The Prostate, Lung, The Prostate, Lung, Colorectal and Colorectal and Ovarian Cancer Ovarian Cancer Screening TrialScreening Trial

Fifth Annual Fifth Annual African-American African-American

Prostate Cancer Disparity Prostate Cancer Disparity SummitSummit

September 24, 2009September 24, 2009

Christine D. Berg, M.D.Christine D. Berg, M.D.Project Officer, PLCOProject Officer, PLCO

Chief, Early Detection Research Chief, Early Detection Research GroupGroup

Division of Cancer PreventionDivision of Cancer Prevention

PLCO Trial: Study PLCO Trial: Study DesignDesign Screening Centers: 10Screening Centers: 10

Participants: 154,935Participants: 154,935 Gender: 50:50Gender: 50:50 Age: 55-74 yearsAge: 55-74 years Recruitment: 1993-2001Recruitment: 1993-2001 Screening: 1993-2006Screening: 1993-2006

PProstate – Annual DRE x 4 and PSA x 6rostate – Annual DRE x 4 and PSA x 6 Follow-up for 14 years (T0 – T13)Follow-up for 14 years (T0 – T13)

Annual surveys: activeAnnual surveys: active Monitoring and QA: activeMonitoring and QA: active Mortality searches: active and NDI, passiveMortality searches: active and NDI, passive Annual interim analysisAnnual interim analysis

PLCO Screening CentersPLCO Screening Centers

PLCO: Selected PLCO: Selected CharacteristicsCharacteristics

0

5

10

15

20

25

30

35

55-59 60-64 65-69 70-74

Screening Control

RaceRace ScreeniScreeningng

ControControll

WhiteWhite 86.286.2 83.883.8

BlackBlack 4.54.5 4.34.3

HispaHispanicnic

2.12.1 2.12.1

AsianAsian 4.04.0 3.93.9

OtherOther 0.80.8 0.90.9

MissinMissingg

2.42.4 5.05.0

Prostate Cancer DetectedProstate Cancer Detectedby 10 years by 10 years

Clinical StageClinical Stage ScreeningScreening ControlControl

II 18 (0.5)18 (0.5) 15 (0.5)15 (0.5)

IIII 3297 (95.5)3297 (95.5) 2790 (93.8)2790 (93.8)

IIIIII 49 (1.4)49 (1.4) 56 (1.9)56 (1.9)

IVIV 73 (2.1)73 (2.1) 79 (2.7)79 (2.7)

UnknownUnknown 15 (0.4)15 (0.4) 34 (1.1)34 (1.1)

Comparison of Gleason Comparison of Gleason ScoresScores

Gleason scoreGleason score

on biopsyon biopsy ScreeningScreening

ControlControl

2 - 42 - 4 222 (6.4)222 (6.4) 137 (4.6)137 (4.6)

5 -65 -6 2047 2047 (59.3)(59.3)

1656 1656 (55.7)(55.7)

77 815 815 (23.6)(23.6)

779 779 (26.2)(26.2)

8 - 108 - 10 289 (8.4)289 (8.4) 341 341 (11.5)(11.5)

Unknown Unknown

79 (2.3)79 (2.3) 61 (2.1)61 (2.1)

Compliance and Compliance and ContaminationContamination

Screening before entry (screening/control)Screening before entry (screening/control) PSA test DRE PSA test DRE

Once: 34.6/34.3 32.8/31/9 Once: 34.6/34.3 32.8/31/9 Two or more: 9.4/9.8 22.2/22.0Two or more: 9.4/9.8 22.2/22.0

ComplianceCompliance PSA 85%; DRE 86%PSA 85%; DRE 86%

Testing in the control groupTesting in the control group PSA: 40% in first year to 52% in sixth yearPSA: 40% in first year to 52% in sixth year DRE: Range from 41 to 46%DRE: Range from 41 to 46%

Andriole GL et al. N Engl J Med 2009;360:1310-1319

Number of Diagnoses of All Prostate Cancers and Number of Prostate-Cancer Deaths

PLCO Trial ResultsPLCO Trial Results Annual screening with DRE and PSA Annual screening with DRE and PSA

results in more prostate cancer compared results in more prostate cancer compared to community screening practicesto community screening practices Seven years: 2820 versus 2322 Seven years: 2820 versus 2322 Ten years: 3452 versus 2974Ten years: 3452 versus 2974

Few Prostate cancer related deaths in Few Prostate cancer related deaths in either groupeither group 50 screening and 44 controls at 7 years50 screening and 44 controls at 7 years 92 screening and 82 control at 10 years92 screening and 82 control at 10 years

Continued follow-up to be doneContinued follow-up to be done

UCLACA-125, PSA Assays

Blood Collection Blood Collection ProtocolProtocol

BiorepositoryEtiology & Early Marker Studies

Serum

T0, T1, T2, T3, T4, T52 ml

S

Serum

T0 (2), T1, T2, T4, T52 ml X 2

SS

Plasma, Buffy Coat, RBC

T0, T32 ml X 4

PP B R

Serum

T02 ml

S

Plasma, Buffy Coat, RBC

T3, T4, T5 (2) 2 ml X 4

PP B R

Whole Blood

T3 (2)2 ml X 6

W WW

W

Samples Collected Per Patient

Serum 13 vials 26 ml

Plasma 12 vials 24 ml

Buffy Coat 6 vials 14 ml

RBC 3 vials 6 ml

Whole Blood 12 vials 24 ml

Total 46 vials 92 ml

Tubes Additive Size Specimens

Red/Gray Clot Activator 6 ml Serum

Red None 10 ml Serum

GreenSodiumHeparin

10 mlPlasma, Buffycoat & RBC

Royal Blue None 7 ml Zinc-free Serum

LavenderLiquidEDTA

10 mlPlasma, BuffyCoat &RBC

Yellow ACD-A 8.5 ml Whole Blood

Specimens Available by Cancer Specimens Available by Cancer Sites and Specimen TypesSites and Specimen Types

0

10,000

20,000

30,000

40,000

50,000

60,000

70,000

80,000

Prost

ate

Breas

t

Lung

Colore

ctal

Mel

anom

a

Bladder

Non-Hodgki

n's ly

mphom

a

Endomet

rium

Leuke

mia

Kidney

Pancr

eas

Ovarie

s(Ova

rian)

Multi

ple M

yelo

ma

Liver

Mouth

Stom

ach

Brain

Thyroid

Laryn

x

Esophag

us

Nu

mb

er o

f V

ials RBC

Buffy Coat*

Plasma

Serum

Whole Blood

75,476

34,043

17,20617,084

9,4908,837

6,7235,734

4,8294,489

1,7351,900

2,1382,289

3,5073,501

1,4341,242

1,1931,086

TMAs with PLCO TumorsTMAs with PLCO Tumors

Supports multiplehistologies per spot

PLCO Trial ConclusionsPLCO Trial Conclusions

PSA not a perfect testPSA not a perfect test Low mortality rates achieved at high rate of Low mortality rates achieved at high rate of

overdiagnosisoverdiagnosis Important to have better biologic Important to have better biologic

understanding of aggressive prostate cancer understanding of aggressive prostate cancer and means of differentiating from indolent and means of differentiating from indolent diseasedisease

PLCO biospecimen repository useful PLCO biospecimen repository useful genetic and somatic risk assessmentgenetic and somatic risk assessment development and validation of early markers of development and validation of early markers of

detectiondetection

With appreciationWith appreciation

PLCO Research ColleaguesPLCO Research Colleagues PLCO Site Coordinators and StaffPLCO Site Coordinators and Staff NCI ColleaguesNCI Colleagues The trial participants without whom The trial participants without whom

these studies would not have been these studies would not have been possiblepossible