Prostate-specific antigen levels and subsequent prostate cancer: potential for screening

Prostate-specific antigen levels are increased in men with prostatic disease, including prostate cancer, and have been used clinically to monitor the response of prostate cancer to therapy. More recently, prostate-specific antigen levels, usually in combination with digital rectal examination or transrectal prostatic ultrasonography, have been suggested to be useful for the detection of prostate cancer. To evaluate the association between a single serum prostate-specific antigen level and the subsequent development of prostate cancer, we measured serum levels in 35 men who donated blood to a community-based serum bank in 1974 and who subsequently developed prostate cancer and in 35 matched controls from the same group of volunteers. Levels of prostate-specific antigen were significantly higher in men who went on to develop prostate cancer, up to 6 years prior to the time of diagnosis in the cases. The level of prostate-specific antigen decreased with increasing time to diagnosis. The mean level for prostate cancer cases diagnosed within the first 3 years of follow-up was 16.2 mug/liter compared to 2.4 mug/liter for controls (P = 0.002). The mean level for cancer cases diagnosed in years 4 through 6 following blood sampling was 9.6 mug/liter compared to 1.3 mug/liter for controls (p = 0.0002). The sensitivity and specificity of a prostate-specific antigen level >/= 4mug/liter up to 3 years prior to the time of clinical diagnosis were both 75% and up to 6 years were 67% and 85%, respectively. Because prostate-specific antigen levels are reasonably sensitive and specific in detecting prostate cancer up to 6 years prior to the time of usual diagnosis, their use in screening for the prevention of prostate cancer mortality should be evaluated in a controlled clinical trial.