Characteristics of prostate cancers detected at low PSA levels

When age-referenced PSA levels as recommended by Oesterling et al.1 were used as a biopsy criterion, only 25% of the cancers detected in a population based PSA Screening Project were organ-confined. This observation led to the decision to use low PSA levels as the sole indication for biopsy. Since 1995 age-referenced PSA levels of 1.25-3.25 ng/ml have been used in combination with a percentage free PSA cutoff of 18%. This PSA cutoff reduction led to a statistically significant migration to lower pathological stages with a decreased prostate cancer mortality in the years 1996-2001. However, concerns have been raised that screening with low PSA levels may detect clinically insignificant cancers.

We evaluated prostate cancer patients with low PSA levels in terms of heterogeneity, clinical significance, multifocality, and tumor biology including ploidy and proliferation index.

Concerning heterogeneity the Gleason score of the needle biopsy failed to predict the Gleason score of the radical prostatectomy specimen in nearly 40% of prostate cancer patients; regarding multifocality 65% of patients with low PSA levels showed multifocal lesions and 36% exhibited tetraploid DNA distribution; more than 50% of tetraploid tumors were found in patients with tumor volumes of less than 0.5 cm(3). Ploidy correlated with the Ki-67 proliferation index, but not with tumor volume.

These results demonstrate that small prostate cancers with low PSA levels and low tumor volumes exhibit all features of prostate cancers with higher tumor volumes and show the characteristics of malignant cancers, i.e., multifocality, tetraploidy, and high proliferative activity.