2. Contents
New WHO Classification
Management options in each sub group and role of RT.
Target Volumes of RT.
3. Introduction
Uterine sarcomas are uncommon : 3% of all uterine
neoplasm.
Heterogeneous group with varying behavior.
Insufficient data to make standard recommendations.
Rarity of disease makes adequately powered
randomized trials impractical.
5. ESS LOW GRADE
Endometrial stromal origin :resembles proliferative phase
Low grade , <1% of uterine malignancy :
(JAZF1rearrangement(7 ,17 translocation)
Mostly indolent ,younger age group
IHC :ER,PR,positive,CD10 +ve, hormones effective.
5yr DFS : Stage I and II :90%, stage III,IV:50%.
Recurrence is common even in stage I
6. ESS HIGH GRADE
Previously was part of undifferentiated endometrial ca .
(WHO 2003 )
Now redefined in the present WHO as high grade ESS
Uniform round cells ,with occasional low grade areas.
ER,PR _ve,CD10 –Ve,Cyclin D1 +Ve
YWHAE - FAM22 fusion +ve .(10:17 translocation)
Hormone treatment is not effective .
Prognosis better than undifferentiated sarcoma.
7. Adenosarcoma
Only mesenchymal component is malignant.
Usually low grade ,ER ,PR positive.
<6 % of uterine sarcomas
Staging and treatment similar to ESS low grade
5 yr. survival :70%
8. LMS
40-60% uterine sarcoma : Most common.
Smooth muscle origin
Associated with tamoxifen therapy
Desmin,+ve, ER,PR +ve ~ 30%
Stage 1 and II 5 yr survival:40-70%
Overall 5 yr survival: 15-25 %
9. UNDIFFERENTIATED UTERINE
SARCOMA
No differentiation, pleomorphic.
classified as Undifferentiated Endometrial Sarcoma WHO
2003. (UES).
High grade ESS is now removed from this group (WHO
2014 )
Prognosis : bad
Die within 2 yrs of diagnosis. PFS:7-10 mths,OS: 11-23 mths
10. CARCINOSARCOMA
Previously known as MMT :Both components are
malignant high grade endometrial carcinoma with
sarcomatous metaplasia.
Behavior is similar to high grade endometrial papillary,
clear cell carcinoma.(peritoneal, nodal mets)
Staging and treatment is similar to high grade
endometrial carcinoma with Sx, chemo and pelvic RT .
11. Evaluation:
Diagnosis mostly post op.
Slide review by an experienced pathologist for typing.
Pre op diagnosis : very rarely either from imaging or from
FC.
CT /MRI scan abdomen ,pelvis ,CT chest.
If there is a highly vascular solid ,solitary tumor on
USS ,
CT :heterogeneous enhancement, Hyper intense on MRI
both T1,T2.
12. Role of surgery
En bloc removal of tumor with hysterectomy.
prophylactic lymphadenectomy is not recommended
except in carcinosarcoma.
Lymph nodal spread : 7-15% in uterine confined ESS and
in LMS its rare.
Lymphadenectomy is done in patients with suspicious
nodes or gross extra uterine spread.
R0 resection is associated with better PFS.
13. Surgery : conservative
Ovarian preservation : in ESS and LMS :in younger age
group (chance of ovarian spread : 3%[Shah et al])
Most retrospective series : no difference in recurrence rate
whether ovaries preserved or not
Morcellation : Contraindicated :~50% increased risk of
recurrence and adversely affects survival.
If morcellation has been done re-surgery is indicated :In
re-surgery ~29% upstaging.
Coservative surgeries like myomectomy :High recurrence
rate
16. RADIOTHERAPY
Routine adjuvant ,historically.
Adjuvant : EBRT to sterilize the microscopic disease in
pelvic nodes and tumor bed .
Palliative RT to pelvis or sites of distant mets/ recurrence.
Medically inoperable.
33. CARCINO SARCOMA : Randomized Trials
study stage yrs RT
details
N MFU OS LRec Dist
met
Reed et
al
EORTC
NO RT
RT
1-II
N=91
1988-
2001
50.4
Gy/28 Fr
45
Vs.
46
NG NG 47%
24%
29%
35%
Wolfson
et al
NO RT
(chemo)
RT
I-IV
N=206
1993-
2005
WA:30G
y,pelvis:
49.8
101
Vs.
105
5.3 yrs. 45%
35%
24%
17%
53%
56%
34. study Arm
s
Stage yrs. N RT MFU
yrs.
Loco
Reg.
Distant
mets.
OS
Sampath
et al
No
RT
RT
I - IV 1980-
2005
638
490
EBRT
+/-
Brach
y
5 20%
Vs.
10%
NA
Smith
SEER
No
Vs.
RT
I - IV 1973-
2003
1571
890
varyin
g
3.9 33%
42%
Gerszten
et al
No
RT
I-III 1977-
92
31
29
45-
50G
2.7
yrs.
55%
3%
53%
83%
At 3yrs
CARCINOSARCOMA -Non randomized Evidence for OS
38. Role of RT ESS
Post op Adjuvant. No level I evidence :retrospective data better LC
Medically inoperable.
Palliative :stage IV, or recurrence
NCCN Category 2B and ESMO guidelines suggest Adj RT in Stage II-
IVA.
39. RADIATION IN LMS
STAGE I-IVA :Improves LRC:
Survival (No level I evidence ).
No improvement in survival probably because of the
high and early metastatic potential.
Other indications :medically inoperable
Palliative /recurrent cases :to reduce bleeding ,pain .
40. CARCINOSARCOMA
Managed similar to endometrial high grade carcinoma
Multi institutional retrospective reviews favour Chemo
and RT ,with sandwitch regimen being slightly better.
With chemotherapy taxol+ carbo 6 cycles and
adjuvant RT.
Level I data for adjuvant RT.
Chemo EBRT vs. Chemo brachy has to be
41. Chemotherapy
The role of chemotherapy as an adjuvant is at best
controversial.
None of the published literature have shown any
statistically significant benefit as regards DFS or OS in
adjuvant setting, except the SARC GYN study,
Most of the trials are underpwered.
42. Chemotherapy in LMS
No randomized trial has shown a significant survival
advantage.
SARC GYN study – DFS improved with adjuvant
chemo+RT compared to RT alone.
Hensley et al reported a 2 yr PFS of 59% in stage I-IV
78% in stage I,II patients.( with Gem-doce followed by
doxo )
GOG 277 – ongoing adjuvant chemo study (Gem +Doce
x4 -Doxo x 4)
43. LMS -Chemo
In recurrent /metastatic setting : PFS improvement with
single agent/combination chemo .
Agents being tried are Ifosfamide,platinum,gemcitabine
,doxorubicin
Second line agents :Trabactedin with or without chemo
/Pazopanib/bevacizumab /mTOR inhibitors.
44. HGUS :Chemo
High chance of local and systemic failure.
In SARC GYN phase III : adjuvant pelvic RT vs Chemo
(doxo,ifos,cis)-RT (9 cases were HGUS.)
3yr DFS 41% vs 55%(p=0.048)
Data suggests the use of chemo followed by RT in high
grade uterine sarcomas .
Standard recommendation not possible.
Participation in multicentre clinical trials is
recommended.
45. Carcinosarcoma
Retrospective reports favour sequential chemotherapy
and RT in adjuvant setting (Menczer et al ,Wong et al)
Managed similar to high grade endometrial cancer .
46. Hormones – Low grade ESS
Progestins are preferred
Aromatase inhibitors also show promise, in ESS.(ORR of
67%)
Duration :
Adjuvant setting 2yrs to 5 yrs and in recurrent/metastatic
setting until progression.
Chemotherapy is of limited use in low grade ESS.
50. RECURRENCE/METS
Locoregional Rec :Resection : if feasible especially in ESS
.
Metastatectomy :for oligo mets :developing after good
DFS, if R0 feasible.
Palliative chemo ,agents tried are Doxorubicin
,Gemcitabine ,taxanes ,Ifosfamide
Targeted agents as second line like Pazopanib
,bevacizumab ,mTOR and multikinase inhibitors with or
without chemo.
Best approach is participation in
multicentre trials.
51. PRACTICE POINTS
Benefit of adjuvant RT is limited to improved LRC.
LRC with Radiation is not translated in to survival .
Ongoing area of research is effective chemo
regimens /targeted agents to control metastasis and to
improve survival.
52. FUTURE
Multi institutional studies IRC :International Rare Cancer
Initiative :
Exploring the role of CTRT vs. Adjuvant chemo /targeted
treatments in each subgroup is warranted.
Comparison of EBRT vs. brachytherapy with newer
effective systemic treatment in each subgroup.
