1. The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial Fifth Annual African-American Prostate Cancer Disparity Summit September 24, 2009 Christine D. Berg, M.D. Project Officer, PLCO Chief, Early Detection Research Group Division of Cancer Prevention

2. PLCO Trial: Study Design Screening Centers: 10 Screening Centers: 10 Participants: 154,935 Participants: 154,935 Gender: 50:50 Gender: 50:50 Age: 55-74 years Age: 55-74 years Recruitment: 1993-2001 Recruitment: 1993-2001 Screening: 1993-2006 Screening: 1993-2006 Prostate – Annual DRE x 4 and PSA x 6 Prostate – Annual DRE x 4 and PSA x 6 Follow-up for 14 years (T0 – T13) Follow-up for 14 years (T0 – T13) Annual surveys: active Annual surveys: active Monitoring and QA: active Monitoring and QA: active Mortality searches: active and NDI, passive Mortality searches: active and NDI, passive Annual interim analysis Annual interim analysis

3. PLCO Screening Centers

4. PLCO: Selected Characteristics RaceScreeningControlWhite86.283.8 Black4.54.3 Hispanic2.12.1 Asian4.03.9 Other0.80.9 Missing2.45.0

5. Prostate Cancer Detected by 10 years Clinical Stage ScreeningControl I 18 (0.5) 18 (0.5) 15 (0.5) 15 (0.5) II II 3297 (95.5) 3297 (95.5) 2790 (93.8) 2790 (93.8) III III 49 (1.4) 49 (1.4) 56 (1.9) 56 (1.9) IV IV 73 (2.1) 73 (2.1) 79 (2.7) 79 (2.7) Unknown Unknown 15 (0.4) 15 (0.4) 34 (1.1) 34 (1.1)

6. Comparison of Gleason Scores Gleason score on biopsy Screening Screening Control Control 2 - 4 2 - 4 222 (6.4) 222 (6.4) 137 (4.6) 137 (4.6) 5 -6 5 -6 2047 (59.3) 2047 (59.3) 1656 (55.7) 1656 (55.7) 7 815 (23.6) 815 (23.6) 779 (26.2) 779 (26.2) 8 - 10 8 - 10 289 (8.4) 289 (8.4) 341 (11.5) 341 (11.5) Unknown Unknown 79 (2.3) 79 (2.3) 61 (2.1) 61 (2.1)

7. Compliance and Contamination 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 22.2/22.0 Two or more: 9.4/9.8 22.2/22.0 Compliance Compliance PSA 85%; DRE 86% PSA 85%; DRE 86% Testing in the control group Testing in the control group PSA: 40% in first year to 52% in sixth year PSA: 40% in first year to 52% in sixth year DRE: Range from 41 to 46% DRE: Range from 41 to 46%

8. 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

9. PLCO Trial Results Annual screening with DRE and PSA results in more prostate cancer compared to community screening practices Annual screening with DRE and PSA results in more prostate cancer compared to community screening practices Seven years: 2820 versus 2322 Seven years: 2820 versus 2322 Ten years: 3452 versus 2974 Ten years: 3452 versus 2974 Few Prostate cancer related deaths in either group Few Prostate cancer related deaths in either group 50 screening and 44 controls at 7 years 50 screening and 44 controls at 7 years 92 screening and 82 control at 10 years 92 screening and 82 control at 10 years Continued follow-up to be done Continued follow-up to be done

10. UCLA CA-125, PSA Assays Blood Collection Protocol Biorepository Etiology & Early Marker Studies Serum T0, T1, T2, T3, T4, T5 2 ml S Serum T0 (2), T1, T2, T4, T5 2 ml X 2 S S Plasma, Buffy Coat, RBC T0, T3 2 ml X 4 P PBR Serum T0 2 ml S Plasma, Buffy Coat, RBC T3, T4, T5 (2) 2 ml X 4 P PBR Whole Blood T3 (2) 2 ml X 6 W WW W Samples Collected Per Patient Serum13 vials26 ml Plasma12 vials24 ml Buffy Coat6 vials14 ml RBC3 vials6 ml Whole Blood12 vials24 ml Total46 vials92 ml TubesAdditiveSizeSpecimens Red/GrayClot Activator6 mlSerum RedNone10 mlSerum Green Sodium Heparin 10 ml Plasma, Buffy coat & RBC Royal BlueNone7 mlZinc-free Serum Lavender Liquid EDTA 10 ml Plasma, Buffy Coat &RBC YellowACD-A8.5 mlWhole Blood

11. Specimens Available by Cancer Sites and Specimen Types 75,476 34,043 17,206 17,084 9,490 8,837 6,723 5,734 4,829 4,489 1,735 1,900 2,138 2,289 3,507 3,501 1,434 1,242 1,193 1,086

12. TMAs with PLCO Tumors Supports multiple histologies per spot

13. PLCO Trial Conclusions PSA not a perfect test PSA not a perfect test Low mortality rates achieved at high rate of overdiagnosis Low mortality rates achieved at high rate of overdiagnosis Important to have better biologic understanding of aggressive prostate cancer and means of differentiating from indolent disease Important to have better biologic understanding of aggressive prostate cancer and means of differentiating from indolent disease PLCO biospecimen repository useful PLCO biospecimen repository useful genetic and somatic risk assessment genetic and somatic risk assessment development and validation of early markers of detection development and validation of early markers of detection

14. With appreciation PLCO Research Colleagues PLCO Research Colleagues PLCO Site Coordinators and Staff PLCO Site Coordinators and Staff NCI Colleagues NCI Colleagues The trial participants without whom these studies would not have been possible The trial participants without whom these studies would not have been possible