Management of endometrial carcinoma

1. MANAGEMENT OF
ENDOMETRIAL CARCINOMA
DR .SAILENDRA NARAYAN PARIDA
POST GRADUATE,FINAL YEAR
DEPT. OF RADIATION ONCOLOGY
AHRCC

2. Management of carcinoma
endometrium constitutes …
1.DIAGNOSIS
2. STAGING
3.TREATMENT
4.FOLLOW UP

3. DIAGNOSIS
A. CLINICAL PRESENTATION AND NATURAL
HISTORY
B. CLINICAL EXAMINATIONS
C. INVESTIGATIONS

4. CLINICAL PRESENTATION AND
NATURAL HISTORY
• Most commonly present with post
menopausal vaginal bleeding or
discharge(75%)
• Majority – Stage I
• Advanced stage-urinary or rectal
bleeding,constipation,pain,lower extremity
lymphedema,abdominal distension.

5. CLINICAL EXAMINATIONS
• General examinations
• Systemic examinations
• Gynecological examinations – bimanual
vaginal examinations.inspection of
vulva,vaginal skin and mucosa,suburethral
area and cervix,per rectal examinations.

6. INVESTIGATIONS
• CBC
• Liver function test
• Renal function test
• S.CA-125
• Chest X ray
• Ultrasonography
• CT scan
• MRI
• Endometrial tissue sampling

7. ENDOMTRIAL SAMPLING
• D & C.
• HYSTEROSCOPY AND BIOPSY.
• PATHOLOGIC REVIEW (OPTIONAL).

8. STAGING
• Prior to 1988-clinical staging was done
• Surgical staging is done now days

10. WHY SURGICAL STAGING???
• Approximately 23% of patients being upstaged
after CSS.
• Pelvic nodal involvement is seen in <3% grade-I
endometrium confined disease but >30% in
grade-3 disease penetrated the outer third of the
myometrium
• Aortic nodal disease,although rare in grade-I
disease or in absence of pelvic node
metastasis,was seen in 14% and 23% of patients
with deeply invasive grade 2 or 3 disease
respectively.

11. • Hence surgical staging was promoted in order
to better estimate 5-year prognosis for
patients and to better tailor adjuvant therapy
to those patients.

12. PROGNOSTIC FACTORS
• Pathological stage is the most significant
predictor of outcome.
• Histological type
• Histological grade
• Depth of myometrial invasion
• LVSI
• Age
• Nodal involvement
• Genetic factors

13. TREATMENT
• SURGERY
• RADIOTHERAPY
• CHEMOTHERAPY
• HORMONAL THERAPY

14. Risk Stratification for Adjuvant Therapy
Low risk Intermediate risk High risk
G1, G2 without myoinvasion G1, G2 with ≤ 50% MI G-3 tumours
No cervix or isthmic invasion No cervix or isthmic inv Myoinvasion>50%
Negative peritoneal cytology Negative peritoneal cytology Adenexal spread
No LVSI No LVSI Cx invasion
No evidence of metastasis No evidence of met Lymphnode Met
Tumour ≤ 2cm Tumour ≤ 2cm LVSI present
UPSC/ Clear Cell
Intra abd.met/
distant met
No further treatment (F UP) Brachytherapy EBRT/
Extended field
RT/ CT if PA
and Common
iliac node +ve

15. SURGERY
• Surgery is the main modality of treatment in
carcinoma endometrium.
– TAH-BSO without ESS followed by more liberal use of post
operative RT
– TAH-BSO with ESS followed by more restricted use of post
operative RT

16. Extensive surgical staging
• Excision or biopsy of any enlarged or suspicious
pelvic or para-aortic nodes
• In absence of nodal enlargement,nodal tissues
should be removed from over the distal venacava
below the IMA,between the aorta and the left
ureter from the inferior mesenteric artery to mid
left common iliac artery,distal half of each
common iliac artery,anterior and medial aspect of
proximal half of the external iliac artery and
vein,distal half of the obturator fat pad anterior
to the obturator nerve.

17. Advantages
• Accurate identification of disease extent
• Adjuvant therapy would be limited to patient who will really benefit
• Cost effective
• Acceptable morbidity
Disadvantages
• More risk of vascular injury
• DVT & pulmonary embolism
• Postoperative complication more in elderly

18. Treatment recommendations in early
stage endometrial cancer(FIGO I-II)
• Stage IA(grade 1,2) and stage IB(grade 1)-
-TAH-BSO alone if LVSI absent
-TAH-BSO+IVB if LVSI prresent
• Stage IA(grade 3)-
A. ESS done-TAH-BSO+IVB
B. ESS not done- TAH-BSO+IVB if <60yrs
TAH-BSO+EBRT if >60yrs

19. • STAGE-IB (grade 2) and STAGE IIA(<50%
MI,grade 1-2)
A.ESS done-if LVSI(-) IVB alone vs
observation in <70yr.if
LVSI(+),>70YRS-EBRT
B.ESS not done-LVSI(+)-IVB
>60yrs-EBRT

23. TREATMENT OF ADVANCED STAGE
ENDOMETRIAL CARCINOMA
• Patients with advanced endometrial carcinoma
have been treated with different approaches in
adjuvant setting,including pelvic RT,extended
fields RT(pelvic plus paraaortic RT),whole
abdominal irradiation.
• Whole abdominal RT is not used now a days after
the result of GOG-122,which demonstrated
superior PFS and OS for patients treated with
doxorubicine and cisplatin.

24. • MEDICAL INOPERABLE CASES-
EBRT to pelvis (include lymphnodes) 45-50Gy
followed by ICBT (7Gy x 3#) for early stage tumours.
• Survival rate of 80-85% at 5yrs
• RECURRENCE CASES
-If no prior RT - EBRT followed by Brachytherapy
boost 60-70Gy.brachytherapy has got a great role as
70-75% of post op cases have recurrence in the vagina.
-Chemotherapy and hormonal therapy may also be
considered.

25. RADIATION THERAPY
• PREOPRATIVE
• POSTOPERATIVE

26. • Preoperative irradiation is less commonly used
in era of ESS,but still have a role in patients
with gross involvement of the cervix or vagina
• ICB alone or combination with pelvic EBRT
may be used.
• If surgery is to be done after EBRT then it
should not be done before 4 to 6 weeks after
completion of EBRT to allow radiation
associated inflammation to subside.

27. • In preoperative EBRT ,GTV includes entire
uterus and cervix,vaginal extension as well as
any gross regional lymphadenopathy.
• CTV includes the GTV as well as pelvic
lymphnode areas i.e. obturator,external and
internal iliacs as well as common iliacs.
• PTV=CTV+ 1cm

28. POSTOPERATIVE EBRT
INDICATIONS-
1. Deeply invasive tumors(stage IC)
2. Poorly differentiated histologies
3. Pathological stage IIB in absence of ESS
4. LVSI present.

30. RADIATION TECHNIQUE
• POSITION-supine
Immobilization
• 4 field box technique is used in conventional method
• Field borders – AP/PA
Superior – top of L5
Inferior – below obturator foramen
Lateral – 2 cm lateral to bony pelvis
• Lateral field:
Superior & inferior same
Anterior- Ant. To Symph. Pubis
Posterior – S2-S3 junction
Dose:- 45 - 50 Gy (1.8 Gy. – 2 Gy. / #)

32. • IMRT technique
• Imobilisation
• CT simulation (2.5 -5 mm slice) from upper border of
L5 to lower border of lesser trochanter)
• Target vol. delineation- GTV includes entire
uterus and cervix,vaginal extension as well as any
gross regional lymphadenopathy.
CTV includes the GTV as well as pelvic
lymphnode areas i.e. obturator,external and
internal iliacs as well as common iliacs.
PTV=CTV+ 1cm

33. POST OPERATIVE INTRACAVITARY
BRACHYTHERAPY
• ADVANTAGES-
a) LOWER MORBIDITY
b) PATIENT CONVINIECE
c) LOWER COSTS
DISADVANTAGES-
It does not address the pelvis and therefore
should be limited to patients in whom the pelvic
recurrence rate is estimated to be low.
• Predictors of vaginal relapse are grade 3 tumors
and presence of LVSI(in MAYO clinic series)

34. • Dose – 60-70Gy to the mucosal surface by LDR
in 72 hrs.
• Dose of HDR brachytherapy as recommended
by American Brachytherapy Society.
• Suggested dose for brachytherapy used alone
as adjuvant therapy in ca endometrium
NO OF HDR FRACTIONS DOSE/# DOSE –specific point
3 7.0 0.5 cm depth
4 5.5 0.5 cm depth
5 4.7 0.5 cm depth
3 10.5 Vaginal surface
4 8.8 Vaginal surface
5 7.5 Vaginal surface

35. • Suggested dose of brachytherapy when used
with 45Gy EBRT
No of HDR fractions Dose /# Dose-specific point
2 5.5 0.5cm depth
3 4 0.5cm depth
2 8 Vaginal surface
3 6 Vaginal surface

38. CHEMOTHERAPY
• Role of chemotherapy in carcinoma
endometrium is limited to advanced disease
and in inoperable and recurrent disease.
• Commonly used agents are-
1. Cyclophosphamide
2. Anthracyclines
3. Platinums
4. Taxens

39. GOG 122 TRIAL
• N=396
• Stage III and IV
• After TAH+BSO+ESS <2cm residual tumour left
• Compared doxorubicin-cisplatin(AP) chemotherapy with
whole abdomen irradiation(30Gy in 20# AP/PA +boost to
pelvic/PA lymphnodes 15Gy in 8 #
• Doxorubicine-cisplatin every 3wk for 8 cycles
• 5yr PFS 38% for WAI Vs 50% in AP
• 5yr OS 42% for WAI Vs 55% in AP
• Recurrence after WAI was 54% Vs 50% in AP
• AP has more grade 3 hematological and gastrointestinal
toxicity than WAI.

41. • According to fleming et at addition of
Paclitaxel to AP in metastatic disease led to
improved response rates (34% to 57%),median
PFS(5.3 to 8.3 months) and median OS(12.3 to
15.3 months)

42. HORMONAL THERAPY-
1.used only in advanced and recurrent disease
2.Drugs-a.medroxyprogesterone
b. megestrol acetate
c. tamoxifen.
• Response occurs in 20 – 40% cases
• In a GOG randomised trial of low dose (200mg) Vs high
dose of oral daily medroxyprogesterone,there was no
advantage to higher dose.
• Use of progestins have been implicated in death due to
cardiovascular events hence their use in adjuvant
setting can not be supported

43. FOLLOW UP
SCHEDULE FREQUENCY
FIRST FOLLOW UP 4-6 wks after radiation therapy
0-2 yrs Every 3-4 months
2-5yrs Every 6 months
After 5yrs annually

44. TAKE HOME MESSAGE-1
• Surgical staging is done in case of carcinoma endometrium
• TAH+BSO+ESS is now the primary modality of treatment in
early stage ca endometrium followed by adjuvant therapy as
indicated.
• Preoperative radiological investigations should not be done as
it does not change the adjuvant treatment recommendations.
• High grade,LVSI,tumour type,depth of myometrial invasion
and age are important prognostic factors.

45. TAKE HOME MESSAGE-2
• Serum CA 125 must be done preoperatively as
value >40 U/L is an indication for pelvic and
paraaortic node dissection.
• Paclitaxel+doxorubicin+cisplatin has got survival
advantages in advanced ca endometrium.
• Role of hormonal and targeted therapy are not
yet established.
• PORTEC,GOG 99 and ASTEC trial are three trials
showing role of adjuvant RT in decreasing
locoregional recurrence but having no survival
benefit in early stage Ca Endometrium