Should Men With Serum PSA Levels of 4.0 ng/mL or Less Undergo a Prostate Biopsy?

J Brantley Thrasher; William L Valk


Nat Clin Pract Urol. 2004;1(1) 

In This Article


There is a general consensus among clinicians that a serum prostate-specific antigen (PSA) level ≥4.0 ng/ml is predictive of prostate cancer, and necessitates a biopsy. But there is a dearth of prospective data on the predictive value of PSA levels below this threshold.

To analyse the prevalence of prostate cancer in men with a serum PSA level ≤4.0 ng/ml.

Assessments of serum PSA levels and digital rectal examinations were performed annually for 7 years on the 18,882 participants in the Prostate Cancer Prevention Trial. This randomized, double-blind, placebo-controlled Phase III trial was designed to test the efficacy of daily finasteride treatment at reducing the prevalence of prostate cancer. A subgroup analysis was performed on the trial's placebo cohort to assess the predictive value of PSA levels ≤4.0 ng/ml. Men from the placebo group whose PSA had never exceeded 4.0 ng/ml, who had never previously undergone a prostate biopsy or transurethral prostate resection, and who had consistently normal results from digital rectal examinations were included in the subgroup analysis. Biopsies were performed and serum PSA levels measured at the end of the trial period.

The predictive value of serum PSA level for the detection of prostate cancer was calculated at study completion. This value was defined as the probability of detecting disease during end-of-study biopsy if serum PSA levels fell within a prespecified range.

The 2950 men that satisfied the selection criteria and consented to an end-of-study biopsy were aged between 62 and 91 years. Prostate cancer was detected in 449 (15%) of these subjects. Men that had developed cancer had higher serum PSA levels than cancer-free men (means 1.78 vs 1.34 ng/ml, P <0.001). The risk of developing cancer increased with rising PSA level, from 6.6% in men with a PSA value ≤0.5 ng/ml to 26.9% in men with 3.1-4.0 ng/ml PSA (odds ratio [OR] for developing prostate cancer, 1.66 per unit increase in serum PSA; 95% CI 1.50 to 1.85). Men whose father, brother(s) or son(s) were, or had been, affected by prostate cancer were significantly more likely to develop the disease (P = 0.004). All staged cancers that developed during the trial were stage T1, with Gleason scores of between 2 and 9. Serum PSA level was positively correlated with high-grade disease (OR for Gleason scores ≥7, 2.10 per unit increase in serum PSA; 95% CI 1.66 to 2.65).

Prostate cancer is surprisingly prevalent in men with serum PSA levels that are considered by many clinicians to be in the normal range (i.e. ≤4.0 ng/ml). Levels <4.0 ng/ml can be predictive of the risk of developing prostate cancer, and of the likelihood of malignancies being high-grade.


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