function quite well with modern prosthetics, depending on the level of the
amputation, their age, and comorbidities, and it should not always be considered a "defeat." (See
"Techniques for lower extremity amputation" and "Lower extremity amputation", section on 'Functional
outcomes'.)
POSTOPERATIVE CARE AND FOLLOWUP — Patients who have received preoperative radiation, or those
who present with large tumors and have significant dead space in the aftermath of major surgical resection,
are those who need particular attention in the postoperative setting. It is important to get patients up and
moving early after surgery, but if they have delicate wounds, rotational or free flaps, and/or skin grafts, more
prolonged bed rest is advised.
For the lower extremity, most patients are able to get out of bed and are ambulating with supports as needed
within one or two days unless the wound is tenuous. For both upper and lower extremity resections, the
wound is monitored until wound healing is progressing, and then physical therapy can be initiated to work on
range of motion of the joint and muscle strengthening. Patients who received radiation therapy (RT; especially
preoperative RT) usually progress more slowly because of the delayed wound healing, but it is important to
work on range of motion early so that mobility is not permanently lost, assuming the wound will tolerate it.
After discharge from the hospital, the wound is checked within two weeks and the patient is followed at
intervals thereafter for local recurrence and metastatic surveillance. (See 'Posttreatment surveillance' below.)
Adjunctive radiation therapy — Adjuvant RT is recommended for most patients who did not receive
preoperative RT. RT at higher doses can improve the outcome in patients with positive margins for whom re
resection of the tumor bed is not feasible [25,71]. (See "Overview of multimodality treatment for primary soft
tissue sarcoma of the extremities and chest wall", section on 'Radiation therapy'.)
As noted above, some patients with lowgrade extremity soft tissue sarcoma (STS) do not appear to require
adjunctive RT. We reserve surgical excision without RT for the following groups (see 'Adjunctive medical
therapies' above):
● Patients with superficial, lowgrade tumors that are 5 cm or less in diameter.
● Carefully selected patients with small, purely intramuscular or subcutaneous tumors, even if higher
grade, provided that adequate surgical margins can be obtained.
● Carefully selected patients with larger, lowgrade lesions that can be resected with wide margins.
For all other patients, including those with lowgrade histology, we advise RT in addition to surgery.
Posttreatment surveillance — Posttreatment cancer surveillance guidelines have not been established
through rigorous clinical investigation [72,73]. Frequent followup is recommended, particularly in the first two
years after treatment, since more than 80 percent of recurrences will be detected during this period [73]. (See
'Recurrence' below.)
Longterm followup and resection site surveillance include periodic physical examination, imaging the
primary site, and chest imaging to rule out metastatic disease.
● Following treatment, for patients with stage II or III disease (table 1), we suggest history, physical
examination, and chest imaging every three to six months for two to three years, then every six months
for the next two years, then annually.
● Following treatment of stage I disease, we suggest a history and physical examination at three to six
month intervals for the first two years and yearly thereafter.
Periodic imaging of the primary site is also indicated in highrisk patients. For patients at higher risk of local
recurrence, such as those with positive margins or whose primary tumor site is not easily examined, a
computed tomography (CT) scan is preferred for imaging the lungs and abdomen, and magnetic resonance
(MR) is preferred for the extremity.
These recommendations are consistent with consensusbased surveillance guidelines from the National
Comprehensive Cancer Network (NCCN); alternative guidelines are available from the European Society for
Medical Oncology (ESMO) [2]. (See "Overview of multimodality treatment for primary soft tissue sarcoma of
the extremities and chest wall", section on 'Posttreatment cancer surveillance'.)
PERIOPERATIVE MORBIDITY AND MORTALITY — The most common perioperative complications are
wound healing delays, wound dehiscence, and infection [70]. (See 'Woundrelated complications' below and
'Strategies to reduce wound complications' above.)
Venous thromboembolism (VTE) prophylaxis protocols used for lower extremity operations are appropriate to
lessen the likelihood of thrombophlebitis, and this may need to be prolonged if the patient has prolonged bed
rest for wound problems. (See 'Venous thromboembolism' below.)
For extremity sarcomas, perioperative mortality is low unless the patient has severe comorbidities
preoperatively. In those patients, serious discussion with all members of the team and consultations with
appropriate medical subspecialties may make it possible to optimize the patient for surgery or lead to a
decision to avoid operative intervention.
Woundrelated complications — Wound healing is affected by the extent of the surgical resection and
variability in the amount and type of tissue removed at resection, the type and timing of radiation therapy
(RT), and chemotherapy. The incidence of postoperative wound infection in one study was 6 percent, but the
relative risk was increased in patients who received RT, had hip and pelvic lesions, or had other factors such
as diabetes and increased body mass index (BMI) [74]. The duration of the surgery, the amount of blood loss,
and the addition of artificial devices such as joint implants also affect the likelihood of surgical site infection
(SSI). One study that compared infections associated with bone versus soft tissue sarcoma (STS) noted that
soft tissue tumors were more commonly polymicrobial [75].
In general, the addition of RT to surgery increases the frequency of wound complications [36,7679].
Preoperative radiation is associated with a higher incidence of acute wound complications compared with
surgery alone or postoperative RT, particularly for lower extremity lesions [29,76]. However, compared with
postoperative RT, lower preoperative doses (50 versus 60 to 66 Gy) and smaller field sizes can be used [76].
With preoperative RT, the higher rate of generally reversible acute wound healing complications in
preoperatively treated patients is offset by a lower rate of generally irreversible late complications. Acute
wound complications can usually be managed and heal in the long run, while latetreatment effects are
generally irreversible.
Complications of graft or flapbased reconstruction include vascular compromise, hematoma, seroma, SSI,
and complications specific to the donor site. These are discussed separately.
Use of negative pressure wound therapy — For patients who develop a perioperative wound
complication, especially partial or total wound dehiscence, negative pressure wound therapy (NPWT) can
facilitate wound healing and primary wound closure, or wound bed preparation for wound coverage with a
graft or flap [8082]. By using controlled negative pressure, NPWT evacuates fluid, stimulates the formation of
granulation tissue, and decreases bacterial colonization. There are potential risks associated with the use of
these devices. The general management of acute and chronic wounds, and specifically the indications and
contraindications and use of NPWT devices, is discussed separately. (See "Basic principles of wound
management" and "Overview of treatment of chronic wounds" and "Negative pressure wound therapy".)
Venous thromboembolism — The rate of venous thrombosis and thromboembolism appears to be similar to
that of other orthopaedic procedures. In one study of bone and soft tissue neoplasms, the detected incidence
of deep vein thrombosis (DVT) was 4 percent and of pulmonary embolism was 1.2 percent [83]. Fatal
pulmonary embolism occurred in 0.4 percent in this study of 94 bone sarcomas and 158 STSs. It should be
noted that not all patients (70 percent) received DVT prophylaxis. Unless the risk of hematoma or bleeding is
high, it is reasonable to use thromboprophylaxis postoperatively, especially in lowerextremity STS resections.
(See "Risk and prevention of venous thromboembolism in adults with cancer", section on 'Surgical patients'.)
Extremity edema — Following resection of STS in the extremities, edema can be related to obstruction of the
lymphatics or venous obstruction [44]. Following radiation and resection for lowerextremity sarcomas,
patients often require physical therapy and compressive stockings postoperatively to help control edema,
particularly if there was extensive dissection involving lymphatics or veins. This is permanent in some patients
but can often be controlled with stockings and other lymphedema treatment techniques. Many centers have
specialized clinics to deal with these issues. (See "Clinical features and diagnosis of peripheral lymphedema"
and "Overview and management of lower extremity chronic venous disease" and "Clinical staging and
conservative management of peripheral lymphedema".)
RECURRENCE — More than 80 percent of recurrences (local, distant) will be detected in the first two years
after resection [73].
https://www.uptodate.com/contents/surgical-resection-of-primary-soft-tissue-sarcoma-of-the-extremities/print?search=sarcoma&source=search_result&select… 10/22
Risk factors — In a review of prognostic factors in 1041 patients with extremity soft tissue sarcomas (STSs),
tumor size and grade were the main predictors of distant recurrence, while age over 50 years and the
presence of positive resection margins predicted local recurrence [8]. Specific histopathologic subtypes were
associated with higher rates of local failure (fibrosarcoma and malignant peripheral nerve sheath tumor
[MPNST]) and worse tumorrelated survival (leiomyosarcoma [LMS] and MPNST).
Local — Local recurrence rates following wide excision are between 8 and 30 percent (table 2). Following
simple excision alone (ie, removal of the gross lesion with only a narrow margin of normal tissue), recurrence
rates are 60 to 90 percent. Following intracompartmental resection, local failure rates are between 10 and 20
percent.
While it is well documented that the risk of a local recurrence is higher for highgrade tumors, it is not
uniformly low for lowgrade tumors. In one of the randomized trials, the improvement in local control in
irradiated patients appeared to be limited to patients with highgrade histopathology [67], but, in the other,
there was a significant reduction in risk for lowgrade tumors as well (5 versus 30 percent local recurrence
rate for patients treated with surgery alone) [84].
A postoperative nomogram, which was based upon data from 684 patients with an extremity sarcoma treated
with limbsparing surgery alone at Memorial Sloan Kettering Cancer Center over a 24year period, was
proposed for predicting local recurrence rates at three and five years after limbsparing surgery without
radiation therapy (RT) [85]. The nomogram includes five independent predictors of recurrence: age, size,
margin status, grade, and histology. While this nomogram may be a useful tool to estimate the risk of a local
recurrence in an individual patient, the appropriate cutoff point for deciding that the risk justifies the addition of
RT is unclear. Furthermore, the nomogram has not been independently validated.
Distant — Isolated limited metastatic tumor to the lung is frequently asymptomatic and can be resected.
Isolated hepatic metastases may also be amenable to potentially curative resection, although there are fewer
available data than with pulmonary metastasectomy. (See "Surgical treatment and other localized therapy for
metastatic soft tissue sarcoma".)
LONGTERM OUTCOMES
Functional — Functional outcomes for patients undergoing limb salvage procedures are reasonable, with
similar outcomes for those who do versus do not require soft tissue reconstruction [7,8690]. Compared with
limb salvage procedures, functional outcome in patients requiring primary amputation is generally considered
to be not as good, although studies to document this are lacking.
A few studies have assessed qualityoflife issues in amputees who had been treated for soft tissue sarcomas
(STSs) with amputation and chemotherapy compared with patients who underwent limb salvage with radiation
therapy (RT) and chemotherapy [91,92]. Contrary to expectations, there were no significant differences in
measures of psychologic outcome. Thus, a psychologic advantage of limbsalvage surgery compared with
amputation has yet to be demonstrated.
Limb salvage — In addition to improving local control, the increased use of adjuvant RT (along with improved
imaging using magnetic resonance [MR] imaging) has had a significant impact on rates of limb salvage for
extremity STS. In the 1970s, up to onehalf of patients with extremity STS underwent primary amputation,
whereas in contemporary series, the rate of amputation has been reduced to approximately 1 percent (without
any measurable fall in overall survival) [7,17,18,58,93,94]. Certainly, adjuvant RT has played a major role in
this improvement, but the ability to plan the operation better with imaging techniques such as MR and greater
experience and specialization of orthopedic and oncology surgeons have also contributed to improved local
control since the 1970s.
Even when the minimum surgical margin is narrow (less than 2 mm), such as with resection of STS in the
hand or foot, limb amputation can be avoided as primary therapy in most patients, and up to twothirds of
patients can retain a normal or fairly normal extremity.
Longterm survival — Longterm survival following surgical treatment of STS of the extremities depends on
the histologic grade and presence of metastatic disease.
STSs of the hand and foot tend to have a slightly better prognosis than do more proximal extremity STSs.
Fiveyear survival rates are approximately 80 percent, which is better than expected for proximal extremity
disease [9597].
Nomograms have been proposed to predict longterm outcomes following resections of sarcomas, some of
which are available online. Their usefulness is still being studied. This subject is discussed in detail
elsewhere. (See "Overview of multimodality treatment for primary soft tissue sarcoma of the extremities and
chest wall", section on 'Prognosis'.)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics"
and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer short, easyto
read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want
indepth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email
these topics to your patients. (You can also locate patient education articles on a variety of subjects by
searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Soft tissue sarcoma (The Basics)")
SUMMARY AND RECOMMENDATIONS
● Soft tissue sarcomas (STSs) are uncommon malignant tumors that arise from skeletal and extraskeletal
connective tissues, including the peripheral nervous system. They can arise from mesenchymal tissue at
any body site. (See 'Introduction' above.)
● Surgical resection of the primary tumor is the essential component of treatment for virtually all patients.
The guiding principle is total resection of the primary tumor with a margin of normal tissue surrounding
the tumor and avoidance of cutting into tumor tissue during the resection. (See 'Wide local excision'
above.)
● For most patients with STS, surgical excision, typically in conjunction with adjunctive medical therapy, is
recommended. What constitutes an "adequate" margin is not well defined and probably depends on the
type of tissue. (See 'Resection margins' above.)
● Certain histologies (synovial sarcoma, the vascular sarcomas, rhabdomyosarcomas [RMSs], and the
epithelioid and clear cell subtypes) have a higher risk of nodal metastases than do other types of adult
STS (11 to 44 percent versus 5 percent). However, we do not routinely perform lymphadenectomy, even
with these histologies. Regardless of the histologic tumor type, regional lymph node dissection is
recommended only if there is clinical or radiologic evidence of regional nodal disease. The role of sentinel
lymph node biopsy (SLNB), even in patients with highrisk subtypes, is unclear. (See 'Lymphadenectomy'
above.)
● For patients with an incompletely resected primary STS, reresection is preferred, if possible. For patients
who are not candidates for reresection, either because of a medical contraindication or the desire to
preserve extremity function, adjuvant radiation therapy (RT) can secure local control in a substantial
proportion. (See 'Inadequate initial resection' above.)
● The combination of RT plus surgery achieves better local control than either modality alone for the
majority of STSs for which adjuvant therapy is indicated. The use of adjuvant radiation lessens the
necessity for primary amputation or radical resection, and it results in reasonable functional outcomes
and acceptable cancer outcomes without the significant morbidity and cosmetic deformity of radical
surgery or amputation. Neoadjuvant RT is generally preferred over postoperative RT for most patients
because of significantly lower rates of late treatmentrelated toxicity. However, surgical resections are
more challenging in a previously irradiated field, and wound healing is challenging in this setting. (See
'Adjunctive medical therapies' above.)
● Neoadjuvant therapy is most often considered in the setting of a large or recurrent highgrade tumor,
particularly if limb salvage is an issue. In these situations, RT is most commonly selected with or without
chemotherapy. The optimal neoadjuvant regimen and how best to integrate radiation therapy,
chemotherapy, and surgery are unknown. (See "Overview of multimodality treatment for primary soft
tissue sarcoma of the extremities and chest wall", section on 'Initial chemoradiotherapy for large high
grade STS'.)
In addition, for patients with large, locally advanced, or recurrent extremity STS, neoadjuvant
chemotherapy can be administered systemically in conjunction with regional hyperthermia or regionally
(intraarterially) using procedures such as isolated limb infusion and isolated limb perfusion. These
treatments are rarely used in the United States, but, where available, they represent potentially limb
preserving options. (See "Treatment of locally recurrent and unresectable, locally advanced soft tissue
sarcoma of the extremities", section on 'Regional chemotherapy'.)
● Following treatment, for patients with stage II or III disease, we suggest history, physical examination,
and chest imaging every three to six months for two to three years, then every six months for the next
two years, then annually. Following treatment of stage I disease, we suggest a history and physical
examination at three to sixmonth intervals for the first two years, and yearly thereafter. Periodic imaging
of the primary site is also indicated in highrisk patients. For patients at higher risk of local recurrence,
such as those with positive margins or whose primary tumor site is not easily examined, magnetic
resonance (MR) imaging is preferred over computed tomography (CT) scanning. (See 'Posttreatment
surveillance' above and "Overview of multimodality treatment for primary soft tissue sarcoma of the
extremities and chest wall", section on 'Posttreatment cancer surveillance'.)
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge David Harmon, MD, who
contributed to an earlier version of this topic review.
Use of UpToDate is subject to the Subscription and License Agreement.
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86. Davis AM, Devlin M, Griffin AM, et al. Functional outcome in amputation versus limb sparing of patients
with lower extremity sarcoma: a matched casecontrol study. Arch Phys Med Rehabil 1999; 80:615.
87. Robinson MH, Spruce L, Eeles R, et al. Limb function following conservation treatment of adult soft
tissue sarcoma. Eur J Cancer 1991; 27:1567.
88. Stinson SF, DeLaney TF, Greenberg J, et al. Acute and longterm effects on limb function of combined
modality limb sparing therapy for extremity soft tissue sarcoma. Int J Radiat Oncol Biol Phys 1991;
21:1493.
89. Cribb GL, Loo SC, Dickinson I. Limb salvage for softtissue sarcomas of the foot and ankle. J Bone Joint
Surg Br 2010; 92:424.
90. Davidge KM, Wunder J, Tomlinson G, et al. Function and health status outcomes following soft tissue
reconstruction for limb preservation in extremity soft tissue sarcoma. Ann Surg Oncol 2010; 17:1052.
91. Weddington WW Jr, Segraves KB, Simon MA. Psychological outcome of extremity sarcoma survivors
undergoing amputation or limb salvage. J Clin Oncol 1985; 3:1393.
92. Sugarbaker PH, Barofsky I, Rosenberg SA, Gianola FJ. Quality of life assessment of patients in
extremity sarcoma clinical trials. Surgery 1982; 91:17.
93. McNeer GP, Cantin J, Chu F, Nickson JJ. Effectiveness of radiation therapy in the management of
sarcoma of the soft somatic tissues. Cancer 1968; 22:391.
94. Canter RJ, Beal S, Borys D, et al. Interaction of histologic subtype and histologic grade in predicting
survival for softtissue sarcomas. J Am Coll Surg 2010; 210:191.
95. Talbert ML, Zagars GK, Sherman NE, Romsdahl MM. Conservative surgery and radiation therapy for
soft tissue sarcoma of the wrist, hand, ankle, and foot. Cancer 1990; 66:2482.
96. Johnstone PA, Wexler LH, Venzon DJ, et al. Sarcomas of the hand and foot: analysis of local control
and functional result with combined modality therapy in extremity preservation. Int J Radiat Oncol Biol
Phys 1994; 29:735.
97. Karakousis CP, De Young C, Driscoll DL. Soft tissue sarcomas of the hand and foot: management and
survival. Ann Surg Oncol 1998; 5:238.
Topic 109748 Version 4.0
GRAPHICS
Soft tissue sarcoma of the extremities and trunk TNM staging AJCC UICC 2017
Primary tumor (T)
T category T criteria
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor 5 cm or less in greatest dimension
T2 Tumor more than 5 cm and less than or equal to 10 cm in greatest dimension
T3 Tumor more than 10 cm and less than or equal to 15 cm in greatest dimension
T4 Tumor more than 15 cm in greatest dimension
Regional lymph nodes (N)
N category N criteria
N0 No regional lymph node metastasis or unknown lymph node status
N1 Regional lymph node metastasis
Distant metastasis (M)
M category M criteria
M0 No distant metastasis
M1 Distant metastasis
Definition of grade (G)
G G definition
GX Grade cannot be assessed
G1 Total differentiation, mitotic count and necrosis score of 2 or 3
G2 Total differentiation, mitotic count and necrosis score of 4 or 5
G3 Total differentiation, mitotic count and necrosis score of 6, 7, or 8
Prognostic stage groups
When T is... And N is... And M is... And grade is... Then the stage
group is...
T1 N0 M0 G1, GX IA
T2, T3, T4 N0 M0 G1, GX IB
T1 N0 M0 G2, G3 II
T2 N0 M0 G2, G3 IIIA
T3, T4 N0 M0 G2, G3 IIIB
Any T N1 M0 Any G IV
Any T Any N M1 Any G IV
Tumor differentiation
Tumor differentiation is histology specific and is generally scored as follows:
Differentiation Definition
score
1 Sarcomas closely resembling normal adult mesenchymal tissue (eg, lowgrade
leiomyosarcoma)
2 Sarcomas for which histologic typing is certain (eg, myxoid/round cell liposarcoma)
3 Embryonal and undifferentiated sarcomas, sarcomas of doubtful type, synovial sarcomas,
soft tissue osteosarcoma, Ewing sarcoma/primitive neuroectodermal tumor (PNET) of soft
tissue
Mitotic count
In the most mitotically active area of the sarcoma, 10 successive highpower fields (HPF; one HPF at 400x
magnification = 0.1734 mm 2) are assessed using a 40x objective.
Mitotic count score Definition
1 0 to 9 mitoses per 10 HPF
2 10 to 19 mitoses per 10 HPF
3 ≥20 mitoses per 10 HPF
Tumor necrosis
Evaluated on gross examination and validated with histologic sections.
Necrosis score Definition
0 No necrosis
1 <50% tumor necrosis
2 ≥50% tumor necrosis
TNM: tumor, node, metastasis; AJCC: American Joint Committee on Cancer; UICC: Union for International Cancer Control.
Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the
AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer International Publishing.
Graphic 110711 Version 5.0
Local failure rate in patients with soft tissue sarcoma of the extremities treated
by planned wide resection
Center Number Percent
Memorial Hospital [1] 70 23
University of Florida [2] 40 15
Swedish Sarcoma Group [3] 103 8
Brigham & Women's Hospital [4] 24 25
Netherlands Cancer Institute [5] 26 19
Milan [6] 417 31
National Cancer Institute [7] 83 0 (amputation)
References:
1. Yang JC, Chang AE, Baker AR, et al. Randomized prospective study of the benefit of adjuvant radiation therapy in
the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 1998; 16:197.
2. Enneking WF, Spanier SS, Malawer MM. The effect of the Anatomic setting on the results of surgical procedures for
soft parts sarcoma of the thigh. Cancer 1981; 47:1005.
3. Alvegard TA, Sigurdsson H, Mouridsen H, et al. Adjuvant chemotherapy with doxorubicin in highgrade soft tissue
sarcoma: a randomized trial of the Scandinavian Sarcoma Group. J Clin Oncol 1989; 7:1504.
4. Singer S, Corson JM, Gonin R, et al. Prognostic factors predictive of survival and local recurrence for extremity soft
tissue sarcoma. Ann Surg 1994; 219:165.
5. Keus RB, Rutgers EJ, Ho GH, et al. Limbsparing therapy of extremity soft tissue sarcomas: treatment outcome and
longterm functional results. Eur J Cancer 1994; 30A:1459.
6. Azzarelli A. Surgery in soft tissue sarcomas. Eur J Cancer 1993; 29A:618.
7. Potter DA, Kinsella T, Glatstein E, et al. Highgrade soft tissue sarcomas of the extremities. Cancer 1986; 58:190.
Graphic 56886 Version 3.0
Contributor Disclosures
Mark C Gebhardt, MD Employment: Clinical Orthopedics and Related Research (journal) [Senior Associate
Editor]. Raphael E Pollock, MD Nothing to disclose Robert Maki, MD, PhD Grant/Research/Clinical Trial
Support: Immunocore [Medical oncology (IMCgp100 and related compounds)]; Regeneron [Medical
oncology (REGN3767, REGN2810)]; Presage [Medical oncology (CIVO device)]; Tracon [Medical oncology
(TRC105)]; Lilly [Medical oncology (Olaratumab)]; Daiichi [Medical oncology (Pexidartinib)].
Consultant/Advisory Boards: AADi [Medical oncology (Investigational agent)]; Arcus [Medical oncology
(Multiple investigational agents)]; Bayer [Medical oncology (Sorafenib, regorafenib)]; Deciphera [Medical
oncology (Investigational agent)]; Janssen [Medical oncology (Trabectedin, liposomal doxorubicin)]; Pharma
Mar [Medical oncology (Trabectedin)]; Karyopharm [Medical oncology (Selinexor)]; Lilly/Imclone [Medical
oncology (Olaratumab)]; SARC [Medical oncology (Multiple commercial agents under clinical trials)]; Tracon
Pharmaceuticals [Medical oncology (TRC105)]; Presage [Medical oncology (CIVO device)]. Kathryn A
Collins, MD, PhD, FACS Nothing to disclose Diane MF Savarese, MD Nothing to disclose
Contributor disclosures are reviewed for conﬂicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
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T3, T4 N0 M0 G2, G3 IIIB

Any T Any N M1 Any G IV

Center Number Percent

Swedish Sarcoma Group [3] 103 8

Milan [6] 417 31

National Cancer Institute [7] 83 0 (amputation)

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