Prospective detection of clinically relevant prostate cancer in the prostate specific antigen range 1 to 3 ng./ml. combined with free-to-total ratio 20% or less: The Aarau experience

Purpose: Little is known about the incidence rate and clinical relevance of prostate cancer in a low prostate specific antigen (PSA) level. In a prosp ective PSA based screening study we investigated the incidence and clinicop athological features of prostate cancer that occurred within PSA range 1 to 3 ng./ml. when the free-to-total ratio was 0.20 or less. Materials and Methods: Men participating in the Aarau, Switzerland, section of the European Randomized Study of Screening for Prostate Cancer between October 1998 and July 2000 were included in the study. As a side study, all men with PSA between 1 and 3 ng./ml. and free-to-total ratio 0.20 or less were invited to undergo further evaluation with ultrasound guided sextant p rostate biopsy. Results: Overall, 168 (7.8%) participants fulfilled inclusion criteria. A t otal of 158 (94%) patients underwent prostate biopsy, and prostate cancer w as detected in 17 (10.8%). There were no statistically significant differen ces between prostate cancer and benign prostatic hyperplasia in regard to p atient age (60.7 versus 59.8 years), prostate volume (23.9 versus 23.0 cc), PSA (1.98 versus 1.86 ng./ml.), free-to-total ratio (0.161 versus 0.160), PSA density (0.089 versus 0.076 ng./ml.) or PSA transition zone density (0. 33 versus 0.24 ng./ml., respectively). Median Gleason score was 5 on prosta te biopsy versus 6 on retropubic prostatectomy specimen. Of the 14 patients who underwent surgery there were positive lymph nodes in 1, stage pT3b Gle ason 7 disease in 1, and pathologically organ confined Gleason 5 in 2, Glea son 6 in 5 and Gleason 7 in 5. Mean tumor volume was 1.01 cc (range 0.02 to 5.17). There were 2 (14.3%) insignificant (less than 0.2 cc, Gleason grade 3 or less), 1 (7.1%) minimal (less than 0.5 cc, Gleason grade 3 or less) a nd 11 (78.6%) clinically relevant and potentially harmful cancers. Conclusions: There is a significant number of prostate cancer cases diagnos ed at PSA as low as 1 to 3 ng./ml. A majority of these tumors are clinicall y significant. This free-to-total ratio range may be helpful for identifyin g prostate cancer. The "window of opportunity" for detection of curable can cer may change in populations with higher life expectancy towards lower PSA . Lack of specificity and characterization of tumor aggressiveness remains an unsolved issue for PSA.