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Transcript of 1 PLCO And The Current State of Screening Andrew W. Swartz, MD Family Physician Emergency Medicine...
1
PLCOAnd
The Current State of Screening
Andrew W. Swartz, MDFamily Physician
Emergency Medicine Physician
Flight Surgeon (Alaska ANG)
Conflicts of Interest
Biases
Am a member of a profession (and specialty) which profits from cancer screening and treatment
No financial interest in any medical patents or products
I do have a small software company, no product relation to topic today
Part of my income is derived from CRC Screening
Not trying to get any votes
Practice in fear of the legal liability associated with “missing something”
May soon be graded by how many of my patients get screened
Am a member of a society whose health care system is in financial jeopardy
Like most rational humans, I strongly desire prevention and screening to work so that my loved ones and I may live longer and suffer less
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Scientific Method
Observe the World(for apparent associations, etc)
[Re] Form Hypothesis
Test Hypothesis with Experiment
Hypothesis NOT disprovedHypothesis disproved
Test further,
Incorporate into Theory,
etc.
4
Hierarchy of Evidence
Cohort Studies
Case-Control Studies
Case-Series and Reports
Expert Opinion
Non-randomized Controlled Trials
RCT’s
Observations
Experiments
Less Bias + Confounding
Reviews + Meta-analyses of RCT’s
Questionnaire
Screening Theory
DeathCancerous Mutation
Unscreened
Screened
Symptomatic Diagnosis
Early Diagnosis
Early Treatment Lifespan Gain
Holy Grail
Background
To be effective, screening must satisfy two criteria:
1. Monographs in Epidemiology and Biostatistics, Volume 19. Morrison A. Screening in Chronic Disease, 2nd Ed. 1992. Oxford University Press. New York.
1. We must be able to diagnose early.
2. Early treatment must be better than late treatment.
Background
“The evaluation of screening must be based on
measures of disease occurrence that will not be
affected by early diagnosis except to the extent
that early treatment is beneficial.1”
1. Monographs in Epidemiology and Biostatistics, Volume 19. Morrison A. Screening in Chronic Disease, 2nd Ed. 1992. Oxford University Press. New York. p16.
DeathCancerous Mutation
NO TREATMENT
Survival
Survival
Lead-time
Unscreened
Screened
Symptomatic Diagnosis
Screening Diagnosis
Lead-Time Bias
Cancerous Mutation
Group-A
Group-B
Treatment Comparisons
Survival
Survival
Rx-B
Rx-A
DeathCancerous Mutation
Unscreened
Screened
Symptomatic Diagnosis
Screening Diagnosis
Lead-Time Bias
Survival
Survival
DeathCancerous Mutation
Unscreened
Screened
Symptomatic Diagnosis
Screening Diagnosis
Lead-Time Bias
Survival
Survival
Background
“The evaluation of screening must be based on
measures of disease occurrence that will not be
affected by early diagnosis except to the extent
that early treatment is beneficial.1”
1. Monographs in Epidemiology and Biostatistics, Volume 19. Morrison A. Screening in Chronic Disease, 2nd Ed. 1992. Oxford University Press. New York. p16.
Background
“The ultimate gains derived from a screening
program are reductions of serious illness and
death among the people screened.1”
1. Mortality
2. Morbidity
1. Monographs in Epidemiology and Biostatistics, Volume 19. Morrison A. Screening in Chronic Disease, 2nd Ed. 1992. Oxford University Press. New York. p16.
15
Ground RulesValid Outcomes in Screening Trials:
1. Mortality
2. Incidence
SurvivalStaging
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Cumulative Case Plots
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Cumulative Case PlotsNo Difference
Time since Randomization
ScreenedControlScreening Period Follow-up Period
Num
ber
of C
ases
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Cumulative Case Plots
Time since Randomization
ScreenedControlScreening Period Follow-up Period
Num
ber
of C
ases
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Mortality Plots
Cumulative Case Plots
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Cumulative Case Plots
Time since Randomization
ScreenedControlScreening Period Follow-up Period
Screen
Control
Num
ber
of D
eath
s
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Cumulative Case Plots
Time since Randomization
ScreenedControlScreening Period Follow-up Period
Screen
Control
Num
ber
of D
eath
s
22
Cumulative Case Plots
Time since Randomization
ScreenedControlScreening Period Follow-up Period
Screen
Control
Num
ber
of D
eath
s
23
Cumulative Case Plots
Incidence Plots
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Cumulative Case Plots
Time since Randomization
ScreenedControlScreening Period Follow-up Period
Ideal
Screen
Control
Num
ber
of C
ance
rs
25
Cumulative Case Plots
Time since Randomization
ScreenedControlScreening Period Follow-up Period
Worst-Case
Screen
Control
Overdiagnosis !!!
Num
ber
of C
ance
rs
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Cumulative Case Plots
Time since Randomization
ScreenedControlScreening Period Follow-up Period
Screen
Control
Num
ber
of C
ance
rs
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Cumulative Case Plots
Time since Randomization
ScreenedControlScreening Period Follow-up Period
Screen
Control
Num
ber
of C
ance
rs
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Cumulative Case Plots
Time since Randomization
ScreenedControlScreening Period Follow-up Period
Screen
Control
?
Num
ber
of C
ance
rs
PLCOProstate, Lung, Colorectal, and Ovarian Screening RCT
The Good,
The Bad,
And the Ugly.
PLCO
One of the most massive undertakings
in the history of medicine.• 5-year design phase (1989-1994) by the National Cancer Institute
• Patient recruitment 1994-2001
• Multi-center w/ competition for participation:1) University of Colorado Health Sciences Center, Denver, CO2) Georgetown University Medical Center, , Washington, DC3) Lombardi Cancer Research Center, Washington, DC4) Pacific Health Research Institute, Honolulu, HI5) Henry Ford Health System, Detroit, MI6) University of Minnesota, Minneapolis, MN7) Washington University School of Medicine, St. Louis, MO8) Cancer Institute of Brooklyn at Maimonides, Brooklyn, NY (discontinued 1997)9) University of Pittsburgh Cancer Institute, Pittsburgh, PA10) Satellites: Latrobe Area Hospital, Latrobe, PA11) Jameson Health System, New Castle, PA12) Trinity Health System, Steubenville, OH13) University of Utah School of Medicine, Salt Lake City, UT14) Satellite: St. Lukes Meridian Medical Center, Boise, ID15) Marshfield Medical Research and Education Foundation, Marshfield, WI16) University of Alabama at Birmingham, Birmingham, AL (added 1997)
PLCO
307 Publications4/17/2013
PLCO Design
154,900
Gender: Men + Women
Age: 55-
74
Exclusions:- PLCO Cancers- Treatment for any
cancer- Recently screened
Usual Care
Yearly DRE x 4y + PSA x 6y
Yearly CXR x 4y
Flex-Sig at 0 and 3-5y
Yearly TVU x 4y + Ca125 x 6y
77,445
Screen
Men Women
Prostate X 38,340
Lung X X 77,445
Colorectal X X 77,445
Ovarian X 39,105
77,455
Control
Randomization
33
Prostate Lung
Colorectal Ovarian
Andriole GL, Crawford DE, et al. Prostate Cancer Screening in the Randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: Mortality Results after 13 Years of Follow-up. J Natl Cancer Inst. 2012;104:125–132.
Oken MM, Hocking WG, Kvale PA, et al; PLCO Project Team. Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial. JAMA. 2011; 306(17):1865-1873.
Schoen R.E., Pinsky P.F., Weissfeld J.L., et al. Colorectal-Cancer Incidence and Mortality with Screening Flexible Sigmoidoscopy. N Engl J Med. 2012 Jun 21;366(25):2345-57.
Buys SS, Partridge E, Black A, et al. Effect of Screening on Ovarian Cancer Mortality: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011;305(22):2295-2303.
Disease-Specific Mortality
LungProstate
Colorectal Ovarian
Screen
Control
Screen
Control
Screen
ControlControl
DRE PSA CXR
FS TVU Ca125
Screen
Control
Control
Screen
Control
Cancer Incidence
Screen
Control
LungProstate
Colorectal Ovarian
DRE PSA CXR
TVU Ca125FS
1886
1274
113
83
Graph Familiarization
RR = x.xx
NNI = y.yy
NS
RR = x.xx
NNI = y.yy
PLCO Trial Results (at 10-13 years)
PLCO Trial Results (at 10-13 years)
PLCO
1999 – 13y
400 / 399
2014 – 11.5y
13,563 / 41,092
2010 – M15y, I10y
57,254 / 113,178
2011 – 10.5
17,136 / 17,136
2012 – 11y
77,445 / 77,455
PLCO-CRC: Comparison with other RCT’s
3.2 : 1
100%77,450
* *
*
Control
CRC Mortality
Control
CRC Incidence
PLCO Trial Results (at 10-13 years)
PLCO: Screening for Ovarian Cancer
ControlIncidence
TVU
113
83
ScreenCa125
Screen
Control
Mortality
Screenees (39,105)
NNH
False-positives: 3,285
12
Abdominal surgeries: 1,080
36
Major Surg. Comps.: 222
176
Background
To be effective, screening must satisfy two criteria:
1. Monographs in Epidemiology and Biostatistics, Volume 19. Morrison A. Screening in Chronic Disease, 2nd Ed. 1985. Oxford University Press. New York.
1. We must be able to diagnose early.
2. Early treatment must be better than late treatment.
47
48
49
SCREENING
50
PLCO References
Prostate
Andriole GL, Crawford DE, et al. Prostate Cancer Screening in the Randomized Prostate, Lung, Colorectal, and
Ovarian Cancer Screening Trial: Mortality Results after 13 Years of Follow-up. J Natl Cancer Inst.
2012;104:125–132.
Lung
Oken MM, Hocking WG, Kvale PA, et al; PLCO Project Team. Screening by chest radiograph and lung cancer
mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial. JAMA. 2011;
306(17):1865- 1873.
Colorectal
Schoen R.E., Pinsky P.F., Weissfeld J.L., et al. Colorectal-Cancer Incidence and Mortality with Screening Flexible
Sigmoidoscopy. N Engl J Med. 2012 Jun 21;366(25):2345-57.
Ovarian
Buys SS, et al. Effect of Screening on Ovarian Cancer Mortality: The Prostate, Lung, Colorectal and Ovarian (PLCO)
Cancer Screening Randomized Controlled Trial. JAMA. 2011;305(22):2295-2303.
51
Flex-Sig RCT References
Telemark
Thiis-Evensen E, Hoff GS, Sauar J, et al. Population-based surveillance by colonoscopy_ effect on the incidence of
colorectal cancer. Telemark Polyp Study I. Scand J Gastroenterol 1999; 34(4):414-20.
NORCCAP
Holme Ø, Løberg M et al. Effect of Flexible Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality: A
Randomized Clinical Trial. JAMA. 2014;312(6):606-615. doi:10.1001/jama.2014.8266.
UK
Atkin WS, Edwards R, Kralj-Hans I, et al. Once-only flexible sigmoidoscopy screening in prevention of colorectal
cancer: a multicentre randomised controlled trial. Lancet 375 (9726):1624-33..
SCORE
Segnan N, et al. Once-Only Sigmoidoscopy in Colorectal Cancer Screening: Follow-up Findings of the Italian
Randomized Controlled Trial—SCORE. J Natl Cancer Inst 2011;103:1310–1322.
52
Thank You
Questions ?