The diagnostic performance of prostate-specific antigen (PSA) in early detection of prostate cancer : considerations of sensitivity, specificity, lead-time and survival
Background: Prostate cancer (PC) is the most common form of cancer, as well as the single major cause of cancer-related mortality among Swedish males. Recent reports indicate that screening of the serum levels of prostate-specific antigen (PSA) in asymptomatic men may result in decreases in both the incidence of metastatic disease and PC-specific mortality. However, the diagnostic performance of PSA-based screening is limited by rather low sensitivity and specificity. An improved understanding of the natural course of PC in relationship to PSA levels at the time of diagnosis is required in order to calculate how much earlier diagnosis can be achieved by screening (the lead-time) and when the beneficial effect in the form of improved survival can be expected to become apparent.
Patients and methods: This study is based on two well-defined cohorts of men both selected randomly from the general population. One of these cohorts (die Stockholm South PC study) included 1782 men who participated in a single intervention study for evaluation of early diagnostic methods in PC detection in 1988-89, whereas the other cohort (n=657) was involved in a screening of general health in men, not including PC, in 1980 (The Study of Men Born in 1913). The diagnostic performance of percentage free PSA (%fPSA) was evaluated in the Stockholm cohort. For estimations of lead-time and PC-specific survival, men from the two cohorts, with a median age of 67 years, were monitored for 12 and 20 years, respectively, following PSA testing. Individuals diagnosed as having PC as well as causes of mortality were ascertained utilizing the national Cancer Registry together with the Cause of Death Registry.
Results and conclusions: Retrospective application of a %fPSA "cut-off 'value of < 18% improved the diagnostic sensitivity among men with normal PSA levels (i.e., < 3.0 ng/ml), whereas a "cut-off" of 22% increased the specificity at slightly elevated PSA levels (3.0-9.9 ng/mL). In men without PC the %fPSA ratios were influenced by age and prostate volume, which at PSA levels in the interval of 4.0-9.9 ng/mL together accounted for much of the variation in this ratio. Men with PSA levels < 1.0 ng/mL were at a very low risk of being diagnosed as having, or of dying from PC during 20 years of follow-up. In the PSA interval of 3.0-9.9 ng/mL the various estimates of median lead-time obtained ranged from 4.5-11.2 years. Successful screening for PC (i.e., decreased mortality) should be discernible after 6 years, since men with PSA levels < 10.0 ng/mL accounted for 62%, 78% and 100% of all PC deaths 6-10, 11-15 and 16-20 years later, respectively. The results of this study support the diagnostic value of %fPSA for early detection of PC. Furthermore, this thesis indicates that intense PSA screening should result in a reduction in PC mortality already before the median lead-time is reached.
List of scientific papers
I. Tornblom M, Norming U, Adolfsson J, Becker C, Abrahamsson PA, Lilja H, Gustafsson O (1999). Diagnostic value of percent free prostate-specific antigen: retrospective analysis of a population-based screening study with emphasis on men with PSA levels less than 3.0 ng/mL. Urology. 53(5): 945-50.
https://pubmed.ncbi.nlm.nih.gov/10223488
II. Tornblom M, Norming U, Becker C, Lilja H, Gustafsson O (2001). Variation in percentage-free prostate-specific antigen (PSA) with prostate volume, age and total PSA level. BJU Int. 87(7): 638-42.
https://pubmed.ncbi.nlm.nih.gov/11350403
III. Tornblom M, Eriksson H, Gustafsson O, Franzén S, Norming U, Lilja H, Hugosson J (2003). Lead-time of screen detected prostate cancers. International Journal of Cancer. [Accepted]
IV. Tornblom M, Eriksson H, Gustafsson O, Franzén S, Norming U, Lilja H, Hugosson J (2003). When is reduced prostate cancer mortality to be expected provided that efficacious PSA screening is introduced? [Submitted]
History
Defence date
2003-10-10Department
- Department of Molecular Medicine and Surgery
Publication year
2003Thesis type
- Doctoral thesis
ISBN-10
91-7349-660-XNumber of supporting papers
4Language
- eng