Transcript ENDOMETRIAL CANCER - urogynaecology.co.za

ENDOMETRIAL CANCER
Nomonde Mbatani
Ca Endometrium
• Most common female genital tract cancer –
Developed areas
• South African females, 7th most common
cancer (1:163) according to SA National
Cancer Registry
The good news
• Prognosis excellent
Ca endometrium
Type 1
Type 2
Obese , hyperlipidaemic.
Peri - menopausal woman
Mature woman
Hyper -estrogenism
Atrophic endometrium
Precursor - Atypical hyperplasia
(EIN)
Serous Intra-epithelial Carcinoma-SIC/
EGD)
Low grade. Less invasive at time
of surgery
High Grade (UPSC, Clear cell, MMMT
?Grade 3)
Favourable prognosis
Poor prognosis
Highly sensitive to progestagens
No response to progestagens
In 80% cases EC
In 15 -20% EC
Prognostic factors
Uterine factors
• Histological type: Endometrioid, Clear cell, UPSC
• Histological grade: 1, 2 or 3 (Grigsby, Portec)
• LVSI
• Cervix involvement
• DNA ploidy – Flow Cytometry
• Depth of myometrial invasion Extra –uterine factors:
More to do with stage!
ROLE OF PATHOLOGIST CRUCIAL!
Endometrial Cancer Profile
• The woman with endometrial cancer:
Morphological , medical challenge .
• Pre –operative workup.
• Anaesthetic assessment
• ICU bookings
Pre-operative Assessment
• Bloods: FBC, U&E, HIV, δGT, ALP
• Ultra sound: Liver, lymphadenopathy
• Depth of myometrial invasion – Role of MRI
• Histological review!
Surgery
• TAH and BSO – Open / Laparoscopic – Curative
for most women
(75% - confined to uterus)
• Laparoscopy: Conversion to open surgery is
higher
• Peritoneal washings – No longer part of staging
• Cuff of vagina – No evidence
Parametrial involvement
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Not part of FIGO staging
Some data – associated with poorer prognosis
Radical Hysterectomy - ? Survival benefit
Small study/ retrospective series
Survival in those who were offered radical
hysterectomy. Selection bias!
• Parametrial involvement :Associated with
increased surgical stage
• Still do simple Hysterectomy
Type 2 Cancers
• Additional pelvic / para-aortic lymph node
dissection (FIGO Staging)
• Omentectomy: Serous and MMT. Peritoneal
spread - ?Benefit
Lymphadenectomy
Role
• Hysterectomy and bilateral salpingo-oophorectomy is the
standard surgery followed by RT depending on risk factors
• Establish extra uterine disease – Stage 3 c(1) or 3c(11)
• What is the extent?
• Only pelvic nodes done up to common iliacs – Criticism!
FIGO
• Groin nodes? – No!
Is there a survival benefit in LND?
A study in Treatment of Endometrial Cancer
(ASTEC Study)
NO!
Survival Effect of Para Aortic Lymphadenectomy
(SEPAL study) Yes!
• Intermediate / high risk groups
• Improved patient survival (OS) in combined
LND group (and chemotherapy,
independently).p=0049
• The higher you go, ……
SEPAL
S
E
P
A
L
Study
design
GSH Protocol
TAH and BSO –
For low risk patients (Stage 1)
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Stage 1a and Grade 1/ 2 and less than 50% invasion
Low risk of recurrence (5%)
No survival benefit
Intermediate risk:
 Grade 1/ 2 with more than 50% mm involvement
 Grade 3 or type 2 cancers
 Cervical involvement
If nodes negative: Vault Brachy only vs WPRT, fewer complications for the patient.
About 75% patients saved from WPRT
Intermediate risk: G. Thomas
 Grade 2 Stage 1b / Grade 3
 WPRT vs Vault Brachytherapy – No survival advantage,
Does not lead to better cure
 Pelvic recurrences: curable with radiotherapy
risks:benefit. First do no harm!
 Keep as Plan B. Especially in patients under age 60yrs
with no LVSI – GOG and Portec seem to suggest!
Challenges
• Stage 111 and 1V disease
• Stage 1V: Adequate cyto reduction – microscopic
disease – determinant of survival
• Other determinants: Age less than 58yrs, good
performance status (Bristow)
• Recurrent disease – Role of surgery
Chemotherapy for EC
• Advanced / recurrent endometrial cancer setting
• Hormonal therapy – hormone receptor positive
tumours (low grade) - (11 to 25% response rates)
• Medroxy - Progesterone, lower doses as effective
- Down regulation of receptors
• Aromatase inhibitors / SERMS- little data
• Combinations: Doxorubicin and Cisplatinum
• Addition of Paclitaxel
• Toxic regimes: already elderly/ medically unwell
patients
Targeted therapies
Cell growth regulation
• Proto- oncogenes – Encourage cell growth
and inhibit cell death.
• Mutation – Oncogenes leading to accelerated
and disorderly cell growth. Dominant genes
• Tumour suppressor genes / anti- oncogenes–
prevent cell growth and encourage apoptosis:
regulate transcription, DNA repair and cell to
cell communication.
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TKR extracellular domain
Cell Membrane
TKR intracellular domain
+P
P
PI3K
KRAS
PIP2
+P
Key
 Hormone ligand
PIP3
-P
PTEN

AKT
✚ Prostaglandin
RAF
mTor
Growth factor ligand
FOXO1
MAPK
Intracellular events
• Proliferation
• Metastasis
• New vessel formation
• Decreased apoptosis
Type One endometrial cancers
Molecular targets
• Grouping of cancers looking at prognosis
• What causes diseases
• What might be manipulated to alter risk / cure
disease
• Design therapeutics
Targeted treatments (the future)
 Molecular profiling
 Targets cancer pathways
 Prevention of cancer
Bevacizumab – VEGF
Lenvatinib
Cell
Membrane
P
P
PI3K
PIP2
PIP3
Key
 Hormone ligand
BRAF
Growth factor ligand
Vemurafenib
AKT
Prostaglandin
MAPK
mTor
Intracellular:
• Proliferation
• Metastasis
• New vessel formation
• Decreased apoptosis
Evorelimus