endometrium Flashcards
What are the endometrial cancer histologies
Endometrioid adenocarcinoma
Clear cell
Papillary serous
Carcinosarcoma (tx as high grade endometrial adenoca)
Leiomyosarcoma / endometrial stromal sarcoma - treat as sarcoma
Squamous, small cell, lymphoma
What are the risk factors for endometrial cancer
Oestrogen exposure - oestrogen only HRT, PCOS, obesity, nulliparity, increasing years of menstruation
Previous breast cancer
Genetic factors - Lynch type II
Atypical endometrial hyperplasia
What is the endometrial management of Lynch syndrome
Yearly TV USS from 35yrs, prophylactic H+BSO from 40
What is the frequency of concurrent ovarian and endometrial carcinoma
8%
If histologies match - treat as endometrial that has spread to the ovary
If different histology = two primaries, and treat highest stage first
What are the molecular subgroups of endometrial carcinoma
EC - POLE mut
EC - dMMR
EC - pMMR, p53 mut - poorest outcome, and greatest benefit from chemo
EC - pMMR, p53 WT - NSMP
How often are POL-E mutations seen in endometrial cancer
What is the consequence
10%
High mutational burden and typically have better outcomes
Can consider de-escalating treatment
What are the four proteins tested for in Lynch syndrome
PMS2, MSH6, MSH2, MLH1
What proportion of endometrial cancers (incl dMMR) are related to Lynch syndrome
3% of endometrial cancers and 10% of dMMR ECs are related to Lynch syndrome
When is the endometrium thickness abnormal
> 3mm if post menopausal and not on HRT
How is endometrial cancer investigated
TV USS + hysteroscopy & biopsy
MRI pelvis
Staging CT
+/- PET
+/- cystoscopy / sigmoidoscopy
What surgery should be done in a Stage 1 serous EC & carcinosarcoma
TAH & BSO, with omentectomy, peritoneal biopsy and LN staging (behaves like ovarian)
When should LN evaluation take place for endometrial cancer
≥Gr3, ≥FIGO IB, non-endometrioid histology,
SNLB or sentinel lymphadenectomy
How can fertility be spared for a stage 1 endometrial cancer
Gr1 stage 1A only
Ovary sparing TAH
Or mirena coil and oral progesterone
Monitor closely - repeat endometrial biopsy at 3 & 9 months.
Hysteroscopy 6 & 12 months.
After 1 year, if CR, can have fertility treatment, followed by complete hysterectomy (discussion)
What is the management of a stage one endometrial cancer
TAH + BSO unless PM and Gr1 stage 1A and fertility sparing is desired
What is the management of a stage 2 endometrial cancer
TAH + BSO + pelvic lymphadenectomy
+ omentectomy if serous histology (behaves like ovarian)
What is the management of a stage 3 endometrial cancer
TAH + BSO + lymphadenectomy
Adj tx
What is the management of a stage 4 endometrial cancer
Operable - consider exenteration & adjuvant treatment
Inoperable - NACT, EBRT (45Gy/25# & boost to macroscopic disease), +/- surgery if disease becomes operable
What is the benefit of adjuvant RT for endometrial cancer
10% improvement in local recurrence risk
No improvement in overall survival
How is a low risk endometrial cancer defined in the adjuvant setting
what adj tx needed
Stage 1A, endometriod, gr1-2, LVSI negative or focal
Or stage 1-3 and POLE-mut
no adj tx indicated
How is an intermediate risk endometrial cancer defined
what tx
All LVSI negative or focal
Stage 1B, gr1-2, endometriod
Stage 1A, gr3, endometrioid
Stage 1A, non-endometrioid histology, any grade (no adj tx)
Stage 2, gr1, endometrioid
Stage 1A, p53 abn (still tx with adj EBRT)
Adjuvant treatment: Vaginal brachytherapy
Can consider omitting if age >60
No adj tx if stage 1A non-endometrioid
How is high-intermediate risk endometrial cancer defined
All endometrioid
Stage 1, high LVSI
Stage 1B, grade 3, any LVSI status
Stage 2, Gr1, LVSI positive
Stage 2, gr2-3, LVSI any
Tx: Adjuvant EBRT
How is a high risk endometrial cancer defined
Stage 3-4A endometroid cancer, with no residual disease
Stage ≥1b, non-endometriod
Stage ≥1b, endometrioid, but p53mut
Tx: Sequential chemotherapy and EBRT
Or concurrent CRT followed by Cht
What RT regimen is given for primary RT to the endometrium
Phase 1 (45Gy/25#) then phase 2 as brachytherapy / Dobbie (7Gy/1#)
Or phase 1 (45Gy/25#) followed by EBRT (20Gy/10#) boost to macroscopic disease
Or SIB (60Gy/25#) to tumour with 45Gy/25# to pelvis
What brachytherapy dose is given post H+BSO to intermediate risk endometrial cancer
21Gy/3# to vaginal vault to reduce risk of local recurrence (15% to 2%)
Prescribed to 0.5cm depth
What volumes are included for adjuvant RT for an endometrial cancer
What is the CTV-PTV margin
CTV1 - parametrium and top 2.5cm of vagina
CTV2 - nodal elective volume - Inguinal, int/ext iliacs, obturator and pre-sacral nodes.
Planned from L5/S1 to approx femoral heads, where ext iliacs leave pelvis
PTV1 -CTV1 + 10mm
PTV2 - CTV2 + 8mm
How is metastatic low vol/indolent endometrial cancer managed
Consider hormonal treatment only - tamoxifen / AI / medroxyprogesterone (Megace)
How is metastatic higher vol / non-indolent endometrial cancer managed
Assess MMR / MSI status
dMMR
1st line - dostarlimab/carboplatin/paclitaxel
2nd line - dostarlimab or pembro if not received 1st line
pMMR:
1st line - carboplatin (AUC5)/paclitaxel (175mg/m2), or single agent doxorubicin or paclitaxel if Pt-ChT not suitable
2nd line - pembro/lenva if pMMR
What is the response rate of metastatic endometrial cancer to megace
What is the side effect
20-30%
Main side effect is cardiac toxicity
What is the management of locally recurrent endometrial cancer
Re-biopsy if possible, repeat imaging and staging
If no RT previously -> EBRT +/- BT
If previous BT only -> EBRT
If prev EBRT -> surgery if amenable, or systemic treatment
What 3 types of uterine sarcoma are most common
Leiomyosarcoma - high local recurrence rate
Endometrial stromal sarcoma
Carcinosarcoma - high risk, all treated with surgery, chemo, RT, vault brachy
How is an endometrial leiomyosarcoma treated
What is the prognosis
Surgery - TAH only, as it doesn’t metastasise to ovaries
Adj ChT & RT
For advanced disease, treat with ifosfamide/doxorubicin or gemcitabine/docetaxel
OS 15-25%
Stage I & II have 5-yr survival rate 40-70%
How is an endometrial stromal sarcoma treated
Surgery - TAH & BSO
Tend to be very hormone sensitive
1st line systemic treatment - AI or progestogen (not tamoxifen)
2nd line - ifosfamide
How is an endometrial carcinosarcoma treated
Surgery, ChT, RT, BT
treat with carboplatin as they behave more like endometrial adenocarcinomas than sarcoma
