Design of the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial

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Abstract

The objectives of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial are to determine in screenees ages 55–74 at entry whether screening with flexible sigmoidoscopy (60-cm sigmoidoscope) can reduce mortality from colorectal cancer, whether screening with chest X-ray can reduce mortality from lung cancer, whether screenng men with digital rectal examination (DRE) plus serum prostate-specific antigen (PSA) can reduce mortality from prostate cancer, and whether screening women with CA125 and transvaginal ultrasound (TVU) can reduce mortality from ovarian cancer. Secondary objectives are to assess screening variables other than mortality for each of the interventions including sensitivity, specificity, and positive predictive value; to assess incidence, stage, and survival of cancer cases; and to investigate biologic and/or prognostic characterizations of tumor tissue and biochemical producs as intermediate endpoints. The design is a multicenter, two-armed, randomized trial with 37,000 females and 37,000 males in each of the two arms. In the intervention arm, the PSA and CA125 tests are performed at entry, then annually for 5 years. The DRE, TVU, and chest X-ray exams are performed at entry and then annually for 3 years. Sigmoidoscopy is performed at entry and then at the 5-year point. Participants in the control arm follow their usual medical care practices. Participants will be followed for at least 13 years from randomization to ascertain all cancers of the prostate, lung, colorectum, and ovary, as well as deaths from all causes. A pilot phase was undertaken to assess the randomization, screening, and data collection procedures of the trial and to estimate design parameters such as compliance and contamination levels. This paper describes eligibility, consent, and other design features of the trial, randomization and screening procedures, and an outline of the follow-up procedures. Sample-size calculations are reported, and a data analysis plan is presented.

References (139)

  • A.W. Partin et al.

    The clinical usefulness of prostate specific antigen: Update, 1994

    J Urol

    (1994)
  • M.K. Brawer et al.

    Screening for prostatic carcinoma with prostate specific antigen

    J Urol

    (1992)
  • M.C. Benson et al.

    Prostate specific antigen density: A means of distinguishing benign prostatic hypertrophy and prostate cancer

    J Urol

    (1992)
  • C.H. Bangma et al.

    Volume adjustment for intermediate prostate-specific antigen values in a screening population

    Eur J Cancer

    (1995)
  • T. Demura et al.

    Measurement of prostate specific antigen and gamma-seminoprotein ratio: A new means of distinguishing benign prostatic hyperplasia and prostate cancer

    J Urol

    (1993)
  • H. Lilja

    Significance of different molecular forms of serum PSA. The free, non-complexed form of PSA versus that complexes to alpha 1-antichymotrypsin

    Urol Clin North Am

    (1993)
  • C.H. Bangma et al.

    The value of screening tests in the detection of prostate cancer. Part I: Results of a retrospective evaluation of 1726 men

    Urology

    (1995)
  • A.R. Vashi et al.

    Determination of the “reflex range” and appropriate cutpoints for percent free prostate-specific antigen in 413 men referred for prostatic evaluation using the AxSYM system

    Urology

    (1997)
  • J.E. Johansson et al.

    Natural history of localised prostatic cancer. A population-based study in 223 untreated patients

    Lancet

    (1989)
  • G.J. Miller

    Histopathology of prostate cancer: Prediction of malignant behavior and correlation with ultrasonography

    Urology

    (1989)
  • M.J. Barry et al.

    Should Medicare provide reimbursement for prostate-specific antigen testing for early detection of prostate cancer? Part IV: Estimating the risks and benefits of an early detection program

    Urology

    (1995)
  • J.R. Beck et al.

    Acritique of the decision analysis for clinically localized prostate cancer

    J Urol

    (1994)
  • G.L. Lu-Yao et al.

    Population-based study of long-term survival in patients with clinically localised prostate cancer

    Lancet

    (1997)
  • A.F. Prestigiacomo et al.

    Physiological variation of serum prostate specific antigen in the 4.0 to 10.0 ng./ml. range in male volunteers

    J Urol

    (1996)
  • L.G. Dales et al.

    Evaluating periodic multiphasic health check-ups: A controlled trial

    J Chronic Dis

    (1979)
  • G.D. Friedman et al.

    Multiphasic health checkup evaluation: A 16-year follow-up

    J Chronic Dis

    (1986)
  • M.R. Melamed et al.

    Screening for early lung cancer. Results of the Memorial Sloan-Kettering study in New York

    Chest

    (1984)
  • R. Shukla et al.

    Survival benefits of x-ray screening for lung cancer after bias adjustments

    Computers and Mathematics with Applications

    (1989)
  • J.D. Hardcastle et al.

    Randomised controlled trial of faecal-occult-blood screening for colorectal cancer

    Lancet

    (1996)
  • O. Kronborg et al.

    Randomized study of screening for colorectal cancer with faecal-occult-blood test

    Lancet

    (1996)
  • J.V. Selby et al.

    Sigmoidoscopy and mortality from colorectal cancer: The Kaiser Permanente Multiphasic Evaluation Study

    J Clin Epidemiol

    (1988)
  • E. Silverberg et al.

    Cancer statistics, 1989

    CA Cancer J Clin

    (1989)
  • (2000)
  • H.H. Gallion et al.

    Adjuvant oral alkylating chemotherapy in patients with stage I epithelial ovarian cancer

    Cancer

    (1989)
  • V.A. Gilbertsen

    Cancer of the prostate gland. Results of early diagnosis and therapy undertaken for cure of the disease

    JAMA

    (1971)
  • C.B. Jenson et al.

    Evaluation of annual examinations in the detection of cancer

    JAMA

    (1960)
  • G.W. Chodak et al.

    Early detection of prostate cancer by routine screening

    JAMA

    (1984)
  • R.J. Babaian et al.

    The relationship of prostate-specific antigen to digital rectal examination and transrectal ultrasonography. Findings of the American Cancer Society National Prostate Cancer Detection Project

    Cancer

    (1992)
  • Z. Wajsman et al.

    Detection and diagnosis of prostatic cancer

  • I.M. Thompson et al.

    Presentation and clinical course of patients ultimately succumbing to carcinoma of the prostate

    Scand J Urol Nephrol

    (1991)
  • M.I. Resnick et al.

    Editorial comment

  • G.W. Chodak et al.

    Progress and problems in screening for carcinoma of the prostate

    World J Surg

    (1989)
  • F. Lee et al.

    Prostate cancer: Comparison of transrectal US and digital rectal examination for screening

    Radiology

    (1988)
  • F. Lee et al.

    Hypoechoic lesions of the prostate: Clinical relevance of tumor size, digital rectal examination, and prostate-specific antigen

    Radiology

    (1989)
  • B.L. McClennan

    Transrectal US of the prostate: Is the technology leading the science?

    Radiology

    (1988)
  • S.T. Torp-Pedersen et al.

    Early prostate cancer: Diagnostic costs of screening transrectal US and digital rectal examination

    Radiology

    (1988)
  • T.A. Stamey et al.

    Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate

    N Engl J Med

    (1987)
  • C.M. Coley et al.

    Early detection of prostate cancer. Part 1: Prior probability and effectiveness of tests. The American College of Physicians

    Ann Intern Med

    (1997)
  • W.J. Catalona et al.

    Measurement of prostate-specific antigen in serum as a screening test for prostate cancer

    New Engl J Med

    (1991)
  • H.B. Carter et al.

    Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease

    JAMA

    (1992)
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    1

    Deceased.

    2

    Retired.

    3

    A roster of the project team appears in the lead paper of this supplement. Other participants in early design considerations for this trial included former National Cancer Institute investigators David P. Byar (deceased) and Charles R. Smart (retired).

    Address reprint requests to: Dorothy Sullivan, Early Detection Research Group, Division of Cancer Prevention, National Cancer Institute, EPN 330, 6130 Executive Blvd., Bethesda, MD 20892-7346.

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