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. 2000 Jan 18;82(3):731–736. doi: 10.1054/bjoc.1999.0988

Adding free to total prostate-specific antigen levels in trials of prostate cancer screening

N J Wald 1, H C Watt 1, L George 1, P Knekt 2, K J Helzlsouer 3, J Tuomilehto 2
PMCID: PMC2363306  PMID: 10682690

Abstract

We used a nested case–control design on data from men in four prospective studies (from the UK, Maryland in the USA, and two from Finland) with available stored serum samples to determine whether there was an advantage in measuring both free prostate-specific antigen (PSA) and total PSA as a potential screening test for prostate cancer. Of these men, 247 were verified through national vital statistics offices as having died of prostate cancer, or having developed the disease, and 953 men who did not develop prostate cancer (controls) were selected, matched to cases for age, study centre and sample storage duration. Fixing the false-positive rate at 1%, the prostate cancer detection rate (sensitivity) over the 3 years following serum collection (based on 14 cancers) increased from an estimated 95% using total PSA to 97% using free and bound PSA (that is, bound to α-antichymotrypsin which together with the free form is total PSA). Over a 6-year period (based on 41 cancers) a similar difference occurred (52% and 56% detection rates respectively). We conclude that there is no material advantage in adding free to total PSA in prostate cancer screening trials. © 2000 Cancer Research Campaign

Keywords: prostate-specific antigen, free prostate-specific antigen, clinical prostate cancer, population screening

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Selected References

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  1. Arcangeli C. G., Ornstein D. K., Keetch D. W., Andriole G. L. Prostate-specific antigen as a screening test for prostate cancer. The United States experience. Urol Clin North Am. 1997 May;24(2):299–306. doi: 10.1016/s0094-0143(05)70376-1. [DOI] [PubMed] [Google Scholar]
  2. Auvinen A., Rietbergen J. B., Denis L. J., Schröder F. H., Prorok P. C. Prospective evaluation plan for randomised trials of prostate cancer screening. The International Prostate Cancer Screening Trial Evaluation Group. J Med Screen. 1996;3(2):97–104. doi: 10.1177/096914139600300211. [DOI] [PubMed] [Google Scholar]
  3. Carter H. B., Pearson J. D., Metter E. J., Brant L. J., Chan D. W., Andres R., Fozard J. L., Walsh P. C. Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease. JAMA. 1992 Apr 22;267(16):2215–2220. [PMC free article] [PubMed] [Google Scholar]
  4. Gann P. H., Hennekens C. H., Stampfer M. J. A prospective evaluation of plasma prostate-specific antigen for detection of prostatic cancer. JAMA. 1995 Jan 25;273(4):289–294. [PubMed] [Google Scholar]
  5. Helzlsouer K. J., Newby J., Comstock G. W. Prostate-specific antigen levels and subsequent prostate cancer: potential for screening. Cancer Epidemiol Biomarkers Prev. 1992 Nov-Dec;1(7):537–540. [PubMed] [Google Scholar]
  6. Jacobsen S. J., Bergstralh E. J., Guess H. A., Katusic S. K., Klee G. G., Oesterling J. E., Lieber M. M. Predictive properties of serum-prostate-specific antigen testing in a community-based setting. Arch Intern Med. 1996 Nov 25;156(21):2462–2468. [PubMed] [Google Scholar]
  7. Knekt P., Aromaa A., Maatela J., Alfthan G., Aaran R. K., Teppo L., Hakama M. Serum vitamin E, serum selenium and the risk of gastrointestinal cancer. Int J Cancer. 1988 Dec 15;42(6):846–850. doi: 10.1002/ijc.2910420609. [DOI] [PubMed] [Google Scholar]
  8. Lein M., Koenig F., Jung K., McGovern F. J., Skates S. J., Schnorr D., Loening S. A. The percentage of free prostate specific antigen is an age-independent tumour marker for prostate cancer: establishment of reference ranges in a large population of healthy men. Br J Urol. 1998 Aug;82(2):231–236. doi: 10.1046/j.1464-410x.1998.00723.x. [DOI] [PubMed] [Google Scholar]
  9. Ornstein D. K., Smith D. S., Rao G. S., Basler J. W., Ratliff T. L., Catalona W. J. Biological variation of total, free and percent free serum prostate specific antigen levels in screening volunteers. J Urol. 1997 Jun;157(6):2179–2182. [PubMed] [Google Scholar]
  10. Parkes C., Wald N. J., Murphy P., George L., Watt H. C., Kirby R., Knekt P., Helzlsouer K. J., Tuomilehto J. Prospective observational study to assess value of prostate specific antigen as screening test for prostate cancer. BMJ. 1995 Nov 18;311(7016):1340–1343. doi: 10.1136/bmj.311.7016.1340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Piironen T., Pettersson K., Suonpä M., Stenman U. H., Oesterling J. E., Lövgren T., Lilja H. In vitro stability of free prostate-specific antigen (PSA) and prostate-specific antigen (PSA) complexed to alpha 1-antichymotrypsin in blood samples. Urology. 1996 Dec;48(6A):81–87. doi: 10.1016/s0090-4295(96)00616-4. [DOI] [PubMed] [Google Scholar]
  12. Puska P., Tuomilehto J., Salonen J., Neittaanmäki L., Maki J., Virtamo J., Nissinen A., Koskela K., Takalo T. Changes in coronary risk factors during comprehensive five-year community programme to control cardiovascular diseases (North Karelia project). Br Med J. 1979 Nov 10;2(6199):1173–1178. doi: 10.1136/bmj.2.6199.1173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Royston P., Thompson S. G. Model-based screening by risk with application to Down's syndrome. Stat Med. 1992 Jan 30;11(2):257–268. doi: 10.1002/sim.4780110211. [DOI] [PubMed] [Google Scholar]
  14. Stenman U. H., Hakama M., Knekt P., Aromaa A., Teppo L., Leinonen J. Serum concentrations of prostate specific antigen and its complex with alpha 1-antichymotrypsin before diagnosis of prostate cancer. Lancet. 1994 Dec 10;344(8937):1594–1598. doi: 10.1016/s0140-6736(94)90405-7. [DOI] [PubMed] [Google Scholar]
  15. Stenman U. H., Leinonen J., Alfthan H., Rannikko S., Tuhkanen K., Alfthan O. A complex between prostate-specific antigen and alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer. Cancer Res. 1991 Jan 1;51(1):222–226. [PubMed] [Google Scholar]
  16. Wald N. J., Cuckle H. S., Densem J. W., Nanchahal K., Royston P., Chard T., Haddow J. E., Knight G. J., Palomaki G. E., Canick J. A. Maternal serum screening for Down's syndrome in early pregnancy. BMJ. 1988 Oct 8;297(6653):883–887. doi: 10.1136/bmj.297.6653.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Wald N. J., Thompson S. G., Densem J. W., Boreham J., Bailey A. Serum vitamin E and subsequent risk of cancer. Br J Cancer. 1987 Jul;56(1):69–72. doi: 10.1038/bjc.1987.156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Whittemore A. S., Lele C., Friedman G. D., Stamey T., Vogelman J. H., Orentreich N. Prostate-specific antigen as predictor of prostate cancer in black men and white men. J Natl Cancer Inst. 1995 Mar 1;87(5):354–360. doi: 10.1093/jnci/87.5.354. [DOI] [PubMed] [Google Scholar]
  19. Woodrum D. L., Brawer M. K., Partin A. W., Catalona W. J., Southwick P. C. Interpretation of free prostate specific antigen clinical research studies for the detection of prostate cancer. J Urol. 1998 Jan;159(1):5–12. doi: 10.1016/s0022-5347(01)63996-x. [DOI] [PubMed] [Google Scholar]
  20. Woodrum D., French C., Shamel L. B. Stability of free prostate-specific antigen in serum samples under a variety of sample collection and sample storage conditions. Urology. 1996 Dec;48(6A):33–39. doi: 10.1016/s0090-4295(96)00607-3. [DOI] [PubMed] [Google Scholar]

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