ovarian cancer screening :

OVARIAN CANCER SCREENING:

Edward J. Pavlik University of Kentucky

Ovarian Cancer Screening Research

ProgramJuly 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

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.

TVS is significantly more accurate (p< 0.001)

Detection TVS PE N =

Overall 85% 44% 289

> 55 yrs 74% 30% 88

> 200 lbs 73% 9% 66

> 200 gram ut 80% 16% 74

#4. Performance: TVS vs Mammography

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

TVS 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 14.5-24.2%

13% NA 21 - 33%

NPV 99.97% NA NA 99 - 100%

N = 37293 1,234,962 1,029,894 969

Humphrey LL, Hefland M, Chan BKS, Woolf, SH. Breast Cancer Screening: A Summary of the Evidencefor the U.S. Preventive Services Task Force. Annals of Internal Med. 137: E347, 2002 (Multi-study report)

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

Elmore JG, Armstrong K, Lehman CD, Fletcher SW. Screening for Breast Cancer. JAMA 293: 1245, 2005

TVS performs similarly to mammography & MRI

TVS screening results in improved survival

#4. Performance: TVS vs Mammography

Perspectives --- Ovarian Screening

What do women want?

#2 What Women Wanthttp://ovarianscreening.info

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%

#2 What Women Wanthttp://ovarianscreening.info

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%

#2 What Women Wanthttp://ovarianscreening.info

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. Pay for ovarian screening no matter what the cost 162 = 23%2. Pay up to $500 for ovarian screening 56 = 8% 3. Pay up to $250 for ovarian screening 100 =

14% 4. Pay up to $150 for ovarian screening 131 = 19% 5. Pay up to $100 for ovarian screening 122 = 18% 6. Pay up to $50 for ovarian screening 110 =

16% 7. 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

* 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

SR: “Screens Recovered” at $25**/screen

Stage IIIC

$-Collections(All)

SR/IIIC case

$- Collections(Chemotherapy)

SR

N = 25* 25

Mean + SEM

$92100 + 10280 3684 $14675 + 1903 587

Median $80200 3208 $13102 524

Highest $239600 9584 $40838 1634

Over 2000 screens can be paid for by preventing a single IIIc cancer and over 500 screens by chemotherapy alone!

#5. Costs & Screens

ASSUMPTION: IIIC expense is if all 68 detected malignancies progressed to IIIC.

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

Cases that can be stopped from progressing to a IIIC expense can pay for a large number of TVS screens.

Cost of Chemotherapy & ScreeningChemotherapy Total Cost

Per caseScreen Equivalents @ $25

(x 51 cancers detected)

1 Carboplatin AUC 6 or 515 mg ($4511.40) + Paclitaxel 135 mg/m2 ($5148.00)

$9659 386 (19704)

2 Taxotere 75 mg/m2] $11644 466 (23754)3 Doxil 40 mg/m2 $8730 349 (17809)4 Cytoxan 50 mg po qd $699 28 (1426)5 Cytoxan 50 mg po qd ($699.10) +

Avastin 15 mg/kg ($140646.00)$141345 5654 (288344)

6 Gemzar 800 mg/m2 $8345 334 (1702)7 Gemzar 800 mg/m2 ($8344.80) +

Taxotere 75 mg/m2 ($11643.75)$19989 800 (40778)

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., 1985http://en.wikipedia.org/wiki/Ovarian_cancer#Notable_victims_of_ovarian_cancerhttp://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

Finding More InformationGoogled 07/21/2011

http://ovarianscreening.info

Women's Health Care - Ovarian Cancer Screening - UK HealthCareukhealthcare.uky.edu/WomensHealth/ovariancancer.aspFeb 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 Programovarianscreening.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 Programovarianscreening.info/Faceswithafuture.htmApr 4, 2011 – Ovarian Cancer. Screening Program. Ovarian Cancer ...

Ovarian Screening Memorials - Ovarian Screening Programovarianscreening.info/Memorials.htmlApr 4, 2011 – The Monroe County Extension Homemakers have initiated ...

Show more results from ovarianscreening.infoOvarian cancer screening : Cancer Research UK : CancerHelp UKcancerhelp.cancerresearchuk.org/.../ovarian.../ovari... - United KingdomNov 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 LawSTEADY YELLOW LIGHT: A red light is about to appear.Stop unless you are already within the intersection. Kentucky Law

STEADY YELLOW LIGHT means stop if you can do so safely. A vehicle mayclear 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.

Ohio LawOhio LawSTEADY YELLOW LIGHT: clearance of vehicle within intersection.

Indiana LawIndiana LawSTEADY YELLOW LIGHT: means that the right-of-way is ending.

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 eligibility2. Pre-existing conditions3. PSA & consequences4. 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 = SensitivitySensitivity = 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?