Annals of Surgical Oncology

, Volume 15, Issue 12, pp 3550–3560 | Cite as

Why Do Patients with Low-Grade Soft Tissue Sarcoma Die?

  • Robert J. Canter
  • Li-Xuan Qin
  • Cristina R. Ferrone
  • Robert G. Maki
  • Samuel Singer
  • Murray F. Brennan
Bone and Soft Tissue Sarcomas



The patterns of failure and mechanisms of sarcoma-specific death are poorly characterized among the minority of patients with low-grade soft tissue sarcoma (STS) who succumb to disease.


Between 1982 and 2006, 2,041 patients aged ≥16 years with low-grade STS of all sites were treated with curative intent and prospectively followed at a single institution.


Among this cohort, 181 (9%) died from disease (DOD). Overall, 105 patients (58%) died from locally recurrent disease (DOLR), and 59 (32%) died from distant disease (DODR). In 17 patients (9%), the mechanism of sarcoma-related death could not be verified. DOD occurred at a median of 62 months, while median disease-specific survival for the entire cohort was not reached. Median follow-up was 66 months (range 2–431 months). On multivariate analysis, DOD was associated with site, size, and less than R0 resection. For DOLR, site, size, positive margins, liposarcoma histology, and local recurrence (by definition) were significant factors. For DODR, site, histology, and positive margins were not significant factors, while size and local recurrence were. Of DOLR, 80% were retroperitoneal, 68% were liposarcoma, and only 2% were extremity. Conversely, of DODR, extremity (47%) and trunk (18%) were the most common sites, but histology was more variable [liposarcoma 35%, malignant fibrous histiocytoma (MFH) 20%, fibrosarcoma 12%, extraskeletal myxoid chondrosarcoma 10%]. High-grade recurrence rates were comparable between DOLR (27%) and DODR (25%).


Among patients with low-grade STS, DOD occurs in approximately 9% of patients. Nonextremity site, larger size, and less than R0 resection are the most important risk factors for DOD, and distinct patterns of recurrence and death are predicted by primary tumor site.


  1. 1.
    Hajdu SI, Shiu MH, Brennan MF. The role of the pathologist in the management of soft tissue sarcomas. World J Surg 1988; 12:326–31PubMedCrossRefGoogle Scholar
  2. 2.
    Deyrup AT, Weiss SW. Grading of soft tissue sarcomas: the challenge of providing precise information in an imprecise world. Histopathology 2006; 48:42–50PubMedCrossRefGoogle Scholar
  3. 3.
    Brennan MF, Singer S, Maki RG, et al. (2005) Sarcomas of the soft tissues and bone. In: DeVita V, Hellman S, Rosenberg S (eds.) Cancer: Principles and Practice of Oncology, 7th Edition. Lippincott, Williams, and Wilkins, pp 1581–637Google Scholar
  4. 4.
    Costa J, Wesley RA, Glatstein E et al. The grading of soft tissue sarcomas. Results of a clinicohistopathologic correlation in a series of 163 cases. Cancer 1984; 53:530–41PubMedCrossRefGoogle Scholar
  5. 5.
    Trojani M, Contesso G, Coindre JM et al. Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading system. Int J Cancer 1984; 33:37–42PubMedCrossRefGoogle Scholar
  6. 6.
    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 1,240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer 2001; 91:1914–26PubMedCrossRefGoogle Scholar
  7. 7.
    Coindre JM, Terrier P, Bui NB et al. Prognostic factors in adult patients with locally controlled soft tissue sarcoma. A study of 546 patients from the French Federation of Cancer Centers Sarcoma Group. J Clin Oncol 1996; 14:869–77PubMedGoogle Scholar
  8. 8.
    Gaynor JJ, Tan CC, Casper ES et al. Refinement of clinicopathologic staging for localized soft tissue sarcoma of the extremity: a study of 423 adults. J Clin Oncol 1992; 10:1317–29PubMedGoogle Scholar
  9. 9.
    Le Doussal V, Coindre JM, Leroux A et al. Prognostic factors for patients with localized primary malignant fibrous histiocytoma: a multicenter study of 216 patients with multivariate analysis. Cancer 1996; 77:1823–30PubMedCrossRefGoogle Scholar
  10. 10.
    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 1996; 14:1679–89PubMedGoogle Scholar
  11. 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 225 patients. Cancer 2003; 97:2530–43PubMedCrossRefGoogle Scholar
  12. 12.
    Kattan MW, Leung DH, Brennan MF. Postoperative nomogram for 12-year sarcoma-specific death. J Clin Oncol 2002; 20:791–6PubMedCrossRefGoogle Scholar
  13. 13.
    Marcus SG, Merino MJ, Glatstein E et al. Long-term outcome in 87 patients with low-grade soft-tissue sarcoma. Arch Surg 1993; 128:1336–43PubMedGoogle Scholar
  14. 14.
    Donohue JH, Collin C, Friedrich C et al. Low-grade soft tissue sarcomas of the extremities. Analysis of risk factors for metastasis. Cancer 1988; 62:184–93PubMedCrossRefGoogle Scholar
  15. 15.
    Mariani L, Miceli R, Kattan MW et al. Validation and adaptation of a nomogram for predicting the survival of patients with extremity soft tissue sarcoma using a three-grade system. Cancer 2005; 103:402–8PubMedCrossRefGoogle Scholar
  16. 16.
    Fletcher CD. The evolving classification of soft tissue tumours: an update based on the new WHO classification. Histopathology 2006; 48:3–12PubMedCrossRefGoogle Scholar
  17. 17.
    Kooby DA, Antonescu CR, Brennan MF, et al. Atypical lipomatous tumor/well-differentiated liposarcoma of the extremity and trunk wall: importance of histological subtype with treatment recommendations. Ann Surg Oncol 2004; 11:78–84PubMedCrossRefGoogle Scholar
  18. 18.
    Prentice RL, Kalbfleisch JD, Peterson AV Jr et al. The analysis of failure times in the presence of competing risks. Biometrics 1978; 34:541–54PubMedCrossRefGoogle Scholar
  19. 19.
    Prentice RL, Kalbfleisch JD. Hazard rate models with covariates. Biometrics 1979; 35:25–39PubMedCrossRefGoogle Scholar
  20. 20.
    Gray RJ. A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988; 16:1141–54CrossRefGoogle Scholar
  21. 21.
    Fine JP, Gray JP. A proportional hazards model for the subdistribution of a competing risk. Jour Am Stat Assoc 1999; 94:496–509CrossRefGoogle Scholar
  22. 22.
    Anderson JR, Cain KC, Gelber RD. Analysis of survival by tumor response. J Clin Oncol 1983; 1:710–9PubMedGoogle Scholar
  23. 23.
    Kandel RA, Bell RS, Wunder JS et al. Comparison between a 2- and 3-grade systems in predicting metastatic-free survival in extremity soft-tissue sarcoma. J Surg Oncol 1999; 72:77–82PubMedCrossRefGoogle Scholar
  24. 24.
    Guillou L, Coindre JM, Bonichon F et al. Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma. J Clin Oncol 1997; 15:350–62PubMedGoogle Scholar
  25. 25.
    Singer S, Corson JM, Gonin R et al. Prognostic factors predictive of survival and local recurrence for extremity soft tissue sarcoma. Ann Surg 1994; 219:165–73PubMedCrossRefGoogle Scholar
  26. 26.
    Koea JB, Leung D, Lewis JJ et al. Histopathologic type: an independent prognostic factor in primary soft tissue sarcoma of the extremity? Ann Surg Oncol 2003; 10:432–40PubMedCrossRefGoogle Scholar
  27. 27.
    Dunn GP, Ikeda H, Bruce AT et al. Interferon-gamma and cancer immunoediting. Immunol Res 2005; 32:231–45PubMedCrossRefGoogle Scholar
  28. 28.
    Dunn GP, Bruce AT, Ikeda H et al. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002; 3:991–8PubMedCrossRefGoogle Scholar
  29. 29.
    Stojadinovic A, Leung DH, Hoos A et al. Analysis of the prognostic significance of microscopic margins in 2,084 localized primary adult soft tissue sarcomas. Ann Surg 2002; 235:424–34PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2008

Authors and Affiliations

  • Robert J. Canter
    • 1
  • Li-Xuan Qin
    • 2
  • Cristina R. Ferrone
    • 1
  • Robert G. Maki
    • 3
  • Samuel Singer
    • 1
  • Murray F. Brennan
    • 4
  1. 1.Department of SurgeryMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Epidemiology and BiostatisticsMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Department of Medicine, Melanoma-Sarcoma ServiceMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  4. 4.Department of Surgery, Benno C. Schmidt Chair in Clinical OncologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA

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