Problems: Description of transrectal ultrasound (TRUS) anatomy in selected healthy men is lacking. Is the prostate gland involved in febrile urinary tract infection (UTI)? Is one negative prostate sextant-biopsy enough to rule out prostate cancer (PC)? What is the risk of diagnosing insignificant PC in men subjected to long-term PSA-screening?Methods: I) 125 healthy men (20-69 years) were investigated by TRUS. II-III) 70 and 55 men, respectively, with febrile UTI were followed 12 months with physical examinations, repeated PSA-testing and TRUS. IV-V) 10.000 men (50-65 years) were randomized to biennial PSA-screening. If elevated PSA digital rectal examination and TRUS-led prostate biopsies were recommended. In 457 men with one set of negative prostate-biopsies, the outcome from two subsequent screening-occasions was studied. The rate of low-volume PC (evaluated in prostatectomy- or biopsy-specimen) was studied in 544 men diagnosed at one of 4 biopsy-occasions. Results: I) Prostate volume (PV) increased with age (19.2-35.5cm3). Sonographic changes were common in all age-groups. II-III) 83% had elevated PSA (>4ng/ml) during febrile UTI. PV and decreased significantly (31%) the infection. Free-PSA normalized after one month. Complexed-PSA slowly decreased during 12 months. Up to six months free-to-total-PSA was similar to PC-values (11-16%). IV) Three groups were found: PC (26%), three negative biopsies (56%) and normalized PSA (17%). In cases with PV <20cm3 either PC or normalized PSA was found. Only follow-up identified the normalized-PSA group. V) Biopsies and cancers detected at four biopsy-rounds were; 1593/389, 571/120, 252/33 and 78/6, respectively. The risk of detecting low-volume cancer was constant (5-7%) at the different sets of biopsies, but the relative ratio of low-volume cancer doubled from 24% (19%) at primary biopsy to 48% (36%) at third biopsy. Conclusions: Various TRUS-findings are common among healthy men. The prostate gland is commonly involved in febrile UTI, with PSA and TRUS-findings during follow-up mimicking PC. Causes for PSA elevation in men with one negative sextant prostate-biopsy are PC, BPH and probably inflammation. The chance of finding significant cancer decreases with the number of previous sets of benign biopsies, while the risk of detecting low-volume cancer is constant
