Transcript Document

Cancers of the Uterine Corpus
SUNY Downstate Medical
Center
Division of Gynecologic
Oncology
Mark Borowsky, MD
American Cancer Society
Female Cancers: 2000 Statistics
• Cancers of the
uterine corpus
are the 4th most
common cancer
in American
women
• Lifetime
incidence ~2-3%
Lifetime risk
Country
Risk (%)
U.S. White
3.05
U.S. Black
1.34
South East
Asia
0.2
American Cancer Society
Female Cancers: 2000 Statistics
•Median Age 61
•25% diagnosed before the menopause
•5% diagnosed before age 40
Post Menopausal
Age 40-50 y/o
Age <40 y/o
American Cancer Society
Female Cancers: 2000 Statistics
6,500 Deaths per year
 8th cause of female cancer
death
 2% of all female cancer death
 Uterine corpus cancer cases
and deaths have increased 25%
and 12% respectively from 1994
to 2004

Cancers of the Uterine Corpus:
Histologic Types
• Carcinoma (94%)
–
–
–
–
–
–
Endometrioid (87%)
Adenosquamous (4%)
Papillary Serous* (3%)
Clear Cell* (2%)
Mucinous (1%)
Other (3%)
• Sarcoma (6%)
–
–
–
–
Carcinosarcoma* (60%)
Leiomyosarcoma* (30%)
Endometrial Stromal Sarcoma (10%)
Adenosarcoma (<1%)
*poor prognosis histology
Endometrial Cancer:
Type I/II Concept
• Type I
–
–
–
–
–
–
Estrogen Related
Younger and heavier patients
Low grade
Background of Hyperplasia
Perimenopausal
Exogenous estrogen
• Type II (~10% of total cases)
–
–
–
–
–
Aggressive
High grade
Unfavorable Histology
Unrelated to estrogen stimulation
Occurs in older & thinner women
• Familial/genetic (~15% of total cases)
• Lynch II syndrome/HNPCC
• Familial trend
Endometrial Cancer: Type I Risk
Factors
Characteristic
Atypical Hyperplasia
Obesity >50 LBS
Obesity >30 LBS
Unopposed Estrogen
E use <5yrs vs. >7yrs
Late Menopause (>52 y/o)
Diabetes
Nulliparous
Early Menarche (<12 y/o)
OCP
Relative Risk [X]
29
10
3
9.5
5-14
4
2.8
2
1.6
0.5
Uterine Cancer: Surgical Staging
• Replaced Clinical Staging 1989
• Conceptual rationale
– Better defines extent of disease (metastases,
depth of invasion, cervix involvement, etc.)
– Minimizes over/under treatment
– Minimally increases perioperative
morbidity/mortality
– Decreases overall Rx risks and costs
– Better allows comparison of therapeutic results
Uterine Cancer: Surgical Staging
• Clinical Stage I will be upstaged 30% of the time at
laparotomy
–
–
–
–
5% for positive adnexa (Surgical Stage IIIa)
6% for positive para-aortic lymph nodes (Surgical Stage IIIc)
9% for positive pelvic nodes (Surgical Stage IIIc)
12% for positive cytology on pelvic washings (Surgical Stage
IIIa)
– 6% other {eg. cervical (St II) or abdominal disease (St IV)}
• Clinical Stage II or III will be upstaged 60% of the
time at laparotomy
Endometrial Cancer: Clinical vs. Surgical Staging
Clinical assessment
No.
5-yr OS (%)
Stage I
245
88
Stage II/III
47
83
Surgical assessment
No. 5-yr OS (%)
Stage I/II
231
93
Stage III
61
67
Lanciano et al: Radiother Oncol 28:189,1993
Endometrial Cancer: FIGO Surgical Stage
Stage I
(73%)
Stage II
(11%)
Confined to uterus
Cervix involved
Stage III
(13%)
Uterine serosa, adnexae, positive
cytology, vaginal metastases,
pelvic/aortic node metastases
Stage IV
(3%)
Bladder, bowel, inguinal node, distant
metastasis
Endometrial Cancer Prognosis:
Survival by Stage:
Stage
% 5yr
survival
IA
91
IB
88
IC
81
IIA
77
IIB
67
IIIA
60
IIIB
41
IIIC
32
IVA
20
IVB
5
•Overall 5Yr Survival 84%
•Stage and Grade are the most
important prognostic factors
•Altered oncogene/tumor suppressor
gene expression is now being
evaluated (molecular staging concept)
Survival by Grade:
Grade
% 5yr
survival
1
92
2
87
3
74
Endometrial Cancer: Poor Prognostic
Factors
• Aggressive Histologic Subtypes (Clear-cell,
Serous)
• Increasing age (over 65)
• Vascular invasion
• Aneuploidy
• Altered oncogene/tumor suppressor gene
expression ( “molecular staging” conceptp53, PTEN, microsatellite instability, MDR-1,
HER2/neu, ER/PR, Ki 67, PCNA, CD
31,EGF-R, MMR genes)
• Race?
Molecular Genetics
• PTEN mutations: 32%
– Tumor suppressor gene (chrom 10)
• Phosphatase
– Early event in carcinogenesis
• Associated with:
– endometrioid histology
– early stage
– favorable survival
Molecular Genetics
• p53 tumor suppressor gene
– Cell cycle and apoptosis regulation
– Most commonly mutated gene in human
cancers
– Overexpression (marker for mutation)
– Associated with poor prognosis
– early stage: 10% have p53 mutation
– advanced stage: 50% have p53
mutation
– not found in hyperplasias
– late event in carcinogenesis
Genetic Syndromes: HNPCC
Hereditary Non-Polyposis Colon Cancer
Lynch II Syndrome
• Autosomal dominant inheritance
– MMR (mismatch repair) mutations
• Genetic instability leads to error-prone DNA replication
– hMSH2 (chrom 2)
– hMLH1 (chrom 3)
• Early age of colon Ca: mean 45.2 years
• Endometrial Ca: second most common
malignancy
– 20% cumulative incidence by age 70
– Earlier age of onset than sporadic cases
• Other: ovary (3.5-8 fold), stomach, small
bowel, pancreas, biliary tract
Five Year Survival by Race:
Stage
White
Black
All Stages
85
54
I
93
73
II
76
27
III
55
17
IV
23
13
Five Year Survival by Race:
Matthews RP, Hutchinson-Colas J, Maiman M, et al.: Papillary Serous and
Clear Cell Type Lead to Poor Prognosis of Endometrial Carcinoma in
Black Women. Gynecol Oncol. 65: 206-212, 1997.
• Retrospective review 401 patients (60% black)
• 5 yr Survival
– Black women: 56% Other races: 71%
• Black women were more likely to have clear cell or
UPSC histology.
• After controlling for stage only clear cell and UPSC
histology independently predicted poor outcome.
• Race not predictive of survival when stage and
histology controlled for.
Diagnosis of disease: Patient Awareness*
• More than 95% of patients with Endometrial
Cancer report having symptoms
–
–
–
–
Postmenapausal bleeding
Menorrhagia
Metrorrhagia
Bloody Discharge
• Endometrial biopsy is the main diagnostic tool
– performed either in the office or via D&C in OR
Post menopausal bleeding
ETIOLOGY
(%)
Exogenous estrogen
30
Atrophy (uterus/vag)
30
Endo. Ca.
15
Polyps
10
Hyperplasia
5
Miscellaneous
10
Postmenopausal Bleeding
Diagnosis of Any Uterine Corpus Cancer,
Hawwa et al., 1970
Age Group
# Cases
# Cancer
%
<50
34
0
0.0
50-59
161
15
9.3
60-69
92
15
16.3
70-79
43
12
27.9
>80
5
3
60.0
Uterine Cancer:
Diagnosis/Screening
•
•
•
•
•
Patient Symptoms/Awareness*
Cytology – Not a satisfactory screening test
Sonography – Not Cost effective
Hysteroscopy – Not Cost effective
Histology – Secondary to symptoms (not as a
screening test)
Cytology – Not sensitive, nor specific
Endometrial Pathology in Women With Any
Endometrial Cells Seen on Pap (Yancey, et al. 1990)
Menopause Status
Number of patients Number (%) of
hyperplasia or any
type malignancy
Premenopausal
61
6 (10%)
Postmenopausal
127
39 (31%)
•Less than 50% of patients with endometrial Ca have
endometrial cells on Pap smear
•Endometrial cells and/or AGCUS on a pap are
frequently a sign of endometrial pathology and deserve
further investigation
Endometrial Cancer:
Transvaginal Ultrasound Screening
Endometrial Cancer:
Transvaginal Ultrasound Screening
Fleischer AC, Wheeler JE, Lindsay I, et al.: An assessment of the value of
ultrasonographic screening for endometrial disease in postmenopausal women without
symptoms. American Journal of Obstetrics and Gynecology 184(2): 70-75, 2001.
•Study of 1,926 asymptomatic postmenopausal women
on idoxifene for transvaginal u/s screening
•All patients agree to biopsy after u/s (1,792 biopsies)
•Using 6 mm cutoff for “Abnormal” the sensitivity of the
test was 33% (missed 67% of atypical hyperplasia and
cancer)
•45% of women were > or = 6mm
•PPV was only 2%
•NPV>99%
Endometrial Cancer:
Transvaginal Ultrasound Screening
Langer RD, Pierce JJ, O'Hanlan KA, et al.: Transvaginal ultrasonography compared with
endometrial biopsy for the detection of endometrial disease. New England Journal of
Medicine 337(25): 1792-1798, 1997.
•448 Women, all asymptomatic and all on HRT
•All agree to TV u/s and biopsy
•Threshold of 5mm used
•4% incidence of cancer
•Test Sensitivity was 90% at threshold of 5mm
•But >50% of women had endometrial thickness
of 5mm or more
Endometrial Cancer:
Transvaginal Ultrasound Screening
N=250
Endometrial Stripe Thickness
11Diagnosis
<5mm 6-10mm
>15mm
15mm
Atrophy
93%
7%
Hyperplasia
58%
42%
Polyp
53%
47%
Cancer
18%
41%
41%
Grigoriou: Maturitus 23:9-14,1996
Endometrial Cancer:
Transvaginal Ultrasound Screening
Rebecca Smith-Bindman, MD; Karla Kerlikowske, MD; Vickie A. Feldstein, MD,
etal: Endovaginal Ultrasound to Exclude Endometrial Cancer and Other
Endometrial Abnormalities. JAMA. 1998;280:1510-1517
•Meta-analysis 35 studies, 5,892 women
•All with PMB, HRT use varied
•5mm threshold used
•Sensitivity 92%
•Specificity 92% for non HRT users
•Specificity 77% for HRT users
Endometrial Cancer:
Transvaginal Ultrasound Screening
Endometrial Cancer:
Transvaginal Ultrasound Screening
Summary: Endometrial Cancer:
Transvaginal Ultrasound Screening
• Normal endometrial stripe:
• Postmenopausal
4- 8 mm
• Postmenopausal on HRT 4- 10 mm
• U/S for Detection of any uterine
pathology
•
•
•
•
Sensitivity: 85-95%
Specificity: 60-80%
PPV 2-10%
NPV 99%
Hysteroscopy – Not satisfactory for
screening test
•Studies of the efficacy of hysteroscopy
as a diagnostic tool vary widely
•Sensitivity reported ranging from 60-95%
compared to D&C obtained at the same
time
•Specificity 50-99%
Normal Endometrium
Endometrial Polyp
Polyp and Atypical Hyperplasia
Focal Simple Hyperplasia
Grade 3 Endometrial cancer
Hysteroscopy and Positive
Cytology?
•Studies have been mixed:
•Some studies suggest an increase in positive
peritoneal cytology seen at staging laparotomy in
patients who have had hysteroscopy
•Other studies have failed to find a difference in
positive cytology in patients diagnosed via
hysteroscopy as compared to office biopsy or D&C
Positive Studies:
Bradley WH, Boente MP, Brooker, D, et al.: Hysteroscopy and Cytology
in Endometrial Cancer. Obstet Gynecol 2004;104:1030-3
Zerbe M, Zhang J, Bristow RE, et al.: Retrograde seeding of malignant
cells during hysteroscopy in presumed early endometrial cancer.
Gynecol Oncol 2000;79:55-8
Obermair A, Geramou M, Gucer F, et al.: Does hysteroscopy facilitate
tumor cell dissemination. Cancer 2000;88:139-43
Increase in positive cytology from ~2-3% to ~10%
(RR 3-4)
Negative Studies:
Gu M, Shi W, Huang J, et al.: Association between initial diagnostic
procedure and hysteroscopy and abnormal peritoneal wahisngs in
patients with endometrial carcinoma. Cancer 2000;90:3:143-7
Selvaggi L Cormio G, Ceci O, et al.: Hysteroscopy does not increase the
risk of microscopic extrauterine spread in endometrial carcinoma. Int J
Gynecol Cancer 2003;13:223-7
Hysteroscopy – Not satisfactory
• Too much cost and risk to be used as a
screening test.
• Useful for evaluation of abnormal uterine
bleeding where office biopsy is unrevealing.
• Use in conjunction with uterine curettage
• Useful to see and resect polyps and small
submucous fibroids
• Useful to perform directed biopsy of small
lesions.
Endometrial Cancer:
Who Needs an Endometrial Biopsy?
•
•
•
•
Postmenopausal bleeding
Perimenopausal intermenstrual bleeding
Abnormal bleeding with history of anovulation
Postmenopausal women with endometrial
cells on Pap
• Thickened endometrial stripe via sonography
Sampling of the Endometrium
• Office biopsy procedures (Pipelle, Vabra aspirator,
Karman cannula) will agree with a D&C performed
in the OR ~95% of the time
• Office biopsy has a 16% false negative rate when
the lesion is in a polyp or the cancer covers less
than 50% of the endometrium
– Guido et al. J Reprod Med. 1995;40:553
• Patients with persistent PMB after negative office
biopsy should have D&C (+/- hysteroscopy)
• D&C is the gold standard sampling method
– preoperative D&C will agree with diagnosis at
hysterectomy 94% of the time
Endometrial cyclic changes
Proliferative phase
Endometrial cyclic changes
Proliferative phase
Endometrial cyclic changes
Early secretory
Endometrial cyclic changes
mid-secretory
Endometrium: Post-menopausal atrophy
Endometrial Simple Hyperlasia
Endometrial Hyperlasia - Complex
Endometrial Hyperplasia - Atypical
Endometrial Atypical Hyperplasia
Endometrial Hyperplasia Classification
and Risk of Progression to Cancer:
Kurman, et al. (Cancer. 1985 Jul 15;56(2):403-12.)
Type of
Total Cases
Hyperplasia (n=170)
Simple
Complex
Atypical,
simple
Atypical,
complex
Years of
Follow up
(mean=13.4)
#
Progressed
to Cancer
%
Progressed
to Cancer
93
29
13
15.2
13.5
11.4
1
1
1
1%
3%
8%
19%
17%
23%
80%
80%
69%
35
11.4
10
29%
14%
57%
Combined No Atypia (n=122)
1.6%
Combined with Atypia (n=48)
23%
%
% Spont.
Persistent Regression
Hyperplasia
(P=0.001)
Mean age at study entry= 40y/o Mean study F/U=13.4yrs
Treatment for Endometrial Hyperplasia
without atypia:
•Progestin therapy continuous or cyclical
•Childbearing age:
•Progestin dominant OCPs or
•Depo-Provera 150mg IM q3 months or
•Provera 10mg po 10 days/month and
•May follow with ovulation induction after
normal biopsy if pregnancy desired
•Peri or Postmenopausal:
•Provera 20mg po 10 days/month or
•Depo-Provera 200mg IM q2 months
•Repeat biopsy in 3-4 months
Treatment for Atypical Endometrial
Hyperplasia:
•23% risk of progression to carcinoma (over
10 years) if untreated.
•Standard treatment when childbearing is
complete is total hysterectomy (abdominal
or vaginal)
•Frozen section to rule out carcinoma (up to
20% have coexisting endometrial cancer)
Treatment for Atypical Endometrial
Hyperplasia:
• Conservative medical therapy can be attempted in
younger patients who request preservation of fertility.
• D&C prior to initiation of medical therapy to rule out
carcinoma
• Megace 40-80mg/day, Norethindrone acetate 5mg/day
• Conservative therapy may also be attempted in
young patients with early, well differentiated
endometrial carcinomas.
• Megace 120-200mg/day, Norethindrone acetate 5-10mg/day
Conservative/Medical Therapy:
Randall TC, Kurman RJ. Progestin treatment of atypical hyperplasia
and well-differentiated carcinoma of the endometrium in women
under age 40. Obstet Gynecol. 1997 Sep;90(3):434-40.
• Objective
– Determine efficacy of conservative treatment of
AH/ECA in patients <40 yrs. of age
• Methods
– Retrospective Study of pathology records of women
age < 40 diagnosed with AH or ECA at Johns
Hopkins Jan/90 - Jan/96
Conservative/Medical Therapy:
• Results
– Among 29 pts treated with progestins
16/17 (94%) w/ AH regressed
9/12 (75%) w/ ECA regressed
– Median length of treatment required for
regression was 9 mos.
T.C.Randall, R.J.Kurman.
Obstet Gynecol 1997;90:434-440
Conservative/Medical Therapy:
• Results
– At a mean f/u of 40 mos all pts were alive
w/o evidence of progressive dz.
– 5 of 25 women attempting pregnancies
delivered healthy full term infants.
T.C.Randall, R.J.Kurman.
Obstet Gynecol 1997;90:434-440
Conservative/Medical Therapy:
Kim YB, Holschneider CH, Ghosh K, Nieberg RK, Montz FJ. Progestin
alone as primary treatment of endometrial carcinoma in premenopausal
women. Report of seven cases and review of the literature. Cancer. 1997
Jan 15;79(2):320-7.
•13 of 20 patients (62%) with well differentiated
endometrial carcinoma regressed with
progestins (3 later recurred).
Gotlieb WH, Beiner ME, Shalmon B, Korach Y, Segal Y, Zmira N,
Koupolovic J, Ben-Baruch G. Outcome of fertility-sparing treatment
with progestins in young patients with endometrial cancer. Obstet
Gynecol. 2003 Oct;102(4):718-25.
•13 of 13 patients regressed with progestin therapy, 6
later recurred
Conservative/Medical Therapy:
• Conclusion
– Treatment of AH/ECA with progestins
appears to be a safe alternative to
hysterectomy in women < 40 yrs of age in
whom fertility is desired.
– Perform hysterectomy after childbearing is
completed.
Endometroid carcinoma, Grading
• FIGO
- Gr 1 - < 5% solid tumor
- Gr 2 - 6 % - 50% solid
- Gr 3 - > 50% solid tumor
• NUCLEAR GRADE
– Size, shape , staining and chromatin, variability,
prominent nucleoli.
– High nuclear grade adds one point to FIGO grade
Grade 1 Endometroid Carcinoma
Grade 3 Endometroid Carcinoma
Endometrial carcinoma:
Poor Prognosis Cell Types - Papillary Serous
Endometrial Carcinoma - Poor Prognosis
Cell Types Clear Cell
Uterine Cancer: Pre-op Evaluation
•CA125
•Chest X-ray
•Mammograms
•Colon Evaluation
•Others as indicated
Uterine Cancer: Pre-op Evaluation
•Transvaginal U/S?
•CT Scan?
•MRI?
Uterine Cancer: Pre-op Evaluation
Uterine Cancer: Surgical Staging
•
•
•
•
•
Preoperative preparation
Antimicrobial prophylaxis
DVT prophylaxis
Steep Trendelenburg
Long instruments available
Endometrial Cancer: Intra-operative
Surgical Principals
• Availability of frozen section to determine the
extent of staging procedure.
• Capability of complete surgical staging
• Capability of tumor reduction if indicated
Endometrial Cancer: Nodal Involvement
Situation
G1, inner 1/3 myometrial
invasion, no extrauterine
disease.
G2 or G3, inner 1/3 invasion,
no extrauterine disease
G3 with outer 1/3 invasion,
and/or extrauterine disease
% Positive Nodes
<1%
5-9% Pelvic
4% Aortic
20-60% Pelvic
10-30% Aortic
Endometrial Cancer: Surgical Approach
• TAH-BSO/washings only
– Endometrioid*
– Grades 1 and < 50% myometrial invasion*
– or Grade 2 and no or minimal invasion
and < 2 cm tumor diameter*
*Verified via frozen section
Endometrial Cancer: Surgical Approach
• Complete Surgical Staging*
– All Grade 3
– Any > 50% myometrial invasion
– Any >2 cm tumor diameter
– All Serous/clear cell subtype**
– Pre operative assessment of advanced
disease (gross cervical or vaginal dz, etc)
*TAH-BSO, washings, lymphadenectomy
**omental/peritoneal biopsy
Laparoscopic Staging:
Magrina JF, Weaver AL. Laparoscopic treatment of endometrial cancer:
five-year recurrence and survival rates. Eur J Gynaecol Oncol.
2004;25(4):439-41.
Holub Z, Jabor A, Bartos P, Eim J, Urbanek S, Pivovarnikova R.
Laparoscopic surgery for endometrial cancer: long-term results of a
multicentric study. Eur J Gynaecol Oncol. 2002;23(4):305-10.
GOG LAP2 Protocol: Randomized study of Total
Hysterectomy, BSO and Staging via Laparotomy vs.
Laparoscopy- study still open
• Previous studies show:
–
–
–
–
–
–
Similar blood loss
Same incidence of complications
Low incidence of conversion of laparoscopy to laparotomy
Longer operative times for laparoscopy (160 min vs. 115min)
Shorter hospital stay (4 vs 7 days) for laparoscopy
No difference in recurrence risk.
Endometrial Cancer: Adjuvant Therapy
•
•
•
•
•
Brachytherapy
External beam radiotherapy
Hormonal therapy
Cytotoxic chemotherapy
Combination therapy
Endometrial Cancer: Adjuvant Radiation
•Stratify patients into risk for recurrence based on Grade
and Stage
•Low Risk (<5% recurrence): Stage IA or superficial IB,
Grade 1 or 2, no LVSI -these patients require no further
treatment after surgery
•Intermediate Risk (5-10% recurrence): Grade 1 with at
least middle third invasion or Stage IB Grade 2 and no
LVSI. No consensus exists for this group.
•High Risk (>10% recurrence): Any Grade 3, Any Stage IC
or greater, Grade 2 with middle third invasion or LVSIthese patients should get adjuvant radiation with either
WPR 4,500-5,000 cGy and/or vaginal brachy therapy.
Endometrial Cancer: Adjuvant Radiation
•GOG 99
•390 patients, Stage IB, IC, IIA or IIB, all grades
(UPSC and clear cell excluded)
•Patients randomized to 5,040 cGy WPR (no brachy
therapy) vs. no RT
•3yr survival 96% vs 89% for RT vs control group
(p=0.009)
• Among patients with Grade 2 or 3, or > middle third
invasion or + LVSI the 5yr recurrence free percentage
was 87% for the RT group vs 73% for the control group
Endometrial Cancer: Adjuvant Postop
Radiotherapy
• Estimated cost 5,040 cGy PRT: $20,000
• Treatment duration: 25 to 30 days
• Morbidity compounded by recent surgery
Endometrial Cancer: Adjuvant Hormonal
Therapy
Number
Deaths
Progestagens x 1 yr
553
61
Placebo
531
62
Vergote et al: Cancer 64:1011, 1989
Endometrial Cancer: Single Agent
Chemotherapy Response Rates
Agent
Paclitaxel
Carboplatin
Doxorubicin
Cisplatin
5-FU
Response
37%
28%
26%
25%
21%
Agent
HMM
Vincristine
Etoposide
Ifosfamide
Cytoxan
Response
17%
16%
14%
14%
11%
GOG Symposium July 1999 Goff
Endometrial Cancer: Chemotherapy
Response Rates
Single Agent
11-37%
CAP
45-56%
AP
33-81%
CA
31-46%
TAX/CARBO
63%
TEP
73%
AP-VP-16
75%
GOG Symposium July, 1999, Goff
Endometrial Cancer: ERT/HRT
• 3 small published studies prior to GOG 137
• GOG 137- closed after WHI study results
• Preliminary results (April 2004: 32 mos F/U) of GOG 137
agree with prior studies: No evidence that ERT/HRT
adversely influences the disease-free survival of women
treated for endometrial cancer
Treatment
Number Patients (n)
Disease Recurrence
ERT (Premarin)
618
14 (2.3%)
Placebo
618
10 (1.6%)
Cancer Deaths
5 (0.8%)
4 (0.6%)
Total Deaths
23 (3.7%)
16 (2.6%)
Endometrial Cancer: Recurrence
•
•
•
•
Pelvic examination
Pap smears
CA125 (high-risk)
Chest X-ray (high-risk)
Endometrial Cancer: Site of Recurrence
In Radiated Patients
Site
%
Distant
65
Pelvic and distant
15
Pelvis only
15
Vagina
5
Endometrial Cancer: Follow-Up
• 75-95% of recurrences are in first 36 months
• 60% of patients have symptoms (pain, wgt
loss, vaginal bleeding)
• Rare to cure distant recurrences
• 50% vaginal recurrences cured
Uterine Sarcomas
• Account for fewer than 10% of all corpus
cancers
• Abnormal vaginal bleeding most frequent
presenting symptom for all histologic
types
• No specific staging system (commonly
use staging of endometrial carcinoma)
Uterine Sarcomas
• Order of incidence: Carcinosarcoma (60%),
leiomyosarcoma (30%), endometrial stromal
sarcoma (10%), and adenosarcoma (<1%)
• Higher rates of MMMT and LMS seen in Black
women (2X greater than whites)
• Exposure to radiation may enhance the
development of pelvic sarcomas (seen mainly in
mixed sarcomas)
• Mean age between 65-75 for carcinosarcoma but
earlier for LMS and ESS
Carcinosarcoma
• Contains both carcinomatous and sarcomatous
elements
• In homologous MMMT, sarcomatous element is
stromal sarcoma in 60% and LMS in the
remainder.
• In heterologous MMMT rhabdomyosarcoma most
common element (others: chondrosarcoma,
osteosarcoma and liposarcoma).
• Carcinomatous element usually adenocarcinoma
(endometrioid,clear cell, PSA)
Carcinosarcoma (MMMT): Homologous
Carcinosarcoma (MMMT): Heterologous
Carcinosarcoma
• Overall 5 year survival poor (25%) and strongly
associated with degree of myometrial invasion.
• ~60% have spread outside the uterus at time of
diagnosis
• ~35% regional lymph node spread in clinical stage 1
patients
• Early hematogenous spread to liver and lung is
common
• In pts without extrauterine disease, 40% chance of
distant recurrence
Leiomyosarcoma
• LMS represent ~30% of uterine sarcomas
• LMS rarely arises from benign leiomyomata
• Arises in the myometrium, unlike all the other
uterine sarcomas (less likely to be detected on
EMC)
Leiomyosarcoma
Leiomyosarcoma
• Tumors usually show high cellularity, marked
pleomorphism, and atypical mitotic figures.
• Two thirds of LMS are intramural and 10%
submucosal
• Need >10 mitoses/ 10hpf for diagnosis
Endometrial Stromal Sarcoma
• Accounts for ~10% of uterine sarcomas
• Tumor group divided into benign stromal
nodule , low-grade ESS and high grade ESS
• Areas of hemorrhage, necrosis, and deep
myometrial invasion common in high grade
ESS and 40% extend beyond the uterus at
the time of diagnosis
Endometrial Stromal Sarcoma
Endometrial Stromal Sarcoma
Endometrial stromal sarcoma
Adenosarcoma
• First described in 1974
• Rare
• Composed of a benign epithelial and a
malignant non-epithelial component
• Mean age between 55 and 60 years
• Tend to be solitary masses in uterine
fundus
Adenosarcoma
• Disease usually limited to endometrium, but
myometrial invasion is possible
• Sarcomatous element usually homologous
and of lower grade compared to MMMT
• Adenosarcoma with Sarcomatous
Overgrowth is a poor prognostic feature
Management of Uterine Sarcomas
• Surgery is the hallmark of treatment with
TAH/BSO being the standard procedure
• For patients with advanced or recurrent
disease, aggressive surgical intervention is
unlikely to influence outcome.
• Bilateral oopherectomy is strongly
recommended for patients with Low grade ESS
Management of Uterine Sarcomas
•Indications for adjunctive RT or primary RT
parallels the indications for endometrial CA
•Adjuvant RT has been shown to improve local
control, effect on overall survival unknown
Management of Uterine Sarcomas
• MMMT- Ifosfamide (25% response),
cisplatinum(18% response).
• LMS- only adriamycin appears to have
significant activity (25% response rate)