1. ADJUANT TREATMENT IN
ENOMETRIAL CANCER
Dr Paul George

3. • Based on retrospective histopathological
analyses and prospective adjuvant studies
three risk groups were characterized: low,
intermediate, and high risk

4. Overall the 5-year survival rates for all grades
and histologic subtypes are approximately
• 78%-90% for stage I,
• 74% for stage II,
• 36%-57% for stage III, and
• 20% stage IV

5. LOW RISK
• Stage IA, Grade 1-2
Stage IB, Grade 1
• Well or MD
• Meta analysis of 8 studies
• 2nd malignancy (hazard ratio [HR], 2.02
• higher risk of mortality (HR, 1.36)and
• had experienced lower quality of life from
significant radiation toxicity

6. • Therefore, patients in the low risk category do
not generally receive adjuvant treatment, but
are followed-up carefully during the
surveillance period

7. INTERMEDIATE RISK

8. RESULTS Adj RT Stage I, II
PORTEC GOG-99
RISK FACTORS AGE >60
G - 3
MYO INV >50%
<50/ <60/<70
2-3
>66%
LVI +
HIGH intermediate RISK 2 OUT OF 3 ANY AGE + 3 FACTORS
>50 + 2 FACTORS
>70 + 1 FACTOR
RESULTS 10 Yr LRR
RT- 5 %
NO Rx- 23%
4 yr result
RT- LRR- 5%,
13% ANY SITE
NO Rx- LRR- 13%,
27 % ANY

9. INTERMEDIATE RISK
• Based on GOG 99 & PORTEC
• LOW IR
Stage IA, grade 3
Stage IB, grade 2
Stage IIA, grade 1-2, <50% MI
• HIR
Stage IB, grade 3
Stage IC, grade 1-2
Stage IIA, grade 3, <50% MI
Stage IIA, grade 1-2,
>50% MI +/-+LVSI
G2-3,LVI, >66%MI
1/3 above w/ age >70
2/3 above w/ age <50
3/3 above w/age <50

11. Adjuant Pelvic RT in Early EC
ALDERS ET AL 1980
PORTEC1
GOG99
ASTEC/EN5

13. • Adjuant pelvic RT improves local control but failed to show
a survival advantage
• In all studies, adjuvant PRT was associated with significant
radiation-related toxicities including diarrhea, fecal leakage,
urinary frequency and urgency, which negatively affected
quality of life.2nd malignancies

14. To circumvent adverse effects related to
radiotherapy, while not compromising
outcomes, a subsequent trial, PORTEC-2
compared vaginal brachytherapy (VBT) to PRT

16. • the VBT group suffered significantly lesser
toxicities compared to the PRT group.
• The rate of acute grade 1-2 gastrointestinal
(GI) toxicity was significantly lower in the VBT
vs. PRT group (12.6% vs. 53.8%).
• These results support using VBT for patients
with patients with HIR early stage EC.

17. Role of chemo
• JGOG 2033 PRT vs Cisplatin based chemo
• EORTC 55991
• Maggi et al
• All studies showed that the use of chemotherapy
lowered the risk of distant metastasis, but did not
improve OS in the overall study population
• Protocols JGOG 2033 and EORTC 55991 demonstrated
an improvement in OS with the use of chemotherapy in
the higher risk subgroup defined as either stage II-IIIA
or stage IC, grade 3 and/or age >70 (73.6% vs. 89.7%,
p=0.006 in JGOG 2033; 75% vs. 82%, p=0.046 in EORTC
55991

18. • To definitively address whether chemotherapy
improves survival in early stage uterine cancer,
protocols PORTEC-3 and GOG 249 were
designed

19. The highly anticipated results of these studies
will definitively answer whether or not
systemic chemotherapy has a place in the
management of high risk early stage EC

20. HIGH RISK
• Stage IC, grade 3
• Stage IIA, grade 3, >50% MI
• Stage IIB, any grade
• UPSC
• CCC
• Stage III-IV

21. TREATMENT FOR ADVANCED STAGE
ENDOMETRIAL CANCER
• WAI/CHEMO
• 1983 Greer and Hamberger shows fiirst series
of adjuant WAI improves OS
• Other retrospective studies have shown that
most of the disease relapses systemically
• The results of these studies reiterated the
concept that stage III &above EC should be
considered a systemic disease, for which
effective systemic therapy is required

22. Role of Multiagent chemo
• GOG 107 & 163 showed improved response
rate for AP regimen in metastatic & recurrent
EC

23. GOG122
This trial set a new standard for patients with locally advanced EC, bringing
systemic chemotherapy to the forefront of EC management
However 18% of patients treated on the AP arm developed
pelvic recurrence as the first site of relapse
despite improved systemic control compared to WAI,
local control remains insufficient

24. Triplet
GOG 177 TAP vs AP
Better RR , PFS & OS in metastatic setting

25. • GOG184
These results suggested that TAP although highly
active in the metastatic setting, is not superior to the doublet
regimen omitting paclitaxel and is too toxic to be administered
routinely after tumor volume directed radiotherapy in
the adjuvant setting.

26. • LESS TOXIC CT (Pacli +carbo)
GOG209
Naakumura et al
Several other studies confirm that CT is not
inferior to TAP and as active as AP
Better toxicity profile favours CT as the std
chemotherapy regimen for Advanced EC

27. • AP, TAP , CT all are active in EC

28. Combined modality treament in locally
advanced EC
30% of patients included in GOG-122
treated with systemic chemotherapy
recurred in the pelvis and in the abdomen.
This observation suggested that patients
treated with systemic chemotherapy experience a finite rate
of local failure, which could compromise in overall survival.
This concern supported including tumor volume directed
radiotherapy in the upfront approach of stage III/IVA
EC, with the intent of preventing local recurrences. Whether
this improved local control translates into an improvement in
OS remains unproven

29. CHEMORADIATION
Several small studies
Onda et al
Bruzzone et al
Hogberg et al
Combination chemoradiation is superior in
terms of PFS & OS
RTOG phase II
ITALIAN study concurrent chemoRT

30. GOG 184
combined approach yielded a three-year DFS of
62%-64% in this setting

31. • The ongoing international protocol GOG 258
compares tumor volume-directed
radiotherapy administered concurrently with
cisplatin and followed by 4 cycles of CT against
CT chemotherapy alone

32. • It is anticipated that GOG 258 will answer critical questions
regarding the
• impact of chemo-radiation on OS,
• the tolerability of the approach, and
• the short- and long-term impact on the quality of life.
• If positive, the combined chemo-radiotherapy approach
would become a new standard of care in locally advanced EC

33. Summarising

34. GENERAL PRINCIPLE OF
MANAGEMENNT
RISK STRATIFICATION
Low risk Int. low risk Int. high risk High risk
Stage IA, Grade 1-2
Stage IA, grade 3
Stage IB, Grade 1
Stage IB, grade 2
Stage IIA, grade 1-2,
<50% MI
Stage IB, grade 3
Stage IC, grade 1-2
Stage IIA, grade 3,
<50% MI
Stage IIA, grade 1-2,
>50% MI +/-+LVSI
G2-3,LVI, >66%MI
1/3 above w/ age
>70
2/3 above w/ age
<50
3/3 above w/age
<50
Stage IC, grade 3
Stage IIA, grade 3,
>50% MI
Stage IIB, any grade
UPSC
CCC
Stage III-IV

35. MANAGEMENT
LOW RISK LOW
INTERMEDIATE
HIGH
INTERMEDIATE
HIGH
OBSERVATION
VBT if Age>60
LVI
Lower uterine
segment
involvement
OBSERVATION/VBT VBT ALONE
PELVIC EBRT IF ESS
NOT DONE
STAGING
LAPAROTOMY+
PELVIC EBRT+
VBT+
CHEMO

36. Hormone Replacement Theraapy
controversial
Reasonable option for Stage I

37. FOLLOW UP
• Physical examination 3-6months for 2-3years
• Annnually thereafter
• CA 125 optional
• Imaging as indicated
• Genetic counselling
• Patient education lifestyle, nutrition obesity,
potential recurrence
• Sexual health , vaginal dillators/lubricants

38. 66yr old lady who is evaluated for postmenopausal
bleeding and diagnosed to have ca
endometriumUnderwent staging lap with TAH+
BSO with lymph node sampling
After complete HPE
MD Endometroid adenoca stage IC G2 with no LVI

39. • RISK?????

40. GENERAL PRINCIPLE OF
MANAGEMENNT
RISK STRATIFICATION
Low risk Int. low risk Int. high risk High risk
Stage IA, Grade 1-2
Stage IA, grade 3
Stage IB, Grade 1
Stage IB, grade 2
Stage IIA, grade 1-2,
<50% MI
Stage IB, grade 3
Stage IC, grade 1-2
Stage IIA, grade 3,
<50% MI
Stage IIA, grade 1-2,
>50% MI +/-+LVSI
G2-3,LVI, >66%MI
1/3 above w/ age
>70
2/3 above w/ age
<50
3/3 above w/age
<50
Stage IC, grade 3
Stage IIA, grade 3,
>50% MI
Stage IIB, any grade
UPSC
CCC
Stage III-IV

41. Adjuant treatment???

42. To circumvent adverse effects related to
radiotherapy, while not compromising
outcomes, a subsequent trial, PORTEC-2
compared vaginal brachytherapy (VBT) to PRT

43. • chemo????

44. • To definitively address whether chemotherapy
improves survival in early stage uterine cancer,
PORTEC-3 and GOG 249 were designed

45. • Thank you……………..
dr paul george