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ERSPC - Section: Sweden (Göteborg)

Location: Department of Urology Sahlgrenska University Hospital 413 45 Gothenburg SWEDEN	Contact address: Professor Jonas Hugosson Department of Urology Sahlgrenska University Hospital 413 45 Gothenburg E-mail: jonas.hugosson@urology.gu.se
Study protocol The ethical committee of Gothenburg University approved the study protocol of the Gothenburg branch of the ERSPC in 1994. The study started in January 1995. The protocol in Gothenburg has some differences compared to the other centres in the ERSPC. All men in the Swedish branch are randomised up-front, it means before the informed consent. The screening population was randomised from the entire population of men born between January 1, 1930 and December 31, 1944, living in the community of Gothenburg at January 1, 1995. Of these all together approximately 32 000 men 10 000 were randomised to a control group and 10 000 to a screening group. 28 men in the screening group and 27 men in the controlgroup were found to already have diagnosis of prostate cancer registered in the regional Cancer Register. This is a very low incidence of prevalent prostate cancer and reflects the very low rate of opportunistic PSA-screening in the Swedish population at that time. It means that this study-group is a population who previously has not been exposed to PSA-screening. Men in the screening arm have been invited every second year for PSA-testing until they turn 70. From the beginning we have used a cut-off of 3 ng/ml for further work-up. Men who have a PSA < 3 ng/ml are not further examined (no digital rectal examination is part of this screening program). Men with elevated PSA are invited for an examination by an experienced urologist. This examination includes medical history, digital rectal examination, transrectal ultrasound and laterally directed sextant biopsies of the prostate. So far six complete rounds of screening have been conducted and for the moment the seventh round is running. During the twelve years that the study has been running there have been some minor changes in the protocol. 1) The PSA cut-off was lowered to 2,54 from the third screening invitation. This lowering of the PSA cut-off was carried out to harmonise with other ERSPC-centres who used the Hybritech assay instead of the Wallac assay, which was used in the present study. 2) In the first and second screening round men with PSA = 7 ng/ml were reexamined after sex months with new PSA and if they still had an elevated value they were invitated for new DRE, TRUS and biopsies. From screening round three however, this was no longer done. 3) During the third screening round only men with PSA = 1 ng/ml during the second screening round were invited. This step was carried out as results showed that no men who had PSA <1 ng/ml in the first screening round had PSA =3 ng/ml during the second screening round. 4) Until round five all men with PIN and ASAP were rebiopsied, from round six rebiopsies were only performed on the men who participated for the last time in the study. So far 73% of the invited men have participated at least once in the program and approximately 50% of men have responded to all invitations. A total of 806 prostate cancer have been detected within the screening program and the cumulative incidence among those who have participated in the screening program is 8% while the cumulative incidence among the control arm is approximately 2,7%. Further results from the study could be achieved from the following publications. Publications: Aus G, Bergdahl S, Lodding P, LIlja H, Hugosson J Prostate cancer screening decreases the absolute risk of being diagnosed with advanced prostate cancer--results from a prospective, population-based randomized controlled trial. Eur Urol. 2007 Mar;51(3):659-64. Epub 2006 Jul 28. Ulmert D, Becker C, NIlsson JA, Piironen JA, Piironen T, Bjork T, Hugosson J, Berglund G, Lilja H Reproducibility and accuracy of measurements of free and total prostate-specific antigen in serum vs plasma after long-term storage at -20 degrees C. Clin Chem. 2006 Feb;52(2):235-9. Epub 2005 Dec 29. Aus G, Damber JE, Khatami A, Lilja H, Stranne J, Hugosson J Individualized screening interval for prostate cancer based on prostate-specific antigen level: results of a prospective, randomized, population-based study. Arch Intern Med. 2005 Sep 12;165(16):1857-61. Bruun L, Becker C, Hugosson J, Lilja H, Christensson A Assessment of intra-individual variation in prostate-specific antigen levels in a biennial randomized prostate cancer screening program in Sweden. Prostate. 2005 Nov 1;65(3):216-21. Hugosson J, Aus G, Lilja H, Lodding P, Pihl CG Results of a randomized, population-based study of biennial screening using serum prostate-specific antigen measurement to detect prostate carcinoma. Cancer. 2004 Apr 1;100(7):1397-405. Zackrisson B, Aus G, Bergdahl S, Lilja H, Lodding P, Pihl CG, Hugosson J The risk of finding focal cancer (less than 3 mm) remains high on re-biopsy of patients with persistently increased prostate specific antigen but the clinical significance is questionable. J Urol. 2004 Apr;171(4):1500-3. Hugosson J, Aus G, Bergdahl S, Fernlund P, Frosing R, Lodding P, Pihl CG, Lilja H Population-based screening for prostate cancer by measuring free and total serum prostate-specific antigen in Sweden. BJU Int. 2003 Dec;92 Suppl 2:39-43. Aus G, Becker C, Franzén S, Lilja H, Lodding P, Hugosson J Cumulative prostate cancer risk assessment with the aid of the free-to-total prostate specific antigen ratio. Eur Urol. 2004 Feb;45(2):160-5. Aus G, Becker C, Lilja H, Khatami A, Pihl CG, Hugosson J Free-to-total prostate-specific antigen ratio as a predictor of non-organ-confined prostate cancer (stage pT3). Scand J Urol Nephrol. 2003;37(6):466-70. Tornblom M, Eriksson H, Franzén S, Gustafsson O, Lilja H, Norming U, Hugosson J Lead time associated with screening for prostate cancer. Int J Cancer. 2004 Jan 1;108(1):122-9. Khatami A, Damber JE, Lodding P, Pihl CG, Hugosson J Does initial surveillance in early prostate cancer reduce the chance of cure by radical prostatectomy?--A case control study. Scand J Urol Nephrol. 2003;37(3):213-7. Hugosson J, Aus G, Lilja H, Lodding P, Pihl CG, Pileblad E Prostate specific antigen based biennial screening is sufficient to detect almost all prostate cancers while still curable. J Urol. 2003 May;169(5):1720-3. Zackrisson B, Aus G, Lilja H, Lodding P, Pihl CG, Hugosson J Follow-up of men with elevated prostate-specific antigen and one set of benign biopsies at prostate cancer screening. Eur Urol. 2003 Apr;43(4):327-32. Aus G, Bergdahl S, Hugosson J, Lodding P, Pihl CG, Pileblad E Outcome of laterally directed sextant biopsies of the prostate in screened males aged 50--66 years. Implications for sampling order. Eur Urol. 2001 Jun;39(6):655-60; discussion 661. Hugosson J, Lilja H, Lodding P, Pihl CG Tumor volume is a valid surrogate endpoint for defining clinically significant prostate cancers. Eur Urol. 2001 Apr;39 Suppl 4:33-4. No abstract available. Lodding P, Aus G, Bergdahl S, Frosing R, Lilja H, Pihl CG, Hugosson J Characteristics of screening detected prostate cancer in men 50 to 66 years old with 3 to 4 ng/ml. Prostate specific antigen. J Urol. 1998 Mar;159(3):899-903.