Adult Soft Tissue Sarcoma Treatment (PDQ®)–Health Professional Version

General Information About Adult Soft Tissue Sarcoma

Incidence and Mortality

Estimated new cases and deaths from soft tissue sarcoma in the United States in 2018:[1]

  • New cases: 13,040.
  • Deaths: 5,150.

Soft tissue sarcomas are malignant tumors that arise in any of the mesodermal tissues of the extremities (50%), trunk and retroperitoneum (40%), or head and neck (10%). The reported international incidence rates range from 1.8 to 5 cases per 100,000 individuals per year.[2]

Risk Factors and Genetic Factors

The risk of sporadic soft tissue sarcomas is increased by previous radiation therapy and, in the case of lymphangiosarcoma, by chronic lymphedema. The chemicals Thorotrast (thorium dioxide), vinyl chloride, and arsenic are established carcinogens for hepatic angiosarcomas.[3-5] The HIV and human herpes 8 have been implicated in the pathogenesis of Kaposi sarcoma.

Soft tissue sarcomas occur with greater frequency in patients with the following inherited syndromes:[3-5]

  • Gardner syndrome (APC mutation).
  • Li-Fraumeni syndrome (TP53 mutation).
  • Nevoid basal cell carcinoma syndrome (Gorlin syndrome: PTC gene mutation).
  • Tuberous sclerosis (Bourneville disease: TSC1 or TSC2 mutation).
  • von Recklinghausen disease (neurofibromatosis type 1: NF1 mutation).
  • Werner syndrome (adult progeria: WRN mutation).

Diagnosis

Soft tissue sarcomas may be heterogeneous, with more than 100 different entities described in the World Health Organization 2013 classification.[6] Adequate tissue should be obtained via either core-needle or incisional biopsy for microscopic examination, with a careful review by a pathologist who is experienced in diagnosing sarcomas. Careful planning of the initial biopsy is important to avoid compromising subsequent curative resection. Complete staging and treatment planning by a multidisciplinary team of cancer specialists is required to determine the optimal treatment for patients with this disease.

There is evidence that at least some favorable clinical outcomes may be associated with referral to a specialized sarcoma treatment center. In a population-based consecutive series of 375 soft tissue sarcoma patients in Sweden, local recurrence rates of resected tumors were higher in patients who were not referred to the specialized center: in 35 of 78 (45%) patients not referred; in 24 of 102 (24%) patients referred after initial surgery or incisional biopsy; and in 36 of 195 (18%) patients referred before any surgical procedure (P= .0001 for the difference between those never referred vs. those referred before any surgical procedure).[7][Level of evidence: 3iDii] However, there were no statistically significant differences in death from sarcoma between the groups of patients.

In a British study of 260 patients with soft tissue sarcoma diagnosed within a 3-year period, 37% of the patients had most of their treatment at a specialist center, and the remaining 63% of the patients were treated at 38 different hospitals. The rate of local recurrence was 39% for patients treated at the district general hospitals compared with 19% for patients treated at the specialist center, even though the tumors in patients treated at the district hospitals were smaller and of lower grade. The most significant factors affecting survival were tumor grade (high-grade vs. low-grade) and the depth of the tumor. Patients treated at the specialist center had a small survival advantage after multivariate analysis.[8]

Prognostic Factors

The prognosis for patients with adult soft tissue sarcomas depends on several factors including:[3-5,9-13]

  • The age of the patient.
  • The size of the tumor, pathologic stage at the time of diagnosis, and histologic grade (incorporating differentiation [histology specific], mitotic rate, and extent of necrosis).

Factors associated with a poorer prognosis include the following:[14]

  • Age older than 60 years.
  • Tumors larger than 5 cm in greatest dimension.
  • High-grade histology.
  • Positive margins after resection.[15]

Although patients with low-grade tumors are frequently curable by surgery alone, higher-grade sarcomas are associated with higher local-treatment failure rates and increased metastatic potential.

Prognostic nomograms incorporating specific variables have been developed for soft tissue sarcomas of the retroperitoneum and the extremities.

Surveillance for Relapse

A retrospective review included 174 consecutive patients with a soft tissue sarcoma of the limb who underwent follow-up by oncologists at a single center from 2003 to 2009.[16] The rate and site of recurrence and mode of detection were analyzed. Eighty-two patients (47%) experienced relapse. Isolated local recurrences occurred in 26 patients and local relapse with synchronous pulmonary metastases occurred in 5 patients. Local recurrences were detected clinically in 30 of the 31 patients; magnetic resonance imaging identified only one local recurrence. Twenty-eight patients developed isolated lung metastases; in 9 patients, the lung metastases were amenable to resections, 7 of whom were free of disease after treatment. Lung metastases were detected by chest x-ray in 19 patients, by computed tomography (CT) scanning in 3 patients, and clinically in 11 patients. Twenty-three patients developed nonpulmonary metastases. More than 80% of the relapses occurred in the first 2 years of follow-up; however, later recurrences were also observed.[16][Level of evidence: 3iiDi] This study supports imaging surveillance for detection of lung metastases, whereas local recurrences at the primary site were usually detected by clinical examination. The impact of picking up metastases on overall survival or quality-of-life data is unknown.

Positron emission tomography and CT imaging may have higher sensitivity than contrast-enhanced CT imaging in the setting of clinical suspicion of recurrent sarcoma. Late recurrences (more than 5 years from diagnosis) are seen with some histologies, such as synovial sarcoma or alveolar soft part sarcoma.[17]

Related Summaries

Other PDQ summaries containing information about soft tissue sarcoma include:

References
  1. American Cancer Society: Cancer Facts and Figures 2018. Atlanta, Ga: American Cancer Society, 2018. Available online. Last accessed August 3, 2018.
  2. Wibmer C, Leithner A, Zielonke N, et al.: Increasing incidence rates of soft tissue sarcomas? A population-based epidemiologic study and literature review. Ann Oncol 21 (5): 1106-11, 2010. [PUBMED Abstract]
  3. Singer S, Nielsen T, Antonescu CR: Molecular biology of soft tissue sarcoma. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1522-32.
  4. Singer S, Maki RG, O’Sullivan B: Soft tissue sarcoma. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1533-77.
  5. Malawer MM, Helman LJ, O’Sullivan B: Sarcomas of bone. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1578-1609.
  6. Fletcher CDM, Bridge JA, Hogendoorn JA, et al., eds.: WHO/IARC Classification of Tumours of Soft Tissue and Bone. Pathology and Genetics. 4th ed. Lyon, France: IARC Press, 2013, pp 218–220.
  7. Gustafson P, Dreinhöfer KE, Rydholm A: Soft tissue sarcoma should be treated at a tumor center. A comparison of quality of surgery in 375 patients. Acta Orthop Scand 65 (1): 47-50, 1994. [PUBMED Abstract]
  8. Bhangu AA, Beard JA, Grimer RJ: Should Soft Tissue Sarcomas be Treated at a Specialist Centre? Sarcoma 8 (1): 1-6, 2004. [PUBMED Abstract]
  9. Coindre JM, Terrier P, Guillou L, et al.: Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer 91 (10): 1914-26, 2001. [PUBMED Abstract]
  10. Kasper B, Ouali M, van Glabbeke M, et al.: Prognostic factors in adolescents and young adults (AYA) with high risk soft tissue sarcoma (STS) treated by adjuvant chemotherapy: a study based on pooled European Organisation for Research and Treatment of Cancer (EORTC) clinical trials 62771 and 62931. Eur J Cancer 49 (2): 449-56, 2013. [PUBMED Abstract]
  11. Zagars GK, Ballo MT, Pisters PW, et al.: Prognostic factors for patients with localized soft-tissue sarcoma treated with conservation surgery and radiation therapy: an analysis of 1225 patients. Cancer 97 (10): 2530-43, 2003. [PUBMED Abstract]
  12. Ramanathan RC, A’Hern R, Fisher C, et al.: Modified staging system for extremity soft tissue sarcomas. Ann Surg Oncol 6 (1): 57-69, 1999 Jan-Feb. [PUBMED Abstract]
  13. Pisters PW, Leung DH, Woodruff J, et al.: Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 14 (5): 1679-89, 1996. [PUBMED Abstract]
  14. Vraa S, Keller J, Nielsen OS, et al.: Prognostic factors in soft tissue sarcomas: the Aarhus experience. Eur J Cancer 34 (12): 1876-82, 1998. [PUBMED Abstract]
  15. Trovik LH, Ovrebo K, Almquist M, et al.: Adjuvant radiotherapy in retroperitoneal sarcomas. A Scandinavian Sarcoma Group study of 97 patients. Acta Oncol 53 (9): 1165-72, 2014. [PUBMED Abstract]
  16. Rothermundt C, Whelan JS, Dileo P, et al.: What is the role of routine follow-up for localised limb soft tissue sarcomas? A retrospective analysis of 174 patients. Br J Cancer 110 (10): 2420-6, 2014. [PUBMED Abstract]
  17. Krieg AH, Hefti F, Speth BM, et al.: Synovial sarcomas usually metastasize after >5 years: a multicenter retrospective analysis with minimum follow-up of 10 years for survivors. Ann Oncol 22 (2): 458-67, 2011. [PUBMED Abstract]