Importance of prostate volume in the European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculators: results from the prostate biopsy collaborative group.

OBJECTIVES: To compare the predictive performance and potential clinical usefulness of risk calculators of the European Randomized Study of Screening for Prostate Cancer (ERSPC RC) with and without information on prostate volume. METHODS: We studied 6 cohorts (5 European and 1 US) with a total of 15,300 men, all biopsied and with pre-biopsy TRUS measurements of prostate volume. Volume was categorized into 3 categories (25, 40, and 60 cc), to reflect use of digital rectal examination (DRE) for volume assessment. Risks of prostate cancer were calculated according to a ERSPC DRE-based RC (including PSA, DRE, prior biopsy, and prostate volume) and a PSA + DRE model (including PSA, DRE, and prior biopsy). Missing data on prostate volume were completed by single imputation. Risk predictions were evaluated with respect to calibration (graphically), discrimination (AUC curve), and clinical usefulness (net benefit, graphically assessed in decision curves). RESULTS: The AUCs of the ERSPC DRE-based RC ranged from 0.61 to 0.77 and were substantially larger than the AUCs of a model based on only PSA + DRE (ranging from 0.56 to 0.72) in each of the 6 cohorts. The ERSPC DRE-based RC provided net benefit over performing a prostate biopsy on the basis of PSA and DRE outcome in five of the six cohorts. CONCLUSIONS: Identifying men at increased risk for having a biopsy detectable prostate cancer should consider multiple factors, including an estimate of prostate volume.

The relationship between prostate-specific antigen and prostate cancer risk: the Prostate Biopsy Collaborative Group.

PURPOSE: The relationship between prostate-specific antigen (PSA) level and prostate cancer risk remains subject to fundamental disagreements. We hypothesized that the risk of prostate cancer on biopsy for a given PSA level is affected by identifiable characteristics of the cohort under study. EXPERIMENTAL DESIGN: We used data from five European and three U.S. cohorts of men undergoing biopsy for prostate cancer; six were population-based studies and two were clinical cohorts. The association between PSA and prostate cancer was calculated separately for each cohort using locally weighted scatterplot smoothing. RESULTS: The final data set included 25,772 biopsies and 8,503 cancers. There were gross disparities between cohorts with respect to both the prostate cancer risk at a given PSA level and the shape of the risk curve. These disparities were associated with identifiable differences between cohorts: for a given PSA level, a greater number of biopsy cores increased the risk of cancer (odds ratio for >6- versus 6-core biopsy, 1.35; 95% confidence interval, 1.18-1.54; P < 0.0005); recent screening led to a smaller increase in risk per unit change in PSA (P = 0.001 for interaction term) and U.S. cohorts had higher risk than the European cohorts (2.14; 95% confidence interval, 1.99-2.30; P < 0.0005). CONCLUSIONS: Our results suggest that the relationship between PSA and risk of a positive prostate biopsy varies, both in terms of the probability of prostate cancer at a given PSA value and the shape of the risk curve. This poses challenges to the use of PSA-driven algorithms to determine whether biopsy is indicated.

Influence of blood sampling on protein profiling and pattern analysis using matrix-assisted laser desorption/ionisation mass spectrometry.

OBJECTIVE: To describe the influence of blood sampling/sampling tubes on mass spectrometric and clustering results, and on clinical blood variables, in blood samples collected from healthy volunteers and patients with prostate cancer. PATIENTS, SUBJECTS AND METHODS: Two venous blood samples were taken from 12 healthy volunteers and 12 patients with localized prostate cancer. Two blood samples were taken from each participant using two different venepuncture systems (group A and group B). The Kolmogorov-Smirnov test was used to identify the peaks distinguishing the different groups. In a 10-fold cross-validation study, decision trees for identifying discriminatory peaks that separate the benign from the malignant were constructed. RESULTS: The decision tree separated samples measured by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) from healthy volunteers from those of patients with prostate cancer, with a sensitivity of 93.6% and a specificity of 91.6%. Of special interest is that one peak at 6941 m/z was produced during blood sample preparation and had a very powerful influence on the results of the classification. CONCLUSION: The results clearly showed that blood-sampling systems have a great influence on the recorded MALDI MS traces, and thus can markedly influence and confound the results of the MS analysis, whereas clinical variables might remain unchanged. MS profiling is a promising method of marker discovery, but as it could be shown well-designed studies are critical to allow proper interpretation for the identification of key variables as well as for the clinical use.

Vascular resistance in the prostate evaluated by colour Doppler ultrasonography: is benign prostatic hyperplasia a vascular disease?

OBJECTIVE: To evaluate prostatic vascular resistance by measuring the resistive index (RI), and flow velocity using colour Doppler ultrasonography (CDUS), in normal prostates and in patients with benign prostatic hyperplasia (BPH) or prostate cancer, as BPH is considered to be a result of urogenital ageing and studies suggest that hyperplasia in the stromal and glandular compartments might be induced by stromal growth secondary to hypoxia, which in turn results from abnormal blood flow patterns. PATIENTS, SUBJECTS AND METHODS: Ninety-two men (22 with normal prostates, 45 with BPH and 25 with prostate cancer; mean age 56 years) were prospectively evaluated by CDUS. The RI values for the peripheral, central and transition zones were assessed by one investigator. The diagnosis of BPH and prostate cancer was established from histological findings. RESULTS: The mean (sd) RI in the transition zone was significantly higher only in patients with BPH, at 0.77 (0.05), vs 0.65 (0.05) in the other two groups. In the peripheral and central zones there was no significant difference in the RI among the three groups. Arterial CDUS flow velocity was increased in the transition zone of patients with BPH, but not in the peripheral and central zones. CONCLUSIONS: The present results support the hypothesis that an age-related impairment of blood supply to the lower urinary tract might have a role in the development of BPH. Although prostate cancer cannot be excluded by measuring RI, high RI values (>0.75) in the transition zone are indicative of BPH.

Factors contributing to the racial differences in prostate cancer mortality.

OBJECTIVE: To analyse, in a retrospective cohort study, differences in rates of surgical treatment for prostate cancer between African-Americans and White Americans, and to evaluate the extent to which these differences are associated with disparities in survival rates between these groups. PATIENTS AND METHODS: Clinical, pathological, and demographic data from 4279 men diagnosed with clinically localized prostate cancer between 1980 and 1997 were used. The variables assessed included age, disease stage, tumour grade, comorbidities, treatment method, and socio-economic status (SES). Kaplan-Meier survival curves were generated and compared using log-rank tests. The Cox proportional hazards method was used for analyses involving adjustments for potential confounding factors. RESULTS: The surgical treatment rate was 17% for African-American and 28% for White patients (P < 0.001). In those patients treated conservatively or by radiation therapy, both crude and cancer-specific survival rates were lower for African-Americans than for Whites (P < 0.001). However, for patients undergoing surgery, differences in survival between African-Americans and Whites were not statistically significant. According to our models, SES explained 50% and surgical treatment rates approximately 34% of the differences in survival between African-Americans and Whites. CONCLUSIONS: This analysis suggests that the lower prostate cancer survival rates for the African-Americans in the present population can be largely explained by differences in SES and lower surgical treatment rates. Efforts to increase awareness of treatment options among African-American patients may be a way of improving survival in this group.

Pathologic characterization of prostate cancers with a very low serum prostate specific antigen (0-2 ng/mL) incidental to cystoprostatectomy: is PSA a useful indicator of clinical significance?

Cystoprostatectomy specimens removed for bladder malignancy (1988-2000) at two referral centers (Mayo Clinic, Rochester, MN, The University Hospital of Innsbruck, Innsbruck, Austria) were examined for the coincidental finding of prostate cancer (PCA). Centralized examination of the prostate by a single uropathologist was performed if at the time of surgery the patient's serum PSA was < or =2.0 ng/mL and there were no suspicious lesions by digital prostate examination. Pathologic grade, stage, morphometric volume, number of tumor foci and association with areas of high grade prostatic intraepithelial neoplasia (HGPIN) were assessed by light microscopy. DNA ploidy and cellular proliferative index were assessed through digital image analysis. Clinically significant cancers were defined as tumors with > or =0.5 cc volume, Gleason 4 or 5 architecture, pT3, positive surgical margin, multifocality >3, nondiploid DNA content or proliferation index >5%. From nearly 1600 cystoprostatectomy specimens, 129 met the enrollment criteria. Thirty-patients (23%) within this group had PCA identified. Sixty percent of these tumors met the criteria for a clinically significant cancer. Nondiploid nuclear content was present in 17%. HGPIN was present in 70% and directly abutting carcinoma in 86% of prostates. The biologic activity of PCA appears to be independent of serum PSA. Any future definition of a clinically significant PCA should not be solely based upon histologic criteria, but needs to encompass clinical parameters (age, co-morbidities) and a noninvasive assessment of tumor volume and biologic doubling time.