OVARIAN CANCER
SCREENING:
Edward J. Pavlik
University of Kentucky
Ovarian Cancer
Screening Research
Program
July 26, 2011
CANCER SCREENING:
Definitions

Cancer Screening: The act of testing for a
condition in a population that is presumed to
be asymptomatic when detection will result in
the possibility of cure or extending life.
Predicting disease is present before it is evident.

Cancer Diagnostic Workup: The act(s) of
testing when clinical evidence or symptoms
indicate that a condition is present and
cancer must be ruled out as an explanation
for this condition.
Perspectives --- Ovarian Screening
1. What are current perceptions about screening?
2. Why screen for ovarian cancer?
3. How good is transvaginal ultrasound screening?
4. What do women want?
5. What about costs?
Perceptions --- Screening
What are current perceptions about screening?
What do we mean by “perceptions?”
Perspectives --- Ovarian Screening
What are current perceptions about ovarian
screening?
My doctor does it
The PAP test does it
I don’t need it
I don’t want to talk about it
It doesn’t work
My insurance doesn’t pay for it
My doctor didn’t tell me about it
The Holy Grail: distinguishing
benign from malignant ovarian
tumors with precision high enough
and cost low enough to please
everyone: the Kentucky ovarian
cancer screening experience with
37,200+ women and 230,000+
screens.
Perspectives --- Ovarian Screening
Why screen for ovarian cancer?
UK Ovarian Screening Program
Ovarian Screening Video
Perspectives --- Ovarian Screening
How good is transvaginal ultrasound screening?
#3. TVS vs Pelvic Exam
Detection
TVS
PE
N=
Overall
85%
44% 289
> 55 yrs
74%
30% 88
> 200 lbs
73%
9%
> 200 gram ut
80%
16% 74
66
TVS is significantly more accurate (p< 0.001)
Ueland, DePriest, DeSimone, Pavlik, Lele, Kryscio, van Nagell JR Jr.
The accuracy of examination under anesthesia and transvaginal sonography in evaluating ovarian size.
Gynecol Oncol. 2005 Nov;99(2):400-3.
#4. Performance: TVS vs Mammography
Mammography
Mammography
US
MRI
Sensitivity 86.4%
27.6 - 89%
27.6, 35.3, 36.1,
54.1 %
71 - 91%
Specificity 98.8%
90.2 - 99.4%
94, 96.2, 99.4
86 - 91%
PPV
14.524.2%
13%
NA
21 - 33%
NPV
99.97% NA
NA
99 - 100%
N=
37293
1,029,894
969
TVS
1,234,962
TVS performs similarly to mammography & MRI
van Nagell JR Jr, DePriest PD, Ueland FR, DeSimone CP, Cooper AL, McDonald, JM, Pavlik EJ, Kryscio
RK. Ovarian Cancer Screening With Annual Transvaginal Sonography. Cancer 2007; 109: 1887-1196
Humphrey LL, Hefland M, Chan BKS, Woolf, SH. Breast Cancer Screening: A Summary of the Evidence
for the U.S. Preventive Services Task Force. Annals of Internal Med. 137: E347, 2002 (Multi-study report)
Elmore JG, Armstrong K, Lehman CD, Fletcher SW. Screening for Breast Cancer. JAMA 293: 1245,
2005
Lehman CD, Gatsonis C, Kuhl CK, Hendrick RE, Pisano ED, Hanna L, Peacock S, Smazal SF, Maki DD,
Julian TB, DePeri ER, Bluemke DA, Schnall MD. MRI Evaluation of the Contralateral Breast in Women
with Recently Diagnosed Breast Cancer. N. Engl. J. Med. 2007; 356:1295
#4. Performance: TVS vs Mammography
TVS screening results in improved survival
Perspectives --- Ovarian Screening
What do women want?
http://ovarianscreening.info
#2 What Women Want
I realize that the risk of ovarian cancer is a lot lower
than breast cancer and I:
A. Feel that ovarian cancer is still a concern or threat
to me
647 = 97%
B. Feel that my chances of getting ovarian cancer are
too low to be concerned with.
22 = 3%
When I am near or at age 50, I feel strongly that I
would:
1. Probably be undecided about ovarian cancer
screening
10 = 2%
2. NOT want to participate in ovarian cancer screening
5 = 1%
3. Might consider ovarian cancer screening 91 = 18%
4. Would definitely want to participate in ovarian
cancer screening
413 = 80%
http://ovarianscreening.info
#2 What Women Want
For what I am paying for medical insurance, my
insurance should:
1. Pay for ovarian screening no matter what the cost
488 = 70%
2. Pay up to $500 for ovarian screening
50 = 7%
3. Pay up to $250 for ovarian screening
44 = 6%
4. Pay up to $150 for ovarian screening
48 = 7%
5. Pay up to $100 for ovarian screening
25 = 4%
6. Pay up to $50 for ovarian screening
13 = 2%
7. Not pay for ovarian screening
27 = 4%
http://ovarianscreening.info
#2 What Women Want
If my medical insurance would NOT pay for ovarian cancer
screening, I consider the risk of ovarian cancer to be
sufficient to pay for screening out of my own pocket so
that I might:
1.
2.
3.
4.
5.
6.
7.
Pay for ovarian screening no matter what the cost
162 = 23%
Pay up to $500 for ovarian screening
56 = 8%
Pay up to $250 for ovarian screening
100 = 14%
Pay up to $150 for ovarian screening
131 = 19%
Pay up to $100 for ovarian screening
122 = 18%
Pay up to $50 for ovarian screening
110 = 16%
I do not consider the risk of ovarian cancer to be worth paying for
screening myself or would never pay for anything that my medical
insurance would not pay for.
12 = 2%
Perspectives --- Ovarian Screening
What about costs?
#5. Cost & Number of Recovered Screens
Stage
IIIC
$-Collections
(All)
SR/IIIC
case
$- Collections
(Chemotherapy)
SR
N=
25*
Mean +
SEM
$92100 + 10280
3684
$14675 + 1903
587
Median
$80200
3208
$13102
524
Highest
$239600
9584
$40838
1634
25
SR: “Screens Recovered” at $25**/screen
Over 2000 screens can be paid for by preventing a single
IIIc cancer and over 500 screens by chemotherapy alone!
* Current Women’s Health Reviews 5, 44-50 (2009)
**Pavlik EJ, van Nagell JR Jr, DePriest PD, Wheeler L, Tatman JM, Boone M, Sollars S, Rayens MK, Kryscio
RK. Participation in transvaginal ovarian cancer screening: compliance, correlation factors, and costs.
Gynecol Oncol. 1995 Jun;57(3):395-400
#5. Costs & Screens
Stage IIIC $-Collections
[A]
Per case
IIIC Expense
[B] = 68 x [A]
Screen
Equivalents
[C] = [B]/$25
N=
25
$25/screen
Mean +
SEM
$92100 + 10280
$6,262,800
250,512 screens
Median
$80200
$5,453,600
218,144 screens
Highest
$239600
$16,292,800
651,712 screens
ASSUMPTION: IIIC expense is if all 68 detected
malignancies progressed to IIIC.
Cases that can be stopped from progressing
to a IIIC expense can pay for a large
number of TVS screens.
Cost of Chemotherapy & Screening
Chemotherapy
Total Cost
Per case
Screen Equivalents @ $25
(x 51 cancers detected)
$9659
386 (19704)
$11644
466 (23754)
$8730
349 (17809)
$699
28 (1426)
$141345
5654 (288344)
$8345
334 (1702)
$19989
800 (40778)
1
Carboplatin AUC 6 or 515 mg
($4511.40)
+ Paclitaxel 135 mg/m2 ($5148.00)
2
Taxotere 75 mg/m2]
3
Doxil 40 mg/m2
4
Cytoxan 50 mg po qd
5
Cytoxan 50 mg po qd ($699.10) +
Avastin 15 mg/kg ($140646.00)
6
Gemzar 800 mg/m2
7
Gemzar 800 mg/m2 ($8344.80) +
Taxotere 75 mg/m2 ($11643.75)
8
Cisplatin 50 mg/m2
$1868
75 (3811)
9
Cisplatin 50 mg/m2 ($1867.50)
+ Paclitaxel 135 mg/m2 ($4290.00)
$6158
246 (12562)
10
Intraperitoneal:
Paclitaxel 135 mg/m2 ($5148.00) +
Cisplatin 100 mg/m2 ($4482.00) +
Paclitaxel 60 mg/m2 ($2376.00)
$12006
480 (24492)
11
Topotecan 1.0 mg.m2
$9788
392 (19968)
#5. Costs & Relativity
$25/screen is within the Co-Pay
#5. Costs & Relativity
$25/screen is less than Styling
Summary of Perspectives
1. Women want ovarian screening
2. TVS outperforms manual PE
3. TVS performs as well as mammography
4. TVS ovarian screening has reasonable cost
Ovarian Cancer






2011: 21,990 new cases/yr;
2011: 15,460 deaths
Fifth leading cause of cancer death among
women
Leading cause of death among gynecologic
malignancies
5 yr survival: Stage I - ~ 90%
Stage III/IV - 20%
Prevalence- 50/100,00 in women > 50 yrs.
75% cases diagnosed with advanced disease
Delay in Diagnosis

Retrospective review of 277 pts.
 On average patients sought medical attention
9 months after onset of symptoms
 On average patients received pelvic exam 9
months after seeking medical attention
 Gilda Radner, Ella Grasso, Madeline Kahn,
Liz Tilberis, Cassandra Hanis-Brosnan,
Coretta Scott King, Patsy Ramsey, Loretta
Young, Dinah Shore, Jessica Tandy, Lauro
Nyro, Joan Hackett, Dixie Lee, Rosalind
Franklin (discoverer of DNA), Sandy Dennis;
Bess Myerson & Carol Channing are
survivors
Sackett, et. al., Clinical Epid., Boston: Little, Brown & Co., 1985
http://en.wikipedia.org/wiki/Ovarian_cancer#Notable_victims_of_ovarian_cancer
http://www.wect.com/Global/story.asp?S=5466000
Transvaginal Sonography (TVS)
Transvaginal Sonography (TVS)
Faces With A Future
Symptoms & Tests
Out of 100 women with symptoms, only 1
will have OvCa.
Symptoms occur in women without OvCa
60-1500 times more than the incidence of
OvCa.
OVA1 is an FDA-cleared blood test that
uses results of 5 biomarkers, with an
algorithm to indicate the probability of
malignancy of an ovarian mass. It is not a
screening or stand alone test.
Transvaginal Sonography (TVS)
Echos not degraded in air-space @
ovary
 Easy to perform
 Well-accepted
 Relatively cost-effective (~$25/screen)
 Acceptable sensitivity

Unresolved Issues
Who should be screened? (Who
decides?)
 What is the optimal screening interval?
 What is the optimal screening
algorithm?
 How should the screening be done?

Disease Prevention Is Related To Education
“The one social factor that researchers agree
is consistently linked to longer lives in every
country where it has been studied is education.
It is more is more important than race; it
obliterates any effects of income.”
And, health economists say, those factors that
are popularly believed to be crucial — money
and health insurance, for example, pale in
comparison.
http://www.nytimes.com/ref/health/newage_index.html
http://ovarianscreening.info
Finding More Information
Googled 07/21/2011
Women's Health Care - Ovarian Cancer Screening - UK HealthCare
ukhealthcare.uky.edu/WomensHealth/ovariancancer.asp
Feb 4, 2010 – Early detection is vital to surviving ovarian cancer. The UK Markey Cancer Center Ovarian
Screening Program was started in 1987 and provides ...
►
Ovarian Screening Program
ovarianscreening.info/
Apr 4, 2011 – Free ovarian cancer screening for women is performed using transvaginal ultrasound as a
protocol to reduce mortality due to ovariancancer.
Ovarian Screening Program
ovarianscreening.info/Faceswithafuture.htm
Apr 4, 2011 – Ovarian Cancer. Screening Program. Ovarian Cancer ...
Ovarian Screening Memorials - Ovarian Screening Program
ovarianscreening.info/Memorials.html
Apr 4, 2011 – The Monroe County Extension Homemakers have initiated ...
Show more results from ovarianscreening.info
Ovarian cancer screening : Cancer Research UK : CancerHelp UK
cancerhelp.cancerresearchuk.org/.../ovarian.../ovari... - United Kingdom
Nov 1, 2010 – Over the next 5 years the researchers in the study will look at whether an ovarian screening
programme using these tests could help to...
CANCER SCREENING:
Science
First:
Global Thoughts on
Cancer Screening in general
Edward J. Pavlik, Director
University of Kentucky
Ovarian Cancer Screening Research Program
July 26, 2011
CANCER SCREENING:
Definitions

Cancer Screening: The act of testing for a
condition in a population that is presumed to
be asymptomatic when detection will result in
the possibility of cure or extending life.
Predicting disease is present before it is evident.

Cancer Diagnostic Workup: The act(s) of
testing when clinical evidence or symptoms
indicate that a condition is present and
cancer must be ruled out as an explanation
for this condition.
Perception vs Preconception:
What Is Reality?
Do you stop?
Do you slow down?
Do you speed up to get
through before it turns
red?
Perception vs Preconception:
What Is Reality?
Colorado Law
STEADY YELLOW
LIGHT: A red light is about
to appear.
Stop unless you are already
within the intersection.
Ohio Law
STEADY YELLOW LIGHT:
clearance of vehicle within
intersection.
Indiana Law
STEADY YELLOW LIGHT:
means that the right-of-way is
ending.
Kentucky Law
STEADY YELLOW LIGHT
means stop if you can do so safely.
A vehicle may
clear an intersection on a red
light, if the vehicle entered the
intersection while the signal was
yellow; but it is against the law to
enter an intersection after the light
turns red.
Perspective
What Is Reality?
Is the glass half empty?
Is the glass half full?
What other quantitative
relationship applies?
Perspective
What Is Reality?
Are too few medical services
provided in the USA?
Could more medical services be
provided?
Are the number of medical
services that could be provided
too great for payer resources in
the USA?
Screening = a medical service
Perspective What Is Reality?
What quantitative
relationship applies?
Is this a full cup?
Is this a full half cup?
Is this a way of adjusting
services (contents) to
perception? (i.e. a consumer
can get all the services a
medical plan provides by
restricting the plan)
Perspective What Is Reality?
Types of Service Plan
Restrictions:
1. Age eligibility
2. Pre-existing conditions
3. PSA & consequences
4. Breast screening (40-50)
Ways of adjusting services
Perspective What Is Reality?
It ALL has to work!
Sometimes half isn’t good enough!
CANCER SCREENING:
Definitions

Cancer Screening: The act of testing for a
condition in a population that is presumed to
be asymptomatic when detection will result in
the possibility of cure or extending life.
Predicting disease is present before it is evident.

Cancer Diagnostic Workup: The act(s) of
testing when clinical evidence or symptoms
indicate that a condition is present and
cancer must be ruled out as an explanation
for this condition.
CANCER SCREENING:
Applications & Controversy
Ways of thinking about screening
Ask the assay
Find the cancer
CANCER SCREENING:
Application
DO YOU KNOW
WHO THIS IS?
CANCER SCREENING:
Application
DO YOU KNOW
WHO THIS IS?
CANCER SCREENING:
Visual Bias / Context
CANCER SCREENING:
Science
Visual Bias / Selective Attention ---1
Task Orientation & Awareness:
The Elephant In The Room
CANCER SCREENING:
Visual Bias / Selective Attention ---1
Did you see Carmen Sandiego?
CANCER SCREENING:
Science
Visual Bias / Selective Attention ---2
Task Orientation & Awareness:
Multiple Events
CANCER SCREENING:
Science
Visual Bias / Selective Attention ---3
Task Orientation & Awareness:
Tracking Multiples
CANCER SCREENING:
Science
Four Questions That Must Be Answered
1. How good is the test when disease is there?
Ability to identify true disease = Sensitivity
Sensitivity = TP/(TP+FN)
2. How good is the test when disease is not
there?
Ability to identify the absence of disease
= Specificity = TN/(TN+FP)
CANCER SCREENING:
Science
Four Questions That Must Be Answered
3. How many of those that are positive really have
the disease?
% of positive subjects who have disease =
Positive Predictive Value = TP/(TP+FP)
4. How many of those that are negative really do
not have the disease?
% of negative subjects who do not have the
disease =
Negative Predictive Value = TN/(TN+FN)
CANCER SCREENING:
Screened Population Features
1. Disease has a high enough
Prevalence to justify screening
2. Medical care available if
screening test is positive
3. Patient is willing & able to
undergo further evaluation
CANCER SCREENING:
Role of Education
What do you have to be able to do?
CANCER SCREENING:
Role of Education
What do you have to be able to do?