Clinical value of human glandular kallikrein 2 and free and total prostate-specific antigen in serum from a population of men with prostate-specific antigen levels 3.0 ng/mL or greater

OBJECTIVES: To investigate the clinical value of human glandular kallikrein 2 (hK2) compared with free (f) and total (t) prostate-specific antigen (PSA) in the early detection of prostate cancer (PCa). METHODS: In PCa screening conducted in 1995 to 1996 in G?teborg, Sweden, 5853 of 9811 randomly selected men (aged 50 to 66 years; median 61) accepted PSA testing; those with tPSA levels of 3. 0 ng/mL or greater were offered digital rectal examination, transrectal ultrasound, and sextant biopsies. Serum from 604 of 611 biopsied men (18% with positive digital rectal examinations, tPSA range 3.0 to 220 ng/mL, 144 men with PCa) was analyzed for hK2 (research assay) and tPSA and fPSA (Prostatus). Sera were stored at -20 degrees C for a maximum of 2 weeks for tPSA and fPSA and 3 years for hK2. RESULTS: hK2 levels and hK2 x tPSA/fPSA values were significantly elevated in men with PCa. Receiver operating characteristic data revealed that the area under the curve for hK2 x tPSA/fPSA was significantly greater than that for tPSA and greater, but not significantly greater, than that for percent fPSA. Also, the cancer-detecting sensitivity was significantly improved (P <0.05) using hK2 x tPSA/fPSA compared with tPSA and percent fPSA at specificity levels of 75% to 90%. At 75% specificity, a sensitivity of 74% was obtained compared with 64% or 54% using percent fPSA or tPSA; at 90% specificity, the corresponding sensitivity level was 55%, 41%, and 36%, respectively. CONCLUSIONS: Discrimination of men with and without PCa in a randomly selected population was improved by measuring hK2 in addition to tPSA and fPSA.     

M1 prostate cancer with a serum level of prostate-specific antigen less than 10 ng/mL

BACKGROUND: M1 prostate cancer, which is invasive, is usually associated with a serum level of prostate-specific antigen (PSA) greater than 10 ng/mL, but cases are occurring where the serum PSA level is less than this. The present study investigated the clinical and pathologic characteristics of these cases of M1 prostate cancer. METHODS: Between April 1989 and March 1998, 167 cases of M1 prostate cancer were diagnosed by transrectal needle biopsy and eight of these with a serum PSA level less than 10 ng/mL were investigated. The patients' ages ranged from 57 to 79 years (median, 73) and the serum PSA levels ranged from less than 4.0 to 9.8 ng/mL. In all cases except one, the distal metastasis was to bones only. All cases had received hormonal therapy as the initial therapy. Immunostaining of PSA, chromogranin A, neuron-specific enolase, carcinoembryonic antigen and vimentin were performed in five of the eight cases. RESULTS: Four cases were poorly differentiated, two were undifferentiated, one was a mixture of poorly differentiated and undifferentiated and one case was moderately differentiated. Of the five cases in the immunohistochemical study, three cases with an undifferentiated carcinoma component showed negative staining reactions for PSA and all cases were positive for carcinoembryonic antigen. Four of the patients died of prostate cancer. In two of these four cases, hormonal therapy was ineffective, but systemic chemotherapy and irradiation therapy had been moderately effective. The overall 3-year survival rate was 33.3%. CONCLUSIONS: The cases of M1 prostate cancer with a serum PSA less than 10 ng/mL are almost always poorly differentiated or undifferentiated and have a poor prognosis compared with the usual M1 prostate cancer. Because hormonal therapy is ineffective in these cases, systemic chemotherapy and irradiation therapy should be chosen as the initial therapy.     

Diagnostic value of free prostate-specific antigen among men with a prostate-specific antigen level of <3.0 microg per liter

Objectives

The percentage of free prostate-specific antigen (%fPSA) improves the diagnostic accuracy for prostate cancer when the serum level of total PSA (tPSA) is elevated. Approximately 14% of men with a tPSA below 3 μg/l have prostate cancer on biopsy, but the diagnostic value of %fPSA in such men is rather unknown. The purpose was to estimate the impact of %fPSA on future prostate cancer risk among men with a normal tPSA in prostate cancer screening.

Subjects and methods

The first round of the Finnish arm of the European Randomized Trial for Screening of Prostate Cancer in 1996 to 1999 comprised 20,793 men aged 55–67 yr. Screen-negative men (tPSA level below 3.0 μg/l, n = 17,680) were followed up until the end of 2003. Cumulative risk of prostate cancer was calculated as a function of %fPSA.

Results

During the median follow-up of 5.8 yr (range, 0–7.7 yr), 327 men were diagnosed with prostate cancer and 25% of them had a Gleason score of 7 or higher. Five years after the first screening, cumulative risk of prostate cancer was 1.7% (95%CI, 1.5–1.9%). Men with a %fPSA in the lowest quartile (<14.2%) showed a 6.9-fold risk compared with those with a level in the highest quartile (>23.7%).

Conclusions

In men with a low serum tPSA, a low %fPSA is a strong predictor of later diagnosis of prostate cancer.     

Volume-adjusted prostate-specific antigen (PSA) variables in detecting impalpable prostate cancer in men with PSA levels of 2-4 ng/mL: transabdominal measurement makes a significant contribution

OBJECTIVE: To examine whether prostate-specific antigen (PSA) levels adjusted according to prostate volume improve prostate cancer detection using transrected biopsies in men with PSA levels of 2-4 ng/mL, and benign findings on a digital rectal examination (DRE). PATIENTS AND METHODS: Men aged < or = 79 years and with serum PSA levels of 2-4 ng/mL and normal DRE findings were prospectively enrolled. Eligible patients were recommended for transrectal prostate biopsies after measuring prostate volumes with transrectal (TRUS) and transabdominal (TAUS) ultrasonography, and transition zone volumes with TRUS. In addition to PSA levels and the free-to-total PSA ratio, volume-adjusted PSA levels, PSA densities determined by TRUS (PSAD(TRUS)), and TAUS (PSAD(TAUS)), and PSA transition zone densities (PSATzD) were compared using receiver operating characteristic analysis. RESULTS: Prostate cancer was diagnosed in 31 (22%) of the 139 men who had prostate biopsies. The area under the curve (AUC) of PSAD(TRUS) (0.796) and PSATzD (0.792) was similar and significantly greater than that of PSA (AUC 0.588) and the free-to-total PSA ratio (AUC 0.658). PSAD(TAUS) was a significantly better indicator of prostate cancer than PSA levels alone (P = 0.043). CONCLUSION: As predictors of prostate cancer, there were no significant differences between PSAD(TRUS) and PSATzD. Although PSAD(TAUS) was worse than PSA variables adjusted by total and transition zone prostate volumes determined by TRUS, it was a better predictor than the PSA value alone in men with a low PSA level. These results indicate that TAUS is worthwhile where the routine use of TRUS before biopsy is difficult.     

Prostate cancer incidence and disease-specific survival of men with initial prostate-specific antigen less than 3.0 ng/ml who are participating in ERSPC Rotterdam

Background

The European Randomised Study of Screening for Prostate Cancer (ERSPC) applies a prostate-specific antigen (PSA) cut-off value ≥3.0 ng/ml as an indication for lateralised sextant biopsy.

Objective

To analyse the incidence and disease-specific mortality for prostate cancer (PCa) in men with an initial PSA <3.0 ng/ml.

Design, setting and participants

From November 1993 to December 1999, a total of 42 376 men identified from population registries in the Rotterdam region (55–74 yr of age) were randomised to an intervention or control arm. A total of 19 950 men were screened during the first screening round.

Intervention

A PSA <3.0 ng/ml was below the biopsy threshold. PCa cases were identified at rescreens every 4 yr or as interval cancers.

Measurements

Distribution of incidence, aggressiveness, and disease-specific mortality of PCa per PSA range was measured. Causes of death were evaluated by an independent committee, and follow-up was complete until 31 December 2008.

Results and limitations

From 1993 to 2008, 915 PCa cases were diagnosed in 15 758 men (5.8%) with an initial PSA <3.0 ng/ml and a median age of 62.3 yr. Median overall follow-up was 11 yr. PCa incidence increased significantly with higher initial PSA levels. Aggressive PCa (clinical stage ≥T2c, Gleason score ≥8, PSA >20 ng/ml, positive lymph nodes, or metastases at diagnosis) was detected in 66 of 733 screen-detected PCa cases (9.0%) and 72 of 182 interval-detected PCa cases (39.6%). Twenty-three PCa deaths occurred in the total population (0.15%), with an increasing risk of PCa mortality in men with higher initial PSA values.

Conclusions

The risk of PCa, aggressive PCa and PCa mortality in a screening population with initial PSA <3.0 ng/ml increases significantly with higher initial PSA levels. These results contribute to the risk stratification and individual management of men in PSA-based screening programmes.     

Serum prostate-specific antigen levels (PSA) in men without clinical evidence of prostate cancer: age-specific reference ranges for total PSA, free PSA, and percent free PSA

Objectives. To investigate the relationship between age and total prostate-specific antigen (tPSA), free PSA (fPSA), and percent free PSA (%fPSA) in men 48 to 79 years old without clinical evidence of prostate cancer. We determined age-specific ranges for each parameter and compared the results with previously published studies in similar populations.Methods. Nine hundred eighty-three men (96% white) from the random-sample community-based Massachusetts Male Aging Study were analyzed. Men with PSA 4.1 ng/mL or greater were referred for biopsy and those with positive biopsies or with medical record, cancer registry, or self-reported evidence of prostate cancer were excluded.Results. The median tPSA increased 38.6% per decade (95% confidence interval 28.7% to 49.3%). Because of the greater variability at older ages, the 95th percentile increased faster than the median, leading to the following age-specific upper limits of normal: 2.84 for 50 to 59 years, 5.87 for 60 to 69 years, and 9.03 for 70 to 79 years. The pattern of association between fPSA and age was similar to tPSA. The 50th and 5th percentiles of %fPSA were 25.3% and 13.2%, respectively, regardless of age.Conclusions. Establishing age-specific screening cutoffs based on the age-specific upper limits of normal will ensure low false-positive biopsy rates but may also lead to low true positive rates (ie, low sensitivity) in older age groups. Both sensitivity and specificity should be considered when counseling patients. The independence of %fPSA with age confirms others’ findings.     

F／T—PSA比值在T—PSA小于10ng／ml时的意义

为研究F／T－PSA比值在PSA 0-10ng/ml时特异性和敏感性,随机选择住院和门诊明确诊断为BPH的病例253例,作肛门指检、经直肠超声检查及血清T－PSA和F－PSA检测。血清T－PSA和F－PSA检测采用单克隆抗体包被管放射免疫分析法。结果：1．随着血清T－PSA的上升,F／T－PSA比值呈现下降,T－PSA值与F／T－PSA比值呈负相关性。2．T－PSA和F－PSA与年龄增长呈正相关（P＜0．01）,F／T－PSA比值与年龄差无相关性。作者认为T－PSA值在正常范围,F／T－PSA比值提高T－PSA的敏感性;T－PSA值增高,F／T－PSA比值提高T－PSA的特异性。这些有助于诊断早期前列腺癌。     

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.     

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.