1

Gynaecological sarcomas

Dr Beatrice Seddon

The London Sarcoma Service, University College Hospital, London, UK

Connective Tissue Oncology Society Annual Meeting

13th November 2008

2

Incidence of gynaecological sarcomas

• < 1% of all gynaecological malignancies

• Majority are uterine tumours

• Also cervix, vagina, vulva, ovary (all rare)

• Includes:

Leiomyosarcoma (uterus, vagina, vulva, ovary)

Endometrial stromal sarcoma

Undifferentiated endometrial sarcoma

Rhabdomyosarcoma (vagina/cervix)

Other soft tissue sarcoma subtypes (MFH, angiosarcoma, ASPS, DFSP)

• Does not include malignant mixed müllerian tumours/carcinosarcomas

• Surgery is main component of management

3

Uterine leiomyosarcoma

• 6.4 cases per million in USA (total ~2000 cases)

• Median age approx 50 years

• 2 - 4 % of all uterine cancers

• Majority (70%) >5 cm in diameter

• Incidence of malignancy in uterine fibroids/leiomyomata 0.2 - 0.7%

• Approximately 50% express ER and PR

4

FIGO Staging Corpus Uteri

Stage I - tumour confined to corpus uteri IA – tumour limited to endometrium

IB – invades ≤ ½ myometrium

IC – invades > ½ myometrium

Stage II - tumour invades cervix but does not extend beyond the uterus IIA – endocrevical gland involvement only

IIB – cervical stromal invasion

Stage III - local and/or regional spread IIIA – tumour involves serosa and/or adnexa and/or +ve peritoneal washings

IIIB – vaginal involvement (direct extension or metastatic spread)

IIIC – metastasis to pelvic and or para-aortic lymph nodes

Stage IVA - tumour invades bladder mucosa and/or bowel mucosa

Stage IVB - distant metastases

5

FIGO stage at presentation

Stage Gaducci et al, 1996

Pautrier et al, 2000

Giuntoli et al, 2003

Kapp et al , 2008

N 126 78 208 1396

I 69.8% 59% 62% 68%

II 1.6% 13% 6% 3%

III 12.7% 9% 9% 7%

IV 15.9% 19% 20% 21%

6

Treatment outcome

Study N Recurrence rate

Progression free survival

Overall survival

Gaducci et al, 1996

126 I/II – 39% III – 81%

5yr PFS 40% -

Pautrier et al, 2000

78 81% 5yr PFS 16% 5yr OS 35%

Livi et al, 2003

72 - - 5yr OS 19%

Kapp et al, 1396 - 5yr DSS: I – 76% 2008 II – 60%

III – 45% IV – 39%

7

Role of adjuvant chemotherapy in uterine leiomyosarcoma

• Outcome for uterine leiomyosarcoma is poor

• Many relapses are distant

• Could use of adjuvant chemotherapy improve outcome?

8

Role of adjuvant chemotherapy in soft tissue sarcoma

• Lancet meta-analysis of 1568 patients in 14 trials of adjuvant chemotherapy in soft tissue sarcoma

• Total group - improved local RFS, distant RFS, overall RFS; but no overall survival benefit

• EORTC adjuvant study also negative (ASCO 2007)

• Subgroups: 263 patients with uterine sarcoma - no survival benefit

Suggestion of benefit in meta-analysis for extremity tumours

? Benefit for selected high risk patients

9

Role of adjuvant chemotherapy

Retrospective series of 208 patients with uterine leiomyosarcoma

Identified prognostic factors:

Prognostic factor Score

Age <51 years 1

Tumour >5 cm 1

FIGO II-IV 1

Intermediate/high grade 2Giuntoli et al, Gynaecol Oncol 2003; 89:460-9

10

Role of adjuvant chemotherapy

Risk assessment:

Score Risk Median survival

0-1 Low >25 years

2-3 Intermediate 6.5 years

4-5 High 2.1 years

Giuntoli et al, Gynaecol Oncol 2003; 89:460-9

11

Role of adjuvant chemotherapy

• Not routine

• Consider treating high risk group in selected patients

• Doxorubicin 60-75 mg/m2, ifosfamide 6-9 mg/m2, q.3/52, 5-6 cycles

• Phase II SARC study of adjuvant gemcitabine and docetaxel in resected uterine sarcoma

12

Endometrial stromal neoplasms

• Stromal nodule (benign lesion)

• Endometrial stromal sarcoma (‘low grade’ lesion)

• Poorly differentiated endometrial sarcoma (‘high grade’ lesion)

• Old classification of low grade and high grade ESS on basis of mitotic count no longer used

13

Endometrial stromal sarcoma

• Clinically indolent course, long natural history

• High relapse rate, late relapses

• Bland histology

• Low mitotic count does not predict ‘bland’ behaviour

• FIGO stage more accurately predicts outcome

• Composed of cells identical to endometrial stromal cells in proliferative phase

• High expression of ER and PR

14

Poorly differentiated endometrial sarcoma

• Anaplastic aggressive uterine tumour

• Lacks endometrial stromal features - does not resemble proliferative phase endometrial cells

• Mostly postmenopausal women >50 years

• High recurrence rates, both locally and distant

• Recurrences usually occur within 12 months of diagnosis

• Outcome poor - 5 year survival 0-32%

15

This morning’s presentations:

• Staging of uterine leiomyosarcomas:

Stage specific outcomes of FIGO and AJCC systems (#34982)

Predictive value of FIGO and AJCC systems (#34970)

• New prognostic marker in high grade uterine sarcoma – WT1 (#34855)

• Role of adjuvant gemcitabine and docetaxel chemotherapy in uterine leiomyosarcoma (#34961)

• Single institution experience of ovarian sarcoma (#35073)