Soft-Tissue Sarcoma Surgical Practice Guidelines
Soft-Tissue Sarcoma Surgical Practice Guidelines
The Society of Surgical Oncology surgical practice guidelines focus on the signs and symptoms of primary cancer, timely evaluation of the symptomatic patient, appropriate preoperative evaluation for extent of disease, and role of the surgeon in diagnosis and treatment. Separate sections on adjuvant therapy, follow-up programs, or management of recurrent cancer have been intentionally omitted. Where appropriate, perioperative adjuvant combined-modality therapy is discussed under surgical management. Each guideline is presented in minimal outline form as a delineation of therapeutic options.
Since the development of treatment protocols was not the specific aim of the Society, the extensive development cycle necessary to produce evidence-based practice guidelines did not apply. We used the broad clinical experience residing in the membership of the Society, under the direction of Alfred M. Cohen, MD, Chief, Colorectal Service, Memorial Sloan-Kettering Cancer Center, to produce guidelines that were not likely to result in significant controversy.
Following each guideline is a brief narrative highlighting and expanding on selected sections of the guideline document, with a few relevant references. The current staging system for the site and approximate 5-year survival data are also included.
The Society does not suggest that these guidelines replace good medical judgment. That always comes first. We do believe that the family physician, as well as the health maintenance organization director, will appreciate the provision of these guidelines as a reference for better patient care.
Symptoms and Signs
- Painless mass growing for a variable length of time
- Mass after an injury that does not rapidly resolve
Evaluation of the Symptomatic Patient
- History and physical examination
- Comprehensive history and physical examinationpersonal or family history of malignancy or genetic disease
- Nature and duration of symptoms
- Prior exposure to chemical toxins or radiation
- Assess the mobility of the mass vs fixity to deep structures.
- Assess the size, depth, and consistency of the mass.
- Ascertain clinical involvement of overlying skin or regional lymph nodes.
- Examine motor and sensory nerve function.
- Examine for swelling distal to the mass or for any ecchymosesoverlying the mass.
- Radiologic and laboratory studies
- Difficult to evaluate on physical examination. However, flank bulging or mass effect on deep abdominal palpation should be evaluated further.
- Pelvic or rectal examination may raise the possibility of anunderlying soft-tissue sarcoma.
- Radiologic and laboratory studies
- Radiologic studies should be performed prior to biopsy.
- CTpelvis, abdomen, retroperitoneum
- Celiac axis arteriogram in selected patients with visceral sarcoma
- CBC, chemistry profile, and chest x-ray
- Incision oriented parallel to the long axis of extremity
- Core needle biopsy for superficial lesions
- Needle aspiration if cytopathology expertise available
- Excisional biopsy is reserved for extremity lesions £ 3 cm.
- Appropriate timeliness of surgical referral
- Soft-tissue sarcoma can grow rapidly and disseminate: therefore, the work-up and biopsy should be performed expeditously in the presence of the above symptoms or signs.
Preoperative Evaluation for Extent of Disease
- Physical examination
- Chest CT
- Obtain chest CT in addition to primary tumor imaging and routine studies in patients with lesions > 5 cm, grade II or III.
- CT scan of the chest, abdomen, and pelvis in selected patients
- Myxoid liposarcomas ³ 5 cm have tendency to metastasize to themediastinum, root of the mesentery, and retroperitoneum.
- CT scan of the head in selected patients
- Alveolar soft-part sarcoma may metastasize selectively to the cen
tral nervous system.
- Liver ultrasound or abdominal CT
- Patients with intra-abdominal, genitourinary, or retroperitoneal leiomyosarcoma have a marked tendency to develop liver metastases.
- As discussed above
Role of the Surgeon in Initial Management
- Preoperative evaluation
- The initial evaluation and diagnostic work-up should be coordinated by the surgeon who will perform the definitive operation.
- Radiotherapy and chemotherapy treatments should be considered only after the diagnostic work-up is completed.
- Surgical considerations
- Surgeon must be able to perform wide local excisions in combination with interstitial or postoperative radiotherapy.Accurate intraoperative surgical field delineation is critical.
- In patients who have received preoperative radiotherapy, the sarcoma surgeon must be capable of resecting disease and managing wounds in an irradiated field.
- Radical amputation in selected patients with extremity sarcoma
- Radical multiorgan/vascular/orthopedic resections for selected in tra-abdominal/retroperitoneal sarcoma
These guidelines are copyrighted by the Society of Surgical Oncology
(SSO). All rights reserved. These guidelines may not be reproduced in any
form without the express written permission of SSO. Requests for reprints
should be sent to: James R. Slawny, Executive Director, Society of Surgical
Oncology, 85 West Algonquin Road, Arlington Heights, IL 60005.
Soft-tissue sarcomas are tumors of putative mesodermal origin that develop in the extraskeletal connective tissues. These tumors constitute < 1% of adult malignancies and approximately 7% of pediatric malignancies, and have an annual age-adjusted incidence of 2 cases per 100,000 population. Approximately 6,300 new cases of soft-tissue sarcoma and 3,100 deaths are reported annually in the United States.
Sarcomas occur most commonly in the extremity in adults and in the head and neck in children. Overall, approximately 50% of soft-tissue sarcomas occur in the extremities, 10% in the head and neck, and 40% in the trunk and retroperitoneum.
There is little evidence to suggest a genetic predilection to the development of soft-tissue sarcomas other than in Li-Fraumeni kindreds, in whom p53 tumor-suppressor gene mutations also create a predisposition to breast carcinoma and a variety of other malignancies. Soft-tissue sarcomas also occur with greater frequency in patients with several other genetic diseases, including basal cell nevus syndrome, tuberous sclerosis, Werner's syndrome, Gardner's syndrome, and von Recklinghausen's disease (patients with von Recklinghausen's disease, for example, have a 10% likelihood of ultimately developing a neurofibrosarcoma).
Environmental factors have not been convincingly demonstrated as relevant to the etiology of soft-tissue sarcoma in humans. However, 3-methylcholanthrene and several viruses have been implicated as etiologic factors in experimental animal studies. There is no demonstrable connection between retained foreign bodies or antecedent trauma and the subsequent development of soft-tissue sarcoma, although previous exposure to ionizing radiation and chronic lymphedema are predisposing factors. In this latter context, however, the most common histology is extraskeletal osteosarcoma followed by malignant fibrous histiocytoma.
Sarcomas are classified by histology as well as grade. The histologic classification seeks to ascribe a putative cell of origin for the tumor. Overall, malignant fibrous histiocytoma is the most common subtype (40% of the total), followed by liposarcoma (25%).
Grade assignment is made on the basis of the number of mitoses per high-powered microscopic field, nuclear morphology, degree of cellularity, cellular anaplasia, degree of necrosis, or other criteria that vary from center to center. Unfortunately, light microscopic determination of histopathology and grade are imprecise, and discordancy rates as high as 40% have been observed prospectively, even among expert sarcoma pathologists.
The American Joint Committee on Cancer (AJCC) staging system (Table 1) is most commonly applied in soft-tissue sarcoma for prognostic and therapeutic purposes, although alternative staging systems have been proposed, including those of the Musculoskeletal Tumor Society and the Memorial Sloan-Kettering Cancer Center. The AJCC system uses the four criteria of tumor, nodal status, grade, and metastasis (TNGM) to assign one of four disease stages.
Overall, tumor size and grade are the most important determinants of prognosis. About two-thirds of all sarcomas are high-grade lesions. Newer information suggests that the prognostic risk for disseminated disease is most dependent on the histopathologic grade in the first 2 or 3 years, but after that the size of the initial lesion becomes at least as important as grade. The overall incidence of nodal metastasis is < 3% and is therefore minimally relevant to prognosis in most patients.
Stage I tumors are low-grade lesions of any size and are generally treated by wide local excision. The addition of radiotherapy is dictated by tumor size and anatomic constraints to a resection with negative margins.
Stage II tumors are intermediate-grade tumors of any size that are usually
treated by surgery in combination with radiotherapy. Use of chemotherapy
is generally reserved for stage II patients with recurrent disease or patients
who need tumor cytoreduction prior to resection with limb sal
Stage III lesions are high-grade lesions of any size that have not developed regional or distant metastases. High-grade tumors > 5 cm diameter have the greatest tendency to metastasize and are treated by surgery in conjunction with radiotherapy. Many patients with these tumors are also eligible for prospective clinical trials of neoadjuvant or adjuvant multidrug chemotherapy.[7,8]
The two drugs with the greatest activity in soft-tissue sarcoma are doxorubicin and ifosfamide (Ifex). However, overall response rates in the best multimodality protocols are only 40% to 60%. Toxicities of chemotherapy are significant and include permanent cardiac muscle damage, transient urothelial injury, and temporary, although potentially life-threatening, myelosuppression.[7,8] Because of these serious toxicities, systemic chemotherapy for soft-tissue sarcoma should be administered only in prospective trials, in which strict criteria for enrollment and follow-up monitoring can be maintained.
Chemotherapy is the mainstay of treatment for stage IV disease (ie, soft-tissue sarcomas with regional or metastatic spread). In stage IV disease, surgery or radiotherapy is usually used solely for palliation. Surgery with curative intent is generally impossible in patients with stage IV disease; the only exception is pulmonary metastasis, for which curative metastatasectomy is possible in selected patients undergoing complete resection of the primary tumor.
Radiotherapy can be administered by external beam preoperatively or postoperatively or, alternatively, as a postoperative interstitial implant (brachytherapy). These various radiotherapy approaches have never been directly compared in prospective, randomized trials.
Preoperative radiotherapy requires approximately 50 Gy to achieve tumor control, which is comparable to the 65-Gy dose required for local control if radiotherapy is given postoperatively. The increased postoperative dose is necessitated by the hypoxic postoperative wound environment, which also mandates a wider radiotherapy field extending beyond the area of surgical resection. However, postoperative radiotherapy avoids the significant wound healing problems of preoperative radiation, the incidence of which approaches 30% in some series.
Brachytherapy results in local control rates comparable to either preoperative or postoperative external-beam radiotherapy (7% to 15% rate of local recurrence for surgery with definitive radiotherapy in most series). In addition, brachytherapy is usually much more convenient for patients and appears to be less expensive. Unlike external-beam radiation, there is minimal scatter radiation with brachytherapy, making this technique optimal for tumors near open epiphyseal plates, gonads, and other structures particularly vulnerable to radiation toxicity.
Soft-tissue sarcomas of the retroperitoneum pose a special challenge because they frequently grow to a large size before causing symptoms. Consequently, resection can be difficult (50% to 60% rate of resectability in most series). Central anatomic tumor involvement of the celiac axis, root of the mesentery, great vessels, or porta hepatis usually precludes resection.
The liver and lungs are equally frequent sites of metastasis from primary retroperitoneal sarcomas. Complete surgical resection is the primary determinant of survival in patients with hepatic metastases; however, hepatic metastasectomy has not been proven to be of value.
In the retroperitoneum, no prospective randomized trials have demonstrated improved overall survival using chemotherapy and/or radiotherapy adjuvantly or neoadjuvantly, although intraoperative radiotherapy may decrease local recurrence.
Survival in soft-tissue sarcomas is driven by the reality that almost 80% of metastases are to the lungs and that these usually occur within 2 to 3 years of initial diagnosis. A 30% survival rate at 3 years can be anticipated if the pulmonary metastases are resectable.
Size, grade, surgical margins, depth of tumor, anatomic location, and previous surgery are all important determinants of outcome. However, these factors have a variable impact on specific survival measures, such as overall survival, disease-free survival, local recurrence, and distant disease-free survival; ie, the prognostic factors predictive of local recurrence differ from those predictive of distant metastases and overall survival.
Unlike some tumor systems, local recurrence of soft-tissue sarcoma is not necessarily a harbinger of uncontrollable distant failure. Therefore, local recurrence should be treated aggressively to preserve the highest quality of life for the patient. Long-term follow-up is required because late recurrence is noted in up to 10% of patients after 5 years.
Patient-based outcomes research, which differs from physician-defined survival research, is still in its infancy for soft-tissue sarcoma. In the future, treatments will be assessed for their impact on survival, cost, and effect on quality of life as a means to maximize overall efficacy. These latter considerations will appropriately assume increasing importance as the percentage of soft-tissue sarcoma patients achieving long-term cure increases beyond the current 50% plateau level.
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