ca endometrium.pptx

ENDOMETRIUm
PRAGATHEESWARI G K

SYNOPSIS
• Anatomy
• Endometrial ca introduction
• C/F , workup
• Staging
• Treatment - stage wise
• Evidence for each treatment
• Other Histology
• Recent Advance
31.07.2022 2
PRAGATHEESWARI, MMC.

UTERUS
• Uterus is the female reproductive child
bearing organ located in the true pelvis
between the bladder and rectum
• Size:8 cm*5cm*2.5cm (adults)
31.07.2022 3

• Uterus is divided into three parts
• Fundus-part above the opening of fallopian tube
• Body –line of division from cervix corresponds to internal os
• Cervix-supravaginal and vaginal portion
• Uterus-hollow muscular organ composed of 3 layers
• Inner –endometrium[tunica mucosa]
• Middle-myometrium[tunica muscularis]
• Outer –perimetium[tunica serosa]
31.07.2022 4

What is
Endometrium??
• Eytmology
Endo : “inner” from latin
Metra: “uterus” from Greek
From Maetra Means Mother
• Uterus is an hollow
muscular organ located in
true pelvis between the
bladder and rectum
• Uterus is divided into
fundus, body(corpus)
and cervix enclosing
uterine cavity
• This uterine cavity is lined
by Endometrium whereas
the wall of the composed
of myometrium (smooth
muscle fibers
5

Is Endometrium just a Lining of
uterine cavity?
• NO!
• It prevents adhesions between opposed walls of
myometrium
• Therefore maintains the patency of Uterine cavity
Endometrial Paradox which is that the endometrium is
the lining of uterine cavity but without endometrium
there would be no uterine cavity
6

Changes in Endometrium during
menstrual cycle
Both Functional layer of endometrium and stroma are
responsive to hormonal influence
➢Estrogen:- proliferative stage(follicular phase)
➢Progestron:- seceretory stage(luteal phase)
7

LYMPHATIC DRAINAGE
• Body of the uterus:- drains to obturator and
internal and external iliac noses
• Fundus of the uterus:- para aorta as the
lymphatics accompany ovarian arteries
8

ENDOMETRIAL CARCINOMA
• Global:- 15th most common carcinoma worldwide
and ranks sixth among cancers affecting women
• India:- 0.88 million cancer cases with an incidence
rate of 105.5 per 100,000 in women.The incidence
of endometrial cancer cases are very low in India
➢ Highest being observed in Bangalore and Delhi
9

WORKUP
• History & Physical Examination
• CBC,RFT, LFT
• Endometrial tissue sampling – Biopsy or D&C
• ER/PR ,Her2neu is recommended for stage III,IV
and recurrent /metastastic settings
• Imaging - USG abdomen and pelvis
- CT/MRI Abdomen
- PET CT (not mandatory)
- Chest CT/ Xray
31.07.2022 11

Major Clinical presentation
• 80 to 90% present with postmenopausal vaginal
bleeding
Thumb rule:- postmenopausal bleeding is assumed to
be endometrial cancer until proven otherwise
(eventhough the incidence of endometrial cancer
presenting with postmenopausal bleeding is around
10% to 15%)
12

Presentations in early stages
• 5% to 10%:- Abnormal vaginal discharge
• 5%:- Asymptomatic
Asymptomatic patients are suspected to have
endometrial cancer in settings of
➢Abnormal pap smear in routine screening
➢Thickened endometrium in routine transvaginal
ultrasound
13

Presentation in advanced stages
❖Urinary or rectal bleeding
❖Constipation
❖Lower limb lymphedema
❖Abdominal distention due to ascities
❖Pain
❖Referred pain to hypogastrium/both iliac fossa
called simpson’s pain
➢ Non severe and tends to occur at the same time each
day, lasting for 1-2 hours
14

Physical Examination
• General examination
• Systemic examination
• Abdominal Examination
• Bimanual per vaginal examination – confirm
uterine size, adnexal mass, involvement of
cervix, vagina
• Digital rectal examination- Rectal mucosa,
sphcinter tone, rectovaginal fistula,
parametrium involvement
31.07.2022 15

Diagnostic work up
Endometrial sampling-
Gold Standard
Endometrial sampline
achieved by two
methods
✓ Biopsy
✓ Dilation and curettage
16

Endometrial Biopsy
• Easily performed in the office with pipelle or similar
device- It is the preferred approach.
• Sensitivity :- postmenopausal status- 99.6%
pre-menopausal status- 91%
• BUT Specificity:- both pre and postmenopausal
women – more than 98%
17

Then where is D&C used?
• Routine D&C Recommended in patients who are
considered for conservative fertility sparing
approaches
• If office sampling is inadequate
• If symptoms persists
18

Can every patient with
postmenopausal bleeding
undergo sampling??
19

• Only 10 to 15% patients with postmenopausal
bleeding have endometrial cancer
• Therefore it is unclear how feasible it is to perform
endometrial sampling on every patient
• Solution:- Transvaginal ultrasound may be
considered as useful tool in assessing pt’s vaginal
bleeding to select patients for sampling
20

Transvaginal Ultrasound
• Normal endometrium
• Thin
• Homogenously
hyperechoic
• Thick
• Heterogenous
Abnormal endometrium
21

Endometrial
Thickness(Premenopausal)
PHASE THICKNESS
Menstruation 2-4 mm
Early proliferative
phase
5-7 mm
Late proliferative Up to 11mm
Secretory phase 7-16 mm
31.07.2022 22

Postmenopausal Endometrial
thickness
Vaginal bleeding (not on tamoxifen)
• Upper limit of normal < 5mm
• Risk of carcinoma is 7% if endometrium is >5mm
No H/o Vaginal bleeding
• Normal Cut off value </= 8 mm, upto 11mm
• Risk of carcinoma is 7% if endometrium is >11mm
• If on Tamoxifen normal < 5mm
31.07.2022 23

CT SCAN
• CT scan – lesion seen as hypodense mass,
diffuse, circumscribed vegetative or
polypoidal mass
• Helpful in assessing regional node and distant
mets
• Loss of periureteral fat – indicates
Parametrium involved
31.07.2022 24

MRI
• Most accurate imaging study to assess tumor extension
in endometrial cancer, especially myometrial invasion
• Clear junctional zone or preservation of sharp
delineation between tumor and myometrium – Disease
limited to endometrium
• Extension of high signal intensity into outer myometrium
with peripheral rim of normal intact myometrium – Deep
myometrial invasion
• MRI helpful in delineate tumor extension into cervix
• Nodal mets- sensitivity is 43.5%,specificity 95.9%
31.07.2022 25

PET SCAN
• Little benefit in assessing extension of tumor
• Nodal mets sensitivity is 72%
specificity is 94%
• Main advantage – accuracy in detection of
distant mets
• Disadvantage: inability to detect mets in
node < 5mm
31.07.2022 27

CA 125
• Cancer Antigen 125
• Elevated CA 125 is seen in 25-48% of endometrial cancer
• Monitoring response to treatment ( declining CA125 in
response to treatment)
• Normal range – 0 to 35 units/ml
• Range >35 – indicates possibility of cancer
• Hsieh et al – found that preoperative level >35 U/ml
correlated significantly with regional lymphnode mets
,suggested such levels could be indication of full pelvic
and para-aortic lymphadenectomy at time of surgical
staging in absence of metastatic disease
31.07.2022 28

Update on CA 125
• Askin et al:-
• High levels of CA 125 significantly correlated with
Advanced stage and lymph node metastasis
• Cut off determined by this study is 20U/ml
With 75% and 69.5% sensitivity and specificity
But has 80.6% PPV and 84.9% NPV
29

31.07.2022 30

Treatment
• Primary treatment is Surgery
• Staging laparotomy- TAH+BSO+ Pelvic node
assessment with/without para aortic node
dissection, peritoneal wash
• why BSA ? - synchronous ovarian ca in 5%
• if age >50 years it increase upto 10%
• Along with visual inspection of peritoneal,
diaphragmatic , serosal surface – suspicious lesion
biopsy should be done, and omental biopsy
• Omental biopsy- commonly done for serous, clear
cell, carcinosarcoma histologies
31.07.2022 31

SURGERY
• TAH+BSO : Laparotomy based approach , simple
hysterectomy is done
• LAPAROSCOPIC VAGINAL HYSTERECTOMY: Minimally
invasive surgery, gained importance recently
• ROBOTIC HYSTERECTOMY : Alternative minimally
invasive surgery in endometrial cancers
• RADICAL HYSTERECTOMY : Not routinely performed
due to low incidence of parametrial involvement
• DEBULKING SURGERY /CYTOREDUCTION : For
recurrent and advanced diseases
31.07.2022 32

Adequate Sampling (perez)
• Five lymphatic station to be removed from
each side – Common iliac, internal iliac ,
external iliac, obturator node and para aortic
node (or)
• Total of 10 nodes to be removed
31.07.2022 33

Sentinel Lymph Node Biopsy
1. The radiolabeled colloid most commonly
injected into the cervix is technetium-
TC99m
2. colored dyes are available in a variety of
forms (Isosulfan Blue 1%, Methylene Blue
1%, and Patent Blue 2.5% sodium).
3. Indocyanine green (ICG) recently emerged
as a useful imaging dye that requires a
near-infrared camera for localization,
provides a very high SLN detection rate,
and is commonly used.
31.07.2022 34

31.07.2022 35

31.07.2022 36

PATHOLOGY ASSESSMENT
• Uterus – Hysterectomy type
Tumor site, size
Histology type
Histology grade
Myometrial invasion
Cervical stromal invasion
LVSI
• Other organ involvement- fallopian tube, ovaries, vagina,
parametrium, omentum
• Peritoneal /ascitic fluid cytology
• Lymph node resected
• Isolated tumor cell in node , NO(i+), should not upstage patient but
should considered in discussion of adjuvant therapy
• ER/Her2 neu Testing
31.07.2022 37

HPE (important factors)
• Histology
• Grade(1,2,3)
• LVSI
• Depth of invasion(myometrium)
31.07.2022 38

31.07.2022 39

Adjuvant Treatment
STAGE I A
• GRADE 1,2
•no myometrial invasion - observation
• < 50% myometrial invasion , age >60yrs, LVI+ - IVRT
•GRADE 3
•no invasion - age <60 yrs no LVSI - Observe
• age >60 yrs and LVI PLUS - IVRT
•< 50 % invasion - ADJ RT PORTEC 1
31.07.2022 40

• STAGE I B
• GRADE 1 & 2 - ADJ RT (PORTEC 1)
31.07.2022 41

PORTEC 1
• AIM OF STUDY: To determine impact of pelvic
irradiation on outcome in patients with early
stage endometrial cancer
• Surgical procedure : TAH + BSO Without any
lymphadenectomy
• Randomized to: NO Adj Therapy(NAT) versus
Pelvic EBRT (46gy)
31.07.2022 42

PELVIC
RT
NO
PELVIC RT
5YR VAGINAL
RECURRENCE/
PELVIC
RECURRENCE
<4% 14%
5YR OVER ALL
SURVIVAL
81% 85%
RESULT:
(PORTEC1)
• OVERALL
SURVIVAL
SIMILAR
• VAGINAL/PELVIS
RECURRENCE
REDUCED AFTER
PELVIC RT
• PELVIC RT
COMPLICATION
ARE
SIGNIFICANTLY
HIGH
31.07.2022 43

• WHY NOT IVRT ALONE vs EBRT?
• PORTEC 2
• SWEDISH TRAIL
• ASTEC/NCIC
31.07.2022 44

PELVIC RT Vs VAGINAL BRACHY
PORTEC 2
• Population : stage IA >/= 60yrs
stage IA grade 3
stage1B grade1,2 of all ages Surgery,
TAH+BSO Without lymphadenectomy
• Randomized to EBRT(46gy) Vs IVRT(21gy/3#)
31.07.2022 45

RESULT(PORTEC-2)
• Vaginal recurrence : 1.9% vs 0.9% (IVRT)
• Pelvic recurrence : 0.6% vs 3.5%(IVRT)
• Portec 2 shows excellent and equivalent
vaginal and pelvic control with both arms
• No significant difference in over all survival
between 2arms(90%)
• This trial shows that intra vaginal Rt alone
suficient to control vagina recurrence with
early stage endometrial carcinoma(uterine
confined) with high risk features
31.07.2022 46

• PORTEC trial exclude STAGE IB grade 3
• Because , in higher grade we have to give
• Omiting pelvic RT in the setting of no
lypmhadenectomy is not advisable
31.07.2022 47

CONCLUSION
• IVRT is very effective in ensuring local control
,keeping to a minimum the risk of vaginal recurrence
• IVRT achieves excellent vaginal control and rates of
locoregional recurrence
• Overall survival is similar to both arm
• Quality of life and gastrointestinal toxic effects aRre
significantly better with VBT
• IVRT is better option in adjuvant treatment of early
endometrial ca
31.07.2022 48

• STAGE I - endocervical mucosal invasion
• incidence 2.3%
• policy IVRT
• as per PORTEC 2
31.07.2022 49

GOG 99
• Patient population: stage 1 & 2
• Excluded - no myometrial invasion
• Surgery: TAH+BSO+ Nodal sampling , pelvic
washing
• Randomized to observe versus pelvic RT
Investigators used Risk factors historical data
from GOG 33
31.07.2022 50

RESULT(GOG 99)
• IRRADIATED PATIENTS had superior pelvic control
• RT Pts had non significant improved overall survival
PELVIC RT NO PELVIC RT
LOCAL
RECURRENCE
3% 12%
OVERALL
SURVIVAL
92% 86%
31.07.2022 51

Here greater benefit from pelvic RT was
observed in HIGH INTERMEDIATE RISK FACTORS
(devita)
1. Advancing age
2. Deep myometrial invasion (outer 1/3)
3. Grade 2 &3
4. LVSI +
31.07.2022 52

31.07.2022 53

STAGE 2
• Cervical mucosa >50 %
invasion
• Grade3
• Cervical mucosa < 50 %
invasion
• grade 1 &2
• adequate LN sampling
• <50 % myometrial invasion
31.07.2022 54

REPORT FROM MSKCC centre
EARLY STAGE - > 50 % myometrial invasion,
grade 3 --- pelvic RT is must even if lymphnode
sample is negative
31.07.2022 55

GOG 249
• 609 patients , with stage 1&2 HIR
• stage 1&2 , clear cell , serous HPE
• randomised to
• Pelvic RT 45 Gy vs IVRT 3 cy carbo + Pacli
• 3yr RFS is same
• os is 91 % vs 88%
• pelvic recurrence 6 % vs 25
• and chemo arm experienced greater toxicity
• further reports are awaited,
• so IT IS CAT 2B as of now
31.07.2022 57

Stage III & IV
• Treatment (stage III & IVA ) – EBRT +
Chemotherapy +/- Vaginal brachy
• Combination therapy is preferred for stage III
• Stage IV B - chemo +/- EBRT +/- Vaginal
brachy
31.07.2022 58

RT vs CHEMO
ADJ RT vs CHEMO RT
CHEMO vs CHEMO RT
31.07.2022 59

CHEMO Vs PELVIC RT
GOG 122 (Stage 3 and 4)
• Assessed optimal adjuvant wholepelvic RT
Versus chemotherapy (7 cycle of doxorubicin
60mg/m2) and cisplatin 50mg/m2 with
additional cycle of cisplatin
• Chemotherapy improved PFS (50%vs 38%) and
OS compared with RT(60% vs 43%)
• RT as single modality is inferior in stage 3 and 4
31.07.2022 60

GOG 122
RECURRENCE RT(EBRT) CHEMO
PELVIC 13% 18%
EXTRA PELVIC 38% 30%
Most recurrence are systemic , not locoregional
Chemo is better in controlling systemic recurrence
in advanced stage, but only after adjusting staging
imbalance
31.07.2022 61

CHEMO vs CHEMO RT
GOG 258
• Compared Chemo Vs Chemo RT in Stage 3 and 4 and
• serous ,clear cell histology (stage I and 2)
• Arm 1- CCRT (Cisplatin 50mg/m2 day1 and 29, pelvic EBRT
45gy +/- brachy) f/b carbo& paclitaxel 4 cycle
• Arm 2– CT (Carboplatin AUC 6 + paclitaxel 175mg/m2 every
21days 6 cycle)
⮚ Vaginal recurrence -2%(CCRT) vs 7%(CT)
⮚ Pelvic recurrence 11%(CCRT) vs 20%(CT)
• ChemoRT is better in vaginal and pelvic recurrence
control than chemo alone
31.07.2022 62

PELVIC RT VS CHEMO RT
PORTEC 3
• High risk stage II/III Endometrial cancer
• After surgery randomized to
• Pelvic RT(48.6gy) alone Vs Chemo RT (48.6Gy + 2cycle
cisplatin ) f/b Adjuvant chemo (4cycle carboplatin+
paclitaxel)
• Primary endpoint: Benefit of chemoRT over and above
adjuvant RT alone by 7% Increase in FFS
5% Increase in overall survival
• FFS 75%(CCRT) vs 68%, OS 81%(CCRT) vs 76%
31.07.2022 63

• PORTEC 3 – Subset analysis(2019) shows
For stage III carcinoma
Significant improvement at 5 years
 FFS By 10%
 OS By 12%
 Serous Histology
 Significant improvement at 5 years
 FFS By 12%
 OS By 18%
31.07.2022 64

Conventional RT
• Position - Prone to displace the small intestines from the radiation
field., or supine with full bladder
• Target volume - pelvic lymph nodes, including obturator, external,
internal, and lower common iliac groups and the proximal two-
thirds of the vagina. The presacral nodes are not included unless
patients have gross cervical involvement.
• Energy : High-energy linear accelerators (15 MV).
31.07.2022 65

Conventional RT
• Technique : Four-field pelvic-box technique
• Borders : AP/PA FIELDS
• superior border - L5-S1
• Inferior border - bottom of the obturator foramina/ ischial tuberosity
• Lateral border - 2 cm lateral to inlet of the true bony pelvis/
femoral pulse.
• LATERAL FIELDS
• Anterior border - front of the pubis symphysis
• Posterior border - S2-S3.
• Superior and Inferior borders are the same for the AP/PA fields
31.07.2022 66

31.07.2022 67

• Dose : 50.4 Gy / 1.8 Gy/#- pelvic radiation is used alone
• 45 Gy/1.8 Gy/# - when combined with intravaginal RT.
• When para-aortic nodes are involved, extended field RT is used.
• CT simulation is crucial for accurate delineation of the kidneys, small bowel,
and liver in addition to nodal target.
• Lower border - same as in pelvic radiation
• Upper border - T12-L1 interspace.
• Lateral Border - Tip of Transverse process of vertebra
• Dose is 45.0 Gy at 1.8 Gy or 1.5 Gy if patients develop GI toxicity.
31.07.2022 68

EXTENDED FIELD RT
• For pts with positive para aortic
nodes.
• It should include the
pelvic nodes,pericaval,interaortocav
al and the para aortic nodes.
• Preferred approach is four field box
technique, in order to lower the
dose to small bowels.
• Field borders:
• UB-T12 /L1 interspace.
• LB -L5/S1 interspace.
• IMRT is the preferred choice to
reduce the toxicity.
69

Brachytherapy
• Is used to deliver high dose to the vagina while minimizing the
dose to the organ at risk .
• The vaginal Cylinder is the most common applicator used .
• The radiation may be delivered as
1) low-dose-rate (LDR) 2)high dose rate(HDR) .
• The LDR to the surface is 50-60 Gy over 60-70 hrs when Used
alone
• The dose is reduced to25-30 Gy in 3# when Combined with EBRT
31.07.2022 70

• OUTPATIENT BASIS- WITHOUT ANAESTHESIA
• 4-6 WKS AFTER SURGERY
• USUALLY THREE FRACTIONS OF 7 GY TO A TOTAL OF
21 GY IN 1TO 2 WEEKS APART
• DOSE IS PRESCRIBED TO 0.5 CM DEPTH FROM
MUCOSAL SURFACE
• USING A 3 CM DIAMETER CYLINDER- 4 TO 7 CM
LENGTH
31.07.2022 71

CHEMOTHERAPY
Role of Chemotherapy
• Absolute in stage III& IV (cat 1)
• serous, clear cell – any stage
• Uterine carcinosarcoma
• Consider in stage IB (grade3) , stage II - adding
chemo to adjuvant RT provide added therapeutic
benefit – decrease in distant metastases – However
NCCN consider adding chemo as
CAT 2B recommendation because OS advantage
has not been shown (GOG 249 results awaited)
31.07.2022 72

CHEMOTHERAPY
⮚ Preferred regimen :
Carboplatin & paclitaxel(cat 1)
GOG 184
• Assessed combination chemotherapy 3drug
(cisplatin+doxorubicin+paclitaxel) + Pelvic RT
Vs 2drug (cisplatin+doxorubicin) + Pelvic RT in stage III & IVA
• Result indicate that 3 drug regimen shows no survival
advantage,
• 3 drug resulted in greater toxicity (hematologic toxicity,sensory
neuropathy,myalgia)
31.07.2022 73

KEY NOTE 775
• phase 3 RCT,
• population - advanced endometrial ca ,
previously treated with platinum based
chemotherapy
• started - june , 2018
• primary completion - oct, 2020
31.07.2022 74

• Lenavtinib 20mg OD + Pembrolizumab
200mg IV on day 1 - Q21 days
Vs
• Doxorubicin 60 mg/m2 + Paclitaxel 80 mg/m2
Q21 days
31.07.2022 75

• END POINTS
• PFS - 6.6 vs 3.8 months
• OS - 17.4 vs 12 months
• Noe for refractory , residual disease it is
recommended as
• CAT 1 by NCCN.
- we are yet to see the 5year survival rate
31.07.2022 76

31.07.2022 77

FERTILITY SPARING
MANAGEMENT
• CRITERIA (all must be met)
✔ Well differentiated endometrioid adenocarcinoma
✔ Disease limited to endometrium on MRI(preferred)/USG
✔ Absence of suspicious mets or metastatic disease on
imaging
✔ No contraindication to medical therapy or pregnancy
✔ Patient should undergo counselling that fertility sparing
option is NOT Standard of care for treatment of
endometrial ca
31.07.2022 78

• If Endometrial
ca present at
6-12 month
TAH/BSO With
staging
• Complete response
at 6 months
• Encourage
conception (with
continued
surveillance /
endometrial
sampling every
6month,
• consider
maintenance
progestin, if patient
not trying to
conceive
Treatment for fertility
sparing
Continous progrestin
based therapy
✔Megestrol
✔Medroxyprogestrone
✔Levonorgestrel IUD
✔Weight
management/life style
modification
Endometrial evaluation
every 3-6month (D&C or
endometrial biopsy)
31.07.2022 79

RECURRENCE
• LOCO REGIONAL
• ISOLATED METS
• DISSEMINATED METS
31.07.2022 80

NO prior RT EBRT+/- BRACHY+/- CHEMO
Prior RT (EBRT) Surgical resection + chemo +/- palliative EBRT
0r
Brachy +/-chemo
Prior RT(BRACHY) Disease confined to vagina or paravaginal
tissue ⮚ Surgical resection F/B EBRT +/- brachy
, chemo
Prior RT(BRACHY) NODAL METS ⮚ Surgical resection of vaginal
recurrence F/B pelvic or para aortic node EBRT
+/- Chemo
ISOLATED METS EBRT (or) consider Resection
Disseminated Mets Systemic therapy +/- palliative RT
31.07.2022 81

OTHER HISTOLOGY
• Serous ca
• Clear cell ca
• Undifferentiated / Dedifferentiated ca
• Carcinosarcoma
31.07.2022 82

Primary treatment:
Suitable for surgery 🡪 TAH+BSO+ Pelvic node
assessment with/without para aortic node
dissection, peritoneal wash , omental biopsy
Not suitable for surgery 🡪 EBRT+ Brachytherapy
+/- chemo
31.07.2022 83

Adjuvant Treatment
• Stage I A
Vaginal brachy + chemotherapy
• Stage I B,II,III,IV
EBRT+ brachy + chemotherapy
31.07.2022 84

LOW GRADE ESS
(Endometrial Stromal Sarcoma)
⮚Surgery: (Total hysterectomy + BSO)
✔Adjuvant Treatment
• Stage I: observe
• Stage II,III,IVA - antiestrogen hormone therapy
( ER/PR receptor positive), +/-EBRT(cat2b)
• Stage IVB - anti estrogen hormone therapy(
ER/PR positive +/- Palliatuve RT)
31.07.2022 85

High grade ESS,UUS,uLMS
(leiomyosarcoma)
⮚Surgery: (Total hysterectomy + BSO)
✔Adjuvant Treatment
⮚Stage I: observe
⮚Stage II,III,IVA : Systemic therapy and or EBRT
⮚Stage IVB : Systemic therapy +/- palliative RT
31.07.2022 86

MOLECULAR TYPES OF
ENDOMETRIAL CA
• POLE(ultramutated)
• MSI (hypermutated)
• COPY NUMBER LOW
• COPY NUMBER HIGH
31.07.2022 88

31.07.2022 89

POLE
(polymerase
epsilon)
MSI COPY NUMBER
LOW
COPY NUMBER
HIGH
COPY NUMBER
ABBERATION
LOW LOW LOW HIGH (P53
MUTATION)
MSI METHYLATION MIXED MSI HIGH MSI STABLE MSI STABLE
HISTOLOGY TYPE ENDOMETRIOID ENDOMETRIOID ENDOMETRIOID SEROUS,
ENDO,MIXED
TUMOUR GRADE MIXED
(GRADE 1-3)
MIXED
(GRADE 1-3)
MIXED
(GRADE 1-3)
GRADE 3
PROGRESSION FREE
SURVIVAL
GOOD INTERMEDIATE INTERMEDIATE POOR
31.07.2022 90

PORTEC 4a(On going Trial)
• PORTEC 4a is first randomised trial to introduce molecular
factors in the adjuvant treatment of endometrial cancer
• Here randomization between
• standard(regular) Vs individualized treatment based on
molecular risk profile
• Population : stage Ia and grade 3
stage Ib grade 1&2 with age > 60 and 0r LVSI
stage Ib ,grade 3 without LVSI
stage II ( grade 1)
31.07.2022 91

31.07.2022 92

• Primary objective : To compare vaginal
recurrence
• Secondary objective : PFS and OS
Portec 4a will provide information whether
vaginal brachy can be safely omitted in patient
with favorable molecular integrated risk profile
Whether intensification is needed in adjuvant
treatment of unfavorable risk profile.
31.07.2022 93

REFERENCE
• B D CHAURASIA Anatomy
• MUDALIAR MENON Obs &Gyn
• DEVITA’ oncology
• Perez oncology
• NCCN guidelines
• PUBMED
31.07.2022 94

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