M. Auprich

Critical assessment of preoperative urinary prostate cancer antigen 3 on the accuracy of prostate cancer staging.

BACKGROUND Knowledge about the staging significance of the prostate cancer antigen 3 (PCA3) score to better identify pathologic features after radical prostatectomy (RP) is limited and controversial. OBJECTIVE Our aim was to study the clinical staging significance of PCA3 to identify pathologic favorable and/or unfavorable features in the RP specimen. DESIGN, SETTING, AND PARTICIPANTS Complete retrospective clinical and pathologic data of consecutive men who had undergone RP from three tertiary referral centers including preoperative PCA3 scores (n=305) and computer-assisted planimetrically measured tumor volume data (n=160) were available. INTERVENTION All patients were treated with RP. MEASUREMENTS PCA3 scores were assessed using the PROGENSA assay (Gen-Probe, San Diego, CA, USA). Beyond standard risk factors (age, digital rectal examination, prostate-specific antigen, prostate volume, biopsy Gleason score, percentage of positive cores), five different PCA3 codings were used in logistic regression models to identify five distinct pathologic end points: (1) low-volume disease (<0.5 ml), (2) insignificant prostate cancer (PCa) according to the Epstein criteria, (3) extracapsular extension (ECE), (4) seminal vesicle invasion (SVI), and (5) aggressive disease defined as Gleason sum ≥7. Accuracy estimates of each end point were quantified using the area under the curve (AUC) of the receiver operator characteristic analysis in models with and without PCA3. RESULTS AND LIMITATIONS PCA3 scores were significantly lower in low-volume disease and insignificant PCa (p ≤ 0.001). AUC of multivariable low-volume disease (+2.4 to +5.5%) and insignificant PCa models (+3 to +3.9%) increased when PCA3 was added to standard clinical risk factors. In contradistinction, regardless of its coding, PCA3 scores were not significantly elevated in pathologically confirmed ECE (p=0.4) or SVI (p=0.5), respectively. Higher PCA3 scores were associated with aggressive disease (p<0.001). Importantly, the addition of PCA3 to multivariable intermediate- and high-grade models did not improve prediction. Despite reporting the largest pathologic PCA3 study, the main limitation resides in its small sample size. CONCLUSIONS PCA3 was confirmed as a valuable predictor of pathologically confirmed low-volume disease and insignificant PCa. Further exploration of its role as an additional marker to select patients for active surveillance may be warranted. In contradistinction, assessment of pathologically advanced or aggressive PCa is not improved using PCA3.

External Validation of Urinary PCA3-Based Nomograms to Individually Predict Prostate Biopsy Outcome

BACKGROUND Prior to safely adopting risk stratification tools, their performance must be tested in an external patient cohort. OBJECTIVE To assess accuracy and generalizability of previously reported, internally validated, prebiopsy prostate cancer antigen 3 (PCA3) gene-based nomograms when applied to a large, external, European cohort of men at risk of prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS Biopsy data, including urinary PCA3 score, were available for 621 men at risk of PCa who were participating in a European multi-institutional study. INTERVENTION All patients underwent a ≥10-core prostate biopsy. Biopsy indication was based on suspicious digital rectal examination, persistently elevated prostate-specific antigen level (2.5-10 ng/ml) and/or suspicious histology (atypical small acinar proliferation of the prostate, >/= two cores affected by high-grade prostatic intraepithelial neoplasia in first set of biopsies). MEASUREMENTS PCA3 scores were assessed using the Progensa assay (Gen-Probe Inc, San Diego, CA, USA). According to the previously reported nomograms, different PCA3 score codings were used. The probability of a positive biopsy was calculated using previously published logistic regression coefficients. Predicted outcomes were compared to the actual biopsy results. Accuracy was calculated using the area under the curve as a measure of discrimination; calibration was explored graphically. RESULTS AND LIMITATIONS Biopsy-confirmed PCa was detected in 255 (41.1%) men. Median PCA3 score of biopsy-negative versus biopsy-positive men was 20 versus 48 in the total cohort, 17 versus 47 at initial biopsy, and 37 versus 53 at repeat biopsy (all p≤0.002). External validation of all four previously reported PCA3-based nomograms demonstrated equally high accuracy (0.73-0.75) and excellent calibration. The main limitations of the study reside in its early detection setting, referral scenario, and participation of only tertiary-care centers. CONCLUSIONS In accordance with the original publication, previously developed PCA3-based nomograms achieved high accuracy and sufficient calibration. These novel nomograms represent robust tools and are thus generalizable to European men at risk of harboring PCa. Consequently, in presence of a PCA3 score, these nomograms may be safely used to assist clinicians when prostate biopsy is contemplated.

Did the rate of incidental prostate cancer change in the era of PSA testing? A retrospective study of 1127 patients

OBJECTIVES To evaluate, in a retrospective study, the impact of routine prostate-specific antigen (PSA) testing on the rate of incidental prostate cancer in patients undergoing surgery for obstructive symptoms caused by presumed benign prostatic enlargement (BPE) and to investigate the indication of a routine biopsy before alternative treatment procedures for BPE. In the pre-PSA era, the diagnosis of incidental carcinoma was exclusively based on normal digital rectal examination (DRE) findings. METHODS Since January 1993, 2422 operations (2283 transurethral resection of the prostate, 139 retropubic adenoma enucleations) for BPE were performed at our institution. The preoperative DRE findings and PSA level were evaluated, and patients with any suspicion for cancer were excluded. The pathologic reports of all patients were reviewed. A diagnosis of incidental carcinoma of the prostate required histologic evidence of cancer and negative DRE findings and a PSA level within age-specific reference ranges preoperatively. RESULTS Of 2422 patients, 1127 (46.5%) had both negative DRE findings and an age-specific PSA level and were evaluated for our study. Overall, prostate cancer was diagnosed by surgery in 314 (13%) of 2422 patients. The rate of incidental prostate cancer in patients with both negative age-specific PSA levels and negative DRE findings was 6.4% (72 of 1127). CONCLUSIONS In our series, the likelihood of detecting incidental prostate cancer by surgery was 6.4%. In the PSA era, the rate of incidental prostate cancer has been decreased by more than 50%. Today, the low rate of incidental carcinoma does not warrant routine histologic evaluation of the prostate if PSA testing and DRE are negative when alternative treatment modalities without tissue sampling are offered for the treatment of BPE.

Prostatic Phyto-Oestrogen Tissue Levels in Different Austrian Regions

Introduction: A number of studies suggest that the low incidence of prostate cancer as well as benign prostatic enlargement in Asia depends on the extended consumption of phyto-oestrogens in these parts of the world. In most Asian men, phyto-oestrogen levels are multiple higher compared to Austrian (European) men. The aim of our study was to evaluate, according to the East-West decline, whether there were significant differences within the Austrian population. We compared prostate phyto-oestrogen tissue levels of men living in three different geographical regions of Austria. We further compared men living in rural and urban environments. Material and Methods: Prostatic tissue samples of 103 men undergoing surgery for benign prostatic hyperplasia or prostate cancer were collected and frozen at –40°C. In tissue samples, enterolactone (representative for lignans) and genistein levels (representative for isoflavones) were determined in duplicate by monoclonal antibody-based immunoassays. We subsequently compared tissue levels of men living in rural and urban environments and different geographical regions of Austria. Results: Prostatic enterolactone tissue levels were similar in men living in an urban (median 19.1 ng/g dry weight, range 1.5–76.4) or rural environment (median 15.7 range 0.6–140.6) p = 0.99. The respective values for genistein were 20.5 ng/g dry weight (range 4.6–47.4) and 9.3 (range 0.1–156.7) p = 0.77. Furthermore, enterolactone (p = 0.1) and genistein (p = 0.65) levels were similar in three different geographic regions in Austria. Conclusion: No significant differences regarding genistein and enterolactone were found between our study populations. However, we found a wide variation between individual patients.