Fluctuation in prostate cancer gene 3 (PCA3) score in men undergoing first or repeat prostate biopsies.

OBJECTIVE: To evaluate the variability in prostate cancer gene 3 (PCA3) score over time in men with elevated serum prostate-specific antigen (PSA) levels who are undergoing first or repeat prostate biopsy. PATIENTS AND METHODS: A total of 360 men from two Italian institutions who had undergone at least two PCA3 assessments were selected. Of these, 97.5% were scheduled for first or repeat prostate biopsy because of elevated PSA level and/or positive digital rectal examination (DRE). We compared the PCA3 scores in men with a negative biopsy (normal parenchyma, benign prostatic hyperplasia [BPH], chronic prostatitis, high-grade prostate intraepithelial neoplasia [HG-PIN]) with those in men with a positive biopsy. We evaluated PCA3 repeated measures biological variability and its possible association with basic patient characteristics (age, family history of prostate cancer, DRE, prostate volume, BPH, prostatitis and HG-PIN). Three different thresholds were used to evaluate the possible changes in risk class: the standard threshold (a PCA3 score of 35), a US Food and Drug Administation-approved PCA3 threshold of 25 and a threshold selected based on our previous research which was a PCA3 score of 50. RESULTS: The PCA3 scores varied significantly (P < 0.001) when comparing men with a negative biopsy with those with a positive biopsy (median [range] PCA3 score: 25 [2-276] vs 43 [7-331]). There was no significant difference in PCA3 scores in men with chronic prostatitis and HG-PIN compared with other men with negative biopsies. The median (range) time between the two PCA3 assessments was 16.2 (3-53.7) months. No association was found between PCA3 repeated measures modifications and age, family history of prostate cancer, DRE, BPH, prostatitis, HG-PIN and use of 5-α-reductase inhibitors. The variability of PCA3 scores on repeated measures confirmed the risk class for about 80% of patients; of the remaining 20% of patients, the risk class was upgraded in two thirds and downgraded in one third. CONCLUSION: PCA3 score can be considered a stable marker over time in most cases but there is a group of men among whom there is clinically notable risk class change. Further investigation is required to determine the genesis of this phenomenon.

Histological chronic prostatitis and high-grade prostate intra-epithelial neoplasia do not influence urinary prostate cancer gene 3 score.

UNLABELLED: What's known on the subject? and What does the study add? While the relationship between PCA3 score and clinical or histological prostatitis was quite proven even in small patient groups, conversely the relationship between PCA3 score and HG-PIN is still under debate. We demonstrated in a large series (432 patients) that histologically documented chronic prostatitis and HG-PIN have similar PCA3 scores to patients with BPH and/or normal parenchyma at biopsy. OBJECTIVE: To determine whether histological chronic prostatitis and high-grade prostate intra-epithelial neoplasia (HG-PIN) influence the prostate cancer gene 3 (PCA3) score in Italian patients with an elevated prostate-specific antigen (PSA) level and a negative digital rectal examination (DRE) who were undergoing a first or repeat prostate biopsy. PATIENTS AND METHODS: A urinary PCA3 test was prospectively performed in 432 consecutive patients who were admitted to Gradenigo Hospital (Turin, Italy) between January and December 2011 and scheduled for first or repeat prostate biopsy as a result of an elevated PSA level and negative DRE. A comparison of the PCA3 score and patients with a negative biopsy (normal parenchyma, benign prostatic hyperplasia, chronic prostatitis, HG-PIN) or positive biopsy was performed. RESULTS: PCA3 median (range) scores varied significantly (P < 0.001) in men with a negative vs positive biopsy: 33 (2-212) and 66 (5-324), respectively. By contrast, men with chronic prostatitis and HG-PIN showed no significant difference with respect to PCA3 score compared to other negative biopsy patients. No correlation was found between the number of positive cores for chronic prostatitis, HG-PIN and PCA3 score. Of all patients with a positive biopsy, 23 (20%) of 114 men had a PCA3 score ≤ 35. In total, 79 (40%) of 197 men with a negative biopsy (normal parenchyma and benign prostatic hyperplasia), 24 (37.5%) of 64 men with chronic prostatitis and 19 (39.6%) of 48 men with HG-PIN had a PCA3 score >35. CONCLUSION: At this early stage of clinical evaluation, cancer specificity of the urinary PCA3 test appears to be maintained in the face of chronic prostatitis and HG-PIN.

Pathological patterns of prostate biopsy in men with fluctuations of prostate cancer gene 3 score: a preliminary report.

BACKGROUND: To evaluate pathological patterns of prostate biopsy in men with changes in risk class by prostate cancer gene 3 (PCA3) score and with elevated serum prostate-specific antigen (PSA) or positive digital rectal examination (DRE), undergoing a repeat biopsy. PATIENTS AND METHODS: A total of 108 males of two Italian Institutions who had undergone at least two PCA3 score assessments with changed PCA3 risk class were selected. Comparison of PCA3 score in patients with negative re-biopsy [normal parenchyma, benign prostatic hyperplasia (BPH), chronic prostatitis, high-grade prostate intraepithelial neoplasia (HG-PIN), atypical small acinar prostate (ASAP)] or positive re-biopsy was performed. RESULTS: The up- and down-grading rates for PCA3 score were 71.3% (n=77) and 28.7% (n=31), respectively. Among the 77 up-graded patients, the median change in PCA3 score was 24 (range=4-69), while among the 31 down-graded ones, the median change was 17 (2 to 55). The PCA3 score in 24 out of 29 (82.7%) patients with prostate cancer (PCa) was up-graded. No association was found for correlation of PCA3 score change with age >65 years (p=0.975), family history of prostate cancer (p=0.796), positive DRE (p=0.179), use of 5-alpha-reductase inhibitors (p=0.793) and BPH/prostatitis/HG-PIN/ASAP diagnosis (p=0.428). CONCLUSION: PCA3 score can be considered a marker that is stable over time in most cases; notably, up to 20% of patients have a clinically relevant change of risk class. The rate of PCa was higher in patients whose PCA3 score was up-graded, even if no robust cut-off for PCA3 score fluctuation was identified.

Comparison of prostate cancer gene 3 score, prostate health index and percentage free prostate-specific antigen for differentiating histological inflammation from prostate cancer and other non-neoplastic alterations of the prostate at initial biopsy.

AIM: To determine if prostate cancer gene 3 (PCA3) score, Prostate Health Index (PHI), and percent free prostate-specific antigen (%fPSA) may be used to differentiate prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH) and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA and negative digital rectal examination (DRE). PATIENTS AND METHODS: in the present prospective study, 274 patients, undergoing PCA3 score, PHI and %fPSA assessments before initial biopsy, were enrolled. Three multivariate logistic regression models were used to test PCA3 score, PHI and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the 'gray zone' of PSA (4-10 ng/ml) cohort (188 individuals). RESULTS: The determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (Odds Ratio [OR]=0.97, 0.96 and 0.94, respectively). Unit increase of PHI was the only risk factor for prostatitis vs. BPH (OR=1.06), and unit increase of PCA3 score for HG-PIN vs. prostatitis (OR=0.98). In the 'gray zone' PSA cohort, the determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (OR=0.96, 0.94 and 0.92, respectively), PCA3 score and PHI for prostatitis vs. BPH (OR=0.96 and 1.08, respectively), and PCA3 score for prostatitis vs. HG-PIN (OR=0.97). CONCLUSION: The clinical benefit of using PCA3 score and PHI to estimate prostatitis vs. PCa was comparable; even %fPSA had good diagnostic performance, being a faster and cheaper marker. PHI was the only determinant for prostatitis vs. BPH, while PCA3 score for prostatitis vs. HG-PIN.

Biopsy and radical prostatectomy pathological patterns influence Prostate cancer gene 3 (PCA3) score.

AIM: To evaluate the relationship between Prostate cancer gene 3 (PCA3) score and prostate cancer as assessed by Gleason Score (GS) and pathological stage in a series of Italian patients, with elevated Prostate specific antigen (PSA) undergoing radical prostatectomy (RP). PATIENTS AND METHODS: A total of 222 patients underwent RP for clinically localized prostate cancer; total PSA, free-PSA (%fPSA) and PCA3 score were collected and the possible associations among PCA3 and histological grade/pathological stage at biopsy and RP were investigated. RESULTS: Median PCA3 scores by GS at radical prostatectomy were 51 vs. 67 (GS <7 vs. GS ≥ 7, p=0.007), while scores at the biopsy were 56 vs. 67 (GS <7 vs. GS ≥ 7, p=0.007), and in pT2 vs. pT3 patients they were 54 vs. 80 (p=0.001). Positive digital rectal examination (DRE) (odds ratio (OR)=5.47, p=0.026), pT3 pathological stage (OR=3.68, p=0.006) and PCA3 ≥ 35 (OR=2.04, p=0.030) were the main risk factors for the presence of an aggressive disease (GS ≥ 7 at RP). CONCLUSION: PCA3 score could play an interesting role in predicting significant disease: positive DRE (OR=5.47, p=0.026), pT3 pathological stage (OR=3.68, p=0.006) and PCA3 ≥ 35 (OR=2.04, p=0.030) were the main independent risk factors for GS ≥ 7 at RP.

Prostate cancer gene 3 urine assay cutoff in diagnosis of prostate cancer: a validation study on an Italian patient population undergoing first and repeat biopsy.

OBJECTIVE: To determine an optimal prostate cancer gene 3 (PCA3) cutoff in predicting prostate cancer in Italian patients undergoing first or repeat biopsy. STUDY DESIGN: In this observational multicenter study 1246 men with elevated prostate specific antigen (PSA) and negative digital rectal examination, with prostate biopsy after PCA3 assessment, were divided into two groups submitted to PCA3 testing before or after previous negative biopsies. Ideal PCA3 cutoff was identified using area under the curve of the receiver operating characteristic analysis. Various cutoff values were used to determine the best predictive score. Univariate and multivariate logistic regression models compared age, PSA, free-PSA, and PCA3 score to predict prostate cancer. RESULTS: PCA3 cutoff 39-50 had the highest accuracy in the repeat biopsy group in which cutoff of 39 could have avoided 51.9% negative repeat biopsies, eventually missing 7.8% of cancers (all low risk); cutoff of 50 would have prevented 56.5% of negative repeat biopsies, missing 29 tumors (10.3%), 5 potentially aggressive. The PCA3 test performed poorly in the first biopsy group. CONCLUSION: We confirm the usefulness of PCA3 in Italian men with a previous negative biopsy. We achieved the best performance at a cutoff of 39. PCA3 did not perform better than PSA in non-biopsy-selected men.