1. SCREENING FOR OVARIAN CANCER
DANIEL
H.
SMITH,
MD
DIRECTOR,
GYNECOLOGIC
ONCOLOGY
AND
MINIMALLY
INVASIVE
GYNECOLOGY
HOLY
NAME
MEDICAL
CENTER
TEANECK,
NEW
JERSEY,
USA
MAY
14,
2013
4. OVARIAN CANCER
EVOLUTION OF THOUGHT, HISTORICALLY
• TRADITIONALLY
CALLED
‘STOMACH
CANCER’
– FEW
LIVED
FOR
VERY
LONG
– TREATMENTS
• SURGERY
–
IF
DIDN’T
DIE
FROM
OPERATION
• CHEMOTHERAPY
– LIFE
COULD
BE
SUSTAINED
– …WITH
COSTS!
• THE
CURE
• CHEMOTHERAPY
– LIFE
COULD
BE
SUSTAINED
– …WITH
COSTS!
– ADVANCED
DISEASE
DAUNTING
• NEW
DRUGS,
TRIALS,
PROCEDURES
• EFFECTIVE?
– EARLY
DISEASE
–
PATIENTS
DO
MUCH
BETTER
• ?EARLIER
DETECTION
– SCREENING
– FINDING
SMALLER
CANCERS
7. WORLD HEALTH ORGANIZATION
1968
1. The
condi,on
should
be
an
important
health
problem.
2. There
should
be
a
treatment
for
the
condi,on.
3. Facili,es
for
diagnosis
and
treatment
should
be
available.
4. There
should
be
a
latent
stage
of
the
disease.
5. There
should
be
a
test
or
examina,on
for
the
condi,on.
6. The
test
should
be
acceptable
to
the
popula,on.
7. The
natural
history
of
the
disease
should
be
adequately
understood.
8. There
should
be
an
agreed
policy
on
whom
to
treat.
9. The
total
cost
of
finding
a
case
should
be
economically
balanced
in
rela,on
to
medical
expenditure
as
a
whole.
10. Case-‐finding
should
be
a
con,nuous
process,
not
just
a
"once
and
for
all"
project.
8.
WHAT DIFFERENCE CAN SCREENING MAKE????
9. SCREENING FOR EARLY DISEASE
OVARIAN CANCER
• METHODOLOGY
– PHYSICAL
EXAMINATION
– SYMPTOMS
and/
or
SIGNS
– TESTING
• IMAGING
• BLOOD
TESTS
• GENETIC
TESTS
10. • PHYSICAL
EXAMINATION-‐
PELVIC
EXAM!
– RARELY
DONE
(ABSOLUTE
NUMBER
STILL
HIGH)
– FINDING
EARLY
DISEASE
???
– SIGNS
OF
ADVANCED
DISEASE
(ASCITES,
MASSES)
• RED
HERRING
–
– NEW
YORK
TIMES,
APRIL
30,
2013
• ADVOCATING
AGAINST
PELVIC
EXAMINATION
• NO
EVIDENCE
THAT
RELEVANT
CONDITIONS
ARE
FOUND
• EVIDENCE
THAT
EXAMINATIONS
CAUSE
UNNECESSARY
SURGEY
SCREENING FOR EARLY DISEASE
OVARIAN CANCER
11. SCREENING FOR EARLY DISEASE
PELVIC EXAMINATION
• AN
EXAM
WITH
POOR
RESULTS
– ROUTINE
PELVIC
CHECKUPS
CAN
CAUSE
MORE
PROBLEMS
THAN
THEY
UNEARTH,
EXPERTS
SAY
– DISCOVERY
OF
BENIGN
CONDITIONS
CAN
LEAD
TO
UNNECESSARY
FOLLOW-‐UP
• 63.4
MILLION
ANNUAL
PELVIC
EXAMINATION
–
USA
• PURPORTED
REASONS
OF
PERFORMING
THE
EXAMINATION
-‐
ALL
OF
WHICH
CAN
BE
PERFORMED
WITHOUT
A
PELVIC
EXAM
– PAP
SMEAR
–
NEW
GUIDELINES
• LONGER
INTERVALS
WITH
NORMAL
HISTORY
• NOT
RECOMMENDED
FOR
MANY
–
OLDER,
YOUNGER,
THOSE
WITH
NEGATIVE
PAP
AND
CO-‐TESTING
– DETECTION
OF
SEXUALLY
TRANSMITTED
DISEASE
– DETECTION
OF
ASYMPTOMATIC
PELVIC
MASSES
– ASSEDSSMENT
FOR
HORMONAL
CONTRACEPTION
NEW
YORK
TIMES,
TUESDAY,
APRIL
30,
2013
-‐
JANE
E.
BRODY
12. SCREENING FOR EARLY DISEASE
PELVIC EXAMINATION
• FOR
WOMEN
WHO
ARE
APPARENTLY
HEALTHY
– ROUTINE
BIMANUAL
EXAMINATION
IS
NOT
SUPPORTED
BY
MEDICAL
EVIDENCE
– INCREASES
COSTS
OF
MEDICAL
CARE
– DISCOURAGES
SOME
WOMEN,
PARTICULARLY
ADOLESCENTS,
FROM
SEEING
DOCTORS
• ROUTINE
EXAMS
IN
USA
– TWICE
THE
INCIDENCE
OF
CERTAIN
SURGERIES
• OVARIAN
CYSTECTOMY
• HYSTERECTOMY
– NATIONAL
CANCER
INSTITUTE
STUDY
–
NO
OVARIAN
CANCERS
FOUND
– ENDORSED
BY
AMERICAN
COLLEGE
OF
OBSTETRICIANS
AND
GYNECOLOGISTS
• ACKNOWLEDGES
THAT
MEDICAL
EVIDENCE
TO
JUSTIFY
IS
LACKING
NEW
YORK
TIMES,
TUESDAY,
APRIL
30,
2013
-‐
JANE
E.
BRODY
13. SCREENING FOR EARLY DISEASE
PELVIC EXAMINATION
• CURRENTLY
A
TRADITION
FOR
ALL
WOMEN
…
EVEN
WITHOUT
SYMPTOMS
• FOR
SYMPTOMATIC
WOMEN
– INDICATED
– OFTEN
NOT
DONE
14. SCREENING FOR EARLY DISEASE
OVARIAN CANCER
• SYMPTOMS
– BLOATING
– CHANGE
OF
BOWEL
HABITS
– CLOTHES
DO
NOT
FIT
– INDIGESTION
• SIGNS
– ABDOMINAL
SWELLING
– LOSS
OF
WEIGHT,
INITIALLY
– NAUSEA
OR
VOMITING
• ALL
OF
THE
ABOVE
ARE
SIGNS
AND
SYMPTOMS
OF
ADVANCED
DISEASE
15. SCREENING FOR EARLY DISEASE
OVARIAN CANCER
• TESTING
CURRENTLY
AVAILABLE
– IMAGING
• U/S
• CT
• MRI
• PET
• RADIONUCLEOTIDE
TAGGING
– BLOOD
TESTS
• TUMOR
MARKERS
– CA125
– OVA
CHECK
– OVA
1
– H4
– GENETIC
TESTS
• LIMITED
APPLICABILITY
• LIMITLESS
POSSIBILITIES
NOT
PROVED
EFFECTIVE
IN
SCREENING
16. SCREENING FOR EARLY DISEASE
OVARIAN CANCER
• COMBINE
TESTS
– IMAGING
• U/S
– BLOOD
TESTS
• TUMOR
MARKERS
– CA125
– OVA
CHECK
– OVA
1
– H4
• DEFINE
AND
TEST
HIGH
RISK
POPULATIONS
17. SCREENING FOR EARLY DISEASE
ULTRASOUND +/- CA125
• GOALS
OF
SCREENING–
– ACHIEVE
EARLIER
DIAGNOSIS
– DECREASE
MORTALITY
18. SCREENING FOR EARLY DISEASE
ULTRASOUND +/- CA125
• USA
(BUYS
et.
al.
–
JAMA
2011;
305-‐2295)
– Prostate,
Lung,
Colon,
Ovary
(PLCO)
TRIAL-‐
2011
• ANNUAL
SCREENING
– FOUR
YEARS
TRANS
VAGINAL
ULTRASOUND
– SIX
YEARS
CA125
TESTING
• NO
CHANGE
IN
STAGE
OR
MORTALITY
• UK
(MENON
et.
al.-‐EVID
BASED
MED
2012:17:47-‐48)
– PLCO
ANALYSIS
• RR
FOR
SCREENED
RELATIVE
TO
CONTROL
WAS
1.18
• 1080/68,557
(~2%)
HAD
SURGERY
FOR
FALSE
POSTIVE
FINDINGS
– 15%
OF
THESE
WOMEN
HAD
SERIOUS
COMPLICATIONS
– UNDERTAKING
MODIFICATIONS
OF
STUDY
• RESULTS
DUE
2015
• JAPAN
(KOBAYASHI
et.
al.-‐INT
J
GYNECOL
CANCER,
2008,MAY-‐JUN;
18
(3):414-‐20.)
– 41,688
SCREENED
WITH
ANNUAL
U/S
+
CA125
=
27
CANCERS
%
STAGE
I
LARGER
(P
>
0.05)
– 40,779
CONTROLS
=
31
CANCERS
– MORTALITY
NOT
DISCLOSED
19. SCREENING FOR EARLY DISEASE
BLOOD MARKER TESTS
• CA125
– TUMOR
ASSOCIATED
ANTIGEN
– LEVELS
OF
SIGNIFICANCE
• ?
BASE-‐LINE
• ?
CHNAGES
IN
LEVEL
– POSITIVITY
• 90
%
OF
WOMEN
WITH
OVARIAN
CANCER
• ONLY
50%
OF
WOMEN
WITH
STAGE
I
DISEASE
• FALSE
POSITIVES
– FIBROIDS,
ENDOMETRIOSIS
– OTHER
CANCERS
– BEST
USE
IS
MONITORING
TREAMENT
PROGRESS
• HE-‐4
– HUMAN
EPIDYDIMIS
4
–
A
GENE
WHICH
MAKES
A
PROTEIN
HE-‐4
– USED
WITH
WOMEN
WITH
NORMAL
CA125
– ELEVATED
WITH
BENIGN
PROCESSES
AND
OTHER
CANCERS
• OVA1
– FIVE
PROTEIN
SIGNATURE
IN
BLOOD
– FOR
PRE-‐OPERATIVE
ASSESSMENT
OF
PELVIC
MASS
20. SCREENING FOR EARLY DISEASE
BLOOD MARKER TESTS
• CA125
• HE-‐4
• OVA1
• OVACHECK
-‐
WITHDRAWN,
RESULTS
NOT
REPRODUCIBLE
21. • COMBINE
TESTS
– IMAGING
• U/S
• CT
• MRI
• PET
• RADIONUCLEOTIDE
TAGGING
– BLOOD
TESTS
• TUMOR
MARKERS
– CA125
– OVA
CHECK
– OVA
1
– H4
– GENETIC
TESTS
• LIMITED
APPLICABILITY
• LIMITLESS
POSSIBILITIES
SCREENING FOR EARLY DISEASE
OVARIAN CANCER
24. ALL CANCER IS GENETIC,
BUT NOT ALL CANCER IS HEREDITARY
SPORADIC
HEREDITARY
FAMILIAL?
SPORADIC
HEREDITARY
FAMILIAL?
25. ALL CANCER IS GENETIC,
BUT NOT ALL CANCER IS HEREDITARY
SPORADIC
HEREDITARY
FAMILIAL?
SPORADIC
HEREDITARY
FAMILIAL?
26.
27. SCREENING FOR EARLY DISEASE
OVARIAN CANCER?????
• PAP
TEST
– UNIVERSALLY
DONE
– ?
OTHER
MATERIAL
THERE
• DNA
FROM
UPPER
TRACT
– UTERUS
– OVARY/FALLOPIAN
TUBE
– CELOEMIC
CAVITY
– APPLICABILITY
– LIMITS
– POSSIBILITIES
28. SCREENING FOR EARLY DISEASE
PAP SMEAR!
• APPLICABILITY
– ANY
WOMAN,
ANY
AGE,
MULTIPLE
DISEASES
– MUST
HAVE
• UTERUS
AND
CERVIX
PRESENT
• FALLOPIAN
TUBES
PRESENT
• CANAL
PATENT
• LIMITS
– SENSITIVITY
– SPECIFICITY
– AGE
– ANATOMIC
BARRIERS
• POSSIBILITIES
– LIMITLESS
29. SCREENING FOR EARLY DISEASE
OVARIAN AND UTERINE CANCER
• LOOKED
AT
PATIENTS
WITH
UTERINE
AND
OVARIAN
CANCER
– RECOGNIZED
A
PANEL
OF
GENES
THAT
ARE
COMMONLY
MUTATED
IN
ENDOMETRIAL
AND
OVARIAN
CANCERS
• CONFIRMED
BY
TESTING
TISSUE
FROM
24
ENDOMETRIAL
CANCERS
AND
22
OVARIAN
CANCERS
• EXAMINED
DNA
FROM
LIQUID
PAP
SMEAR
SPECIMENS
– IDENTIFIED
TUMOR
PROTEIN
IN
100%
(24
OF
24)
PATIENTS
WITH
ENDOMETRIAL
CANCER
– IDENTIFIED
TUMOR
PROTIEN
IN
41%
(9
OF
20)
PATIENTS
WITH
OVARIAN
CANCER
KINDE
et
al.
SCIENCE
TRANSLATIONAL
MEDICINE.
5:
JAN
9,
2013;
167
30. SCREENING FOR EARLY DISEASE
COLON CANCER AND POLYPS
• COLOGARD
• STUDIED
DNA
IN
STOOL
SPECIMENS
– +
IN
92%
OF
PATIENTS
WITH
COLON
CANCER
– +
IN
42%
PRECANCEROUS
POLYPS
– FALSE
+
13%
• Epi
proColon
– BLOOD
TEST
FOR
GENETIC
VARIANT
– DETECTED
71%
OF
CANCERS
(NOT
FOR
POLYPS)
– 19%
FALSE
POSITIVES
• HEMOCCULT
(BLOOD
IN
STOOL)
– DETECTS
~80
CANCERS
– DETECTS
20-‐40%
POLYPS
– COSTS
$25
• COLONOSCOPY
STILL
THE
GOLD
STANDARD
– ONLY
50%
OF
PEOPLE
OVER
50
YEARS
OF
AGE
ARE
SCREENED
KINDE
et
al.
SCIENCE
TRANSITIONAL
MEDICINE.
5:
JAN
9,
2013,
167.
32. PREVENTION
OVARIAN CANCER
• PREVENT
GENE
MUTATIONS
• MEDICATIONS
TO
BLOCK
CANCER
FORMATION
• SURGICAL
PROCEDURES
TO
LOWER
CANCER
RISK
• IDENTIFY
HEREDITY
FACTOR
33. PREVENTION
OVARIAN CANCER
• PREVENT
GENE
MUTATIONS
– ENVIRONMENT-‐
WHERE
YOU
LIVE
– CHEMICALS
–
TO
WHAT
YOU
ARE
EXPOSED
– VIRUSES
–
EXPOSURE
TO
INFECTIOUS
AGENTS
– LIFESTYLE
–
SMOKING,
EATING,
CLOTHING
34. PREVENTION
OVARIAN CANCER
• PREVENT
GENE
MUTATIONS
– ENVIRONMENT-‐
LIVE
IN
SCANDANAVIA
(USE
SUNBLOCK!)
– CHEMICALS
–
LIVE
FAR
FROM
URBAN
AREAS
(UP
WIND)
– VIRUSES
–
GET
VACCINATED/BE
A
HERMIT
(FOREGO
FAMILY)
– LIFESTYLE
–
HOPE
FOR
BETTER
THINGS?
?
35. SIMILARITIES
IN
GENETICS
OF
MULTIPLE
CANCERS
• BREAST
CANCER
• COLON
CANCER
• ENDOMETRIAL
CANCER
• OVARIAN
CANCER
• ACUTE
MYELOID
LEUKEMIA
• LUNG
CANCER
NEW
YORK
TIMES,
THURSDAY,
MAY
1,
2013
36. SIMILARITIES
IN
GENETICS
OF
MULTIPLE
CANCERS
• ABILITY
TO
STRATIFY
FOR
RISK
• ENDOMETRIAL
CANCER
• ACUTE
MYELOID
LEUKEMIA
• SUSCEPTIBILITY
TO
DRUGS
USED
FOR
OTHER
CANCERS
• LUNG
CANCER
NEW
YORK
TIMES,
THURSDAY,
MAY
1,
2013
37. SIMILARITIES
IN
GENETICS
OF
MULTIPLE
CANCERS
NEW
YORK
TIMES,
THURSDAY,
MAY
1,
2013
LUNG
CANCER
ENDOMETRIA
L
CANCER
OVARIAN
CANCER
COLON
CANCER
ACUTE
MYEOLID
LEUKEMIA
BREAST
CANCER
38.
39.
40. GENETIC
STUDIES
AND
CORRELATIONS
• CANCER
DETECTION
• CANCER
TREATMENT
• CANCER
PREVENTION
41. • FACTORS
MODIFYING
MUTATION
BEHAVIOR
– MEDICATIONS
• HORMONE
RECEPTOR
BLOCKING
–
TAMOXIFEN
• HORMONAL
MODIFICATION
OF
PRECUSORS
–
PROGESTERONE
• PREVENTION
OF
PHYSICAL
INJURY
–
ORAL
CONTRACEPTIVES
• SUPPLEMENT
DEFICIENCIES
CAUSED
BY
GENETIC
MALFUNCTION
-‐
VITAMIN
C
– SURGICAL
PROCEDURES
• REMOVE
TARGET
ORGAN
• REMOVE
ORGAN
INCITING
OR
PROMOTING
EFFECTS
OF
GENETIC
MALFUNCTION
PREVENTION
OVARIAN CANCER
43. HEREDITARY SYNDROMES
…IN WOMEN?
• BREAST OVARIAN CANCERS (BrCa 1 or 2)
– BREAST
– OVARIAN
– BOTH
• HEREDITARY NON-POLYPOSIS COLON CANCER
SYNDROME (HNPCC or LYNCH II)
• LI FRAUMENI
• RETINOBLASTOMA
44. MECHANISM OF ACTION
LOSS OF HETEROZYGOSITY ON CHROMOSOME 17
SUPPRESSOR
ACTION
BRCA1
MUTATION
BRCA1
MUTATION
NORMAL
BRCA1
NEW
MUTATION
TIME
MUTATION
EVENT
N Y N N
47. BREAST CANCER – 40-80%
MALE BREAST CANCER – 6%
OVARIAN CANCER – 15-25%
INCREASED RISK OF PROSTATE,
PANCREATIC, GALLBLADDER/BILE DUCT,
GASTRIC, HEAD AND NECK CANCERS
AND MELANOMA
BRCA2-ASSOCIATED
CANCERS:
LIFETIME RISKS
49. FOUNDER EFFECT
A HIGH FREQUENCY OF A SPECIFIC GENE MUTATION IN A
POPULATION FOUNDED BY A SMALL ANCESTRAL GROUP
ORIGINAL
POPULATION
MARKED
POPULATION
DECREASE,
MIGRATION, OR
ISOLATION
GENERATIONS
LATER
52. RISK REDUCTION BSO
• CAN BE DELAYED TO ALLOW COMPLETION OF CHILDBEARING
• LAPAROSCOPIC APPROACH MINIMIZES HOSPITAL STAY/RECOVERY
• ?ROLE OF HRT
• DECREASES OVARIAN/FALLOPIAN TUBE CANCERS AND MAY PROTECT
AGAINST BREAST CANCER
53. PROACTIVE CANCER MANAGEMENT
REDUCES THE RISKS
(BRCA1/2 Patients)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
BREAST CANCER OVARIAN CANCER
TAMOXIFEN
MASTECTOMY
OOPHORECTOMY
ORAL
CONTRACEPTIVES
54. ALL CANCER IS GENETIC,
BUT NOT ALL CANCER IS HEREDITARY
SPORADIC
HEREDITARY
FAMILIAL?
SPORADIC
HEREDITARY
FAMILIAL?
55. MEDICAL ONCOLOGY
CENTRAL REGIS
RISK REDUCTION BSO
• CAN BE DELAYED TO ALLOW COMPLETION OF CHILDBEARING
• LAPAROSCOPIC APPROACH MINIMIZES HOSPITAL STAY/RECOVERY
• ?ROLE OF HRT
• DECREASES OVARIAN/FALLOPIAN TUBE CANCERS AND MAY
PROTECT AGAINST BREAST CANCER
57. WORLD HEALTH ORGANIZATION
1968
1. The
condi,on
should
be
an
important
health
problem.
2. There
should
be
a
treatment
for
the
condi,on.
3. Facili,es
for
diagnosis
and
treatment
should
be
available.
4. There
should
be
a
latent
stage
of
the
disease.
5. There
should
be
a
test
or
examina,on
for
the
condi,on.
6. The
test
should
be
acceptable
to
the
popula,on.
7. The
natural
history
of
the
disease
should
be
adequately
understood.
8. There
should
be
an
agreed
policy
on
whom
to
treat.
9. The
total
cost
of
finding
a
case
should
be
economically
balanced
in
rela,on
to
medical
expenditure
as
a
whole.
10. Case-‐finding
should
be
a
con,nuous
process,
not
just
a
"once
and
for
all"
project.
