PSA doubling time as a predictor of the outcome of random prostate biopsies prompted by isolated PSA elevation in subjects referred to an outpatient biopsy facility in a routine clinical scenario.

AIM: To assess the validity of PSA doubling time (PSADT) as a predictor of prostate sextant biopsy outcome in patients with PSA levels in the 4-10 ng/mL range. MATERIAL AND METHODS: A consecutive series of 355 sextant biopsies performed during 2001-2007 in subjects with negative digital rectal examination and transrectal ultrasonography was considered. Variables tested as possible predictors were age, total and free/total PSA value, PSA velocity and PSA doubling time. While PSA at time of biopsy and free/total PSA were determined with a standardized method undergoing strict quality control, previous PSA values used to assess velocity/doubling time came from other labs using different assays over widely varying intervals of time. The association with biopsy outcome (cancer vs non-cancer) was investigated by univariate and multivariate analysis. RESULTS: Apart from free/total PSA ratio, no other studied variable showed a statistically significant and independent association with biopsy outcome, either at univariate or multivariate analysis. No studied variable had a good performance as a biopsy indicator. Depending on the variable considered, 1.17 to 1.97 cancers would be missed to spare 10 benign biopsies. CONCLUSION: When based on PSA data determined with different assays over widely varying intervals and in the absence of an underlying protocol for PSA surveillance, PSA velocity and doubling time should never discount a biopsy prompted by total PSA elevation.

On the clinical usefulness of the free-to-total prostate-specific antigen ratio.

The free-to-total prostate-specific antigen ratio (F/T PSA) is associated with the presence of prostate cancer and is thus used as an indicator for suspicion of prostate cancer and as a determinant for biopsy. We reviewed a recent retrospective series of 966 consecutive prostate biopsies where F/T PSA was blindly determined and did not influence biopsy indication. We simulated the association of F/T PSA with biopsy outcome and its impact as a biopsy determinant. When adopting an F/T PSA cutoff of 10%, 13%, 16% or 20% among random sextant biopsies in the 4-10 ng/mL total PSA range, the sensitivity was 15%, 37%, 55% and 72% and the specificity 89%, 80%, 64% and 44%, respectively. Using F/T PSA as a biopsy determinant, from 1.7 to 2.6 cancer biopsies would have been delayed to avoid 10 benign biopsies. As this balance is not acceptable, F/T PSA has no role as a biopsy indicator and its clinical use is questionable.

Association of human papillomavirus with prostate cancer: analysis of a consecutive series of prostate biopsies.

The study purpose was to investigate the association of human papillomavirus (HPV) infection with prostate cancer. The presence and type of HPV DNA were investigated by polymerase chain reaction in the preservation fluid of 60 consecutive prostate core biopsies (29 benign, 31 malignant). The material was inadequate (no DNA found at beta-globin testing) in four benign and five cancer biopsies. HPV DNA was found in 17 of 26 (65.3%) cancer and 12 of 25 (48.0%) benign biopsies (chi2 = 0.94, p = 0.33). High-risk HPV type positivity was observed in 14 of 26 (53.8%) cancer and in five of 25 (20.0%) benign biopsies (chi2 = 4.38, p = 0.03). Twenty-three of 29 cases were positive at L1 region testing with MY09/11 primers; testing with primers directed to the E6/E7 region revealed six further HPV-positive cases (four cancer, two benign). The presence of HPV in prostate tissue suggests a possible reservoir for sexual transmission of types with oncogenic potential. Our findings also suggest a possible role of high-risk HPV infection in the etiology of prostate cancer and encourage further research into this issue.