Gynecologic Malignancies

Sharee A. Umpierre, M.D.

Associate Professor
Director Division of Gynecologic Oncology
Department of Obstetrics and Gynecology
UPR School of Medicine
MS-III 2012-2013

OVARIAN CANCER
American Cancer Society estimates
for 2010
New cases 21,880
Deaths

13,850

Ovarian Cancer
Second most common gynecologic
malignancy in the US
Responsible for 25,000 cases annually
14,500 deaths annually

Most lethal gynecologic malignancy

70% of patients present with
advanced disease
American Cancer Society 2000

Ovarian Cancer: Histologic

Distribution
8%
25%

Epithelial

65%

Germ Cell

Sex Cord Stroma

Ovarian Cancer: Stage

Distribution and Survival
Stage

%cases

Survival

24

95%

II

65%

III

55

15-30%

IV

15

0-20%

overall

50%
American Cancer
Society 2000

Relative Survival: Ovarian &

Breast Cancers
Five-Year Relative Survival Rates by
Stage at Diagnosis
Stage

Ovary

Breast

Local

93%

97%

Regional

55%

76%

Distant

25%

21%

All Stages

50%

84%

Ovarian Cancer: Risk Factors

Increase

Decrease

Age

OCPs

Family history

Pregnancy

Infertility/low
parity
Personal cancer
history

Tubal ligation
Breast-feeding

Ovarian Cancer: Hereditary

Risks
Family History of Ovarian
Cancer
None
1 first-degree relative
2 first-degree relatives
Hereditary ovarian cancer
syndrome
Known BRCA1 or BRCA2
germline mutation

Lifetime
Risk
1.5%
5%
7%
40%

35-65%

Ovarian Cancer: Hereditary

Syndromes
Account for only 10% of EOC
Autosomal dominant inheritance
Incomplete penetrance
Associated with breast, colon,
prostate and endometrial cancers
BRCA1, BRCA2, mismatch repair
genes

Ovarian Cancer: Risk Reduction

& Prevention
OCP RR 0.5 after 5 or more years of
use, reduction persists for 10 years
First full-term pregnancy < age 25;
number of pregnancies
Breast-feeding
BTL/Hysterectomy RR 0.33/0.67
Prophylactic Oophorectomy (risk of
primary peritoneal cancer remains)

Ovarian Cancer: Screening

Recommendations
Comprehensive family history on all
patients
None or 1 family member
Annual rectovaginal pelvic exam

2 or more family members

Genetic counseling,
Annual rectovaginal pelvic exam, CA125,
transvaginal ultrasound

Consider clinical trial participation

Ovarian Cancer: Diagnostic

Modalities
Rectovaginal pelvic exam
TVS and/or CT scan or MRI
CA125
If diagnosis uncertain, laparoscopy
may be useful diagnostic tool
Surgical exploration

Ovarian Cancer: CA125 Testing

CA125
Is elevated in greater than 80% of
advanced EOCs
Is elevated in 25-50% of
Stage I cancers
Has poor specificity, especially in
premenopausal women
NOT a screening test for the general
population

Ovarian Cancer: Ultrasound

Screening Studies
Screening of 5,000 women
65 exploratory surgeries for every case
of ovarian cancer

Screening of 1,600 women with a

family history
12 exploratory surgeries for every case
of ovarian cancer

Survival benefit unproven

Ovarian cancer screening

Ongoing screening studies:
UK >200K patients with Ca-125/US
algorithm
US: ROCA modeling of risk algorithm
using sequential Ca-125 followed by US
Newer marker combinations: He4, Ova1

Ovarian Cancer: Symptoms

95% of women DO report symptoms.
Symptoms can be vague and not
gynecologic:

Abdominal bloating, increased girth

Fatigue
Gastrointestinal disturbances
Urinary symptoms
Abdominal/pelvic pain
Menstrual irregularities

Ovarian Cancer: Surgical Rx

for Early Stage Disease
Optimal therapy: TAH BSO + staging
(including pelvic and PALN)
In younger women, reproductive
conservation may be appropriate
Approximately 30% will have
histologic evidence of metastatic
disease

Ovarian Cancer: Surgical

Treatment for Advanced Disease
Significant survival advantage for
women optimally cytoreduced
Procedures may include:
En bloc resection of uterus, ovaries and
pelvic tumor
Omentectomy
Bowel resection
Removal of diaphragmatic and peritoneal
implants
Splenectomy, appendectomy

Ovarian Cancer: Survival by

Residual Disease

GOG Protocols (PR) 52

and 97

Ovarian Cancer: Chemotherapy

All patients should receive a taxane
and a platinum
73% response rate
Median survival: 38 months for Stage
III/IV
IP therapy, addition of Bev
Encourage clinical trial participation

Ovarian Cancer: Follow-up

Healthcare
RV pelvic exam and CA125 q 3-4 mo
x 2 years, q 6 mo for years 3-5
CT scan for symptoms
General health maintenance
(mammography, Pap smear, bone
density, colon-rectal screening,
cholesterol, etc.)
Discuss HRT, diet, exercise

Ovarian Cancer: Recurrence

75% of patients relapse
Treatment options include:
Secondary cytoreduction
Retreatment with platinum/taxane
Second-line therapies, including chemo,
radiation, immunologic, gene therapies
Encourage clinical trials

Ovarian Cancer: Future

Directions

Cost-effective screening
Early detection
Prevention
Reversing chemoresistance
Immunotherapy
Gene therapy

Cervical Cancer: Incidence

American Cancer Society
estimates for 2010
12,200 new cases of invasive
cervical cancer annually in the U.S.
4,2100 of these women die

International estimates
Approximately 500,000 deaths
expected worldwide each year!
Number one cancer killer of women
worldwide

Cervical Cancer: Have we decreased

the incidence in the U.S.?

Reprinted by
permission of the
American Cancer
Society, Inc.

With the advent of

the Pap Smear the
incidence of cervix
cancer has
decreased

The curve has been

stable for the past
decade because we are
not reaching the
unscreened population.

Cervical Cancer: Risk Factors

Early age of intercourse
Number of sexual partners
Smoking
Lower socioeconomic status
High-risk male partner
Other sexually transmitted
diseases
Up to 50% of the U.S. population
is infected with HPV

Cervical Cancer: Etiology

Cervical cancer is a sexually transmitted
disease.
HPV DNA is present in virtually all cases of
cervical cancer and precursors.
Some strains of HPV have a predilection to the
genital tract and transmission is usually
through sexual contact.
Little understanding of why small subset of
women are affected by HPV.
HPV may be latent for many years before
inducing cervical neoplasia.

Cervical Cancer: HPV

Prevention
Educate all providers, men and
women regarding HPV and the link
to cervical cancer.
Adolescents are an especially highrisk group due to behavior and
cervical biology.
Delay onset of sexual intercourse.
Condoms may help prevent sexually
transmitted disease.

Cervical Cancer: Interpret your

Results
The Bethesda system
LGSIL
HGSIL
AGUS/ASCUS

Histologic diagnoses

CIN 1
CIN 2
CIN 3/CIS
Invasive cancer

Cervical Cancer: Screening

Window of Opportunity
Single Pap false negative rate is 20%.
The latency period from dysplasia to
cancer of the cervix is variable.
50% of women with cervical cancer
have never had a Pap smear.
25% of cases and 41% of deaths
occur in women 65 years of age or
older.

Cervical Cancer: Who Is Not

Getting a Pap Smear?
Uninsured
Elderly
Ethnic minorities, especially Hispanic and
African-American women
Poor women, especially in rural areas
Developing nations
Reasons for lack of screening
Attitudes and concerns
Logistical problems

Cervical Cancer: Signs and

Symptoms of Invasive Disease

May be silent until advanced disease develops

Post-coital bleeding
Foul vaginal discharge
Abnormal bleeding
Pelvic pain
Unilateral leg swelling or pain
Pelvic mass
Gross cervical lesion

Cervical Cancer: Microinvasive

Disease
Squamous carcinoma of the cervix that has
<3mm invasion from the basement membrane
The diagnosis must be based on a cone or
hysterectomy specimen.
No lymph-vascular invasion
May be successfully treated with fertility
preservation in selected patients
These patients should all be referred for
consultation.

Cervical Cancer: Treating Early

Cervical Cancer
Conization or simple hysterectomy
(removal of the uterus) microinvasive cancer
Radical hysterectomy - removal of
the uterus with its associated
connective tissues, the upper vagina,
and pelvic lymph nodes. Ovarian
preservation is possible.
Chemoradiation therapy

Cervical Cancer: Treating

Advanced Cervical Cancer
Chemoradiation is the mainstay of treatment
4-5 weeks of external radiation
Two or more implants (brachytherapy)
Concurrent Cisplatin-based chemotherapy
significantly improves the chances of
survival
Radiation treats the primary tumor and
adjacent tissues and lymph nodes
Chemotherapy acts as a radiation sensitizer
and may also control distant disease

Cervical Cancer: Five-Year

Survival
Stage

Chemo/XR
Rad Hyst
T

Ib

85-95%

85-90%

IIb

N/A

70-80%

IIIb

N/A

55-65%

Cervical Cancer:
Surveillance Post-therapy
Post-treatment surveillance is, by definition,
applied to asymptomatic patients.
Reassurance is an important component.
An acceptable schedule of follow-up visits is
every 3-4 months during the first 2 years, every
6 months for the next 3 years, and annually
thereafter.
The most critical component of the follow-up
visit is a thorough pelvic exam.
Many gynecologic oncologists recommend
periodic Pap smears and chest radiographs.

Cervical Cancer: Signs and

Symptoms of Recurrent Disease

Weight loss, fatigue and anorexia

Abnormal vaginal bleeding
Pelvic pain
Unilateral leg swelling or pain
Foul discharge
Signs of distant metastases
NOTE: must distinguish radiation
side effects from recurrent cancer

Cervical Cancer: Management

of Recurrence
Chemoradiation may be curative or
palliative, especially in women who
have not received prior radiation
therapy.
Isolated soft tissue recurrence may
occasionally be treated by resection
with long-term survival.
Chemotherapy is palliative in nature.

Cervical Cancer: Quality of Life

Issues
Areas of concern and study

Reproductive function
Sexual function
Urinary and bowel effects
Self-image
Issues surrounding sexual transmission
of HPV

Cervical Cancer:How do we
eradicate cervical cancer?
HPV VACCINE
Covers 6, 11, 16 and 18 which
account for 90% of
warts/preinvasive disease and 70%
of invasive cancer
Females ages 9 to 26
Vaccines are designed for
prophylaxis & given at 0, 2 and 6
mo.

Endometrial Cancer Incidence & Mortality

Acs estimates
Year

Cases

Deaths

2000

36,100

6,500

2010

43,470

7,950

Endometrial Cancer: Risk

Factors
Characteristic

Relative Risk

Obesity
>30 LBS

>50 LBS

10

Nulliparous

Late Menopause

Unopposed Estrogen

9.5

Atypical Hyperplasia

29

Diabetes

2.8

Hypertension

1.5

Endometrial Cancer: Types

Type I
Estrogen Related
Younger and heavier patients
Low grade
Perimenopausal
Exogenous estrogen
Type II
Aggressive
Unrelated to estrogen stimulation
Occurs in older & thinner women
Potential genetic basis
Lynch syndrome
Familial trend

Endometrial Cancer:
Screening

Patient Primary
Cytology Not satisfactory
Histology - Secondary
Hysteroscopy Not satisfactory
Sonography Cost-effective
issue

Endometrial Cancer: Who

Needs an Endometrial Biopsy?
Postmenopausal bleeding
Postmenopausal women with
endometrial cells on Pap
Perimenopausal intermenstrual bleeding
Abnormal bleeding with history of
anovulation
Thickened endometrial stripe via
sonography

Endometrial Cancer: Survival

by Clinical Stage
Stage

I
II
III
IV

70.2
17.8
8.1
3.6

Survival
(%)
76.3
59.2
29.4
10.3

Modified: FIGO 1991

Endometrial Cancer: Poor

Prognostic Factors

Increasing age (over 65)

Stage (> IB)
Vascular invasion
Grade
Histologic Subtypes (Clear-cell, Serous,
Adenosquamous)
Aneuploidy
Cytokinetics
Altered oncogene/tumor suppressor gene
expression
Other

Endometrial Cancer: Nodal

Involvement
Situation

% Positive Nodes

G1, no myometrial
invasion,
no extrauterine disease.

<1%

G2 or G3, inner 1/3

invasion,
no extrauterine disease

5-9% Pelvic
4% Aortic

G3, outer muscle, and/or

extrauterine disease

20-60% Pelvic
10-30% Aortic

Endometrial Cancer: Pre-op

Evaluation
CA125
Chest X-ray
Mammograms
Colon Evaluation
Transvaginal Ultrasound
Others as indicated

Endometrial Cancer: Principles for

Management

Knowledge of natural history

Intraoperative skills
Postoperative management
Indications for adjuvant treatment

Endometrial Cancer: Intraoperative Surgical Principals

Availability of frozen section
Capability of complete surgical
staging
Capability of tumor reduction
if indicated

Endometrial Cancer: Surgical

Staging
Conceptual rationale
Defines extent of disease
Minimizes over/under treatment
Minimally increases perioperative
morbidity/mortality
Decreases overall Rx risks and costs
Allows comparison of therapeutic results

Endometrial Cancer: Surgical

Approach
TAH-BSO/washings only

Grades 1, 2*
< 50% myometrial invasion*
Endometrioid*
< 2 cm tumor diameter*

*Verified via frozen section

Endometrial Cancer: Surgical

Approach
Complete Surgical Staging*

Grade 3
> 50% myometrial invasion
>2 cm tumor diameter
Serous/clear cell subtypes
Advanced stages
*TAH-BSO, washings, lymphadenectomy,
omental/peritoneal biopsy

Endometrial Cancer: Adjuvant

Therapy
Brachytherapy
External beam radiotherapy
Hormonal therapy
Cytotoxic chemotherapy
Combination therapy

Endometrial Cancer: Determinants

of Adjuvant Therapy

Stage
Histologic subtype
Staging completeness
Tumor biology
Medical conditions

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:
Chemotherapy Response Rates
Single Agent
CAP
AP
CA
TAX/CARBO
TEP
AP-VP-16

11-37%
45-56%
33-81%
31-46%
63%
73%
75%

GOG Symposium July, 1999, Goff

Endometrial Cancer: Follow-Up

Pelvic examination
Pap smears
CA125 high-risk
Chest X-ray high-risk

Endometrial Cancer:
Recurrence
80% of recurrences happen first 3
years
Most will be symptomatic
Rare to cure distant recurrences
50% vaginal recurrences cured

Endometrial Cancer: Site of

Recurrence
Site

Distant

65

Pelvic and
distant

15

Pelvis only

15

Vagina

Endometrial Cancer:
ERT/HRT
3 published studies
No evidence that ERT/HRT
adversely influences the diseasefree survival of women treated for
endometrial cancer

Endometrial Cancer:
Surgical Staging
Preoperative preparation
Antimicrobial prophylaxis
Steep Trendelenburg
Long instruments available

Endometrial Cancer: Adjuvant Postop

Radiotherapy

Estimated cost 5,040 cGy PRT:

$20,000
Treatment duration: 25 to 30
days
Morbidity compounded

Endometrial Cancer:

Single Agent

Chemotherapy Response Rates

Agent

Response

Agent

Response

Paclitaxel

37%

HMM

17%

Carboplatin

28%

Vincristine

16%

Doxorubicin

26%

Etoposide

14%

Cisplatin

25%

Ifosfamide

14%

5-FU

21%

Cytoxan

11%

GOG Symposium July 1999 Goff

Endometrial Cancer: Treatment

Reassessment

Clinical trials
Surgical management
Adjuvant therapy
Salvage therapy

Endometrial Cancer: Tumor Biology

Objective
Pretreatment risk assessment using
molecular determinants

Aim
Triaging of patients at risk for advanced
disease and/or recurrence

Purpose
Facilitate evaluation of treatment
approaches via clinical trials

Endometrial Cancer: Molecular

Staging
Pretreatment risk identification
Readily affords high-risk patients
access to special expertise in
managing advanced or recurrent
disease
Would facilitate the evaluation and
application of new or modified
therapeutic modalities

Endometrial Cancer: Evolution of Molecularbased Therapies