gynaecological sarcomas
DESCRIPTION
Gynaecological sarcomas. Dr Beatrice Seddon The London Sarcoma Service, University College Hospital, London, UK Connective Tissue Oncology Society Annual Meeting 13 th November 2008. Incidence of gynaecological sarcomas. < 1% of all gynaecological malignancies - PowerPoint PPT PresentationTRANSCRIPT
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)