1 British Journal of Cancer 2008 Vol: 99(8):1210-1215. DOI: 10.1038/sj.bjc.6604527

Endometrial stromal sarcoma: a population-based analysis

To determine independent prognostic factors for the survival of patients with endometrial stromal sarcoma (ESS), data were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute from 1988 to 2003. Kaplan–Meier and Cox proportional hazards models were used for analyses. Of 831 women diagnosed with ESS, the median age was 52 years (range: 17–96 years). In total, 59.9% had stage I, 5.1% stage II, 14.9% stage III, and 20.1% had stage IV disease. Overall, 13.0, 36.1, and 34.7% presented with grades 1, 2, and 3, respectively. Patients with stage I–II vs III–IV disease had 5 years DSS of 89.3% vs 50.3% (P<0.001) and those with grades 1, 2, and 3 cancers had survivals of 91.4, 95.4, and 42.1% (P<0.001). In multivariate analysis, older patients, black race, advanced stage, higher grade, lack of primary surgery, and nodal metastasis were independent prognostic factors for poorer survival. In younger women (<50 years) with stage I–II disease, ovarian-sparing procedures did not adversely impact survival (91.9 vs 96.2%; P=0.1). Age, race, primary surgery, stage, and grade are important prognostic factors for ESS. Excellent survival in patients with grade 1 and 2 disease of all stages supports the concept that these tumors are significantly different from grade 3 tumors. Ovarian-sparing surgeries may be considered in younger patients with early-stage disease.

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Figures
Figure 1: Kaplan–Meier disease-specific survival based on (A) age (P<0.001), (B) race (P=0.001), (C) surgery (P<0.001), (D) stage (P<0.001), (E) grade (P<0.001), (F) nodal metastasis (P<0.001), and (G) oophorectomy in younger women (<50 years) with stage I–II disease (P=0.1).
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References
  1. Amant F, De Knijf A, Van Calster B, Leunen K, Neven P, Berteloot P, Vergote I, Van Huffel S, Moerman PClinical study investigating the role of lymphadenectomy, surgical castration, and adjuvant hormonal treatment in endometrial stromal sarcoma. Br J Cancer 97: 1194-1199 , (2007) .
    • . . . Moreover, despite traditional recommendations to include bilateral salpingo-oophorectomy in the primary surgical management of ESS, some investigators have advocated preserving ovarian function, particularly in younger women (Gadducci et al, 1996; Chu et al, 2003; Li et al, 2005; Amant et al, 2007) . . .
    • . . . Similar findings were described by Amant et al (2007) in a multicenter analysis of 34 women with ESS . . .
  2. Brooks SE, Zhan M, Cote T, Baquet CRSurveillance, Epidemiology, and End Results analysis of 2677 cases of uterine sarcoma 1989-1999. Gynecol Oncol 93: 204-208 , (2004) .
    • . . . In uterine sarcomas, Brooks et al (2004) found a survival difference among racial groups, but this was no longer present after adjusting for treatment differences . . .
  3. Chan JK, Zhang M, Hu JM, Shin JY, Osann K, Kapp DSRacial disparities in surgical treatment and survival of epithelial ovarian cancer in United States. J Surg Oncol 97: 103-107 , (2008) .
    • . . . Racial and ethnic differences in treatment and survival have been previously reported for several gynecologic malignancies, including ovary and uterine cancers (Wingo et al, 1996; Madison et al, 1998; Maxwell et al, 2006; Morris et al, 2006; Chan et al, 2008) . . .
  4. Chu MC, Mor G, Lim C, Zheng W, Parkash V, Schwartz PELow-grade endometrial stromal sarcoma: hormonal aspects. Gynecol Oncol 90: 170-176 , (2003) .
    • . . . Moreover, despite traditional recommendations to include bilateral salpingo-oophorectomy in the primary surgical management of ESS, some investigators have advocated preserving ovarian function, particularly in younger women (Gadducci et al, 1996; Chu et al, 2003; Li et al, 2005; Amant et al, 2007) . . .
    • . . . These results were also confirmed by others (Gadducci et al, 1996; Chu et al, 2003) . . .
  5. Denschlag D, Masoud I, Stanimir G, Gilbert LPrognostic factors and outcome in women with uterine sarcoma. Eur J Surg Oncol 33: 91-95 , (2007) .
    • . . . Most of the earlier studies have been limited by a small number of patients from academic institutions with associated biases (Echt et al, 1990; Haberal et al, 2003; Denschlag et al, 2007; Leath et al, 2007) . . .
    • . . . Earlier studies on the importance of age in ESS have been inconclusive. Denschlag et al (2007) reported on 28 patients with ESS, and found overall better survival was significantly associated with younger patient age . . .
    • . . . Similar to other reports, our analysis found that stage and grade were important predictors of overall improved survival (Echt et al, 1990; Kokawa et al, 2006; Denschlag et al, 2007) . . .
  6. Echt G, Jepson J, Steel J, Langholz B, Luxton G, Hernandez W, Astrahan M, Petrovich ZTreatment of uterine sarcomas. Cancer 66: 35-39 , (1990) .
    • . . . Endometrial stromal sarcomas (ESSs) are rare tumors of the uterus accounting for 0.2–1% of all uterine malignancies and approximately 6–20% of all uterine sarcomas (Koss et al, 1965; Harlow et al, 1986; Echt et al, 1990; Larson et al, 1990) . . .
    • . . . Most of the earlier studies have been limited by a small number of patients from academic institutions with associated biases (Echt et al, 1990; Haberal et al, 2003; Denschlag et al, 2007; Leath et al, 2007) . . .
    • . . . Similar to other reports, our analysis found that stage and grade were important predictors of overall improved survival (Echt et al, 1990; Kokawa et al, 2006; Denschlag et al, 2007) . . .
  7. Field RW, Smith BJ, Platz CE, Robinson RA, Neuberger JS, Brus CP, Lynch CFLung cancer histologic type in the Surveillance, Epidemiology, and End Results registry versus independent review. J Natl Cancer Inst 96: 1105-1107 , (2004) .
    • . . . Several studies have demonstrated the accuracy of pathology from the SEER database (Glaser et al, 2001; Field et al, 2004) . . .
  8. Gadducci A, Sartori E, Landoni F, Zola P, Maggino T, Urgesi A, Lissoni A, Losa G, Fanucchi AEndometrial stromal sarcoma: analysis of treatment failures and survival. Gynecol Oncol 63: 247-253 , (1996) .
    • . . . The standard surgical procedure has included a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and radical cytoreductive surgery of extra-uterine disease (Gadducci et al, 1996) . . .
    • . . . This has also been demonstrated by others (Gadducci et al, 1996; Leath et al, 2007) . . .
    • . . . These results were also confirmed by others (Gadducci et al, 1996; Chu et al, 2003) . . .
  9. Glaser SL, Dorfman RF, Clarke CAExpert review of the diagnosis and histologic classification of Hodgkin disease in a population-based cancer registry: interobserver reliability and impact on incidence and survival rates. Cancer 92: 218-224 , (2001) .
    • . . . Several studies have demonstrated the accuracy of pathology from the SEER database (Glaser et al, 2001; Field et al, 2004) . . .
  10. Goff BA, Rice LW, Fleischhacker D, Muntz HG, Falkenberry SS, Nikrui N, Fuller Jr AFUterine leiomyosarcoma and endometrial stromal sarcoma: lymph node metastases and sites of recurrence. Gynecol Oncol 50: 105-109 , (1993) .
    • . . . Other reports have also suggested that the rates of lymph node involvement in ESS may be higher than expected (Goff et al, 1993; Reich et al, 2005; Riopel et al, 2005) . . .
  11. Haberal A, Kayikcioglu F, Boran N, Caliskan E, Ozgul N, Kose MFEndometrial stromal sarcoma of the uterus: analysis of 25 patients. Eur J Obstet Gynecol Reprod Biol 109: 209-213 , (2003) .
    • . . . Most of the earlier studies have been limited by a small number of patients from academic institutions with associated biases (Echt et al, 1990; Haberal et al, 2003; Denschlag et al, 2007; Leath et al, 2007) . . .
    • . . . Grade has also long been recognized as an important factor in ESS (Norris and Taylor, 1966; Pautier et al, 2000; Haberal et al, 2003; Leath et al, 2007) . . .
  12. Harlow BL, Weiss NS, Lofton SThe epidemiology of sarcomas of the uterus. J Natl Cancer Inst 76: 399-402 , (1986) .
    • . . . Endometrial stromal sarcomas (ESSs) are rare tumors of the uterus accounting for 0.2–1% of all uterine malignancies and approximately 6–20% of all uterine sarcomas (Koss et al, 1965; Harlow et al, 1986; Echt et al, 1990; Larson et al, 1990) . . .
  13. Jaffe ES, Harris NL, Stein H, Vardiman JWPathology and Genetics of Tumors of the Breast and Female Genital Organs. WHO Classification of Tumours , (2001) .
    • . . . Furthermore, as high-grade ESS lack specific differentiation, recent modifications to pathologic classifications of uterine sarcoma have been recommended to rename high-grade ESS as undifferentiated endometrial sarcoma (Jaffe et al, 2001; Moinfar et al, 2007). . . .
    • . . . The 2003 World Health Organization Classification of tumors employs this new nomenclature, as does the current pathology literature, where the term of ESS is used to describe low-grade stromal sarcomas only (Jaffe et al, 2001; Moinfar et al, 2007). . . .
  14. Kokawa K, Nishiyama K, Ikeuchi M, Ihara Y, Akamatsu N, Enomoto T, Ishiko O, Motoyama S, Fujii S, Umesaki NClinical outcomes of uterine sarcomas: results from 14 years worth of experience in the Kinki district in Japan (1990-2003). Int J Gynecol Cancer 16: 1358-1363 , (2006) .
    • . . . Denschlag et al (2007) reported on 28 patients with ESS, and found overall better survival was significantly associated with younger patient age. Similarly, Kokawa et al (2006) showed that younger age was an independent predictor of improved survival in multivariate analysis of 15 cases of ESS . . .
    • . . . Similar to other reports, our analysis found that stage and grade were important predictors of overall improved survival (Echt et al, 1990; Kokawa et al, 2006; Denschlag et al, 2007) . . .
  15. Koss LG, Spiro RH, Brunschwig AEndometrial Stromal Sarcoma. Surg Gynecol Obstet 121: 531-537 , (1965) .
    • . . . Endometrial stromal sarcomas (ESSs) are rare tumors of the uterus accounting for 0.2–1% of all uterine malignancies and approximately 6–20% of all uterine sarcomas (Koss et al, 1965; Harlow et al, 1986; Echt et al, 1990; Larson et al, 1990) . . .
  16. Larson B, Silfversward C, Nilsson B, Pettersson FEndometrial stromal sarcoma of the uterus. A clinical and histopathological study. The Radiumhemmet series 1936-1981. Eur J Obstet Gynecol Reprod Biol 35: 239-249 , (1990) .
    • . . . Endometrial stromal sarcomas (ESSs) are rare tumors of the uterus accounting for 0.2–1% of all uterine malignancies and approximately 6–20% of all uterine sarcomas (Koss et al, 1965; Harlow et al, 1986; Echt et al, 1990; Larson et al, 1990) . . .
  17. Leath III CA, Huh WK, Hyde Jr J, Cohn DE, Resnick KE, Taylor NP, Powell MA, Mutch DG, Bradley WH, Geller MA, Argenta PA, Gold MAA multi-institutional review of outcomes of endometrial stromal sarcoma. Gynecol Oncol 105: 630-634 , (2007) .
    • . . . On account of significant differences in the clinical behaviour of ESS patients, Norris and Taylor first described the prognostic significance of histologic grade in ESS, and their findings have been subsequently confirmed by others (Norris and Taylor, 1966; Pautier et al, 2000; Leath et al, 2007) . . .
    • . . . Most of the earlier studies have been limited by a small number of patients from academic institutions with associated biases (Echt et al, 1990; Haberal et al, 2003; Denschlag et al, 2007; Leath et al, 2007) . . .
    • . . . Grade has also long been recognized as an important factor in ESS (Norris and Taylor, 1966; Pautier et al, 2000; Haberal et al, 2003; Leath et al, 2007) . . .
  18. Li AJ, Giuntoli II RL, Drake R, Byun SY, Rojas F, Barbuto D, Klipfel N, Edmonds P, Miller DS, Karlan BYOvarian preservation in stage I low-grade endometrial stromal sarcomas. Obstet Gynecol 106: 1304-1308 , (2005) .
    • . . . Moreover, despite traditional recommendations to include bilateral salpingo-oophorectomy in the primary surgical management of ESS, some investigators have advocated preserving ovarian function, particularly in younger women (Gadducci et al, 1996; Chu et al, 2003; Li et al, 2005; Amant et al, 2007) . . .
    • . . . This study showed that ovarian-sparing surgeries in the subset of younger women (<50 years) with otherwise early-stage disease did not adversely impact survival. Similarly, Li et al (2005) found that ovarian preservation did not affect recurrence or survival in women with stage I low-grade ESS . . .
  19. Li N, Wu LY, Zhang HT, An JS, Li XG, Ma SKTreatment options in stage I endometrial stromal sarcoma: a retrospective analysis of 53 cases. Gynecol Oncol 108: 306-311 , (2008) .
    • . . . In contrast, in a recent analysis of 53 patients, investigators found that ovarian preservation resulted in higher recurrence rates of 9 of 9 patients vs 10 of 44 (P<0.001) in those who had bilateral salpingo-oophorectomy (Li et al, 2008) . . .
  20. Madison T, Schottenfeld D, Baker VCancer of the corpus uteri in white and black women in Michigan, 1985-1994: an analysis of trends in incidence and mortality and their relation to histologic subtype and stage. Cancer 83: 1546-1554 , (1998) .
    • . . . Racial and ethnic differences in treatment and survival have been previously reported for several gynecologic malignancies, including ovary and uterine cancers (Wingo et al, 1996; Madison et al, 1998; Maxwell et al, 2006; Morris et al, 2006; Chan et al, 2008) . . .
  21. Maxwell GL, Tian C, Risinger J, Brown CL, Rose GS, Thigpen JT, Fleming GF, Gallion HH, Brewster WRRacial disparity in survival among patients with advanced/recurrent endometrial adenocarcinoma: a Gynecologic Oncology Group study. Cancer 107: 2197-2205 , (2006) .
    • . . . Racial and ethnic differences in treatment and survival have been previously reported for several gynecologic malignancies, including ovary and uterine cancers (Wingo et al, 1996; Madison et al, 1998; Maxwell et al, 2006; Morris et al, 2006; Chan et al, 2008) . . .
  22. Moinfar F, Azodi M, Tavassoli FAUterine sarcomas. Pathology 39: 55-71 , (2007) .
    • . . . Furthermore, as high-grade ESS lack specific differentiation, recent modifications to pathologic classifications of uterine sarcoma have been recommended to rename high-grade ESS as undifferentiated endometrial sarcoma (Jaffe et al, 2001; Moinfar et al, 2007). . . .
    • . . . The 2003 World Health Organization Classification of tumors employs this new nomenclature, as does the current pathology literature, where the term of ESS is used to describe low-grade stromal sarcomas only (Jaffe et al, 2001; Moinfar et al, 2007). . . .
  23. Morris AM, Wei Y, Birkmeyer NJ, Birkmeyer JDRacial disparities in late survival after rectal cancer surgery. J Am Coll Surg 203: 787-794 , (2006) .
    • . . . Racial and ethnic differences in treatment and survival have been previously reported for several gynecologic malignancies, including ovary and uterine cancers (Wingo et al, 1996; Madison et al, 1998; Maxwell et al, 2006; Morris et al, 2006; Chan et al, 2008) . . .
  24. Nordal RR, Kristensen GB, Kaern J, Stenwig AE, Pettersen EO, Trope CGThe prognostic significance of surgery, tumor size, malignancy grade, menopausal status, and DNA ploidy in endometrial stromal sarcoma. Gynecol Oncol 62: 254-259 , (1996) .
    • . . . In contrast, Nordal et al (1996) studied 48 patients with ESS and found that age was not significantly correlated to survival . . .
  25. Norris HJ, Taylor HBMesenchymal tumors of the uterus. I. A clinical and pathological study of 53 endometrial stromal tumors. Cancer 19: 755-766 , (1966) .
    • . . . On account of significant differences in the clinical behaviour of ESS patients, Norris and Taylor first described the prognostic significance of histologic grade in ESS, and their findings have been subsequently confirmed by others (Norris and Taylor, 1966; Pautier et al, 2000; Leath et al, 2007) . . .
    • . . . Grade has also long been recognized as an important factor in ESS (Norris and Taylor, 1966; Pautier et al, 2000; Haberal et al, 2003; Leath et al, 2007) . . .
  26. Pautier P, Genestie C, Rey A, Morice P, Roche B, Lhomme C, Haie-Meder C, Duvillard PAnalysis of clinicopathologic prognostic factors for 157 uterine sarcomas and evaluation of a grading score validated for soft tissue sarcoma. Cancer 88: 1425-1431 , (2000) .
    • . . . On account of significant differences in the clinical behaviour of ESS patients, Norris and Taylor first described the prognostic significance of histologic grade in ESS, and their findings have been subsequently confirmed by others (Norris and Taylor, 1966; Pautier et al, 2000; Leath et al, 2007) . . .
    • . . . Grade has also long been recognized as an important factor in ESS (Norris and Taylor, 1966; Pautier et al, 2000; Haberal et al, 2003; Leath et al, 2007) . . .
  27. Reich O, Winter R, Regauer SShould lymphadenectomy be performed in patients with endometrial stromal sarcoma? Gynecol Oncol 97: 982; author reply 982-983 , (2005) .
    • . . . Other reports have also suggested that the rates of lymph node involvement in ESS may be higher than expected (Goff et al, 1993; Reich et al, 2005; Riopel et al, 2005) . . .
  28. Riopel J, Plante M, Renaud MC, Roy M, Tetu BLymph node metastases in low-grade endometrial stromal sarcoma. Gynecol Oncol 96: 402-406 , (2005) .
    • . . . Other reports have also suggested that the rates of lymph node involvement in ESS may be higher than expected (Goff et al, 1993; Reich et al, 2005; Riopel et al, 2005) . . .
  29. Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER 12 Regs Public-Use, November 2004 Sub (1988-2001), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch. Available at: Link Released on April 2005 , .
    • . . . Demographic, clinico-pathologic variables, treatment data, and survival information of women diagnosed with ESS were extracted from the Surveillance, Epidemiology, and End Results (SEER) database of the United States National Cancer Institute for the 15-year period from 1 January 1988 to 31 December 2003 . . .
  30. Wingo PA, Bolden S, Tong T, Parker SL, Martin LM, Heath Jr CWCancer statistics for African Americans, 1996. CA Cancer J Clin 46: 113-125 , (1996) .
    • . . . Racial and ethnic differences in treatment and survival have been previously reported for several gynecologic malignancies, including ovary and uterine cancers (Wingo et al, 1996; Madison et al, 1998; Maxwell et al, 2006; Morris et al, 2006; Chan et al, 2008) . . .
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