Clinical Health Updates

Elevated PSA should be confirmed before biopsy

Clinical Question:
How often does an elevated PSA level return to normal?

Bottom Line:
Isolated elevations of serum prostate-specific antigen (PSA) frequently return to normal. Clinicians and their patients with an elevated PSA have 3 choices: (1) immediate referral for biopsy; (2) immediate repeat of the PSA test; or (3) wait 4 to 6 weeks and repeat the test. The repeat testing interval of 4 to 6 weeks is based on studies reporting the time needed for an elevated PSA to return to normal after biopsy or surgery for noncancerous conditions. Studies of prostate cancer progression conclude that a delay of several months from diagnosis to surgery does not affect outcomes. Thus, choice #3 is likely the best one for most patients before proceeding with further testing or referral. (LOE = 2b)

Reference:
Eastham JA, Riedel E, Scardino PT, et al. Variation of serum prostate-specific antigen levels. An evaluation of year-to-year fluctuations. JAMA 2003: 289:2695-700.

Study Design:
Cohort (prospective)

Synopsis:
Serum prostate-specific antigen (PSA) testing is frequently used in early detection programs for prostate cancer. While PSA testing has resulted in an increase in prostate cancer detection, its routine use has been questioned because of a lack of specificity. The authors determined whether year-to-year fluctuations in PSA levels are due to natural variation and render a single PSA test result unreliable. They did a retrospective analysis of an unscreened population of 972 men (median age, 62 years) participating in the Polyp Prevention Trial (1991-1998). Five consecutive blood samples were obtained during a 4-year period and were assessed for total and free PSA levels. Abnormal PSA test result based on a PSA level higher than 4 ng/mL; a PSA level higher than 2.5 ng/mL; a PSA level above the age-specific cutoff; a PSA level in the range of 4 to 10 ng/mL and a free-to-total ratio of less than 0.25 ng/mL; or a PSA velocity higher than 0.75 ng/mL per year. Prostate biopsy would have been recommended in 207 participants (21%) with a PSA level higher than 4 ng/mL; in 358 (37%) with a level higher than 2.5 ng/mL; in 172 (18%) with a level above the age-specific cutoff; in 190 (20%) with a level between 4 and 10 ng/mL and a free-to-total ratio of less than 0.25 ng/mL; and in 145 (15%) with a velocity higher than 0.75 ng/mL per year. Among men with an abnormal PSA finding, a high proportion had a normal PSA finding at 1 or more subsequent visits during 4-year follow-up: 68 (44%) of 154 participants with a PSA level higher than 4 ng/mL; 116 (40%) of 291 had a level higher than 2.5 ng/mL; 64 (55%) of 117 had an elevated level above the age-specific cutoff; and 76 (53%) of 143 had a level between 4 and 10 ng/mL and a free-to-total ratio of less than 0.25 ng/mL.