Complexed prostate specific antigen (PSA) reduces unnecessary prostate biopsies in the 2.6-4.0 ng/mL range of total PSA

OBJECTIVE: To compare the performance of complexed prostate-specific antigen (cPSA) to total PSA (tPSA) and percentage free PSA (f/tPSA) in the diagnosis of prostate cancer for the tPSA range 2.6-4.0 ng/mL. PATIENTS AND METHODS: Consecutive men scheduled for prostate biopsy were enrolled prospectively at 14 different sites in two multicentre studies in Europe and the USA. Serum obtained before biopsy was tested with the ACS:180 and Immuno 1 tPSA and cPSA assays (Bayer Diagnostics, Tarrytown, NY, USA) and the Access fPSA and tPSA assays (Beckman, Inc., San Diego, CA, USA). Receiver operating characteristics (ROC) curves were generated to compare the diagnostic performance of tPSA, cPSA and f/tPSA. RESULTS: Of 316 men with a tPSA of 2.6-4.0 ng/mL, 82 (26%) were diagnosed with prostate cancer on biopsy. ROC analysis of all 316 men showed an area under the curve (AUC) for cPSA of 0.63, significantly greater than the AUC for tPSA of 0.56 (P = 0.008). At a sensitivity of 95%, threshold values of 2.3 ng/mL for cPSA and 2.73 ng/mL for tPSA provided specificities of 20.1% and 9.8%, respectively. f/tPSA was only available for 205 of the 316 (65%) men and the AUC for cPSA was 0.63, and did not significantly differ from the f/tPSA AUC of 0.64 (P = 0.58). CONCLUSIONS: As a single test, cPSA provides improved specificity over tPSA and comparable specificity to f/tPSA for detecting prostate cancer, and may reduce the number of unnecessary prostate biopsies in the 2.6-4.0 ng/mL tPSA range.     

Prostate-specific antigen (PSA) complexed to alpha1-antichymotrypsin improves prostate cancer detection using total PSA in Japanese patients with total PSA levels of 2.0-4.0 ng/mL

OBJECTIVE: To assess the utility of prostate-specific antigen (PSA) complexed to alpha1-antichymotrypsin (PSA-ACT) in prostate cancer screening in Japanese men with a total PSA level of 2.0-4.0 ng/mL, as improving cancer detection in men with these total PSA levels is a challenge for clinical urologists. PATIENTS AND METHODS: Total PSA and PSA-ACT were prospectively assessed and prostate biopsy recommended for patients who met either of two thresholds, i.e. a total PSA of > or = 2.0 ng/mL or a PSA-ACT of > or= 1.5 ng/mL. The diagnostic ability of total PSA and PSA-ACT, and free-to-total PSA ratio and prostate volume-adjusted density were evaluated by receiver operating characteristic (ROC) analysis. RESULTS: Of 1003 men enrolled, 547 met the biopsy criteria and a biopsy was taken in 315 (57.6%) patients. The area under the ROC curve for PSA-ACT (0.679) was significantly greater than that for total PSA (0.601, P = 0.04) and equivalent to that for the free-to-total ratio (0.686, P = 0.911) in 116 men, including 27 with cancer with total PSA levels of 2.0-4.0 ng/mL. PSA-ACT was more specific than the free-to-total ratio at a sensitivity of 95% (36% vs 18%, P < 0.05). The best variable for discriminating between cancer and benign disease in men with PSA levels of 2.0-4.0 ng/mL was PSA-ACT density (area under the curve 0.852) which provided 66% specificity at a sensitivity of 90%. CONCLUSIONS: PSA-ACT is better than total PSA and equivalent to the free-to-total ratio for detecting prostate cancer in men with PSA levels of 2.0-4.0 ng/mL, and is thus useful for reducing the number of unnecessary biopsies.     

前列腺特异性抗原(PSA)及其相关参数在PSA灰区诊断前列腺癌的临床研究

为临界值,以提高前列腺在灰区的断特异度和敏感度.     

前列腺特异性抗原(PSA)及其相关参数在PSA灰区诊断前列腺癌的临床研究

为临界值,以提高前列腺在灰区的断特异度和敏感度.     

Tumour markers for managing men who present with metastatic prostate cancer and serum prostate-specific antigen levels of <10 ng/mL

OBJECTIVE: To define immunohistochemical features of the primary cancers that might help in the differential diagnosis and monitoring of treatment in men presenting with metastatic prostate cancer and low serum levels of prostate-specific antigen (PSA), who can be difficult to diagnose and manage. PATIENTS AND METHODS: Paraffin blocks of prostate biopsies were obtained for 33 patients presenting with untreated metastatic prostate cancer and serum PSA levels of <10 ng/mL. Sections were immunostained for PSA, prostatic acid phosphatase (PAP), prostate-specific membrane antigen (PSMA), androgen receptor (AR), chromogranin A and CD 56. RESULTS: The combined Gleason scores were 8-10 in 25 men (76%) and 6 or 7 in the other eight (24%). Morphologically, there were no neuroendocrine features. PSA immunostaining was equivocal in 12 (36%) cases and in a further 19 (58%) was strong but focal and could be missed on biopsy sampling. PSMA was expressed in 90% of cases, and staining was widely distributed in nine of the 12 in which PSA staining was equivocal. There was strong AR expression in 30 (91%) cases and it was present in areas where PSA was absent. CONCLUSION: In this patient group, immunohistochemical assessments of PSMA and AR are potentially useful as diagnostic markers.     

The effect of percentage free prostate-specific antigen (PSA) level on the prostate cancer detection rate in a screening population with low PSA levels

OBJECTIVE: To evaluate the prostate cancer detection rate at low total prostate-specific antigen (tPSA) ranges of 2.6-4 and 4.1-10 ng/mL, according to different percentage free (f/t) PSA levels in a screening population. SUBJECTS AND METHODS: In all, 1809 consecutive screening volunteers with a tPSA level of 2.6-10.0 ng/mL were assessed. Ten systematic ultrasonography-guided prostate biopsies and, since 2000, an additional five Doppler-enhanced targeted biopsies were taken on the basis of age-specific tPSA reference ranges. We analysed the detection rate of prostate cancer according to f/tPSA ranges of 0-9%, 10-14%, 15-18% and >18%. RESULTS: The detection rates for the subgroups with tPSA levels of 2.6-4.0 and 4.1-10.0 ng/mL were 20.2% and 27.0%, respectively. The cancer detection rate in the first group (2.6-4.0 ng/mL) at 0-10% fPSA was 22.9%, and that in the second group (4.1-10.0 ng/mL) at 0-10% was 36.9%. There were significant differences between these groups. If the f/tPSA was 10-15%, the cancer detection rate for the two groups were 22.6% and 32.5%, respectively (P < 0.05). There was no statistically significant difference in the cancer detecting rates at an f/tPSA of 15-18% or >18%. CONCLUSION: There is a statistically significantly higher cancer detection rate when the f/tPSA is <15% than in groups of men with a f/tPSA of >15% in screening population assessed primarily using tPSA level.     

Measurement of serum zinc improves prostate cancer detection efficiency in patients with PSA levels between 4 ng/mL and 10 ng/mL

Aim： To investigate whether the measurement of serum zinc may improve the detection of prostate cancer （PCa） in men who had total prostate-specific antigen （PSA） levels higher than 4.1 ng/mL. Methods： A mass screening for PCa of 3940 men over 50 years old was undertaken using total serum PSA. Of the 190 men （4.8 %） with elevated PSA, 143 （3.6 %） underwent a transrectal ultrasonography （TRUS）-guided biopsy of the prostate, and 42 men （1% of total and 29.3 % of men undergoing biopsy） were found to have cancer. The areas under the receiver operating characteristic curves （ROC-AUC） were used to compare the diagnostic power of cancer detection by means of serum zinc, and free PSA/total PSA ratio （fit）. Results： The men with levels of serum zinc that ranged from 40 ng/mL-60 ng/mL, had an age-adjusted odds ratios（OR） of 5.0. A cutoff value of 100 gg/mL for-serum zinc concentration provided a sensitivity of 90.5 % and a specificity of 32.7 % in elevated PSA range, and a sensitivity of 93.3 % and specificity of 27.1% in gray zone, respectively. In the gray zone ranges of 4.1 ng/mL-10.0 ng/mL, the ROC-AUC for zinc was 73.0 % higher than 62.7 % of f/t PSA ratio and 56.7 % of total PSA. Conclusion： PCa displays a lower serum zinc concentration. The measurement of zinc levels improves PCa detection in the gray zone compared with the f/t PSA ratio and total PSA. （Asian J Androl 2005 Sep; 7： 323-328）     

The significance of the free-to-complexed prostate-specific antigen (PSA) ratio in prostate cancer detection in patients with a PSA level of 4.1-10.0 ng/mL

OBJECTIVE: To compare the ratio of free prostate specific antigen (fPSA), total PSA (tPSA) and complexed PSA (cPSA, measured using a novel immunoassay) with other variables used to detect prostate cancer in patients with intermediate serum PSA levels of 4.1-10.0 ng/mL. PATIENTS AND METHODS: From July 1997 to August 1998, 140 consecutive patients were assessed; all had intermediate serum PSA levels and/or abnormal findings on a digital rectal examination. All patients underwent transrectal ultrasonography (TRUS)-guided biopsy, and the prostate and transition zone volumes were determined by TRUS. Free and tPSA were measured using the Tandem-R assay (Hybritech Corp., San Diego, CA). PSA complexed with alpha1-antichymotrypsin (cPSA) was measured using an appropriate assay. The ability of cPSA, free-to-total PSA ratio (f/tPSA), free-to-complexed PSA ratio (f/cPSA), tPSA density of the whole prostate (PSAD), of the transition zone (tPSATZ), and cPSA density of the whole prostate (cPSAD) and of the transition zone (cPSATZ) to improve the power of PSA in detecting prostate cancer was evaluated using receiver operating characteristic (ROC) curves. Results Of the 140 patients, 126 had histologically confirmed benign disease and 14 had prostate cancer. The cPSA alone had better specificity for detecting prostate cancer than had tPSA alone but the difference was not significant. The area under the ROC curve for f/cPSA was larger than those for all other variables. With a 93% sensitivity for detecting prostate cancer, a f/cPSA threshold of 25% would result in fewer unnecessary biopsies (40% f/cPSA specificity) than with all other PSA variables. The difference in the resolution was significant between f/cPSA and tPSA, cPSA, tPSAD and tPSATZ, but not with f/tPSA, cPSAD or cPSATZ. In patients with a prostate volume of < 30 mL, the cPSATZ showed better specificity for prostate cancer than tPSA alone. CONCLUSION: Measuring the level of cPSA and its derivatives may provide better differentiation of prostate cancer and benign disease than tPSA alone in patients with a tPSA level of 4.1-10.0 ng/mL.     

Biochemical disease-free survival in patients with a high prostate-specific antigen level (20-100 ng/mL) and clinically localized prostate cancer after radical prostatectomy

OBJECTIVE: To examine our experience with radical prostatectomy (RP) in patients with a serum prostate-specific antigen (PSA) level of > 20 ng/mL (who are sometimes considered poor candidates for RP) to determine the outcome and possible predictors of a favourable outcome. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 79 patients who underwent RP with an initial PSA of 20-100 ng/mL. Biochemical disease-free survival (BDFS) was assessed using the Kaplan-Meier method and predictors of treatment outcome examined by uni- and multivariate analysis. Patients excluded from the analysis were 11 (14%) whose surgery was aborted after finding cancerous pelvic nodes and who did not undergo RP; four others with normal nodes during RP who had metastatic tumour on permanent sections; and 14 who had follow-up data for < 2 years. RESULTS: The mean (sd) age of the 50 patients in the final study population was 63 (7) years and the mean PSA 37.9 (16.0) ng/mL. The median (range) follow-up was 54 (24-120) months. The BDFS was 60% at 3 years and 48% at 5 years of follow-up. Two patients developed a local recurrence and eight developed metastatic disease. On logistic regression analysis of factors influencing BDFS, only extracapsular extension of disease was predictive of PSA recurrence; no preoperative factor was significant. When time to PSA recurrence was assessed by Cox regression analysis, again only extracapsular extension was predictive, with no preoperative variable a statistically significant predictor. CONCLUSIONS: Patients with a high serum PSA level (20-100 ng/mL) may be appropriate candidates for RP. While the cancer-free survival is not as good as in patients with a lower PSA, a significant percentage of patients achieve BDFS. No preoperative variables were predictive of disease-free survival or time to PSA recurrence.     

Prostate-specific antigen (PSA) isoform p2PSA significantly improves the prediction of prostate cancer at initial extended prostate biopsies in patients with total PSA between 2.0 and 10 ng/ml: results of a prospective study in a clinical setting

Background

Total prostate-specific antigen (tPSA), ratio of free PSA (fPSA) to tPSA (%fPSA), and PSA density (PSAD) testing have a very low accuracy in the detection of prostate cancer (PCa). There is an urgent need for more accurate biomarkers.

Objective

To compare the diagnostic accuracy of PSA isoform p2PSA and its derivatives in determining the presence of PCa at initial biopsy with the accuracy of other predictors in patients with tPSA 2.0-10 ng/ml.

Design, setting, and participants

We conducted an observational prospective study in a real clinical setting of consecutive men with tPSA 2.0-10 ng/ml and negative digital rectal examination who were scheduled for prostate biopsy at a tertiary academic center.

Intervention

Outpatient transrectal ultrasound-guided prostate biopsies were performed according to a standardized institutional saturation scheme (18-22 cores).

Measurements

We determined the diagnostic accuracy of serum tPSA, %fPSA, PSAD, p2PSA, %p2PSA [(p2PSA/fPSA) × 100] and the Beckman Coulter Prostate Health Index (phi; [p2PSA/fPSA × √tPSA]).

Results and limitations

Overall, 107 of 268 patients (39.9%) were diagnosed with PCa at extended prostate biopsies. Statistically significant differences between patients with and without PCa were observed for age, prostate and transition zone volume, PSAD, %p2PSA, and phi (all p values < 0.05). In univariate accuracy analysis, phi and %p2PSA were the most accurate predictors of PCa (area under the curve: 75.6% and 75.7%, respectively), followed by transition zone volume (66%), prostate volume (65%), patient age (63%), PSAD (61%), %fPSA (58%), and tPSA (53%). In multivariate accuracy analyses, both phi (+11%) and %p2PSA (+10%) significantly improved the accuracy of established predictors in determining the presence of PCa at biopsy (p < 0.001). Although %p2PSA and phi were significantly associated with Gleason score (Spearman ρ: 0.303 and 0.387, respectively; p ≤ 0.002), they did not improve the prediction of Gleason score ≥7 PCa in multivariable accuracy analyses (p > 0.05).

Conclusions

In patients with a tPSA between 2.0 and 10 ng/ml, %p2PSA and phi are the strongest predictors of PCa at initial extended biopsies and are significantly more accurate than the currently used tests (tPSA, %fPSA, and PSAD) in determining the presence of PCa at biopsy.     

Predictors of prostate cancer on repeat prostatic biopsy in men with serum total prostate-specific antigen between 4.1 and 10 ng/mL

OBJECTIVES: We determine whether the different molecular forms of prostate-specific antigen (PSA) and other PSA variables can predict prostate cancer in men undergoing repeat prostate needle biopsy. METHODS: Between 1997 and 2001, repeat biopsy was performed in 97 patients who had undergone prior negative prostate biopsy. The ability of total PSA (tPSA), complexed PSA (cPSA), free PSA (fPSA), free-to-total PSA (fPSA/tPSA), free-to-complexed PSA (fPSA/cPSA), complexed-to-total PSA (cPSA/tPSA), tPSA density (tPSAD), cPSA density (cPSAD), transition zone tPSA density (tPSATZ) and transition zone cPSA density (cPSATZ) was assessed by univariate and multivariate analyzes as well as receiver operating characteristics (ROC) curves. RESULTS: Prostate cancer on repeat biopsy was detected in 24% of subjects (23 of 97) who had a negative initial biopsy. The PSA parameters cut-off to ensure a 96% sensitivity of cancer detection, were 29% using fPSA/tPSA, 32% using fPSA/cPSA, 0.18 ng/mL/cc using tPSATZ and 0.16 ng/mL/cc using cPSATZ. The fPSA/tPSA would have prevented 32% of negative biopsies, the fPSA/cPSA 28%, the tPSATZ 23% and the cPSATZ 30%. ROC curve analysis fPSA/tPSA, fPSA/cPSA ratios, tPSATZ and cPSATZ were significantly better predictors of repeat biopsy results than tPSA or cPSA, but there was no significant difference in the ROC curves among these four PSA parameters. In the multivariate logistic regression analysis these four PSA parameters were significant predictors for cancer detection in the repeat biopsy group (P < 0.001). CONCLUSION: fPSA/tPSA ratio, fPSA/cPSA ratio, tPSATZ and cPSATZ enhance the specificity of PSA testing compared to tPSA or cPSA when determining which patients should undergo repeat biopsy.     

Annual PSA tests are not necessary for men with a PSA level below 2 ng/mL: Findings of the Imari prostate cancer screening program

BACKGROUND: Annual changes in prostate specific antigen (PSA) levels detected by the Imari prostate cancer screening program were evaluated to establish a more efficient and cost-saving screening system, especially for men with low PSA levels. METHODS: Prostate specific antigen-based annual mass screenings for prostate cancer were conducted for men aged 60-69 in the Imari district, Saga, Japan. Between 1992 and 2000, 1822 men had their PSA levels tested. A total of 4661 PSA tests were conducted. Changes in PSA levels over the following 1 to 5 years were analyzed in men with PSA levels of 3 ng/mL or less, a range in which the detection rate of prostate cancer would seem to be negligibly low. RESULTS: The overall detection rate of prostate cancer between 1992 and 2000 was 0.73%. The detection rate in men with a PSA level between 3.1 and 3.9 ng/mL, and between 4 and 9.9 ng/mL was 1.6% and 8.3%, respectively. Of 4661 determinations of PSA, 2553 (54.8%) were found to be < or = 1 ng/mL, 1273 (27.3%) were between 1.1 and 2 ng/mL, and 401 (8.6%) were between 2.1 and 3 ng/mL. Four hundred and thirty-four men (9.3%) had PSA levels > or = 3.1 ng/mL, with possible indications for prostate biopsy. Of the men tested, 1.4% with an initial PSA level of < or = 2 ng/mL and 22.3% with an initial level between 2.1 and 3 ng/mL had a PSA level of > or = 3.1 ng/mL after 1 year. Almost the same rate of PSA increase was observed between the two PSA tests conducted at 2 to 5-year intervals. Of the men tested, 2.2% with an initial PSA level of < or = 2 ng/mL, and 21.9% with an initial level between 2.1 and 3 ng/mL, had a level of > or = 3.1 ng/mL after 5 years. CONCLUSION: Levels of PSA in men with an initial level below 2 ng/mL remained stable for up to 5 years. Levels of PSA in 97.8- 98.8% of men remained below 3 ng/mL after 1 to 5 years. In contrast, 18-35.3% of men with an initial PSA level between 2.1 and 3 ng/mL showed PSA progression to 3.1 ng/mL or more within 5 years. Our present data suggest that annual PSA testing is not necessary for men with a PSA level below 2 ng/mL. Prostate specific antigen testing could therefore be conducted at longer intervals in such individuals.     

Prostate gland volume is a strong predictor of biopsy results in men 70 years or older with prostate-specific antigen levels of 2.0–10.0 ng/mL

PURPOSE: The incidence of prostate cancer, benign prostatic enlargement and serum level of prostate-specific antigen (PSA) increase with patient age. Intermediate elevation of PSA in elderly populations is apt to be considered insignificant. We evaluated the impact of PSA and prostate volume on the presence of non-palpable prostate cancer in elderly men with an intermediate level of PSA. MATERIALS AND METHODS: Clinical records of 154 men 70 years or older, with non-cancerous digital rectal examination findings and with serum PSA levels of 2.0-10.0 ng/mL, who underwent initial 6- to 10-core transrectal prostate biopsy, were reviewed for prostate volume, number of biopsy cores, PSA and associated parameters. Stepwise logistic regression and receiver operating characteristic (ROC) models were used to determine the impacts of the parameters on the biopsy results. RESULTS: Overall cancer detection rate was 40/154 or 26.0%. Prostate-specific antigen showed no significant association with the presence of prostate cancer (P = 0.59, Mann-Whitney U-test), while prostate volume did (P < 0.0001). On stepwise logistic regression analysis, prostate volume (P = 0.024, 95% CI 1.008-1.116) and biopsy core density (P = 0.017, 95% CI 4.76-7.12 x 10(6)) were independently associated with a cancer diagnosis, whereas PSA density was not an independent factor for a positive biopsy result. The area under the ROC curve for prostate volume was significantly superior to that of PSA (0.802 vs. 0.529; P = 0.012). CONCLUSIONS: In men 70 years or older with gray zone PSA, prostate cancer patients are equally distributed over any PSA range. Although PSA has less impact on cancer presence than mere prostate volume, prostate cancer would be detected in a substantial proportion of older patients with PSA levels of 2.0-10.0 ng/mL.     

Prostate cancer detection in men with a 'normal' total prostate-specific antigen (PSA) level using percentage free PSA: a prospective screening study

OBJECTIVE: To assess the utility of percentage free/total prostate-specific antigen (f/tPSA) levels for detecting prostate cancer in a prospectively screened population of men with a 'normal' total PSA level. PATIENTS AND METHODS: Men aged 50-65 years were contacted via their general practitioner and invited for prostate cancer screening. All had their total and f/tPSA levels measured; those meeting the biopsy criteria (PSA 1.1-3.99 ng/mL and f/tPSA < or = 20%) were offered a biopsy. The cancer detection rate was then evaluated and compared with other methods of detection. In all, 773 men were screened, of whom 115 met the criteria and agreed to undergo a prostate biopsy. RESULTS: Cancer was detected in 13 of the 115 men (11.3%) of whom most would have been missed by lowering the age-adjusted threshold for total PSA to 2.5 ng/mL. There was no significant difference in total and f/tPSA values in men with and without prostate cancer. Those cancers that could be evaluated were found to be clinically significant. CONCLUSION: In this study prostate cancer was detected solely on the basis of a low f/tPSA value. Most men with cancer would have been missed by simply lowering the age-adjusted threshold for total PSA. Using the f/tPSA level may allow the detection of clinically significant cancer in men at a time when they are most likely to benefit from treatment.     

Characterizing prostatic adenocarcinomas in men with a serum prostate specific antigen level of < 4.0 ng/mL

OBJECTIVE: To characterize prostate cancer in men undergoing radical prostatectomy who have a prostate-specific antigen (PSA) level of < 4.0 ng/mL, hypothesizing that a low PSA is not caused by diminished tumour production of PSA, nor does it signify clinically insignificant disease. PATIENTS AND METHODS: Seventy-nine men (mean age 59.3 years, range 43-77) with a PSA level of < 4.0 ng/mL were identified from 702 who had a radical prostatectomy between 1994 and 2000. Demographic and clinical data were analysed; pathological specimens were evaluated by routine haematoxylin and eosin staining and immunohistochemistry with anti-PSA antibody, for both pathological staging and grading, and for the presence of PSA production. Tumours were classified as 'clinically insignificant' if the tumour volume was < 0.5 mL and the Gleason score < 7. RESULTS: The mean (SD, range) preoperative PSA level was 3.04 (0.85, 0.8-3.8) ng/mL Indications for biopsy included an abnormal digital rectal examination (61%), a PSA velocity of > 0.75 ng/mL/year (12%), a strong family history of prostate cancer (3%), obstructive urinary symptoms (2%), or no obvious indication (23%). Thirty-eight (48%) tumours were clinically insignificant. Of 41 clinically significant cancers, 13 had a final Gleason score of > or = 7, 20 had extraprostatic extension and 11 had a tumour volume of > or = 10 mL Of the 79 prostate cancer specimens 78 stained strongly for PSA; the exception was a Gleason 9 tumour. With a mean (range) follow-up of 3.5 (0.18-6) years only one patient had a biochemical recurrence (PSA > or = 0.1 ng/mL). CONCLUSIONS: Most prostate cancers in men with a PSA level of < 4.0 ng/mL are clinically significant and PSA-producing. Many of these tumours are high-grade, high-volume and extraprostatic. We are currently exploring factors to explain why serum PSA is not elevated in these men, including tumour location, pattern of invasion and microvessel density.     

Racial differences in serum prostate-specific antigen (PSA) doubling time, histopathological variables and long-term PSA recurrence between African-American and white American men undergoing radical prostatectomy for clinically localized prostate cancer

OBJECTIVE: To determine if there are significant differences in biochemical characteristics, biopsy variables, histopathological data, and rates of prostate-specific antigen (PSA) recurrence between African-American (AA) and white American (WA) men undergoing radical prostatectomy (RP), as AA men are twice as likely to die from prostate cancer than their white counterparts. PATIENTS AND METHODS: We established a cohort of 1058 patients (402 AA, 646 WA) who had RP and were followed for PSA recurrence. Age, race, serum PSA, biopsy Gleason score, clinical stage, pathological stage, and PSA recurrence data were available for the cohort. The chi-square test of proportions and t-tests were used to assess basic associations with race, and log-rank tests and Cox regression models for time to PSA recurrence. Forward stepwise variable selection was used to assess the effect on the risk of PSA recurrence for race, adjusted by the other variables added one at a time. RESULTS: The AA men had higher baseline PSA levels, more high-grade prostatic intraepithelial neoplasia (HGPIN) in the biopsy, and more HGPIN in the pathology specimen than WA men. The AA men also had a shorter mean (sd) PSA doubling time before RP, at 4.2 (4.7) vs 5.2 (5.9) years. However, race was not an independent predictor of PSA recurrence (P = 0.225). Important predictors for PSA recurrence in a multivariable model were biopsy HGPIN (P < 0.014), unilateral vs bilateral cancer (P < 0.006), pathology Gleason score and positive margin status (both P < 0.001). CONCLUSIONS: This study indicates that while there are racial differences in baseline serum PSA and incidence of HGPIN, race is not an independent risk factor for PSA recurrence. Rather, other variables such as pathology Gleason score, bilateral cancers, HGPIN and margin positivity are independently associated with PSA recurrence. The PSA doubling time after recurrence may also be important, leading to the increased mortality of AA men with prostate cancer.     

Over-diagnosis and under-diagnosis of screen- vs non-screen-detected prostate cancers with in men with prostate-specific antigen levels of 2.0-10.0 ng/mL

OBJECTIVES

To evaluate possible over‐ and under‐diagnosis of prostate cancer in a screened vs a referral population in the same range of prostate‐specific antigen (PSA).

PATIENTS AND METHODS

In all, 1445 patients undergoing radical prostatectomy and with a PSA level of <10 ng/mL were evaluated; 237 were from outside Tyrol (Austria) and represented the unscreened group, and 1208 were Tyrolean screening volunteers. Over‐diagnosis was defined as a pathological stage of pT2a and a Gleason score of <7 with no positive surgical margins. Under‐diagnosis was defined as a pathological stage of ≥pT3a or positive surgical margins. The chi‐square test was used to assess the differences, with P < 0.05 considered to indicate statistical significance.

RESULTS

There were no significant differences in patient age or PSA levels between the study groups. There was over‐diagnosis in the screening and referral groups in 17.4% and 8.9%, respectively, and under‐diagnosis in 18.6% and 42.2%, respectively.

CONCLUSION

This study suggests that patients with prostate cancer participating in a screening programme are less likely to be under‐diagnosed or have extracapsular disease than their counterparts in a referral population, even in the same PSA range, after radical prostatectomy. Furthermore, there was more under‐diagnosis in the referral group than over‐diagnosis in the screened group.     

Use of prostate-specific antigen (PSA) isoforms for the detection of prostate cancer in men with a PSA level of 2-10 ng/ml: systematic review and meta-analysis

OBJECTIVE: Measurement of serum prostate-specific antigen (PSA) for the detection of prostate cancer has poor specificity in men with PSA levels between 2 and 10 ng/ml. It has been suggested that measurement of the ratio of free to total PSA (f/tPSA) or complexed PSA (cPSA) might offer an improvement. We performed a systematic review and meta-analysis to evaluate the diagnostic performance of these tests among men with PSA levels between 2 and 10 ng/ml. METHODS: Data on sensitivity and specificity were extracted from 66 eligible studies. Likelihood ratios and summary receiver operating characteristic curves were estimated and possible sources of heterogeneity between studies examined. RESULTS: Use of the f/tPSA or the cPSA test improved diagnostic performance among men with a total PSA (tPSA) of 2-4 or 4-10 ng/ml compared to tPSA alone. The diagnostic performance of the f/tPSA test was significantly higher in the tPSA range of 4-10 ng/ml compared to a tPSA range of 2-4 ng/ml (p < 0.01); at a sensitivity of 95%, the specificity was 18% in the 4-10 ng/ml tPSA range and 6% in the 2-4 ng/ml tPSA range. Among studies that measured both isoforms, the diagnostic performance of the f/tPSA test and the cPSA was equivalent in both PSA ranges. CONCLUSIONS: The use of the f/tPSA or cPSA test among men with PSA levels between 2 and 10 ng/ml can reduce the number of unnecessary biopsies whilst maintaining a high cancer detection rate.