Screening (Scanning) for

Ovarian Cancer
Hennie Botha
2010

Mortality: Incidence ratio

Ovary

0.67

Uterine corpus

0.18

Cervix

0.39

UK Office of national statistics, 2001

Rationale for Screening

Most

deadly gynaecological cancer

Most common after menopause
Advanced disease at diagnosis

Malignant Tumours
Epithelial

tumours
Stromal tumours
Germ cell tumours
Metastatic tumours

metastatic

germ cell
epithelial
stromal

Clinical Features
Ovarian Carcinoma
Vague

symptoms
Abdominal discomfort, distention
Pain and nausea
Anorexia

Prognostic Factors
factors: stage at diagnosis,
residual disease after surgery, volume of
ascites, age, performance status
Histological type, differentiation, extent of
anaplastic change
Genetic factors, ploidy
Clinical

WHO Criteria
Screening Program
Important

health problem
Natural history understood
Recognisable early or latent phase
Treatment available
Suitable test
Facilities for diagnosis and treatment

Ideal for Screening?

No

premalignant precursor
Relatively rare disease
Test?
Survival?
Cost effective?

Sensitivity and Specificity

Sensitivity

- proportion of cancers
detected by a positive test
Specificity - proportion of those without
cancer identified by a negative test
Usually sensitivity will specificity

Challenge of OC Screening
High sensitivity

Detect preclinical or early disease

Early intervention improve outcome
Lead time of marker

Challenge of OC Screening
High specificity

If test positive - surgery

Minimum specificity of 99.6% to achieve
PPV of 10%
Even 98% specificity 50 operations for
one case detected

Screening Strategies
Clinical

examination
Biochemical markers
Morphological markers
Vascular markers
Combining tests

Clinical Examination
Palpable

ovary syndrome
Baber and Garber

Sensitivity

of pelvic examination for

detection of OC is unknown
150 pts EUA - ovaries were detected
clinically in <30% of women 55 years
Ueland, 2005

Biochemical Markers
CA 125
Coelomic

(peritoneum, pleura) and

Mullerian (tube, endom, endoCx)
epithelium
30-35 U/ml
Raised 50% stage I
Raised >90% cases of advanced disease
Lead time 1.5 1.9 years
Bast 1983

Biochemical Markers
CA 125
Benign
TB
Cirrhosis
Endometriosis
Fibroids
Pneumonia
PID
Pregnancy

Malignant
Pancreas
Lung
Breast
Endometrium

Biochemical Markers
CA 125

N = 751

Final diagnosis in women with raised Ca 125 in clinical practice

Moss 2005

Biochemical Markers
CA72-4

or TAG 72
M-CSF, OVX1, LPA
Prostasin, Osteopontin
Inhibin
Kallikrein
SMO 47

Morphological Markers
Ultrasound
Benign
Malignant

<5 cm
Unilateral
Smooth capsule
Mobile
Thin walled, cystic
Unilocular
No projections
No ascites

>5 cm
Bilateral
Irregular
Fixed
Solid, thick walled
Multilocular
Papillary projections
Ascites

Morphological Markers
Ultrasound
Ovarian

Tumour Analysis (IOTA) group

guidelines in 2000
Standardise terminology
Describe morphology and ovarian
volume

IOTA Morphologic features

Septum

Complete or incomplete
Papillary

projections
Cystic vs. solid
Other features

tumour wall
evidence of metastases
presence of ascites
bilateral lesions

Complete septum
Tissue strand running across cyst cavity
Measurement

Diameter of thickest septum where it appears

at its widest

Ultrasound beam direction

Incomplete septum
Tissue strand running across cyst cavity from
one internal surface to the contra-lateral side
but not complete in some scanning planes
Seen in hydrosalpinges

Solid
High echogenicity - presence of tissue
(myometrium, ovarian stroma, myomas)
Solid mass vs clot

Push transducer gently towards the structure

-internal movement
Colour doppler is diagnostic for solid tissue
The absence of flow is not diagnostic

Cystic mass
Anechoic

(black)
Low level echogenic (mucinous tumor
appears similar to amniotic fluid)
Ground glass (homogenously
dispersed echogenic cystic contents as
in endometriotic cysts)
Hemorrhagic (with internal thread-like
structures representing fibrin strands)

Cystic masses

Papillary projections
Any

solid projections into cyst cavity from

cyst wall with height of >3mm

Internal wall
Smooth

or irregular
External wall of the cyst not taken into
account

Inner wall

Ascites or free fluid in POD

Measurement of the lesion

Size

of both ovaries and the lesion(s)

measured - largest 3 diameters in 2
perpendicular planes

IOTA: Morphological
classification
Unilocular cyst
Unilocular solid cyst
Multilocular cyst
Multilocular solid cyst
Solid tumor
Not classifiable poor visualization due to
acoustic shadowing

IOTA (N=300)
Numbe
r

Ca

% Ca

Unilocular cyst

86

Unilocular solid

34

16

47

Multilocular cyst

60

1.7

Multilocular
solid

70

35

50

Solid tumor

50

31

60

Tumor type

Vascular Markers
Neovascularization
Less

smooth muscle - less resistance to

flow
Color-flow Doppler - lower PI
Not better than morphological
evaluation

Combining Tests
Multimodal

screening

Sequential CA125 and TVS - spec 99.9%,

PPV 26.8% (4 operations / case OC)

ROC algorithm age and serial CA125 profile
Jacobs 1993, 1996

UK Collaborative Trial of Ovarian

Cancer Screening (UKCTOCS)
Randomised

to three groups 2:1:1

Half (n = 101 359) no intervention
Rest two screening strategies
One group (n = 50 640) annual CA 125
followed by TVU if abnormal - multimodal
screening (MMS) group
Another group (n = 50 639) annual TVU

UKCTOCS
Significantly

specificity MMS vs TVU

>40% cancers diagnosed Stage 1
Morbidity cost (nr ops/ case cancer)

35 TVU
3 MMS group
?

Screening will change mortality still

needs further study

Conclusion
Accurate

morphological description
Refrain from histological diagnosis
(except perhaps dermoid tumours)
Communicate with clinician

Great idea,
requires some
refinement