Many abnormal PSA test results normalize over time

Journal of Family Practice, Sept, 2003 by Robert Gramling

Eastham JA, Riedel E, Scardino PT, et al. Variation of serum prostate-specific antigen levels. An evaluation of year-to-year fluctuations. JAMA 2003; 289:2695-2700.

* PRACTICE RECOMMENDATIONS

A significant proportion of prostate-specific antigen (PSA) tests with abnormal results--nearly half--normalize over 1 to 4 years of fellow-up without any medical or surgical intervention. This information can be used by physicians and their patients in shared decision-making about both PSA screening and in deciding how to follow up an abnormal result.

* BACKGROUND

PSA is frequently used for prostate cancer screening. Positive screening values often lead to biopsy and other invasive interventions, but the long-term natural history of PSA levels is not known.

* POPULATION STUDIED

The researchers studied PSA levels of men previously enrolled in a dietary intervention trial to reduce the recurrence of colon polyps (Polyp Prevention Trial, 1991-1998). The trial included men aged >35 years having a colon adenomatous polyp removed within 6 months of the trial.

The researchers excluded men with familial adenomatous polyposis or premature colon polyps (<35 years), invasive large bowel cancers, or inflammatory bowel disease. They also excluded men with prior prostate cancer and those not completing all yearly blood samples.

Of 1351 men in the original trial, 972 were included in this report. Approximately one third were aged <60 years, one third were aged 60-69 years, and one third were aged >70 years (only 1 was >80 years).

* STUDY DESIGN AND VALIDITY

This is a descriptive, 4-year longitudinal cohort from a randomized controlled trial conducted between 1991 and 1998. The researchers analyzed PSA results from frozen blood samples collected in the original trial at baseline and at four 1-year intervals. Previous work demonstrated acceptable long-term stability of frozen total PSA.

The researchers excluded 26 subjects from a portion of their analysis due to prostate cancer development during the study period (23 documented and 3 highly suspicious PSA trajectories). This was appropriate given the paper's focus on natural history.

A simple sensitivity analysis of the scenario most likely to bias the reported observations is thus appropriate. Using a scenario in which it is assumed that:

* all 26 men with prostate cancer had PSA levels in the abnormal range for all criteria

* at least 2 blood draws remained after the abnormal result

* the PSA levels would never normalize then alternative results, using this scenario, are presented in brackets after the values round in the original analysis. This secondary analysis does not reflect any predictive values of the PSA itself, but rather reframes the study observations to more accurately reflect real-world results.

* OUTCOMES MEASURED

The study measured PSA levels (ng/mL) at the following clinical standards: total PSA >2.5, total PSA >4.0, age-specific total PSA levels, free/total PSA <0.25, or PSA velocity >0.75.

* RESULTS

For the criterion of total PSA >2.5, 37% of men had at least 1 positive value. Among the 291 [317] men with an abnormal value and at least 1 remaining blood draw, 40% [36%] had values return to the normal range on at least 1 subsequent occasion. For 62 [88] men who had at least 2 subsequent blood draws remaining, 65% [45%] had 2 consecutive normal levels.

For the criterion of total PSA >4.5, 21% of men had at least 1 positive value. Among the 154 [180] men with an abnormal value and at least 1 remaining blood draw, 44% [37%] had values return to the normal range on at least 1 subsequent occasion. For 40 [66] men who had at least 2 subsequent blood draws remaining, 80% [48%] had 2 consecutive normal levels.

For the age-specific PSA criteria, 18% of men had at least 1 positive value. Among the 117 [143] men with an abnormal value and at least 1 remaining blood draw, 55% [44%] had values return to the normal range on at least 1 subsequent occasion. For 35 [61] men who had at least 2 subsequent blood draws remaining, 83% [47%] had 2 consecutive normal levels.

For the free-total PSA criterion, 20% of men had at least 1 positive value. Among the 143 [169] men with an abnormal value and at least 1 remaining blood draw, 53% [45%] had values return to the normal range on at least 1 subsequent occasion. For 43 [69] men who had at least 2 subsequent blood draws remaining, 74% [46%] had 2 consecutive normal levels.

Robert Gramling, MD, Department of Family Medicine, Brown Medical School, Providence; Memorial Hospital of Rhode Island, Pawtucket. E-mail: Robert_Gramling@Brown.edu.