Assay-specific artificial neural networks for five different PSA assays and populations with PSA 2–10 ng/ml in 4,480 men

Use of percent free PSA (%fPSA) and artificial neural networks (ANNs) can eliminate unnecessary prostate biopsies. In a total of 4,480 patients from five centers with PSA concentrations in the range of 2–10 ng/ml an IMMULITE PSA-based ANN (iANN) was compared with other PSA assay-adapted ANNs (nANNs) to investigate the impact of different PSA assays. ANN data were generated with PSA, fPSA (assays from Abbott, Beckman, DPC, Roche or Wallac), age, prostate volume, and DRE status. In 15 different ROC analyses, the area under the curve (AUC) in the PSA ranges 2–4, 2–10, and 4–10 ng/ml for the nANN was always significantly larger than the AUC for %fPSA or PSA. The nANN and logistic regression models mostly also performed better than the iANN. Therefore, for each patient population, PSA assay-specific ANNs should be used to optimize the ANN outcome in order to reduce the number of unnecessary biopsies.     

The relation of prostate biopsy results and ratio of free to total PSA in patients with a total PSA between 4–20 ng/mL

Objective: In this study our aim was to investigate the efficacy of free tototal PSA ratio in discrimination of benign prostate hyperplasia andprostate cancer.Materials and methods: A total of 194 patients, 52 to 82 years old (mean66.06 ± 0.47 years) with PSA levels between 4 to 20 ng/mL wereincluded into this study. Each patient underwent sextant prostate biopsyunder transrectal ultrasound guidance. The patients were divided into twogroups as PSA 4–10 and 10–20 ng/mL. Patients with benign and malignresults were compared with respect to age, total PSA level, free PSA leveland free/total (f/t) PSA ratio.Results: Biopsies revealed prostate cancer in 16 of 130 patients (12.3%)with serum PSA 4–10 ng/mL and in 10 of 64 patients (15.6%) with serumPSA 10–20 ng/ml. In both PSA groups free PSA and f/t PSA levels werestatistically significant, where total PSA levels were not. In patients with4–20 ng/mL total PSA levels and a cut off level of < 0.18 for f/t PSA, thesensitivity, specificity and positive predictive value for prostate cancerwere 88.5%, 53.6% and 20.4% respectively.Conclusion: Higher levels of PSA suggest prostate cancer, but stilladditional parameters are needed for patients with PSA 4–20 ng/mL, suchas free PSA and f/t PSA. Although a cut off level of < 0.18 for f/t PSA seemsto be the most accurate one to discriminate benign and malign diseasesfurther studies on larger groups of patients are needed.     

Free/total PSA ratio can help in the prediction of high gleason score prostate cancer in men with total serum prostate specific antigen (PSA) of 3–10 ng/ml

Purpose We evaluate the use of free/total prostate specific antigen (PSA) ratio in improving the prediction of cancers of higher Gleason scores. Patients and methods A total of 164 patients with total serum PSA of 3.0–10.0 ng/ml underwent extended TRUS-guided core biopsy. In each man serum free PSA was measured and the free/total (F/T) PSA ratio was calculated. Out of the 164 patients who underwent TRUS-biopsy, cancer was detected in 62 (37.8%) patients. The mean age for the 62 patients with histologically proven prostate cancer was 62.3 ± 5.5 years (49–73). The histological findings were compared with the free/total PSA ratio. Pearson Correlation Coefficient test and Chi-Square test (χ²-test) were used for statistical analysis and p < 0.05 was considered statistically significant. ResultsOf the 62 patients, 37 (59.7%) patients had cancers of low Gleason scores (score 2–6) and 25 (40.3%) patients had cancers of high Gleason scores (score 7–10). Free PSA < 0.15% was found in 19 (30.6%) patients, from 15 to 20% in 23 (37.1%) patients and > 20% in 20 (32.3%) patients. There was a significant positive correlation between total PSA and Gleason score (Pearson Correlation Coefficient test, r = 0.328, p < 0.01). Also, there was a significant increase in Gleason score with lower F/T PSA ratio (r = −0.668, p < 0.001). Among the 19 patients with free PSA ratio < 15%, 14 (73.7%) patients had cancers of high Gleason score while 5 (26.3%) patients had cancers of low Gleason score. In patients (n = 23) with free PSA ratio15–20%, 10 (43.5%) had cancers of high Gleason score and 13 (56.5%) had cancers of low Gleason score. In the 20 patients with free PSA ratio > 20%, 1 patient (5%), had prostate cancer of high Gleason score and the remaining 19 (95%) patients had low Gleason scores. There was a significant relation between lower F/T PSA ratios and higher Gleason scores, Chi-Square test, χ² = 19.3, p < 0.01. Conclusions In this study, men with prostate cancer and lower F/T PSA ratio were at a higher risk of having higher Gleason scores (7–10) and those with higher F/T PSA ratio were more likely to have lower Gleason scores.     

Does PSA velocity predict prostate cancer in pre-screened populations?

PSA-driven screening has been applied to a large part of the male population in many countries. An elevated PSA in secondary screens may indicate benign enlargement of the prostate rather than prostate cancer. In such cases the yearly rate of increase of PSA (PSA velocity [PSAV]) may improve the test characteristics of PSA. MATERIALS AND METHODS: Data from the European Randomized Study of Screening for Prostate Cancer Rotterdam are used to study the issue. Relative sensitivity, relative specificity, and positive predictive value (PPV) are calculated. Logistic regression analysis is used to compare odds ratios for positive biopsies. The relationship between PSAV and parameters of tumour aggressiveness is investigated. RESULTS: Five hundred eighty-eight consecutive participants were identified who presented at their first screening with PSA values <4.0 and who progressed to PSA values >4.0 ng/ml four years later. None were biopsied in round one, all were biopsied in round two. Relative sensitivity and specificity depend strongly on PSAV cut-offs of 0.25-1.0 ng/ml/yr. The use of PSAV cut-offs does not improve the PPV of the PSA cut-off of 4.0 ng/ml, nor do any of the PSAV cut-offs improve the odds ratio for identifying prostate cancer with respect to the cut-off value of 4.0 ng/ml. The rate of aggressive cancers seems to increase with increasing PSAV. CONCLUSIONS: PSAV does not improve the detection characteristics of a PSA cut-off of 4.0 ng/ml in secondary screening after four years.     

Repeating an abnormal prostate-specific antigen (PSA) level: how relevant is a decrease in PSA?

To examine the practice of repeating an abnormal prostate-specific antigen (PSA) level before proceeding to prostate biopsy, we assessed the pattern of PSA change following an initially raised (>or=4.0 ng ml(-1)) PSA, and the relationship of this to prostate cancer diagnosis. In 7052 men, 71.2% with initially raised PSA had a reduction in PSA, with values <4.0 ng ml(-1) in 37.8%. A total of 43.0% of men with prostate cancer showed a PSA decrease below their baseline level. Short-term decreases in PSA may occur in men with prostate cancer, including high-grade cancer, and so should not influence the decision to proceed to prostate biopsy.     

Are PSA density and PSA density of the transition zone more accurate than PSA in predicting the pathological stage of clinically localized prostate cancer?

PURPOSE: To assess whether PSA density (PSAD) and PSA density of the transition zone (PSADTZ) are more accurate than PSA alone in predicting the pathological stage of prostate cancer. MATERIALS AND METHODS: One hundred and nine consecutive patients with clinically localized prostate cancer and preoperative PSA values over the whole range, treated with radical retropubic prostatectomy and limited pelvic lymph node dissection were included in this prospective study. Total prostate and transition zone volumes were measured by transrectal ultrasound using the prolate ellipsoid method. PSA, PSAD, and PSADTZ were compared to percentage of positive biopsy cores (% PC), biopsy and surgical Gleason score, and pathological stage, using univariate and multivariate analysis. RESULTS: Pathological stage was pT2a, pT2b, pT3a, and pT3b in 25.6%, 37.7%, 25.6%, and 11.1% of patients, respectively. Lymph node metastases were found in 4.6% of patients. PSA, PSAD, and PSADTZ were significantly related to % PC, biopsy, and surgical Gleason score and pathological stage (P < 0.001), and were equally able to predict higher pathological stage, i.e., seminal vesicle invasion and lymph node metastases. Only by adding % PC in multivariate analysis was it possible to discriminate intra- from extracapsular tumors. CONCLUSIONS: The results of the present study demonstrate that PSAD and PSADTZ failed to outperform PSA in preoperative stage prediction of prostate cancer, possibly because the formula used to calculate them does not eliminate the contribution to total PSA of the nonmalignant portion of the gland.     

Prostate-specific Antigen (PSA) Testing Is Prevalent and Increasing in Stockholm County,Sweden, Despite No Recommendations for PSA Screening: Results from a Population-based Study, 2003–2011

Background

Prostate-specific antigen (PSA) testing has increased in several countries. There is incomplete knowledge of PSA testing patterns.

Objective

Determine the prevalence of PSA testing and explore patterns of PSA retesting in Stockholm County, Sweden.

Design, setting, and participants

A population-based study was performed. Through registry linkages, we collected population information, data on PSA tests, pathology reports, and clinical information. The study population comprised males living in Stockholm County in 2011 (n = 1 034 129), of which 229 872 had a PSA test during the period 2003–2011.

Outcome measurements and statistical analysis

We determined limited-duration-point prevalence of PSA testing and performed survival analysis on PSA retesting for men aged 40–89 yr.

Results and limitations

The number of PSA tests increased from 54 239 in 2003 to 124 613 in 2011. During the 9-yr study period, 46%, 68%, and 77% of men without a prior prostate cancer (PCa) diagnosis and aged 50–59 yr, 60–69 yr, and 70–79 yr, respectively, had a PSA test. During 2010 and 2011, 25%, 40%, and 46% of men aged 50–59 yr, 60–69 yr, and 70–79 yr, respectively, had a PSA test. The prevalence of PSA testing increased from 2003 to 2011. The probability of retesting was PSA and age dependent, with a 26-mo cumulative incidence of 0.337 (95% confidence interval, 0.333–0.341) if the first PSA value was <1 ng/ml. The main limitations were (1) that PSA data prior to 2003 were not available and (2) that the study cohort was restricted to men who were alive in 2011.

Conclusions

Although screening for PCa is not recommended in Sweden, PSA testing in Stockholm County was high across ages ranging from 40 to 89 yr and increased during the period 2003–2011. The probability of PSA retesting was high, regardless of the original PSA level. These results contrast with current clinical recommendations and raise calls for a change, either through structured PCa testing or more detailed guidelines on PSA testing.     

游离PSA/总PSA比值诊断前列腺癌的临床意义

目的　探讨血清游离前列腺特异抗原（ｆＰＳＡ）／ 总前列腺特异抗原（ｔＰＳＡ）比值对前列腺癌的诊断价值。方法　用酶联双抗夹心法检测２２ 例前列腺癌,４８ 例前列腺增生（ＢＰＨ） 和２０ 例正常对照组的血清ｆＰＳＡ、ｔＰＳＡ,并计算ｆＰＳＡ／ｔＰＳＡ 比值,评价其对前列腺癌的诊断价值。结果　以ｆＰＳＡ／ｔＰＳＡ０．１５ 为判断上限时,其诊断敏感性为９０ ．９％ ,特异性为８７．５％ ,诊断准确性为８８ ．６ ％ ,明显优于ｔＰＳＡ和ｆＰＳＡ 单独测定结果。结论　ｆＰＳＡ／ｔＰＳＡ可更有效地诊断前列腺癌。     

Diagnostic significance of [−2]pro-PSA and prostate dimension-adjusted PSA-related indices in men with total PSA in the 2.0–10.0 ng/mL range

Purpose

One of the most important issues to address when developing an optimal screening system for prostate cancer is investigating appropriate biopsy indications following serum prostate-specific antigen (PSA) measurements in order to maintain high sensitivity and avoid unnecessary biopsy.

Methods

Between April 2004 and December 2007, 239 consecutive men with total PSA levels of 2.0–10.0 ng/mL underwent measurements of PSA, free PSA, and [?2]pro-PSA. We assessed the significance of laboratory-based PSA-related indices including free PSA/total PSA (%f-PSA), p2PSA/free PSA (%p2PSA), p2PSA/%f-PSA, Prostate Health Index (phi, an index combining PSA, free PSA, and p2PSA), total prostate volume (TPV)-adjusted PSA-related indices, including PSA density, %p2PSA density, p2PSA/%f-PSA density, and phi density, and transition zone (TZ) prostate volume-adjusted PSA-related indices such as PSA TZ density (PSATZD), %p2PSA TZD, p2PSA/%fPSA TZD, and phi TZD.

Results

The positive biopsy rate was 22.2 %. When sensitivity was fixed at 95 %, unnecessary biopsies could be avoided in 28 % of men when phi was used as a biopsy indication. In cases where total and transition zone prostate volumes were available, the use of %p2PSA density, phi density, p2PSA/%f-PSA TZD, and phi TZD resulted in the avoidance of 48, 47, 54, and 54 % of unnecessary biopsies, respectively, while maintaining a high sensitivity of 90 %.

Conclusions

At 90 and 95 % sensitivity, laboratory-based indices containing p2PSA, particularly phi, showed significantly greater specificity for prostate cancer as compared with %f-PSA. The diagnostic accuracy of prostate volume-adjusted p2PSA-related indices could be excellent, particularly the transition zone volume-adjusted indices at fixed sensitivities of 95 and 90 %.     

Prostate cancer survival in Trinidad: Is PSA a prognostic factor?

Background:

Prostate cancer is the most common malignancy among men in the western hemisphere, including Trinidad and Tobago. The aim of this study is to describe the epidemiological features of prostate cancer among patients admitted to a tertiary level teaching hospital during 2002 to 2005. We assessed the long-term survival of patients with prostate cancer and the epidemiology of the disease.

Methods:

We reviewed the admissions data for the period 2002–2005. Demographic, clinical and outcomes (survival or death) data were collected and analysed, using SPSS version 16. Statistical analysis included Kaplan-Mier survival analysis, Cox regression models and the log-rank test. A p value of <0.05 was considered statistically significant.

Results:

Of the 1250 cases reviewed, 242 participants were selected. Patients of African ancestry, older than 60 years and a Gleason score greater than 7 had an increased risk of mortality. Patients with prostate-specific antigen (PSA) ≥100 ng/L had a 3-fold increased risk of mortality. Survival rates declined between 2002 and 2005.

Conclusion:

This is the first study of its kind to demonstrate survival rates among patients with prostate cancer in Trinidad. The following epidemiological features were identified: average age of occurrence of 71 years, ethnic disparity with higher occurrence in African men than all other ethnic groups and a PSA of >100 ng/dL. These features were associated with a 3-fold higher risk of death. A Gleason score of 8 to 10 was also associated with lower survival rates.     

结合PSA及游离PSA/总PSA比值在前列腺癌诊断中的作用的前瞻性研究

赵来越多的患者因为血清总PSA的升高而行前列腺活检,但总PSA缺乏足够的特异性.PSA以游离形式及几种结合形式存在,已有报告称游离/总PSA比值可以提高PSA处于灰区的前列腺癌的诊断率,也有研究认为患前列腺癌时变化更多的是结合PSA.     

筛选志愿者血清中总PSA,游离PSA及游离PSA百分比的生物变异

筛选志愿者血清中总ＰＳＡ，游离ＰＳＡ及游离ＰＳＡ百分比的生物变异［ＯｒｎｓｔｅｉｎＤＫ，ｅｔａｌ．ＪＵｒｏｌ，１９９７，１５７∶２１７９］血清ＰＳＡ的测定及直肠指诊被广泛地用于前列腺癌的早期诊断。血清肿瘤标记能否在临床上得到正确的应用取决于该肿瘤标记...     

PSA应用的注意事项

目的 论述PSA应用的注意事项，包括PSA组成，PSA生理、病理和医源性影响因素以及PSA的临床扩大应用。结论 医护人员要综合考虑PSA结果，对不同患者要在不同时间选择不同的PSA参数。     

射精对血清中总PSA和游离PSA的影响

为了阐明射精对血清前列腺特异抗原（ＰＳＡ）的影响，对２２例年龄５１～６７岁，总ＰＳＡ（ｔＰＳＡ）持续低于４μｇ／Ｌ，无前列腺癌病史的男性，禁欲５天后排精，并分别于射精后１、６和２４小时接受血清ｔＰＳＡ和游离ＰＳＡ（ｆＰＳＡ）的测定，以禁欲时的测得值为...     

PSA生物化学的研究进展

前列腺特异性抗原（ＰＳＡ）是前列腺表皮细胞产生的蛋白水解酶，是精浆的组成成份，但在血清中常可微量检出。多数情况下前列腺癌（ＰＣａ）病人血清ＰＳＡ升高。由于前列腺增生症（ＢＰＨ）病人血清ＰＳＡ亦增高，故ＰＳＡ不是肿瘤特异性标记物。为提高其特异性，最近对ＰＳＡ的分子亚型（游离ＰＳＡ，ＰＳＡ－ＡＣＴ复合物）进行了研究。本文综述ＰＳＡ的生化研究进展及其临床意义，特别是对游离ＰＳＡ与总ＰＳＡ的比值来提高ＰＣａ和ＢＰＨ的鉴别