Screening for Prostate Cancer in Older Patients (PLCO Screening Trial)

This clinical trial studies whether screening methods used to diagnose cancer of the prostate, lung, colon, rectum, or ovaries can reduce deaths from these cancers. Screening tests may help doctors find cancer cells early and plan better treatment for prostate cancer

PRIMARY OBJECTIVES:

I. To determine whether screening with digital rectal examination (DRE) plus serum prostate-specific antigen (PSA) can reduce mortality from prostate cancer in men aged 55-74 at entry.

SECONDARY OBJECTIVES:

I. To assess screening variables, other than mortality, for each of the interventions including sensitivity, specificity, and positive predictive value.

II. To assess the incidence, stage, and survival of cancer cases. III. To investigate the mortality predictive value of biologic and/or prognostic characterizations of tumor tissue as intermediate endpoints.

IV. To conduct biomolecular and genetic research into factors associated with cancer carcinogenesis and promotion, as well as the early detection of these factors.

OUTLINE: Participants in the overall PLCO study are stratified by screening center, gender, and age (55-59 vs 60-64 vs 65-69 vs 70-74). Participants are randomized to 1 of 2 arms (control vs screening).

ARM I (Control): Participants receive standard medical care. Participants complete a Diet History Questionnaire (DHQ) at baseline.

ARM II (Prostate Screening): Participants undergo blood sample collection for PSA analysis at baseline and annually for 5 years. Serum that is not used in the study will be stored in an NCI biorepository. Participants also undergo a DRE at baseline and annually for 3 years. A scheduling and tracking procedure is implemented to ensure regular attendance at repeat screens for participants screened negative or for those who are designated suspicious or positive at screening but for whom subsequent diagnostic procedures do not reveal prostate cancer (follow-up diagnostic procedures are through their own medical care environment). Participants diagnosed with prostate cancer via a screening test are referred for treatment in accordance with current accepted practice for appropriate stage of disease, patient age, and medical condition; a procedure is provided for contact with qualified medical personnel to insure appropriate therapy.

Participants complete a Dietary Questionnaire (DQX) at baseline and DHQ at year 3. An Annual Study Update (ADU) (previously referred to as the Periodic Survey of Health [PSH] questionnaire) is mailed to each participant annually for 13 years to identify all prevalent and incident prostate cancers as all deaths that occur among both screened and control subjects during the trial.

After completion of screening, participants are followed up for at least 13 years.

• Other: cytology specimen collection procedure
  Undergo blood sample collection for PSA analysis
  Other Name: cytologic sampling
• Procedure: examination
  Undergo DRE
  Other Names:

  • Exam
  • Medical Assessment
  • Medical Exam
  • Medical Examination
  • Medical Inspection
• Other: screening questionnaire administration
  Undergo questionnaire assessments

• No Intervention: Control
  Participants receive standard medical care. Participants complete a DHQ at baseline.
• Active Comparator: Prostate Screening
  Participants undergo blood sample collection for PSA analysis at baseline and annually for 5 years. Serum that is not used in the study will be stored in an NCI biorepository. Participants also undergo a DRE at baseline and annually for 3 years. Participants complete a DQX at baseline and DHQ at year 3. An ADU (previously referred to as the PSH questionnaire) is mailed to each participant annually for 13 years to identify all prevalent and incident prostate cancers as all deaths that occur among both screened and control subjects during the trial.
  Interventions:

  • Other: cytology specimen collection procedure
  • Procedure: examination
  • Other: screening questionnaire administration

• Rogal SS, Pinsky PF, Schoen RE. Relationship between detection of adenomas by flexible sigmoidoscopy and interval distal colorectal cancer. Clin Gastroenterol Hepatol. 2013 Jan;11(1):73-8. doi: 10.1016/j.cgh.2012.08.002. Epub 2012 Aug 16.
• Schoen RE, Pinsky PF, Weissfeld JL, Yokochi LA, Church T, Laiyemo AO, Bresalier R, Andriole GL, Buys SS, Crawford ED, Fouad MN, Isaacs C, Johnson CC, Reding DJ, O'Brien B, Carrick DM, Wright P, Riley TL, Purdue MP, Izmirlian G, Kramer BS, Miller AB, Gohagan JK, Prorok PC, Berg CD; PLCO Project Team. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med. 2012 Jun 21;366(25):2345-57. Epub 2012 May 21.
• Oken MM, Hocking WG, Kvale PA, Andriole GL, Buys SS, Church TR, Crawford ED, Fouad MN, Isaacs C, Reding DJ, Weissfeld JL, Yokochi LA, O'Brien B, Ragard LR, Rathmell JM, Riley TL, Wright P, Caparaso N, Hu P, Izmirlian G, Pinsky PF, Prorok PC, Kramer BS, Miller AB, Gohagan JK, Berg CD; PLCO Project Team. Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial. JAMA. 2011 Nov 2;306(17):1865-73. Epub 2011 Oct 26.
• Buys SS, Partridge E, Black A, Johnson CC, Lamerato L, Isaacs C, Reding DJ, Greenlee RT, Yokochi LA, Kessel B, Crawford ED, Church TR, Andriole GL, Weissfeld JL, Fouad MN, Chia D, O'Brien B, Ragard LR, Clapp JD, Rathmell JM, Riley TL, Hartge P, Pinsky PF, Zhu CS, Izmirlian G, Kramer BS, Miller AB, Xu JL, Prorok PC, Gohagan JK, Berg CD; PLCO Project Team. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011 Jun 8;305(22):2295-303.
• Berg CD. The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial: the prostate cancer screening results in context. Acta Oncol. 2011 Jun;50 Suppl 1:12-7.
• Pinsky PF, Blacka A, Kramer BS, Miller A, Prorok PC, Berg C. Assessing contamination and compliance in the prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Clin Trials. 2010;7(4):303-11. Epub 2010 Jun 22.
• Troy JD, Hartge P, Weissfeld JL, Oken MM, Colditz GA, Mechanic LE, Morton LM. Associations between anthropometry, cigarette smoking, alcohol consumption, and non-hodgkin lymphoma in the prostate, lung, colorectal, and ovarian cancer screening trial. Am J Epidemiol. 2010 Jun 15;171(12):1270-81. Epub 2010 May 21.
• Croswell JM, Kramer BS, Kreimer AR, Prorok PC, Xu JL, Baker SG, Fagerstrom R, Riley TL, Clapp JD, Berg CD, Gohagan JK, Andriole GL, Chia D, Church TR, Crawford ED, Fouad MN, Gelmann EP, Lamerato L, Reding DJ, Schoen RE. Cumulative incidence of false-positive results in repeated, multimodal cancer screening. Ann Fam Med. 2009 May-Jun;7(3):212-22.
• Tammemagi MC, Freedman MT, Pinsky PF, Oken MM, Hu P, Riley TL, Ragard LR, Berg CD, Prorok PC. Prediction of true positive lung cancers in individuals with abnormal suspicious chest radiographs: a prostate, lung, colorectal, and ovarian cancer screening trial study. J Thorac Oncol. 2009 Jun;4(6):710-21.
• Partridge E, Kreimer AR, Greenlee RT, Williams C, Xu JL, Church TR, Kessel B, Johnson CC, Weissfeld JL, Isaacs C, Andriole GL, Ogden S, Ragard LR, Buys SS; for the PLCO Project Team. Results From Four Rounds of Ovarian Cancer Screening in a Randomized Trial. Obstet Gynecol. 2009 Apr;113(4):775-782.
• Andriole GL, Grubb RL 3rd, Buys SS, Chia D, Church TR, Fouad MN, Gelmann EP, Kvale PA, Reding DJ, Weissfeld JL, Yokochi LA, Crawford ED, O'Brien B, Clapp JD, Rathmell JM, Riley TL, Hayes RB, Kramer BS, Izmirlian G, Miller AB, Pinsky PF, Prorok PC, Gohagan JK, Berg CD; the PLCO Project Team. Mortality Results from a Randomized Prostate-Cancer Screening Trial. N Engl J Med. 2009 Mar 18; [Epub ahead of print]
• Lacey JV Jr, Kreimer AR, Buys SS, Marcus PM, Chang SC, Leitzmann MF, Hoover RN, Prorok PC, Berg CD, Hartge P; Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial Project Team. Breast cancer epidemiology according to recognized breast cancer risk factors in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial Cohort. BMC Cancer. 2009 Mar 17;9:84.
• Tammemagi CM, Freedman MT, Church TR, Oken MM, Hocking WG, Kvale PA, Hu P, Riley TL, Ragard LR, Prorok PC, Berg CD. Factors associated with human small aggressive non small cell lung cancer. Cancer Epidemiol Biomarkers Prev. 2007 Oct;16(10):2082-9.
• Lacey JV Jr, Greene MH, Buys SS, Reding D, Riley TL, Berg CD, Fagerstrom RM, Hartge P. Ovarian cancer screening in women with a family history of breast or ovarian cancer. Obstet Gynecol. 2006 Nov;108(5):1176-84.

Exclusion Criteria:

• Men who at the time of randomization are less than 55 or greater than or equal to 75 years of age
• Individuals undergoing treatment for cancer at this time, excluding basal-cell and squamous-cell skin cancer

• Individuals with known prior cancer of the colon, rectum, lung, prostate

  • This includes primary or metastatic PLCO cancers
• Individuals with previous surgical removal of the entire colon, one lung, or the entire prostate
• Individuals who are participating in another cancer screening or cancer primary prevention trial

• Males who have taken Proscar/Propecia/finasteride in the past 6 months

  • NOTE: Individuals who are already enrolled in the trial when their physician prescribes finasteride are not prevented from taking this medication. As a result, these participants will continue to be screened and followed just as those participants who are not on finasteride.
  • NOTE: Men who are taking Tamoxifen are not excluded from any part of the PLCO Screening Trial.
• Individuals who are unwilling or unable to sign the informed consent form
• Males who have had more than one PSA blood test in the past three years
• Individuals who have had a colonoscopy, sigmoidoscopy, or barium enema in the past three years