CaP Diagnosis Research Articles

Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia

BackgroundCommunity-acquired pneumonia (CAP) is the most frequent infection-related cause of death. The reference standard to diagnose CAP is a new infiltrate on chest radiograph in the presence of recently acquired respiratory signs and symptoms. This study aims to evaluate the diagnostic and prognostic accuracy of clinical signs and symptoms and laboratory biomarkers for CAP.Methods545 patients with suspected lower respiratory tract infection, admitted to the emergency department of a university hospital were included in a pre-planned post-hoc analysis of two controlled intervention trials. Baseline assessment included history, clinical examination, radiography and measurements of procalcitonin (PCT), highly sensitive C-reactive protein (hsCRP) and leukocyte count.ResultsOf the 545 patients, 373 had CAP, 132 other respiratory tract infections, and 40 other final diagnoses. The AUC of a clinical model including standard clinical signs and symptoms (i.e. fever, cough, sputum production, abnormal chest auscultation and dyspnea) to diagnose CAP was 0.79 [95% CI, 0.75–0.83]. This AUC was significantly improved by including PCT and hsCRP (0.92 [0.89–0.94]; p < 0.001). PCT had a higher diagnostic accuracy (AUC, 0.88 [0.84–0.93]) in differentiating CAP from other diagnoses, as compared to hsCRP (AUC, 0.76 [0.69–0.83]; p < 0.001) and total leukocyte count (AUC, 0.69 [0.62–0.77]; p < 0.001). To predict bacteremia, PCT had a higher AUC (0.85 [0.80–0.91]) as compared to hsCRP (p = 0.01), leukocyte count (p = 0.002) and elevated body temperature (p < 0.001). PCT, in contrast to hsCRP and leukocyte count, increased with increasing severity of CAP, as assessed by the pneumonia severity index (p < 0.001).ConclusionPCT, and to a lesser degree hsCRP, improve the accuracy of currently recommended approaches for the diagnosis of CAP, thereby complementing clinical signs and symptoms. PCT is useful in the severity assessment of CAP.

Telomere Attrition in Isolated High-Grade Prostatic Intraepithelial Neoplasia and Surrounding Stroma Is Predictive of Prostate Cancer

The causes of early genomic events underlying the development of prostate cancer (CaP) remain unclear. The onset of chromosomal instability is likely to facilitate the formation of crucial genomic aberrations both in the precursor lesion high-grade prostatic intraepithelial neoplasia (HPIN) and in CaP. Instability generated by telomere attrition is one potential mechanism that could initiate chromosomal rearrangements. In this study, normalized telomere length variation was examined in a cohort of 68 men without CaP who had HPIN only on prostatic biopsies. Multiple significant associations between telomere attrition and eventual diagnosis of CaP in the HPIN and in the surrounding stroma were found. Kaplan-Meier analysis of telomere length demonstrated a significantly increased risk for the development of cancer with short telomeres in the surrounding stroma [P = .035; hazard ratio (HR) = 2.12; 95% confidence interval (95% CI) = 0.231-0.956], and a trend for HPIN itself (P = .126; HR = 1.72; 95% CI = 0.287-1.168). Cox regression analysis also demonstrated significance between the time from the original biopsy to the diagnosis of cancer and telomere length in HPIN and in the surrounding stroma. These analyses showed significance, both alone and in combination with baseline prostate-specific antigen, and lend support to the hypothesis that telomere attrition in prostatic preneoplasia may be fundamental to the generation of chromosomal instability and to the emergence of CaP.

Measurement of blood E2F3 mRNA in prostate cancer by quantitative RT-PCR: a preliminary study

The use of serum prostate-specific antigen (PSA) measurements necessitates biopsies for accurate prostate cancer (CaP) diagnosis. Overall efficiency of accurate diagnosis, when PSA levels are used alone, is less than 60%. E2F3 was evaluated as an alternative biomarker using patient blood samples. Expression levels were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and correlated with accurate clinicopathological data. Statistical analysis demonstrated significant differences in E2F3 expression levels (p<0.0001), and high levels of discrimination (receiver operator curve/area under curve analysis values (AUC) >0.88), in particular at early stages of disease development, between benign disease and localized CaP. Limited levels of discrimination were observed at the later stages of disease development, between localized and metastatic disease (p=0.076, AUC=0.633). A cut-off point of 0.34 with high specificity for benign disease (92.3%) and sensitivity for CaP diagnosis (81.0%) was identified. At this cut-off point, 85% patients were correctly diagnosed with either malignant or benign disease. This study demonstrates the strength of E2F3 as a potential marker for discriminating benign and malignant disease, addressing the current limitations of serum PSA measurements.

Telomere dysfunction in prostatic carcinogenesis

10021 Background: Telomeres are composed of tandemly repeated DNA sequences (TTAGGG) and specific binding proteins located at the ends of eukaryotic chromosomes. They stabilize chromosomal ends; telomere shortening is an important mechanism of genomic instability and can lead to end-to-end chromosomal fusion, rearrangements and cell death. Here we evaluate the hypothesis that telomere shortening contributes to the development of prostate cancer (CaP). Methods: We used telomeric, centromeric and chromosome specific peptide-nucleic acid probes with z-stacked quantitative fluorescence in-situ hybridisation analysis to initially analyse 15 radical prostatectomy specimens and then subsequently sextant core biopsies from 80 men obtained in 1998–2001 containing high-grade prostate intraepithelial neoplasia (HPIN) only. The biopsy cohort outcome is blinded to prevent experimental bias and has a minimum follow-up of 2 years with 41 men diagnosed subsequently with CaP and 39 men without CaP on rebiopsy. Regions of interest were identifying with an overlying haematoxylin and eosin slide. Results: We found a significant decrease in telomere length in both HPIN and CaP in comparison to normal prostatic epithelium accompanied by elevated rates of aneusomy. Telomere erosion in HPIN was more common in regions of the prostate-containing CaP. We now have analyzed ∼4000 cells of matching HPIN and surrounding stroma. Preliminary analysis demonstrated that the median telomere length in HPIN is approximately 27% of the surrounding stroma with upper and lower quartiles being 16% and 38% respectively. Logistic regression analysis is in progress to determine whether the length of the shortest telomeres or the average telomeric length in a sample predicts for subsequent diagnosis of CaP. Secondary analyses are examining the effect of telomere length on the interval to the diagnosis of CaP, the effect of age on telomere length and the eventual Gleason score. Conclusions: Analysis of telomere length holds great promise for developing improved prognostic markers in prostatic carcinogenesis. This is a first of its kind study in the field. No significant financial relationships to disclose.

Relationship Among Initial Serum Prostate Specific Antigen, Prostate Specific Antigen Progression and Prostate Cancer Detection at Repeat Screening Visits

We evaluated the probability of positive serum PSA (3 ng/ml or greater) and CaP detection at annual followup visits in men with negative initial PSA (less than 3 ng/ml) to optimize the re-screening schedule. Data on 5,387 men 45 to 80 years old with negative PSA and no CaP diagnosis at the first screening visit were obtained from the Laval University Prostate Cancer Screening Program database. Accelerated failure time regressions were fitted to time from baseline to positive PSA and to time from positive PSA to CaP detection. The models were combined to estimate the cumulative probability of positive PSA followed by CaP detection at re-screening. The 5-year cumulative probability of detecting CaP at annual visits in men with baseline PSA up to 1.5 ng/ml remained below 0.8%, while it was 1.3%, 4.8% and 8.3% in men with PSA 1.5 to less than 2, 2 to less than 2.5 and 2.5 to less than 3 ng/ml, respectively. Time to positive PSA significantly decreased with increasing baseline PSA and age, while the time between positive PSA and CaP detection depended only on age. Men with PSA below 1.0 ng/ml could wait for 4 to 5 years before being re-tested, while men with PSA between 1.0 and 1.5 ng/ml should be screened every second year and men with PSA 1.5 ng/ml or greater should be screened every year. The proposed retesting schedule using current PSA and age decreases the number of visits by 38.1%, while delaying the detection of only 2.4% of CaPs that would have been detected using annual PSA testing.

Impact of Race, Age, Income, and Residence on Prostate Cancer Knowledge, Screening Behavior, and Health Maintenance in Siblings of Patients with Prostate Cancer

ObjectiveThis study evaluates self-reported changes in knowledge of prostate cancer (CaP), CaP screening behavior and other health-related activities in men whose brothers have been diagnosed with prostate cancer and to characterize those demographic subgroups of siblings at particular risk of failure to change their behavior. Methods112 men were surveyed to self-assess their knowledge of CaP both before and after their brother’s diagnosis. In addition, siblings were questioned with regard to other health-related behaviors before and after their brother’s diagnosis. Demographic characteristics including age, race, income, and area of residence were also reported. Results were analyzed to determine how a brother’s diagnosis with CaP affects changes in prostate cancer knowledge, screening behavior and other health related activities in these high-risk patients. ResultsThe impact of a brother’s diagnosis of CaP affects only 40% of siblings with regard to CaP knowledge. This knowledge appears to translate into increased screening behavior and other-health-related activity in these men. Unfortunately, more than half of men have no change in CaP knowledge and correspondingly no change in screening behavior. Siblings who are older, earn less, and live in rural areas have a lower baseline knowledge of CaP and are less likely to improve their self-assessed knowledge. On regression analysis, correlates of improvement in CaP knowledge included (1) those discussing with their primary physician (OR=6.6), (2) Caucasians (OR=2.7) and (3) non-smokers (OR=3.1). Improvements in prostate cancer knowledge were found to be predictive of subsequent participation in CaP screening and annual physical exams. ConclusionsIncreased attention should be paid to siblings of CaP patients in efforts to improve their knowledge and thereby participation in screening as these patients are at an increased risk of development of this disease. Efforts should be made to educate siblings who are older, of lower income, African American, and rural residents with regard to CaP, as these subgroups appear less likely to change their knowledge and screening behavior despite their sibling’s diagnosis.

Catastrophic antiphospholipid antibody syndrome following initiation of hemodialysis

Antiphospholipid syndrome (APS) is associated with arterial and venous thrombosis, pregnancy morbidity, and thrombocytopenia. Some APS patients develop rapid and disseminated microthrombosis and are known as having catastrophic APS or CAPS. We document here a case of CAPS in a patient who presented with various clinical symptoms and serious abnormalities of blood coagulation following initiation of hemodialysis after bilateral nephrectomy due to renal cancer. The patient developed multiple organ symptoms, including melena, visual disturbances, skin eruptions, lymph node swelling, urinary tract bleeding, backache, arteriovenous fistula occlusion, and chest pain. Based on the clinical course and serological and histological examinations, a diagnosis of CAPS was established. The patient recovered by following intensive anticoagulation and steroid therapy. Although CAPS is rare, once symptoms develop the condition deteriorates rapidly. Because of the associated high mortality, early diagnosis and prompt treatment are necessary.

Prostate brachytherapy for localized prostate cancer

After skin cancer, prostate cancer (CaP) is the most common cancer diagnosed in men. As a result of screening with prostate-specific antigen, CaP is being caught earlier than it was in the past. This has led to an increase in cure rates across all treatment modalities. There are no firm, reproducible data that demonstrate the superiority of one modality over another. The expectations for cure should be approximately 90% for low-risk patients and approximately 80% for intermediate-risk patients, regardless of treatment modality. The toxicity of available treatment modalities discriminates among them. All modalities have acute toxicity of similar severity; however, prostate brachytherapy (PI) has the least amount of long-term toxicity when compared with external beam radiotherapy and radical prostatectomy. Therefore, a patient who is confronted with the diagnosis of CaP is counseled to choose among the modalities based on the toxicity rather than the efficacy of the treatment options available. Adopting this evidence-based algorithm has led to the increased application of PI.

The use of Raman spectroscopy to differentiate between different prostatic adenocarcinoma cell lines

Raman spectroscopy (RS) is an optical technique that provides an objective method of pathological diagnosis based on the molecular composition of tissue. Studies have shown that the technique can accurately identify and grade prostatic adenocarcinoma (CaP) in vitro. This study aimed to determine whether RS was able to differentiate between CaP cell lines of varying degrees of biological aggressiveness. Raman spectra were measured from two well-differentiated, androgen-sensitive cell lines (LNCaP and PCa 2b) and two poorly differentiated, androgen-insensitive cell lines (DU145 and PC 3). Principal component analysis was used to study the molecular differences that exist between cell lines and, in conjunction with linear discriminant analysis, was applied to 200 spectra to construct a diagnostic algorithm capable of differentiating between the different cell lines. The algorithm was able to identify the cell line of each individual cell with an overall sensitivity of 98% and a specificity of 99%. The results further demonstrate the ability of RS to differentiate between CaP samples of varying biological aggressiveness. RS shows promise for application in the diagnosis and grading of CaP in clinical practise as well as providing molecular information on CaP samples in a research setting.

Use of thymosin β15 as a urinary biomarker in human prostate cancer

Additional prostate cancer (CaP) biomarkers are needed to increase the accuracy of diagnosis and to identify patients at risk of recurrence. In tissue-based assays, thymosin beta15 (Tbeta15) has been linked to an aggressive CaP phenotype and correlated with future tumor recurrence. We hypothesized that Tbeta15 may have clinical utility in biological fluids. Tbeta15 was measured in urine from CaP patients; untreated (N = 61), prostatectomy (RP, N = 46), androgen deprivation therapy (ADT, N = 14) and control groups; normal (N = 52), genitourinary carcinoma (N = 15), non-malignant prostate disease (N = 81), and other urology (N = 73). We evaluated the utility of urinary Tbeta15 for CaP diagnosis, alone or in combination with prostate-specific antigen (PSA), and the relationship to CaP progression. A normal threshold of 40 (ng/dl)/(mug_protein/mg_creatinine) was defined using receiver operating characteristic analysis and marked the 19th centile for age-matched controls. The proportion of untreated CaP patients with urinary Tbeta15 above the threshold was significantly higher than normal and genitourinary disease controls (P < 0.001). RP caused urinary Tbeta15 to drop significantly (P = 0.005). Pre-surgery Tbeta15 concentrations greater than the normal threshold may confer greater risk of CaP recurrence. Relative to normal controls, patients receiving ADT for aggressive CaP were 12 times more likely to have elevated urinary Tbeta15 (P = 0.001, 95% CI = 2.8, 51.8). Combining PSA and Tbeta15 (PSA > 4, or PSA > 2.5, Tbeta15 > 40, or PSA = 2.5, Tbeta15 > 90) provided the same sensitivity as a 2.5 ng/ml PSA cutoff, but markedly improved diagnostic specificity. We report that Tbeta15 is a urinary biomarker for CaP and suggest that Tbeta15, in combination with PSA, can be used to improve both the sensitivity and specificity of CaP diagnosis.

MONITORING THE SEROLOGICAL PROTEOME: THE LATEST MODALITY IN PROSTATE CANCER DETECTION

Various strategies have recently emerged to improve the diagnostic prediction of prostate cancer (CaP). One such strategy includes the mass profiling of serum protein fractions selectively adsorbed onto chemically modified probes. In the current study we further validated this approach, while offering a more versatile, less expensive and yet equally predictive alternative to existing technologies. A solid core lipophilic C-18 resin was used to extract and enrich the low molecular weight protein fraction from patient serum for further analysis by mass spectrometry. Mass spectra generated from a 48 patient training set were data mined using multivariate analysis to identify diagnostically significant protein peaks. These peaks were then used to test a blinded study set comprising 168 patients with common statistical algorithms and commercially available software packages. A total of 36 peaks generated from the training set were used to test the combined set of 168 serum samples obtained from 98 healthy individuals and 70 patients with CaP. We report a sensitivity of 94.1% and a specificity of 99.0% with 1 false-positive, 4 false-negative and 5 nondiagnosed cases. Our results further indicate that mass profiling of serological proteins provides a means for the accurate detection of CaP. In addition, our approach was found to be superior to chip based protocols, generating rich, sharp, highly reproducible spectra attainable in a high throughput manner and at minimal cost. This technique is also scaleable for subsequent protein characterization using multidimensional protein identification technologies. Finally, analyses of mass spectra with commercially available statistical applications was found to be highly effective in generating highly discriminatory m/z values for CaP diagnosis.

Role of Tissue Polypeptide Specific Antigen in the Detection of Prostate Cancer

Objective: The aim of the present study was to evaluate the role of tissue polypeptide specific antigen (TPS) in the diagnosis of different stages of prostatic cancer (CaP) and to compare the diagnostic efficacy of serum TPS in respect to total prostate-specific antigen (tPSA) and free/total (f/t) PSA ratio. Patients and Methods: Patients with BPH (n = 58), localized CaP (n = 37) and metastatic CaP (n = 16) were compared by measuring serum TPS, tPSA and f/t PSA ratio. Results: Serum TPS was significantly increased only in patients with metastatic CaP (p < 0.05) and TPS levels was not significantly different between patients with BPH and localized CaP. Both f/tPSA and tPSA showed better sensitivity, specificity and receiver operating curve analysis in the differential diagnosis of BPH and localized CaP. Conclusion: In conclusion, serum TPS measurement was found to be significantly increased in metastatic prostatic carcinoma cases but was not useful in the early detection of prostatic carcinoma. Although there are several studies demonstrating the usefulness of TPS in the differential diagnosis of prostate cancer, there is increasing evidence for the use of this molecule in the late period of the disease or as an adjunct to other molecules in the detection of recurrences.

Macrophage migration inhibitory factor evaluation compared with prostate specific antigen as a biomarker in patients with prostate carcinoma.

Cytokines are polypeptides that constitute a class of chemical mediator molecules that modulate cell growth by inducing specific target gene expression. The objective of this study was to evaluate the clinical usefulness of serum evaluation of the cytokine macrophage migration inhibitory factor (MIF) in patients undergoing routine prostate specific antigen (PSA) screening. In this preliminary, retrospective study, the authors report the development of an enzyme-linked immunosorbent assay (ELISA) for MIF determination in serum samples. A polymerase chain reaction (PCR)-based assay investigated associations between MIF expression and prostate carcinoma (CaP). The authors developed a relative quantitative reverse transcriptase-PCR assay to determine MIF mRNA amounts within laser-capture microscopy (LCM)-dissected prostate epithelial cells. A comparison of serum MIF levels and total PSA levels identified a positive correlation (correlation coefficient [r2] = 0.61; P < 0.001; n = 509 patients), suggesting an association between elevated serum concentrations of these proteins and CaP. A correlation of serum MIF levels with a diagnosis of CaP demonstrated that patients with a previous CaP diagnosis had significantly elevated serum MIF concentrations (mean +/- standard deviation, 6.8 +/- 0.87 ng/mL; P < 0.001). To associate altered serum MIF levels with MIF mRNA expression within prostate epithelial cells, LCM-dissected prostate epithelial cells (formalin fixed biopsies from three different patients) were used to determine MIF mRNA amounts by PCR analysis. On average, MIF mRNA amounts were 6.5 times higher in CaP epithelial cells that were invasive to the margin compared with MIF mRNA amounts in normal prostate epithelial cells within the same biopsy specimen. The ELISA data from the current study suggested an association between increased MIF expression and CaP and suggested that serum MIF concentration may serve as a prognostic marker for CaP.

Diagnosis and management of chronic prostatitis by primary care providers.

To describe the etiology, clinical manifestations, differential diagnosis, and treatment of chronic bacterial and chronic abacterial prostatitis (CBP and CAP respectively) in the primary care setting. Selected research, clinical guidelines, and research-based articles in the scientific literature. Most cases of CBP can be appropriately diagnosed and treated in the primary care office. In the case of a diagnosis of CAP, initial therapy can be started by the nurse practitioner (NP) with referral to a urologist for refractory cases. Complete eradication of pathogens in CBP is not always possible. Assisting patients to carefully follow their treatment regimens, including completion of all antibiotic therapy, will reduce the frequency and severity of symptoms. Successful management of chronic prostatitis symptoms can result in an improved quality of life and an increased ability to perform activities of daily living for patients. Chronic abacterial prostatitis may require referral to a urologist or mental health professional for co-management of symptoms.

Diagnosis of pneumonia and monitoring of infection eradication.

Pneumonia can be classified as community-acquired (CAP) or hospital-acquired (nosocomial). Both are frequent infections that demand a great amount of medical resources. The diagnosis of CAP is based on clinical signs and the presence of a pulmonary infiltrate visible on chest radiograph. For practical purposes, CAP has been classified as typical, with an acute onset in which the most representative microorganism is Streptococccus pneumoniae, and atypical, with a subacute onset (Mycoplasma pneumoniae). Nevertheless, so far no studies have clearly demonstrated the utility of this classification in predicting the aetiology. Guidelines on CAP recommend associating the aetiology of CAP with comorbidity, age and severity. The microbiological diagnosis relies mainly on Gram stain and sputum culture, but this technique has disadvantages such as frequent contamination of the sample with oropharyngeal commensal flora, frequent sterile cultures associated with previous antibiotic treatment, and the fact that approximately 40% of patients are not able to expectorate. Other diagnostic techniques such as blood cultures, serological tests and fibreoptic bronchoscopy must be reserved for patients who are hospitalised, especially if they need admission to an intensive care unit. Compared with CAP, nosocomial pneumonia has major diagnostic problems due to the presence of other diseases able to mimic pneumonia and frequent bacterial colonisation of the lower respiratory tract. Most of the diagnostic techniques produce a high percentage of false-negative and false-positive results. This is especially true for ventilator-associated pneumonia. There is controversy over using a comprehensive aetiological work-up based on bronchoscopic techniques or only on quantitative culture of endotracheal aspiration. By contrast, there is consensus about the importance of the adequacy of empirical antibiotic treatment, since mortality rates are higher in patients who are inadequately treated. Once treatment of pneumonia has begun, it must be maintained for 48 to 72 hours because this is the minimum time to evaluate a clinical response. Antibacterial agents have to be adjusted according to microbiological findings. In nonresponding patients, pneumonia-related complications and the presence of multiresistant micro-organisms or non-covered pathogens must be ruled out.

ATYPICAL PATHOGENS IN COMMUNITY-ACQUIRED PNEUMONIA

The atypical pathogens are an important and significant cause of CAP. The clinical and radiologic manifestations of CAP caused by these pathogens are modulated by the immunologic and physiologic status of the host, and therefore are not pathogen-specific. The range of frequencies found in various studies for the atypical pathogens among the causes of CAP is broad. These frequencies are affected by very important factors that should be recognized. In a significant percentage of patients, an atypical pathogen can be identified together with an additional cause. The significance of multiple causes has not been clarified sufficiently. The principal diagnostic techniques in use today for the causative diagnosis of CAP are serologic tests. Different serologic methods have been used in various studies and diagnostic criteria are not standardized. In the future it is likely that diagnostic testing will be based on the PCR technique on serum samples. The effectiveness and importance of antimicrobial therapy in some patients with atypical pathogen CAP are unclear. The accepted therapy today for atypical pathogen CAP, which is based on erythromycin, will probably be changed in the near future in favor of the new generations of fluoroquinolone or the new macrolide preparations.

Growth factors in expressed prostatic fluid from men with prostate cancer, BPH, and clinically normal prostates.

Although growth factors such as epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, and TGF-beta are important regulators of prostate cell growth in vitro and in animal models, evidence to support their role in human prostate cancer development remains sparse. We previously showed that men without prostate cancer have concentrations of EGF and TGF-alpha in expressed prostatic fluid (EPF) that are individually distinct and stable over time. This study addressed whether growth factor levels in EPF are associated with the presence or progression of prostate cancer. We measured levels of immunoreactive EGF, TGF-alpha, and TGF-beta1 in stored EPF samples from three age-matched groups: 19 men with untreated, histologically diagnosed prostate cancer (CaP), 38 with benign prostate hyperplasia (BPH), and 19 with normal prostate glands (NPD). Median TGF-alpha was lower in the BPH group (0.45 ng/ml) than in either CaP (0.63 ng/ml) or NPD (0.58 ng/ml) groups (P = 0.03 and 0.12, respectively). For EGF, the median was lowest in the CaP group and highest in the NPD group (92.5 ng/ml vs. 175.5 ng/ml, P = 0.006). For TGF-beta1, the median level in CaP was 2.7 times higher than the median level among all controls (6.65 ng/ml vs. 2.46 ng/ml, P = 0.002). Growth factor levels were not associated with tumor stage or Gleason score. However, the single case with distant metastases had TGF-beta1 levels 23-fold higher than the CaP median. The results suggest that at the time of CaP diagnosis, EGF levels in EPF are significantly lower, and TGF-beta1 levels significantly higher, than normal. Marked overexpression of TGF-beta1 in advanced CaP might be reflected in extremely high EPF levels.

Percent free prostate-specific antigen in assessing the probability of prostate cancer under optimal analytical conditions

Although general consensus exists that percent free prostate-specific antigen (PSA) is superior to total immunoreactive PSA for prostate cancer (CaP) detection, its diagnostic performance is not yet well established. Analytical problems may account for difficulties in evaluating percent free PSA because the free PSA concentration is substantially lower than that of total PSA. The aim of the present study was to establish the diagnostic performances of the IMMULITE percent free PSA assay from Diagnostics Products Corp. under experimental conditions optimized to minimize analytical variability. Eighty-five patients with untreated primary CaP and 261 with untreated benign prostate hypertrophy (BPH) were prospectively enrolled. The Diagnostics Products IMMULITE total (Third Generation) and free PSA were measured by the same technician, using the same instrument and the same reagent batch. We calculated the post-test probability to express how the likelihood of the diagnosis of CaP changed after the percent free PSA was determined. Areas under the ROC curves of percent free PSA were better than those of total PSA in every evaluated range of total PSA. The percent free PSA could have reduced the rate of unnecessary biopsies by 47% in patients with total PSA >/=4 microg/L with only 3.8% false-negative results. The post-test probability of percent free PSA was, however, <50% in men 50-70 years of age, using cutoff points providing sensitivity from 99% to 80%. Percent free PSA is superior to total PSA in distinguishing primary CaP from BPH in patients with total PSA between 2 and 30 microg/L. In men with low total PSA, the diagnostic performance of the percent free PSA assay may be optimized by controlling methodological variability. The percent free PSA assay is effective in reducing the rate of unnecessary biopsies in men with total PSA >4 microg/L. However, the post-test probability provided by percent free PSA is relatively low in asymptomatic patients 50-70 years of age.

Analytical Performance of Free PSA Immunoassays: Results from an Interlaboratory Survey,

Prostate-specific antigen (PSA) is a glycoprotein that is secreted by the prostate into the seminal fluid. Low concentrations of the protein are normally released into blood, but in prostate cancer (CAP) as well as in a high proportion of subjects with benign prostatic hyperplasia (BPH), serum PSA concentrations frequently increase above normal values (4 μg/L). Therefore, immunoassays measuring serum PSA concentration are routinely carried out to diagnose prostate diseases and to monitor progress of the disease and relapse of CAP after removal of the prostate (1)(2)(3). A few years ago, PSA was reported to be present in serum in three different forms. The predominant molecular form is complexed to α1-antichymotrypsin, whereas a minor fraction circulates in a free noncomplexed form. These two forms are both measured by PSA assay. Only a very small proportion of PSA circulates bound to α2-macroglobulin; this third form, however, is a nonimmunoreactive complex. The free, noncomplexed form of PSA is reported to constitute a minute proportion of the serum PSA in patients with CAP, but to be significantly greater in subjects affected by BPH. On the basis of this observation the simultaneous measurement of total PSA (tPSA) and free PSA (fPSA) has been suggested. The computed ratio fPSA/tPSA is considered a useful tool to better discriminate between BPH subjects and CAP patients and therefore to improve the early diagnosis of CAP (4). …

Correlation of pretherapy prostate cancer characteristics with histologic findings from pelvic lymphadenectomy specimens

Purpose : The purpose of this study was to identify pretherapy factors associated with pelvic lymph node involvement (LNI) in patients with localized prostatic carcinoma (CaP), and to develop a model that would allow for estimation of this risk at the time of initial diagnosis. Methods and Materials : Between January 1988 and December 1992, 2439 patients with clinical Stage T1a-3cN0-XM0 CaP underwent radical retropubic prostatectomy and bilateral pelvic lymph node dissection as sole initial therapy at a single medical institutions. Preoperative factors were evaluated for their association with pelvic LNI in univariate and multivariate logistic regression analysis. A model was developed that incorporated independent predictive variables, and probability plots were generated to estimte the likelihood of pelvic LNI in the patient with a new diagnosis of localized CaP. Results : Within clinical tumor stage, three groups (T1a-2a, T2b,-c, and T3) were identified in which the observed rate of pelvic LNI was distinctly different. Gleason primary grades were also combined (1–2, 3, and 4–5) because of a similar observation. Univariate analysis identified clinical tumor stage ( p < 0.0001), Gleason primary grade ( p < 0.0001), and serum prostate-specific antigen ( p < 0.0001), with pelvic LNI. Each of these variables retained independent significance (p ⩽ 0.0002) in the multivariate model. Patient age ( p = 0.12) and history of prior transurethal resection of the prostate ( p = 0.36) were not found to correlate with this endpoint. Probability plots provided an estimate of the likelihood for pelvic LNI according to the combination of pretherapy clinical tumor stage, Gleason primary grade, and serum prostate-specific antigen level. Conclusion : Clinical tumor stage as determined by digital rectal examination, Gleason primary grade of the diagnostic biopsy specimen, and pretherapy serum prostate-specific antigen value can be combined to estimate the probability of pelvic LNI for the patient with a new diagnosis of localized CaP. This information may be of value in directing the pretherapy diagnostic evaluation, as an aid in radiation therapy treatment planning, and in the conduct of clinical research efforts.