Location of
screening centers:

Helsinki University Central Hospital
Stenbäckinkatu 9
FIN-00290 Helsinki
FINLAND

Tampere School of Public Health
University of Tampere
FIN-33014 Tampere
FINLAND

Contact address:

Anssi Auvinen, MD, PhD
Professor of epidemiology
Tampere School of Public Health
University of Tampere
FIN-33014 Tampere
FINLAND
E-mail: Anssi.Auvinen@uta.fi

Study protocol

The study population in the Finnish trial on prostate cancer screening consists of 79,494 men born in 1929-1944 in the metropolitan areas of Helsinki and Tampere. Of them, 30,403 have been randomised into the screening arm. Approximately 88% of the men are still alive, residing in the study area and free of prostate cancer. The first screening round was carried out in 1996-99 and the second round will be completed in 2003. The third and final screening round commences in 2004 with smaller target population (excluding men aged >71 years). Yet, they will remain in follow-up for cancer incidence and mortality. The men in the control arm are not contacted, except a random sample for assessing quality of life and prevalence of unorganised screening and prostate disease.

A letter of invitation is mailed to the men in the screening arm, asking them to attend the screening center (local cancer society clinic) at a specified time for blood drawing. An information package about the study and prostate cancer in general, as well as an informed consent form are enclosed. They are also asked to fill in a questionnaire regarding urological symptoms and treatment, as well as risk factors for prostate cancer. The blood samples are analysed centrally at the Laboratory Diagnostics unit of Helsinki University Hospital. The PSA determinations are performed using the Hybritech Tandem-E assay, as in other centers participating in the European study. Quality control follows the guidelines provided by the collaborative study.

A screening positive finding is defined as a serum PSA concentration of 4.0 g/l or greater. Furthermore, among men with serum PSA between 3.0 g/l and 4.0 g/l, those with a low free to total PSA ratio (0.16 or below) are also referred to diagnostic examinations. Men with a screening positive finding are referred to the local urology clinic, including Helsinki University Hospital (with Peijas-Rekola Hospital, Jorvi Hospital) and Tampere University Hospital for diagnostic procedures including digital rectal examination (DRE), transrectal ultrasound (TRUS) and biopsy. The biopsy protocol initially comprised of sextant biopsy and with focal lesion also a directed biopsy and was modified in fall of 2002 to decrease false negative biospies so that 10 to 12 biopsies are performed depending on prostate volume (with cut-off of 40 ml) and specifically targeting apex. As the trial is a multicenter study and has several hospitals with independent pathology, grading and staging of all cancers is re-assessed retrospectively by study pathologists (Paula Martikainen and Marita Laurila). In addition, quality assurance of the pathology is conducted as a part of the European study led by prof van der Kwast, Erasmus University Rotterdam. Serum samples of all attenders have been stored for future analyses since the second study year.

The screen-detected cancers are treated according to the established guidelines at the time of the diagnosis. A strict treatment protocol would impair the comparability of the patients from screening arm and control arm and it is thus not desirable or feasible. Instead, it is crucial for comparability of the results to treat patients with similar disease with similar techniques in both arms, i.e. using similar treatment options given age, stage and grade. As new treatment options are developed and adopted, they will be incorporated to the protocol. Currently, the treatment options for localised cancer include radical prostatectomy, radical radiotherapy and for small, well-differentiated tumors, watchful waiting (Consensus conference 1987). For non-local disease, endocrine treatment is recommended with orchidectomy, LHRH agonist, antiandrogen and maximal androgen blockade as treatment options.

The main end-point is prostate cancer mortality and a cause of death committee has been established to evaluate all causes of death among men diagnosed with prostate cancer. Prof Pekka Karhunen is the chair of the CoD committee and other members include Jussi Aro, urologist and Jorma Lahtela, internist. Causes of death are evaluated from medical records in a blinded fashion (unaware of the trial arm) following decision rules established for the trial.