Clinical Question: Does the rate of increase in prostate-specific antigen (PSA) levels predict the outcome following radical prostatectomy in men with prostate cancer?

Setting: Inpatient (any location) with outpatient follow-up

Study Design: Cohort (prospective)

Synopsis: The PSA velocity, the rate of increase in PSA levels, has been associated with the stage and grade of prostate cancer at the time of detection. In this study, 1,804 men entered a program for prostate cancer screening, were diagnosed with prostate cancer, and were treated with radical prostatectomy. Of this group, 1,095 had a PSA test preoperatively and one year earlier and did not undergo adjuvant hormonal therapy or radiotherapy. All of the men underwent radical prostatectomy. Most had relatively low PSA values: 43 percent had a level of less than 4.0 ng per mL; 52 percent had a level between 4.0 and 10.0 ng per mL. Most also had a low to moderate Gleason score (84 percent scored 6), which indicated a less aggressive tumor. All of the patients had stage 1c (71 percent), 2a (24 percent), 2b (4 percent), or 2c (less than 1 percent) disease. The authors do not mention whether the pathologists were blinded to the PSA scores.

The median duration of follow-up was 5.1 years, and data were available for approximately 97 percent of patients. As with previous studies, a PSA velocity of more than 2.0 ng per mL per year during the year before treatment was associated with lymph node metastasis, a more advanced pathologic stage, and higher clinical grade disease. It also was associated with a greater likelihood of recurrence (adjusted relative risk [ARR] = 1.6; 95 percent confidence interval [CI], 1.1 to 1.9), a higher rate of death from prostate cancer (ARR = 9.8; 95 percent CI, 2.8 to 34.3), and death from any cause (ARR = 1.9; 95 percent CI, 1.2 to 3.2). Regarding the risk of death from prostate cancer, this ARR (7.4) was similar to that of tumor stage 2 versus tumor stage 1c and greater than that of Gleason score 8 to 10 versus Gleason score 2 to 6 (ARR = 3.4). Among the 833 men with a PSA velocity of 2.0 ng per mL or less per year at diagnosis, only three died during the five-year follow-up, compared with 24 deaths out of 262 men with PSA velocity of more than 2.0 ng per mL per year (0.4 versus 9.2 percent).

Bottom Line: The rate of increase in PSA levels is a strong independent predictor of outcome following radical prostatectomy in men with stage 1 or 2 prostate cancer. Specifically, an increase of more than 2.0 ng per mL per year is associated with lymph node metastasis and higher grade disease. This information may help guide follow-up and the use of adjuvant treatments in future studies. (Level of Evidence: 1b)