Prostate-specific Antigen Values In Patients Research Articles

JNK promotes the progression of castration-resistant prostate cancer.

Prostate cancer is one of the most common cancers in men worldwide. This study aims to elucidate the roles of c-Jun N-terminal kinase (JNK) in the progression of castration-resistant prostate cancer (CRPC). JNK overexpressing and knockdown cell lines were established on the PC-3 prostate cell line. qPCR and Western blotting were performed to determine the mRNA and protein levels of target genes in prostate tissues and cell lines. MTT and Matrigel invasion assays were conducted to evaluate the cell viability and invasive ability, respectively. The Kaplan-Meier estimator was performed to estimate the overall survival rate and second progression-free survival rate. Pearson's correlation coefficient was used to evaluate the relationship between JNK and prostate-specific antigen (PSA). Relative JNK expression was correlated with Gleason score and PSA value in patients with CRPC. Kaplan-Meier analysis revealed that patients with low JNK expression exhibited high overall survival and second progression-free survival rate. In vitro assays demonstrated that JNK overexpression promoted cell viability and invasion as well as the protein expressions of extracellular signal-regulated kinase (ERK) and matrix metalloproteinase 1 (MMP1) in PC-3 cell lines. JNK overexpression promotes the development of CRPC via the regulation of ERK and MMP1.

Predictive value of Prostate Specific Antigen variations in the last week of salvage radiotherapy for biochemical recurrence of prostate cancer after surgery: A practical approach.

BackgroundAbout a third of patients who underwent radical prostatectomy for prostate cancer (Pca) develop a biochemical failure (BF) within 10 years from surgery, and about a half of them receive salvage radiation therapy (SRT). Factors to predict risk to relapse after SRT are still lacking. Dynamic models, based on the assessment of changes in Prostate Specific Antigen (PSA) postsurgery seem to show good reliability.AimsThe goal of the study was to identify a simple analytical method for the postsalvage radiation therapy biochemical failure (post‐SRTBF) prediction before the end of the SRT, regardless of the PSA value at the beginning of the treatment (PSA start), measuring the PSA values at the start and 1 week before the end of SRT.MethodsIn a series of 83 patients treated with SRT for BF of Pca we measured PSA values at the first day and 1 week before the end of SRT. These values were used to define an analytical method for the post‐SRTBF prediction.ResultsPSA value in patients without post‐SRTBF show a significant difference in term of difference during the SRT with respect to patients with post‐SRTBF. Starting from this difference, we identified a simple and practical analytical method for the post‐SRTBF prediction before the end of the SRT. The data corresponds with the model and the analytical method is highly predictive (Sensitivity = 81%, Specificity = 85%, Accuracy = 83%).ConclusionThis study offers a new tool to early predict Pca relapse overtime and to select patients who can benefit from an early additional systemic treatment.

Circulating tumor cell (CTC) number as a response endpoint in metastatic castration resistant (mCRPC) compared with PSA across five randomized phase 3 trials.

5007 Background: Radiographic progression and overall survival (OS) are the traditional clinical benefit measures for mCRPC trials. Reliable indicators of response that occur early are a critical unmet need in practice and clinical research. We explored a week 13 CTC and prostate-specific antigen (PSA) endpoint relative to baseline in 5 prospective randomized phase 3 registration trials that enrolled 5912 pts. OS was the primary endpoint. Methods: CTC number (CellSearch) and PSA values in patients who survived at least 13 weeks were evaluated as response endpoints in COU-AA-301, AFFIRM, ELM-PC-5, ELM-PC-4 and COMET-1. Pts with missing values at week 13 were considered non-responders. The endpoints considered are shown in Table 1. Results: The discriminatory strength of the response endpoints with respect to OS was estimated using the weighted c-index. To summarize discrimination results for each measure, the mean and the standard deviation based on the weighted c-indices from the 5 studies were computed. Conclusions: CTC0 and CTC conversion endpoints had the highest discriminatory power for OS relative to the % decline in CTC or PSA endpoints. The percent of pts eligible and evaluable for the CTC0 endpoint was significantly higher than the conversion endpoint, 75% vs. 51%, respectively. These two absolute measures of CTC can be considered meaningful response indicators in mCRPC clinical trials. [Table: see text] [Table: see text]

Comparación de los valores de antígeno prostático específico en pacientes con y sin obesidad abdominal del servicio de urología de una unidad médica de tercer nivel de atención

BackgroundThere is evidence of the relation between obesity and an increase in prostate-specific antigen, albeit some is contradictory. AimsOur aim was to compare prostate-specific antigen values in patients with and without abdominal obesity that were seen at the urology service of a tertiary care medical unit, and to analyze the results. Material and methodsA cross-sectional analytic study was conducted within the time frame of June to October 2014. It included first-time urology consultation patients that were referred due to presenting with prostate disease and that had not received medication modifying prostate-specific antigen values. Waist circumference and serum prostate-specific antigen levels were measured. The Student's t test was used for the independent samples and the Pearson and Spearman correlations and the Mann-Whitney U test were used to evaluate the correlation between waist circumference and prostate-specific antigen levels. ResultsA total of 110 patients were included that were first-time referrals to the urology service due to prostate pathology. Calculated as means, patient age was 62.6±7.5 years (range: 48-79), waist circumference was 104.5±10.6cm (range: 57-130), and prostate-specific antigen level was 3.4±2.5ng/dl (range: 0.46-21). The mean prostate-specific antigen level was 1.2±6.3ng/dl (range: 0.46-10.0) for the patients with obesity and 0.4±1.9ng/dl (range: 1.21-21) for the patients without obesity. ConclusionThere was no statistically significant difference in prostate-specific antigen values in the comparison of the populations presenting with and without obesity.

Effect of histological inflammation on total and free serum prostate-specific antigen values in patients without clinically detectable prostate cancer.

PurposeWe are often confronted with patients in the "gray zone" (prostate-specific antigen [PSA]<10 ng/mL) whose biopsies reveal no malignancy but only inflammation. We investigated the relationship between histological inflammation and total PSA (tPSA), free PSA (fPSA), and percentage of free PSA (f/tPSA) levels in patients without prostate cancer (PC).Materials and Methods We studied 106 men with tPSA<10 ng/mL who had undergone biopsy that was negative for PC and who had no clinical prostatitis. Inflammation observed at biopsies was scored for inflammation type in each biopsy core by use of a four-point scale and was then correlated with tPSA, fPSA, and f/tPSA.ResultsDifferent patterns of inflammation were found in each set of biopsies. Regression factor analysis was used to form two groups according to inflammation type: more chronic and more acute. Median tPSA, fPSA, and f/tPSA levels in the more chronic and more acute inflammation groups were 6.4 ng/mL, 1.09 ng/mL, and 15%, and 7.3 ng/mL, 0.79 ng/mL, and l2%, respectively. A significant difference was found in fPSA (p=0.003) and f/tPSA (p<0.001), whereas the difference in tPSA was not significant (p=0.200). Total PSA correlated with fPSA (r=0.4, p<0.001) but not with inflammation type (r=0.12, p>0.010). A correlation existed between inflammation type and fPSA (r=-0.31, p=0.001) and f/tPSA (r=-0.43, p<0.001) in that the fPSA and f/tPSA were lower in the group with more acute inflammation.ConclusionsSubclinical inflammation has a significant influence on fPSA in patients with tPSA<10 ng/mL but without PC or clinical prostatitis. Subclinical inflammation is not characterized by elevated tPSA alone but also by a decreased fPSA, a tendency similar to that in PC.

2205 PCA3 TEST AS AN ADJUNCT IN DIAGNOSIS OF PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: Early diagnosis of prostate cancer is conventionally done with serum prostate specific antigen (PSA) test and digital rectal examination, but these tests lack specificity. Many men worldwide undergo repeated, sometimes unnecessary prostate biopsies due to suspicious or rising PSA levels. A urine test PCA3 is gaining popularity, predominantly in the field of managing patients with suspicious PSA and previous benign biopsies. In this multinational study we assessed the performance of the PCA3 urine test in patients who were candidates for prostate biopsies due to high or rising PSA’s. METHODS: The PCA3 scores were determined in urine samples in these men A PCA3 scores of 35 or higher were considered higher probability of cancer. Subsequent biopsy was performed as per current best practice and at the discretion of the urologist in concert with the patient. To retrospectively assess the performance of PCA3, we used multiple logistic regression analysis and receiver operating characteristic (ROC) curves were constructed to evaluate PCA3 as a prognostic factor compared with PSA and evaluated the influence of PCA3 testing on the decision making. RESULTS: 401 patients had PCA3 score available. The most common indication was rising or high PSA after previous negative biopsies -in 256 patients (63.8%), followed by the finding of high grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation (ASAP) on previous biopsy in 101 patients (25.2%). Forty four subjects (11%) did not undergo prostate biopsy prior to PCA3 testing. PCA3 scores were significantly lower in patients without malignancy using a cutoff score of 35 (OR 2.99 (95%CI) (1.42, 6.30), p 0.004). On ROC curve analysis PCA3 area under the curve of 0.722 was significantly greater than PSA (0.4837). Sensitivity and specificity of PCA3 score using the 35 cutoff were 63.6% and 63.0%, respectively. When a cutoff score of 20 was used, the sensitivity and specificity of PCA3 score were 86.4% and 41.3%, respectively. The PCA3 test influenced the clinical course of the patient in 73.5% of cases. The follow-up PSA values in patients who did not perform biopsy after PCA3 testing had, without exception, remained stable or dropped (7.86 vs. 6.22, p 0.003) with follow-up of at least 6 months. CONCLUSIONS: In this multinational study we demonstrate that urine PCA3 score test out-performs PSA in decision making in men facing possibility of repeat prostate biopsy. We recommend that the PCA3 results should be integrated with other relevant data and rather be used in continuous fashion, and not with certain cutoff value.

Variations PSA Value in Patients Candidate to Biopsy of the Prostate

Subclinical infections of the prostate can increase the prostate-specific antigen (PSA) values in patients with normal digital rectal examination. This study aimed to evaluate the role of short-term antimicrobial therapy in reducing the PSA value in patients as candidates for transrectal biopsy. Fifty-eight patients with negative digital rectal examination and PSA values between 4 and 20 ng/mL were included in the study. Antibiotics were administered to all patients for 3 weeks, and the PSA was reassessed 10 days after the end of the treatment. Patients were subsequently submitted to prostate biopsy. A reduction in PSA was detected in 34 patients (59%). Mean percentage reduction was 32%. In only six patients (10%) did the PSA return to normal levels. Prostate biopsy revealed prostate cancer in 26 patients (45%). Prostate cancer was not detected in patients with PSA levels above 4 ng/mL. Prostate biopsy can be avoided only in a small number of patients showing the normalization of PSA levels after short-term antimicrobial therapy. These patients should be strictly monitored with frequent PSA determinations.

Ethnic differences in the age-related distribution of serum prostate-specific antigen values: a study in a healthy Korean male population

Objectives. To further improve the use of prostate-specific antigen (PSA) as a screening test for prostate cancer in Asian countries, we sought to establish the normal distribution of serum PSA values in Korean men, because, until recently, studies conducted to establish normal serum PSA values have involved few Asian populations. Methods. Between May 1995 and June 1997, 5805 healthy Korean men 30 to 79 years old who visited our hospital for a routine health checkup were entered into a prospective study of early screening for prostate cancer. All men underwent detailed clinical examinations, including a digital rectal examination and serum PSA determination. All men who were more than 50 years old with abnormal digital rectal examination findings and/or an elevated serum PSA level (greater than 4.0 ng/mL) also underwent transrectal ultrasound-guided sextant biopsy. Four were found to have cancer and were excluded from the analysis. Results. The median serum PSA concentration (5th to 95th percentile range) was 0.8 ng/mL (0.2 to 1.8) for patients 30 to 39 years old (n = 1382); 0.8 ng/mL (0.2 to 2.0) for patients 40 to 49 years old (n = 1776); 0.9 ng/mL (0.2 to 2.4) for those 50 to 59 years old (n = 1775); 1.0 ng/mL (0.2 to 3.9) for men 60 to 69 years old (n = 746); and 1.3 ng/mL (0.5 to 6.3) for patients 70 to 79 years old (n = 122). The serum PSA concentration correlated with age ( P <0.001), with an increase by approximately 1.2% annually, although the statistical correlation was weak ( r = 0.16). Almost no change occurred in the median serum PSA value in patients 50 years old or younger; a gradual increase was observed in patients older than 50. In those 50 years old or older, the median and 95th percentile serum PSA values for Korean men were lower than those for white men. Conclusions. Contrary to earlier observations that the serum PSA level strongly correlates with age, the influence of age on serum PSA was found to be weaker in this study. Moreover, the results also demonstrated that the distribution of the serum PSA level differs along ethnic lines. The cutoff value for serum PSA in mass screening for prostate cancer should be adjusted in nonwhite races.

Pretreatment prostate-specific antigen values in patients with prostate cancer: 1989 patterns of care study process survey

A Patterns of Care Study (PCS) national survey was conducted to show the national averages for processes of radiation therapy care for prostate cancer patients in 1989. In the current study we report an analysis of pretreatment prostate-specific antigen (PSA) by stage, grade, and ethnic origin. Process data were collected from 672 patients treated in 1989 at 71 separate institutions. Four hundred and twenty-seven (64%) of these patients had a pretreatment PSA value recorded. Three hundred and forty-three of the 427 patients were treated with external beam irradiation alone and were selected for the current analysis. The 1992 AJCC staging system was used. There was a significant increase in pretreatment PSA with increasing stage. The median values of PSA were 8.3 ngm/ml in the T1 group (n = 65), 11.2 ngm/ml in the T2 group (n = 178), and 20.9 ngm/ml in the T3 group (n = 90) (p < 0.001). Ten patients were not staged. There was a significant increase in pretreatment PSA with decreasing differentiation. The median pretreatment PSA was 9.7 ngm/ml in well-differentiated tumors (n = 109), 13.0 ngm/ml in moderately differentiated tumors (n = 163), and 22.0 ngm/ml in poorly differentiated tumors. (n = 61) (p < 0.001). Ten patients had no differentiation recorded. African Americans (24) showed a significant increase in pretreatment PSA compared to Caucasians (304). The respective medians were 23.2 ng/ml and 11.9 ng/ml (p = 0.04). They also show more poorly differentiated tumors (33% vs. 17%) and more T3 tumors (46% vs. 25%). Other minorities, although small in number (n = 9) were similar to African Americans. Pretreatment PSA levels were established for patients treated with external beam irradiation in 1989 in the United States. They increase with stage and decreasing differentiation. African Americans and other minorities show a doubling of median values compared to Caucasians' pretreatment PSA with an increase in stage and grade. The adverse prognosis observed for African Americans is predicted by their pretreatment PSA. The cause of this PSA elevation is not known and may be related to lack of access to care or to a more aggressive biology for prostate cancer in African Americans.

Prostate Specific Antigen in Hormonally Treated Stage D2 Prostate Cancer: Is it always an Accurate Indicator of Disease Status?

The clinical significance of serum prostate specific antigen (PSA) values in hormonally treated prostate cancer patients and the effect of hormonal therapy on the serum PSA concentration, independent of the response observed from its antitumor activity, are not well defined. To elucidate further the influence of antiandrogen therapy on serum PSA expression, 81 randomly selected patients with stage D2 prostate cancer were evaluated with respect to serum PSA concentration. These patients were divided into 2 groups on the basis of previous hormonal therapy.Group 1 consisted of 43 patients 55 to 89 years old (mean age 71 years) who had received no prior therapy for prostate cancer. Group 2 included 38 men 58 to 84 years old (mean age 72 years) who had received only androgen deprivation therapy with either bilateral orchiectomy or diethylstilbestrol. The mean interval between initiation of antiandrogen therapy and evaluation of these patients was 14 months (range 8 to 31 months). At the time of PSA determination both groups were similar in all respects, including tumor grade, disease symptoms and bone scan findings.The median serum PSA concentration was 96.0ng./ml. in group 1 and 16.5ng./ml. in group 2 (p <0.001), despite both groups having similar symptoms and widespread metastatic disease on radionuclide bone scan. In group 1 only 1 patient (2%) had a serum PSA level less than 4.0ng./ml., whereas 13 men (34%) in group 2 had a serum PSA concentration below 4.0ng./ml. (p <0.001). Of the patients in group 1, 2% and of the men in group 2, 45% had a serum PSA concentration less than 10ng./ml. (p <0.0001).These findings demonstrate that the serum PSA level in prostate cancer patients treated hormonally may have a significantly different meaning than the same serum PSA value in patients without hormonal therapy. In addition, these observations suggest that PSA expression may be under hormonal regulation and that androgen deprivation therapy may have a direct effect on the serum PSA concentration, independent of the response obtained from any antitumor activity. However, the exact mechanism of this androgenic influence on PSA expression awaits further investigation at the cellular level.

Determination of prostate volume with transrectal US for cancer screening. Part I. Comparison with prostate-specific antigen assays.

To investigate whether radiologists can objectively define a high-risk group for prostate cancer, the researchers measured gland volume and compared it with results of a screening blood test, prostate-specific antigen (PSA) assay. A total of 768 men, aged 55-71 years, were self-referred to two prostate cancer screening programs using transrectal ultrasound (US) and digital rectal examination. In patients with no evidence of cancer, statistically significant increases in mean PSA values were noted with increasing gland volume ranges (P less than .05). PSA values in patients with cancer were more likely to exceed the volume-adjusted 95th percentile (mean + [1.65.standard deviation]) than those in patients with negative biopsy results (P less than .005). Patients with PSA values above the volume-adjusted 95th percentile have an estimated risk for prostate cancer up to nine times that of the general screening population. The researchers conclude that knowledge of transrectal US gland volume and prostate-specific antigen assay type are important objective variables for future prostate cancer screening programs. The volume-adjusted 95th percentiles presented may help guide cost-effective management of current early detection efforts.