Annals of Surgical Oncology

, 15:2739

New Perspectives for Staging and Prognosis in Soft Tissue Sarcoma

  • G. Lahat
  • D. Tuvin
  • C. Wei
  • D. A. Anaya
  • B. N. Bekele
  • A. J. Lazar
  • P. W. Pisters
  • D. Lev
  • R. E. Pollock
Bone and Soft Tissue Sarcomas

Abstract

Background

Data suggest that the current American Joint Committee on Cancer (AJCC) soft tissue sarcoma (STS) staging criteria merit further evaluation. We sought to identify and validate factors as enhanced descriptors of STS clinical behavior.

Methods

Prospectively accrued data were analyzed for 1,091 AJCC stage I to III primary STS patients who had complete macroscopic resection at our institution from 1996 to 2007. Study factors were examined by univariable and multivariable analyses to identify independent prognostic factors for disease related mortality and overall survival (OS).

Results

In contrast to the current AJCC STS staging system, which stratifies size into T1 (≤5 cm) and T2 (>5 cm) groups, we demonstrated three distinct cohorts (P < 0.0001): T1 (≤5 cm; 5-year OS 85%), T2 (5 to 15 cm; OS 68%), and T3 (>15 cm; OS 52%). A two-category system of histologic grade was demonstrably as informative as the current four histologic grade AJCC system. A multivariable Cox proportional hazard model identified tumor size (5 to 15 cm vs. ≤5 cm, P = 0.03; or >15 cm vs. ≤5 cm; P < 0.0001), nonextremity primary site (P = 0.0016), disease of high histologic grade (P = 0.001), specific histology (P = 0.001), and margin positivity (P < 0.0001) as statistically significant adverse independent prognostic factors. Recurrence during follow-up was the most significant risk factor for STS-specific mortality (P < 0.0001).

Conclusion

Tumor size and grade in the AJCC STS staging system need revision; moreover, primary site, histologic subtype, margin status, and recurrence offer additional relevant prognostic insight. Incorporation of these factors may enhance the AJCC staging system, thereby further facilitating individualized therapeutic strategies for STS patients.

Keywords

Soft tissue sarcoma Staging Prognostic factors Recurrence Survival 

References

  1. 1.
    Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J Clin 2006; 56:106–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Lahat G, Lazar AJ, Lev D. Sarcoma epidemiology and etiology: potential environmental and genetic factors. Surg Oncol Clin N Am (in press)Google Scholar
  3. 3.
    Fletcher CD, Unni KK, Mertens F. (2002) World Health Organization classification of tumors. Pathology and genetics. Tumors of soft tissue and bone. Lyon: IARC Press.Google Scholar
  4. 4.
    Clark MA, Fisher C, Judson I, et al. Soft-tissue sarcomas in adults. N Engl J Med 2005; 353:701–11.PubMedCrossRefGoogle Scholar
  5. 5.
    Brennan MF. Staging of soft tissue sarcomas. Ann Surg Oncol 1999; 6:8–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Collin C, Godbold J, Hajdu S, et al. Localized extremity soft tissue sarcoma: an analysis of factors affecting survival. Ann Surg Oncol 1987; 5:601–12.Google Scholar
  7. 7.
    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; 10:1317–29.PubMedGoogle Scholar
  8. 8.
    Heise HW, Myers MH, Russell WO, et al. Recurrence-free survival time for surgically treated soft tissue sarcoma patients. Multivariate analysis of five prognostic factors. Cancer 1986; 57:172–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Rooser B, Attewell R, Berg NO, et al. Prognostication in soft tissue sarcoma. A model with four risk factors. Cancer 1988; 61:817–23.PubMedCrossRefGoogle Scholar
  10. 10.
    Rydholm A, Berg NO, Gullberg B, et al. Prognosis for soft-tissue sarcoma in the locomotor system. A retrospective population-based follow-up study of 237 patients. Acta Pathol Microbiol Immunol Scand 1984; 92:375–86.Google Scholar
  11. 11.
    Singer S, Corson JM, Gonin R, et al. Prognostic factors predictive of survival and local recurrence for extremity soft tissue sarcoma. Ann Surg 1994; 219:165–73.PubMedCrossRefGoogle Scholar
  12. 12.
    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; 33:37–42.PubMedCrossRefGoogle Scholar
  13. 13.
    Ueda T, Aozasa K, Tsujimoto M, et al. Multivariate analysis for clinical prognostic factors in 163 patients with soft tissue sarcoma. Cancer 1988; 62:1444–50.PubMedCrossRefGoogle Scholar
  14. 14.
    Stotter AT, A’Hern RP, Fisher C, et al. The influence of local recurrence of extremity soft tissue sarcoma on metastasis and survival. Cancer 1990; 65:1119–29.PubMedCrossRefGoogle Scholar
  15. 15.
    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; 14:1679–89.PubMedGoogle Scholar
  16. 16.
    Ramanathan RC, A’Hern R, Fisher C, et al. Modified staging system for extremity soft tissue sarcomas. Ann Surg Oncol 1999; 6:57–69.PubMedCrossRefGoogle Scholar
  17. 17.
    Stojadinovic A, Leung DH, Allen P, et al. Primary adult soft tissue sarcoma: time-dependent influence of prognostic variables. J Clin Oncol 2002; 20:4344–52.PubMedCrossRefGoogle Scholar
  18. 18.
    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; 235:424–34.PubMedCrossRefGoogle Scholar
  19. 19.
    Stefanovski PD, Bidoli E, De Paoli A, et al. Prognostic factors in soft tissue sarcomas: a study of 395 patients. Eur J Surg Oncol 2002; 28:153–64.PubMedCrossRefGoogle Scholar
  20. 20.
    Zagars GK, Ballo MT, Pisters PW, et al. Prognostic factors for disease-specific survival after first relapse of soft-tissue sarcoma: analysis of 402 patients with disease relapse after initial conservative surgery and radiotherapy. Int J Radiat Oncol Biol Phys 2003; 57:739–47.PubMedGoogle Scholar
  21. 21.
    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 2003; 97:2530–43.PubMedCrossRefGoogle Scholar
  22. 22.
    Eilber FC, Rosen G, Nelson SD, et al. High-grade extremity soft tissue sarcomas: factors predictive of local recurrence and its effect on morbidity and mortality. Ann Surg 2003; 237:218–26.PubMedCrossRefGoogle Scholar
  23. 23.
    Kattan MW, Leung DH, Brennan MF. Postoperative nomogram for 12-year sarcoma-specific death. J Clin Oncol 2002; 20:791–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Eilber FC, Brennan MF, Eilber FR, et al. Validation of the postoperative nomogram for 12-year sarcoma-specific mortality. Cancer 2004; 101:2270–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Riad S, Griffin AM, Liberman B, et al. Lymph node metastasis in soft tissue sarcoma in an extremity. Clin Orthop Relat Res 2004; 426:129–34.PubMedCrossRefGoogle Scholar
  26. 26.
    Behranwala KA, A’Hern R, Omar AM, et al. Prognosis of lymph node metastasis in soft tissue sarcoma. Ann Surg Oncol 2004; 11:714–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Blazer DG 3rd, Sabel MS, Sondak VK. Is there a role for sentinel lymph node biopsy in the management of sarcoma? Surg Oncol 2003; 12:201–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Fletcher CD, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol 2002; 33:459–65.PubMedCrossRefGoogle Scholar
  29. 29.
    Kaplan EL, Meier MP. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53:448–57.CrossRefGoogle Scholar
  30. 30.
    Gooley TA, Leisenring W, Crowley J, et al. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 1999; 18:695–706.PubMedCrossRefGoogle Scholar
  31. 31.
    Rosthoj S, Andersen PK, Abildstrom SZ. SAS macros for estimation of the cumulative incidence functions based on a Cox regression model for competing risks survival data. Comput Methods Programs Biomed 2004; 74:69–75.PubMedCrossRefGoogle Scholar
  32. 32.
    Gray RJ. A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988; 16:1141–54.CrossRefGoogle Scholar
  33. 33.
    Gray B. Cmprsk: subdistribution analysis of competing risks. Version 2.1-7. Available at: http://cran.r-project.org/web/packages/cmprsk/index.html. Accessed May 16, 2008
  34. 34.
    The Mianalyze procedure. SAS onlineDocTM. Chapter 10. Version 8. Available at: http://support.sas.com/rnd/app/papers/mianalyzev802.pdf. Accessed May 16, 2008
  35. 35.
    Balch CM, Buzaid AC, Atkins MB, et al. A new American Joint Committee on Cancer staging system for cutaneous melanoma. Cancer 2000; 88:1484–91.PubMedCrossRefGoogle Scholar
  36. 36.
    Russell WO, Cohen J, Enzinger F, et al. A clinical and pathological staging system for soft tissue sarcomas. Cancer 1977; 40:1562–70.PubMedCrossRefGoogle Scholar
  37. 37.
    Fleming ID, Cooper JS, Henson DE. AJCC Cancer Staging Manual. 5th ed. Philadelphia: Lippincott-Raven, 1997.Google Scholar
  38. 38.
    Greene FL, Page DL, Fleming ID. (2002) AJCC Cancer Staging Manual. 6th edn. New York: Springer.Google Scholar
  39. 39.
    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; 53:530–41.PubMedCrossRefGoogle Scholar
  40. 40.
    Rubin BP, Fletcher CD, Inwards C, et al. Protocol for the examination of specimens from patients with soft tissue tumors of intermediate malignant potential, malignant soft tissue tumors, and benign/locally aggressive and malignant bone tumors. Arch Pathol Lab Med 2006; 130:1616–29.PubMedGoogle Scholar
  41. 41.
    Gutierrez JC, Perez EA, Franceschi D, et al. Outcomes for soft-tissue sarcoma in 8249 cases from a large state cancer registry. J Surg Res 2007; 141:105–14.PubMedCrossRefGoogle Scholar
  42. 42.
    Pisters PWT, Brennan MF. (1995) Sarcomas of soft tissue. In: Abeloff MAJ, Lichter A, et al. (ed) Clinical oncology. New York: Churchill Livingstone. pp 1799–832Google Scholar
  43. 43.
    Devita VT, Rosenberg SASH. (2004) Cancer: Principles and practice of oncology. 7th edn. Philadelphia: Lippincott.Google Scholar
  44. 44.
    ten Heuvel SE, Hoekstra HJ, van Ginkel RJ, et al. Clinicopathologic prognostic factors in myxoid liposarcoma: a retrospective study of 49 patients with long-term follow-up. Ann Surg Oncol 2007; 14:222–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Fiore M, Grosso F, Lo Vullo S, et al. Myxoid/round cell and pleomorphic liposarcomas: prognostic factors and survival in a series of patients treated at a single institution. Cancer 2007; 109:2522–31.PubMedCrossRefGoogle Scholar
  46. 46.
    Gronchi A, Casali PG, Mariani L, et al. Status of surgical margins and prognosis in adult soft tissue sarcomas of the extremities: a series of patients treated at a single institution. J Clin Oncol 2005; 23:96–104.PubMedCrossRefGoogle Scholar
  47. 47.
    Packeisen J, Korsching E, Herbst H, et al. Demystified...tissue microarray technology. Mol Pathol 2003; 56:198–204.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2008

Authors and Affiliations

  • G. Lahat
    • 1
    • 2
  • D. Tuvin
    • 1
    • 2
  • C. Wei
    • 3
  • D. A. Anaya
    • 1
  • B. N. Bekele
    • 4
  • A. J. Lazar
    • 2
    • 5
  • P. W. Pisters
    • 1
  • D. Lev
    • 2
    • 6
  • R. E. Pollock
    • 1
    • 2
  1. 1.Department of Surgical OncologyUniversity of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Sarcoma Research CenterUniversity of Texas M. D. Anderson Cancer CenterHoustonUSA
  3. 3.Division of Quantitative SciencesUniversity of Texas M. D. Anderson Cancer CenterHoustonUSA
  4. 4.Department of BiostatisticsUniversity of Texas M. D. Anderson Cancer CenterHoustonUSA
  5. 5.Department of PathologyUniversity of Texas M. D. Anderson Cancer CenterHoustonUSA
  6. 6.Department of Cancer BiologyUniversity of Texas M. D. Anderson Cancer CenterHoustonUSA

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