General Information About Adult Soft Tissue Sarcoma

Incidence and Mortality

Estimated new cases and deaths from soft tissue sarcoma in the United States in 2011:[1]

• New cases: 10,980.
• Deaths: 3,920.

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Soft tissue sarcomas are malignant tumors that may arise in any of the mesodermal tissues of the extremities (50%), trunk and retroperitoneum (40%), or head and neck (10%). Soft tissue sarcomas occur with greater frequency in patients with the following:[2]

• Basal cell syndrome.
• Gardner syndrome.
• Li-Fraumeni syndrome (p53 mutations).
• Tuberous sclerosis.
• von Recklinghausen disease (neurofibromatosis).
• Werner syndrome

Soft tissue sarcomas may be heterogeneous, so adequate tissue should be obtained via either core-needle or incisional biopsy for microscopic examination to determine histologic type and tumor grade. Careful planning of the initial biopsy is important to avoid compromising subsequent curative resection. Since the selection of treatment is determined by the grade of the tumor, it is essential to have a careful review of the biopsy tissue by a pathologist who is experienced in diagnosing sarcomas. Complete staging and treatment planning by a multidisciplinary team of cancer specialists is required to determine the optimal treatment for patients with this disease.

In most cases, a combined modality approach of preoperative or postoperative radiation therapy is used, rather than the radical surgical procedures that were used in the past. The role of chemotherapy is less well defined. Because of the evolving nature of the state of the art in the treatment of this disease, all patients with such lesions should be included in a clinical trial whenever possible.

The prognosis for patients with adult soft tissue sarcomas depends on several factors, including:[3,4,5]

• The patient's age.
• The size, histologic grade, and stage of the tumor.

Factors associated with a poorer prognosis include:[6]

• Age older than 60 years.
• Tumors larger than 5 cm.
• High-grade histology.

While low-grade tumors are usually curable by surgery alone, higher-grade sarcomas (as determined by the mitotic index and by the presence of hemorrhage and necrosis) are associated with higher local-treatment failure rates and increased metastatic potential.[7] When feasible, wide margin function-sparing surgical excision is the cornerstone of effective treatment, with the goal of preservation of a functional extremity.[8,9] This may be facilitated by soft tissue reconstructive surgery.[10] Mohs surgical technique may be considered as an alternative to wide surgical excision for small, well-differentiated sarcomas when cosmetic results are considered to be very important, as margins can be assured with minimal normal tissue removal.[2,11] High-grade soft tissue sarcomas of the extremities can often be effectively treated while preserving the limb with combined-modality treatment consisting of preoperative or postoperative radiation therapy to reduce local recurrence. A phase II trial (SWOG-9119) of neoadjuvant therapy with DOX/DTIC/IFF was conducted for poor prognosis soft tissue sarcoma.[8,12,13,14,15,16,17,18,19] In adults, local control of high-grade soft tissue sarcomas of the trunk and the head and neck can be achieved with surgery, often in combination with radiation therapy with or without chemotherapy.[20]

Effective treatment of retroperitoneal sarcomas requires removal of all gross disease while sparing adjacent viscera not invaded by tumor. The prognosis for patients with high-grade retroperitoneal sarcomas is less favorable than for patients with tumors at other sites, partly because of the difficulty in completely resecting these tumors and the limitations placed on high-dose radiation therapy.[2,21]

Several prospective randomized trials have been unable to confirm conclusively whether doxorubicin-based adjuvant chemotherapy benefits adults with resectable soft tissue sarcomas. The majority of these studies accrued small numbers of patients and did not demonstrate a metastasis-free survival or an overall survival (OS) benefit for adjuvant chemotherapy.[20] A small study of adjuvant chemotherapy showed a positive impact in disease-free survival and OS in patients treated with postoperative chemotherapy.[22] There was wide interstudy variability among the numerous trials, including differences in therapeutic regimens, drug doses, sample size, tumor site, and histologic grade. A quantitative meta-analysis of updated data from 1,568 individual patients from 14 trials of doxorubicin-based adjuvant therapy showed an absolute benefit from adjuvant therapy of 6% for local relapse-free interval (95% confidence interval [CI], 1–10), 10% for distant relapse-free interval (95% CI, 5–15), and 10% for recurrence-free survival (95% CI, 5–15); however, there was no OS benefit at 10 years.[23][Level of evidence: 1iiDii] Patients with high-grade tumors (grades 3 or 4) larger than 5 cm in diameter have the greatest tendency for disease to metastasize and are eligible for prospective clinical trials of adjuvant chemotherapy.

With distant metastases (stage IV), surgery with curative intent is possible for patients selected for optimal underlying biologic behavior (i.e., patients with a limited number of metastases, with a long disease-free interval, and with slow clinical growth) with pulmonary metastases who have undergone or are undergoing complete resection of the primary tumor.[24,25,26] Doxorubicin alone or with dacarbazine is considered the best chemotherapeutic regimen for advanced sarcoma.[27,28,29] A randomized trial of 340 patients with advanced sarcoma showed a higher response rate (32% vs. 17%, P < .002) and longer time-to-progression (6 months vs. 4 months, P < .02) for doxorubicin, dacarbazine, ifosfamide, and mesna (MAID) versus doxorubicin and dacarbazine alone.[30][Level of evidence: 1iiDiii] The increased response rate of the MAID regimen may be justified in preoperative management of younger patients with borderline resectability, but the increased toxic effects argue against its use in older patients.[30]

Complete surgical resection is often difficult for sarcomas of the retroperitoneum because of their large size before detection and anatomic location.[31,32] Prospective randomized trials have not shown improved survival with preoperative or postoperative adjuvant chemotherapy for this subgroup.[23]

Related Summaries

Note: Other PDQ summaries containing information about soft tissue sarcoma include:

• Childhood Soft Tissue Sarcoma Treatment
• Ewing Sarcoma Family of Tumors Treatment
• Gastrointestinal Stromal Tumors Treatment
• Kaposi Sarcoma Treatment
• Uterine Sarcoma Treatment

References:

Cellular Classification of Adult Soft Tissue Sarcoma

Soft tissue sarcomas are classified histologically according to the soft tissue cell of origin, though the cell type is not part of the prognostic staging system. Additional studies, including electron microscopy, histochemistry, flow cytometry, cytogenetics, and tissue culture studies may allow identification of particular subtypes within the major histologic categories.

The histologic grade reflects the metastatic potential of these tumors more accurately than the classic cellular classification listed below.[1,2,3] Overall, malignant fibrous histiocytoma is the most common histologic type (40% of the total) followed by liposarcoma (25%); however, frequency of histologic type is site-dependent. Pathologists assign grade based on the number of mitoses per high-powered field, presence of necrosis, cellular and nuclear morphology, and the degree of cellularity; discordance among expert pathologists can reach 40% on prospective review.[3,4]

• Alveolar soft-part sarcoma.[5]
• Angiosarcoma.[6,7,8]
• Dermatofibrosarcoma protuberans.[9]
• Epithelioid sarcoma.
• Extraskeletal chondrosarcoma.
• Extraskeletal osteosarcoma.
• Fibrosarcoma.
• Gastrointestinal stromal tumor (GIST). (Refer to the PDQ summary on Gastrointestinal Stromal Tumors Treatment for more information.)
• Leiomyosarcoma.
• Liposarcoma.
• Malignant fibrous histiocytoma.
• Malignant hemangiopericytoma.
• Malignant mesenchymoma.
• Malignant schwannoma.
• Malignant peripheral nerve sheath tumor.
• Peripheral neuroectodermal tumors.
• Rhabdomyosarcoma. (Refer to the PDQ summary on Childhood Rhabdomyosarcoma Treatment for more information.)
• Synovial sarcoma.
• Sarcoma, NOS (not otherwise specified).

References:

Stage Information for Adult Soft Tissue Sarcoma

Note: This stage information section has been updated to include information from the seventh edition (2010) of the American Joint Committee on Cancer's AJCC Cancer Staging Manual. The PDQ Adult Treatment Editorial Board, which is responsible for maintaining this summary, is currently reviewing the new staging categories to determine whether additional changes need to be made to other parts of the summary. Any necessary changes will be made as soon as possible.

Staging has an important role in determining the most effective treatment of soft tissue sarcomas. The stage is determined by the size of the tumor, the histologic grade, and whether it has spread to lymph nodes or distant sites. Intracompartmental or extracompartmental extension of extremity sarcomas is also important for surgical decision making. For complete staging, a thorough physical examination, x-rays, laboratory studies, and careful review of all biopsy specimens (including those from the primary tumor, lymph nodes, or other suspicious lesions) are essential. Computed tomographic scan of the chest is recommended for sarcomas larger than 5 cm (T2) or with moderate to poor differentiation (grades 2–4). Nodal involvement is rare, occurring in less than 3% of patients with sarcoma.[1]

The American Joint Committee on Cancer (AJCC) has designated staging by the four criteria of tumor size, nodal status, grade, and metastasis (TNGM).[2]

Definitions of TNM and Grade

Table 1. Primary Tumor (T)a,b

Table 2. Regional Lymph Nodes (N)a

Table 3. Distant Metastasis (M)a

Table 4. Anatomic Stage/Prognostic Groupsa

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

Stage I Adult Soft Tissue Sarcoma

Low-grade soft tissue sarcomas (grade 1 or 2) have little metastatic potential, but they may recur locally if they are inadequately treated. Accordingly, surgical excision with negative tissue margins of 2 cm or larger in all directions is the treatment of choice for patients with these early-stage sarcomas.[1] Mohs surgical technique may be considered as an alternative to wide surgical excision for small, well-differentiated sarcomas when cosmetic results are considered to be very important, as margins can be assured with minimal normal tissue removal.[2,3]

Carefully executed high-dose radiation therapy using a shrinking-field technique may be beneficial for unresectable tumors or for resectable tumors in which a high likelihood of residual disease is thought to be present, when margins are known to be smaller than 2 cm, and when wider resection would require either an amputation or the removal of a vital organ.[4] Because of the low metastatic potential of these tumors, chemotherapy is usually not given.[5]

Standard treatment options:

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I adult soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

Stage II and III Adult Soft Tissue Sarcoma

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

High-grade localized soft tissue sarcomas have an increased potential for metastatic spread. For sarcomas of the extremities, local control comparable to that obtained with amputation may be achieved with limb-sparing surgery that involves wide local excision in combination with preoperative or postoperative radiation therapy and in some instances, chemotherapy.[1,2,3,4]

Several prospective randomized trials have been unable to confirm conclusively whether doxorubicin-based adjuvant chemotherapy benefits adults with resectable soft tissue sarcomas. The majority of these studies accrued small numbers of patients and did not demonstrate a metastasis-free survival or an overall survival (OS) benefit for adjuvant chemotherapy.[5] Interstudy variability was wide among the numerous trials, including differences in therapeutic regimens, drug doses, sample size, tumor site, and histologic grade. A quantitative meta-analysis of updated data from 1,568 individual patients from 14 trials of doxorubicin-based adjuvant therapy showed an absolute benefit from adjuvant therapy of 6% for local relapse-free interval (95% confidence interval [CI], 1–10), 10% for distant relapse-free interval (95% CI, 5–15), and 10% for recurrence-free survival (95% CI, 5–15); however, there was no OS benefit at 10 years.[6][Level of evidence: 1iiDii] Patients with high-grade tumors (grades 3 or 4) larger than 5 cm in diameter have the greatest tendency for disease to metastasize and are eligible for prospective clinical trials of adjuvant chemotherapy.

Complete surgical resection is often difficult for sarcomas of the retroperitoneum because of their large size before detection and anatomical location.[7,8] As opposed to soft tissue sarcomas of the extremities, local recurrence is the most common cause of death in patients with retroperitoneal soft tissue sarcomas. Complete surgical resection (i.e., removal of all of the gross tumor) is the most important factor in preventing local recurrence and, in many instances, requires resection of adjacent viscera. The role of adjuvant radiation therapy in the treatment of patients with retroperitoneal sarcoma has not been clearly defined. Prospective randomized trials have not shown improved survival with preoperative or adjuvant chemotherapy for this subgroup.[6,9]

Standard treatment options:

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II adult soft tissue sarcoma and stage III adult soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

Stage IV Adult Soft Tissue Sarcoma

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Nodal Disease

Stage IV sarcomas are tumors that have metastatic involvement of regional lymph nodes or have spread to distant organs. Soft tissue sarcomas that more commonly spread to lymph nodes include synovial cell sarcomas, epithelioid sarcomas, and rhabdomyosarcomas. For stage IV sarcomas, local control of the primary tumor is probably best obtained by resection with negative margins, lymphadenectomy when appropriate, and postoperative external-beam radiation therapy.[1]

Standard treatment options:

Visceral Disease

With distant metastases, surgery with curative intent is possible for patients with limited pulmonary metastases who are also undergoing or have undergone complete resection of the primary tumor.[7,8,9] The role of adjuvant therapy for pulmonary nodules has been clinically evaluated in trials such as the EORTC-62933 trial.

The value of resection of hepatic metastases is unclear. Doxorubicin alone or with dacarbazine is considered one of the most frequently used chemotherapeutic regimens for advanced sarcoma.[10,11,12] When used as single agents, only doxorubicin and ifosfamide show greater than 20% response rates; less active drugs include dacarbazine, cisplatin, methotrexate, and vinorelbine.[13] A randomized trial of 340 patients with advanced sarcoma showed a higher response rate (32% vs. 17%, P < .002) and longer time-to-progression (6 months vs. 4 months, P < .02) for doxorubicin, dacarbazine, ifosfamide, and mesna versus doxorubicin and dacarbazine alone.[14][Level of evidence: 1iiDiii] For older patients, sequential use of single agents with each recurrence is a better strategy for palliation. High-dose chemotherapy (with or without transplantation) has not influenced disease-free survival or overall survival in published studies so far, but it remains under clinical evaluation for patients with metastatic disease in first complete remission, after resection of pulmonary nodules, or for inoperable large primaries.[15][Level of evidence: 3iiiDiv]

Standard treatment options:

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV adult soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

Recurrent Adult Soft Tissue Sarcoma

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Treatment of recurrent soft tissue sarcomas depends on the type of initial presentation and treatment. Patients who develop a local recurrence often can only be salvaged by aggressive local therapy: local excision plus radiation therapy after previous minimal therapy or amputation after previous aggressive treatment.[1,2] For selected patients who received radiation therapy, preoperative radiation therapy and wide local excision may avoid the need for amputation.[3,4,5] Metastases to the lung as first recurrence usually occur within 2 to 3 years of initial diagnosis and should be treated as described under treatment for stage IV disease. [6,7,8] A 30% survival rate at 3 years is noted if limited pulmonary metastases are resectable.

Doxorubicin alone or with dacarbazine is one of the most frequently used chemotherapeutic regimens for advanced sarcoma.[9,10,11] When used as single agents, only doxorubicin and ifosfamide show response rates greater than 20%; less active drugs include dacarbazine, cisplatin, methotrexate, and vinorelbine.[12] In a small study, pegylated liposomal doxorubicin has shown similar activity to doxorubicin, with fewer toxic effects.[13][Level of evidence: 3iiiDiv] A randomized trial of 340 patients with advanced sarcoma showed a higher response rate (32% vs. 17%, P < .002) and longer time-to-progression (6 vs. 4 months, P < .02) for doxorubicin, dacarbazine, ifosfamide, and mesna versus doxorubicin and dacarbazine alone.[14][Level of evidence: 1iiDiii] Sequential use of doxorubicin followed by ifosfamide or other drugs with each subsequent recurrence is frequently preferred. Clinical trials of phase I and II agents should be considered for subsequent recurrences. High-dose chemotherapy (with or without transplantation) has not influenced disease-free survival or overall survival in published studies, but it remains under clinical evaluation for patients with metastatic disease in first complete remission, after resection of pulmonary metastases, or for inoperable large primaries.[15,16,17]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent adult soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

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Changes to This Summary (10 / 21 / 2011)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

General Information About Adult Soft Tissue Sarcoma

Updated statistics with estimated new cases for 2011 (cited American Cancer Society as reference 1).

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About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult soft tissue sarcoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board. Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Adult Soft Tissue Sarcoma Treatment are:

• Russell S. Berman, MD (New York University School of Medicine)
• Minh Tam Truong, MD (Boston University Medical Center)

Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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National Cancer Institute: PDQ® Adult Soft Tissue Sarcoma Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/adult-soft-tissue-sarcoma/HealthProfessional. Accessed <MM/DD/YYYY>.

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Last Revised: 2011-10-21