PCPT and SELECT Cancer Cohorts

• Briefly describe PCPT and SELECT trial designs

• Current follow-up status for each cohort

• SELECT Centralized Follow-up

• Data elements and biologic samples collected

• Events ascertained, verification

• Process for Proposing Research Using Cohorts

Cathy Tangen and Phyllis Goodman, 3/24/14, Survivorship Affinity Group

Presentation

PCPT Schema

Enrollment

Randomize

Finasteride 5 mg Placebo

Interim Prostate Cancer

EOS Biopsy

Interim Prostate Cancer

EOS Biopsy

For-cause Biopsy

(PSA or DRE)

Lost to F/U Died

Refused Biopsy

Lost to F/U Died

Refused Biopsy

1993-1997

1994-1997

2001-2003 7-year Period

Prevalence 7-year Period

Prevalence

SELECT Schema

Calendar Year 2001 - 2013

Randomized

Pre-Randomization Period

Follow - up Prostate cancer, other cancer, death

Placebo +

Selenium

Placebo +

Placebo

Vitamin E +

Placebo

Vitamin E +

Selenium

Calendar Year 2001 – 2004

(Planned 2001 – 2006)

Current Follow-up Status - PCPT

• Cancer endpoint assessment and follow-up for entire trial ended 12/03.

• Tried to conduct a long-term follow-up of men diagnosed with prostate cancer but proved infeasible accrual-wise. Closed 5/09

• Recent SSDI search (98% of participants reported SSN) led to recent survival publication of PCPT, 3422 deaths found.

• Missing piece of puzzle: cause of death. Plans for NDI search, have funding.

• Plans to link CDMS database to evaluate longterm effects of finasteride and other research aims.

Current Status of Follow-up for SELECT

• Study site closure 6/10-4/11, close out visit • Move subjects into centralized cohort followed by SWOG

Statistical Center • 17,747 transitioned to cohort (n=35,533 randomized)

– Challenge getting revised consent from participant locally and direct contact info given to Statistical Center

– Data collected by mailed booklets initially: cancer diagnosis, prostate cancer treatment, ancillary studies follow-up, source documents and prostate tissue requested

– June 2011 on-line data submission implemented – Phone call primary means of contact now – contracted

interviewers – Wrapping up final calls now, ending summer 2014. – NDI search, CDMS merge plans

PCPT (n=18,880)

SELECT Trial (n=35,533)

SELECT CFU (n=17,747)

N % N % N %

Age at enrollment (median [IQR],y)

63 [59-67] 62 [58-67] 62 [58-67]

50-54 2 0.0% 1,728 4.9% 633 3.6% 55-59 5,909 31.3% 11,341 31.9% 5,933 33.4% 60-64 5,793 30.7% 9,281 26.1% 4,866 27.4% 65-69 4,331 22.9% 6,917 19.5% 3,514 19.8% ≥70 2,845 15.1% 6,266 17.6% 2,801 15.8%

Current age (median [IQR],y) 79 [76-83] 72 [67-77] 72 [68-77] 58-69 1 0.0% 12,334 35.1% 6,385 36.0% 70-79 7,017 37.2% 14,980 42.2% 8,295 46.7% 80-89 6,292 33.3% 4,726 13.3% 2,650 14.9% ≥90 721 3.8% 324 0.9% 129 0.7% N/A (Deceased) 4,849 25.7% 3,169 8.9% 288 1.6%

Race/Ethnicity White 17,382 92.1% 27,592 77.7% 14,753 83.1% African American 712 3.8% 4,907 13.8% 1,990 11.2% Hispanic (not AA) 481 2.5% 1,946 5.5% 555 3.1% Hispanic (AA) 12 0.1% 356 1.0% 71 0.4% Other 293 1.6% 732 2.1% 378 2.1%

Baseline Characteristics

PCPT (n=18,880)

SELECT Trial (n=35,533)

SELECT CFU (n=17,747)

N % N % N %

History of prostate cancer in 1st degree relative

2,913 15.4% 6,609 18.6% 3,453 19.5%

PSA at entry (median [IQR], ng/ml) 1.1 [0.7-1.7] 1.1 [0.6-1.8] 1.1 [0.7-1.9] 0-<1.0 9,132 48.4% 17,177 48.3% 8,436 47.5% 1.0-<2.0 6,708 35.5% 10,895 30.7% 5,579 31.4% 2.0-<3.0 3,039 16.1% 4,815 13.6% 2,410 13.6% 3.0-<4.0 1 0.0% 2,646 7.4% 1,322 7.4%

Education (highest level) ≤ High school graduate or GED 3,569 18.9% 8,100 22.8% 2,854 16.1% Some college/vocational school 5,509 29.2% 9,451 26.6% 4,634 26.1% ≥ College graduate 9,790 51.9% 17,613 49.6% 10,130 57.1%

Cigarette smoking Never 6,218 32.9% 15,107 42.5% 8,158 46.0% Former 11,171 59.2% 17,333 48.8% 8,524 48.0% Current 1,486 7.9% 2,898 8.2% 1,010 5.7%

Body mass index (kg/m2) <25 4,817 25.5% 7,129 20.1% 3,571 20.1% 25-<30 9,499 50.3% 16,991 47.8% 8,692 49.0% ≥30 4,378 23.2% 11,198 31.5% 5,408 30.5%

Baseline Characteristics

Cancer reported by participant to Study

Site

Source documentation obtained and submitted to Statistical Center

Endpoint Review Committee reviews documentation and codes cancer

site/cause of death

Study Site learns of participant

death

Additional deaths from Social Security Death Index (SSDI)

and planned National Death Index search

Endpoint form submitted

PCPT: Review of Other Cancers and Deaths

Other cancers • Reported by the participant to study site staff • Source documentation submitted to the Statistical Center • Upon the interest of an investigator, source documents can be

reviewed and coded Deaths • Sites collected source documentation for coding cause of death

on study forms • Source documentation was not submitted to the Statistical Center • Social Security Death Index (SSDI) search was performed in 2012 • National Death Index search planned 2014-2015

SELECT: Data Collection for Other Cancers and Deaths

PCPT SELECT Trial

Medical history, limited Physical Exam , height, weight, demographics

√ √

Quality of Life (SF-36) √ √ Subset

Family history cancer √ Prostate only √ Prostate, lung, colon Anthropometric measures √

PSA Measured at central facility

Participant report or done at study site

Diet and supplement use At year 1 √ Physical activity √

Baseline Data Collected

PCPT SELECT Trial SELECT CFU

Frequency Every 3 months Every 6 months Annual

Medical events/side effects

√ √

Macular degeneration, diabetes, colorectal screen procedures

Medications Limited Extensive Finasteride, statins, aspirin, NSAIDs

Prostate health √ (annually) √

PSA, treatments for men diagnosed with prostate cancer

AUA symptom score √ (annually)

PSA and DRE (annually) PSA measured at central facility; DRE by study site

Participant report or done at study site

Updated supplement use √ Adherence assessment √ √ Updated smoking history √ √ Weight √ √ √ Quality of Life (SF-36) √ √ On subset

Follow-Up Data Collected

Epidemiologic Sub-studies Nested Within PCPT and SELECT

• Case-control study within PCPT: Approx. 1800 prostate cancer cases and 1800 biopsy proven controls at 7 yrs. Frequency matched on treatment arm, family history of CaP and age group. Over-sampled African Americans

• Case-cohort within SELECT: cases= all prostate cancers, cohort stratified on age group and race (AA vs. not) was selected, sampling weights needed

Plasma Serum RBC WBC Prostate tissue

Toenail

PCPT • Blood sample at baseline • Annually during follow-up

X x x

SELECT

• Blood sample at baseline and Year 5

• 7.8% subset at 6 months, Year 1, 2, 4, 6 and 8;

• post-diagnostic sample for those with prostate cancer.

• Toenails at baseline.

X x x x X

WBC = white blood cell/buffy coat, RBC=red blood cell

Samples Collected

Cancer site Total reported

Some source documentation

Baseline plasma specimen

Year 5 plasma specimen2

Total with Buffy Coat available

Prostate1 2,494 2,012 2,321 1,710 2,370

Bladder 249 229 227 156 230

Colorectal 323 298 293 172 298

Lung 381 352 349 139 351

Melanoma 333 311 308 254 315

Pancreatic 118 100 104 29 104

Renal 110 101 103 76 105

Other cancers 807 730 729 414 743

Non-cancers 30,948 N/A 27,934 19,424 28,406

SELECT: Cancers and Samples Collected

Serum Samples

# Additional Pre-diagnostic Serum Samples DNA source

Cancer site Total Baseline 0 1 2 3+ DNA Serum1

Prostate 2,401 2,261 3 169 118 2,111 1,420 857

Bladder 146 137 10 39 20 77 71 56

Colorectal 210 196 29 43 34 104 82 101

Lung 255 235 35 57 31 132 62 131

Melanoma 158 148 9 15 9 125 90 55

Pancreatic 38 32 2 14 2 20 6 18

Renal 56 53 7 10 8 31 22 25

Other 474 450 53 86 58 277 153 246

Non-cancers 15,301 14,328 26 1,735 655 12,885 7,845 5,757

1Among cases with no WBC or DNA available

PCPT: Cancers and Samples Collected

Data Request Process

Brief description of proposed data for epidemiologic or statistical research • Approximately 2 pages • Specific aims • Data elements required

PCPT/SELECT Cohorts Executive Committee • Availability of data • Overlap with other approved projects

SWOG Executive Committee • Review for regulatory issues • Meets weekly

Data Usage Agreement • Who will have access to the individual participant data • Data not to be shared with others or used for other projects

Biologic Specimens Requests

SWOG webpage (www.swog.org) Visitors Biospecimens Application not to exceed 5 pages: • Specific aims • Background and significance • Preliminary results (if available) • Experimental methods and design • Type and volume of samples • Why are the PCPT/SELECT specimens and associated clinical data necessary • Why is the use of the SELECT/PCPT biorepository needed or advantageous.

PCPT/SELECT Cohorts Executive Committee • Feasibility (population, study design, sample size, sample and data needs) • Availability of biospecimens • Overlap with other approved projects

SWOG Executive Committee • Further scientific review • Meets weekly

• Materials reserved for 3 years • Letter of support from SWOG for any applications for funding (i.e. R01s, DoD) • SWOG will work with the investigator to obtain external funding • Material Usage Agreements and Data Usage Agreements (local IRB approval)

PCPT SELECT

Deaths

Total 5,125 3,071

Prostate cancer 18 12

Other cancer 579 723

Cardiovascular 602 746

Other 495 671

Unknown/SSDI* 3,431 919

* Planned NDI search for cause

Deaths

PCPT SELECT Trial SELECT CFU

Prostate cancer End of study biopsy and interim cancers

Study site report confirmed by central lab

Participant report; Medical records/tissue requested

Other cancer Source docs collected, adjudicated

Source docs collected, not adjudicated

Participant report; Medical records requested

Deaths Source docs collected, adjudicated; SSDI

Site reports; SSDI SSDI, NDI

Cardiovascular Participant report Participant report None

Summary: Endpoint Assessments

Unique Features of Cohorts • Follow-up: median 9 yrs. SELECT, 17 yrs. PCPT

• 15% AA participation in SELECT

• Test and validation with both cohorts

• Nested case-control and case-cohort studies with measures stored at Statistical Center

• Longitudinal QOL assessment

• Careful longitudinal assessment of meds and dietary supplements on SELECT

• RCT underpinnings with significant treatment results – may provide keys to mechanistic pathways

Resources for Future Research

• Upcoming National Death Index Search for PCPT and SELECT

• SWOG has access to CDMS database – Link procedures and medications, long-term effects to

both trials/cohorts.

• Contribute to NCI Cancer Cohort Consortium approved projects

• Solicit projects from scientific community, TM and data analyses, collaborate on grants

• WHI strategic collaborations