Impact of prostate size on biopsy outcome at low PSA levels

One of the central concerns hampering specific cancer detection is the ability of BPH to generate PSA such that, at low levels, the relative contributions of BPH and adenocarcinoma may be indistinguishable. Attempts to define the relationship between these factors and PSA have led to a plethora of refinements in the test (various PSA fractions) and various statistically determined PSA parameters (ie, density, velocity, age specific, and free:total ratio). Often, these improve specificity, but at the expense of sensitivity.

This article explains how prostatic volume can be used to stratify risk of prostate cancer and discusses the nomogram our group has developed based on this concept.

Volume as a cancer predictor

Many authors have identified reducing yield from sextant prostatic biopsies with increasing gland volume (Urology 1995; 46:831-6; Urology 1997; 49:55-9; J Urol 1998; 160:1718-21). The general response to the perceived lack of cancer detection has been increasingly vigorous biopsy schedules (J Urol 2003; 169:125-9; J Urol 2001; 166:86-92). Detection rates improve with extended biopsy protocols, but the definition of clinically significant disease remains elusive. Although disease-specific mortality would appear to be improving as a result of radical prostatectomy, a group of men remain over-investigated and over-treated (N Engl J Med 2005; 352:1977-84).

The possibility arises that the lower biopsy yield for large glands represents not undersampling, but the existence of fewer large-volume cancers and that the PSA reflects adenoma, rather than adenocarcinoma. Certainly, it has been demonstrated previously that although prostate cancer produces about 10 times the serum PSA as does BPH, the latter is responsible for a steady linear increase in serum PSA at a rate of 0.25 to 0.3 ng/mL per gram of adenoma (J Urol 1995; 153:111-4).