Free Prostate-specific Antigen Levels Research Articles

Serum ACSL4 levels in prostate cancer patients and its relationship between patient prognosis: A prospective observational study.

In this prospective observational study, our objective was to investigate the serum levels of Acyl-CoA synthetase long-chain family member 4 (ACSL4) in prostate cancer (PCa) patients and examine its association with other serum biomarkers, and the clinical outcomes of PCa patients. This prospective observational study was conducted from January 2019 to October 2021, including 103 cases of PCa patients and 101 cases of benign prostate hyperplasia (BPH) patients who received treatment at our hospital. All patients had their serum ACSL4 levels measured using enzyme-linked immunosorbent assay before treatment. The clinical outcomes included age, body mass index, gender, systolic blood pressure, diastolic blood pressure, tumor node metastasis stage, Gleason scores, and prostate volume and serum biomarkers were collected. All patients were followed up for 36 months, the overall survival and disease-free survival were recorded for all patients. All data used SPSS 26.0 for analysis. The phosphorus (P) and serum low-density lipoprotein cholesterol levels were significantly higher in PCa patients compared to BPH patients. Furthermore, compared to the BPH patients, the serum ACSL4 and free prostate-specific antigen levels were significantly decreased while serum total prostate-specific antigen (tPSA) levels were significantly elevated in PCa patients. Pearson correlation analysis showed a positive correlation between ACSL4 levels and free prostate-specific antigen levels, while a negative correlation was observed with P and tPSA levels. ACSL4 might serve as a biomarker for diagnosing PCa with the AUC was 0.747, cutoff value of 33.68 ng/mL, sensitivity of 70.3%, and specificity of 60.2%. Finally, we found that ACSL4, tPSA, and P were identified as risk factors associated with PCa patients. Our findings indicated that the serum levels of ACSL4 were significantly decreased in PCa patients compared to BPH patients. Serum ACSL4 could be used as a potential biomarker for early PCa diagnosis and prognosis.

Prognostic value of E‑26 transformation‑specific‑related gene in prostate cancer based on immunohistochemistry analysis.

E-26 transformation-specific-related gene (ERG) has been implicated in prostate cancer; however, its prognostic role remains unclear. Therefore, the present study aimed to investigate the association of ERG with the prognosis after radical prostatectomy in patients with prostate cancer. Patient data were collected at the Huadong Hospital, affiliated with Fudan University, between January 2016 and March 2020. ERG protein expression was detected using immunohistochemistry. Independent-sample t-tests and χ2 tests were used to evaluate prostate cancer prognosis depending on ERG levels. The Kaplan-Meier method was used to estimate biochemical failure-free survival (BFFS) and the log-rank test was used to test the distribution. Prognostic factors were determined using Cox regression analysis. The median patient age was 69 years (range, 47-82 years). The median prostate-specific antigen (PSA) and free-PSA levels before treatment were 9.58 ng/ml (range, 0.003-187.400 ng/ml) and 1.13 ng/ml (range, 0.0059-30.6100 ng/ml), respectively. ERG protein expression was positive in 43 (16.6%) and negative in 216 (83.4%) cases. The median follow-up period and BFFS were 30 and 28 months, respectively. There was a significant difference in biochemical recurrence (P=0.017) between patients with positive and negative ERG expression. Patients with positive ERG expression had significantly worse BFFS curves compared with those with negative ERG expression (P=0.0038). In the multivariate Cox regression analysis, positive ERG expression was found to be an independent prognostic factor in patients with prostate cancer who underwent radical prostatectomy (hazard ratio, 4.08; 95% confidence interval, 2.03-8.17; P=0.000074). In conclusion, positive ERG expression is an independent prognostic risk factor for prostate cancer. These findings may be valuable for improvements in the clinical application of ERG immunohistochemistry.

Correlation Analysis between Apparent Diffusion Coefficient of Prostate Cancer and other Prostate Cancer Indicators

Background: There are very few reports on the correlation between the apparent diffusion coefficient (ADC) of magnetic resonance parameters and other laboratory indicators of prostate cancer in China, and there is no unified clinical conclusion at present from the other parts of the world. Therefore, this study analyzed the correlation between ADC and laboratory indicators, such as serum total prostate specific antigen (TPSA), complex prostate specific antigen (CPSA), free prostate specific antigen (FPSA), Gleason score, and left and right diameters of the prostate so as to provide a basis for the diagnosis and treatment of prostate cancer. Methods: A total of 104 patients of all age groups with prostate cancer diagnosed in the General Hospital of Wanbei Coal and Electricity Group, Wanbei, China, from January 2017 to December 2022 were retrospectively analyzed as the experimental group. At the same time, 63 patients with benign prostatic hyperplasia who received health examinations were selected as the control group. TPSA, CPSA, FPSA, CPSA/TPSA, FPSA/TPSA, Gleason score, left and right diameters of the prostate, and magnetic resonance parameter ADC were detected in all patients. At the same time, we analyzed the correlation between ADC and other parameters in prostate cancer patients. Results: The serum levels of TPSA, CPSA, and FPSA in prostate cancer patients were significantly higher (P<0.001) than in those in the control group. The differences between CPSA/TPSA and FPSA/TPSA in the two groups were not statistically significant. Meanwhile, ADC and left and right diameters of the prostate were significantly lower in prostate cancer patients than in subjects in the control group, and the differences were statistically significant (P<0.001). In addition, serum TPSA, CPSA, and FPSA in high-risk prostate cancer patients were found to be significantly higher than in cases in the medium-risk and low-risk groups. The results of our study also revealed that ADC was moderately negatively correlated with FPSA (r=-0.415, P<0.001) and weakly negatively correlated with TPSA (r=-0.222, P=0.024). Conclusion: There is a correlation between ADC, TPSA, and FPSA in patients with prostate cancer, and there were significant differences in TPSA, CPSA, and FPSA between patients with prostate cancer and patients with benign prostatic hyperplasia. The three parameters can be combined for the diagnosis of prostate cancer.

Combination of [68Ga]Ga-PSMA PET/CT and [18F]FDG PET/CT in demonstrating dedifferentiation in castration-resistant prostate cancer

Aim of the studyIn this study, we aimed to determine the factors affecting increased glucose metabolism, which is one of the dedifferentiation mechanisms, by using [18F]FDG and [68Ga]Ga-PSMA PET/CT in patients with castration-resistant prostate cancer (CRPC). Materials and methodNinety-three patients with CRPC were included in the study. Gleason score (GS), and total PSA and free PSA levels of the patients were recorded. Patient- and organ-based evaluations were performed according to the lesion uptakes as follows: score 0: PSMA (-) FDG (-), score 1: PSMA (+) FDG (-), score 2: PSMA (+) FDG (+) (FDG < PSMA), score 3: PSMA (+) FDG (+) (FDG = PSMA), score 4: PSMA (+) FDG (+) (FDG > PSMA), and score 5: PSMA (-) FDG (+). scores 1 and 2 were classified as group 1, and scores 3 to 5 were classified as group 2. ResultsThe median age of our patients was 70 (51–88) years. Eighty-eight patients (94.6%) were PSMA-positive, 78 patients (83.8%) were FDG-positive, and 89 patients (95.6%) were or PSMA or FDG positive. When the two groups were compared in terms of patient-based parameters, the median age and GS were found to be significantly higher in group 2. ROC analyses revealed that age and GS were significant in predicting group 2. ConclusionSince glucose metabolism can increase in CRPC patients with advanced age and high GS, we recommend combining [18F]FDG PET/CT with [68Ga]Ga-PSMA PET/CT in routine clinical practice in order to identify this patient subset and refer them to additional therapies.

Clinical Application of Prostatic Exosomal Protein and Prostate-Specific Antigen Levels in the Detection of Prostate-Related Diseases.

Our aim was to study the use of prostatic exosomal protein (PSEP) and prostate-specific antigen (PSA) in diagnosis of prostate-related diseases. A total of 54 cases of acute prostatitis (AP), 72 cases of chronic prostatitis (CP), and 36 cases of prostate cancer (PCa) were enrolled. Levels of PSEP and PSA were analyzed. The positive rate and level of PSEP in CP was highest (both P < .05). The total PSA (tPSA) level in PCa was the highest (P < .05), followed by AP and CP. The free PSA (fPSA) level was lowest in CP (P < .05); fPSA/tPSA in AP was the highest (P < .05). The PSEP level in type II CP was higher than in type IIIa and type IIIb (both P < .05), and it was higher in type IIIa than in type IIIb (P < .05). The tPSA level in type IIIb was the lowest in the 3 types (both P < .05). The fPSA/tPSA in type IIIb was the highest in the 3 types (P < .05). The PSEP combined with PSA better distinguishes prostate-related diseases.

Label-Free Determination of PSA and Free PSA Using MA-SERS

Prostate cancer is one of the compelling types of cancer diagnosed in men. Development of screening analytical methods, which provide fast and reliable results is, thus, demanding. Currently applied methods are usually based on the determination of serum prostate-specific antigen (PSA), where several limitations were identified. However, scientific reports have shown a direct correlation between the percentage of free PSA and prostate volume, and indirect correlation between the unfavorable course of the disease of prostate cancer and the percentage of free PSA in men with elevated PSA levels. Parallel analysis of PSA and free PSA presents an interesting alternative. Here, we present a new analytical method for a parallel analysis of PSA and free PSA in a whole human blood based on MA-SERS. The method is based on magnetic Fe3O4@Ag nanocomposite functionalized using anti-PSA. The method can distinguish between levels of PSA and free PSA within a single analytical run with limits of detection of 0.62 ng/ml for PSA and 0.49 ng/ml for free PSA, respectively.

Frequency of Prostate Cancer in Men with Low Percent Free Prostate Specific Antigen in the Serum

Introduction: Prostate cancer is the utmost communal type of cancer in adult men. Assessment of serum total prostate specific antigen (PSA) is broadly cast-off as a screening assistance in the prompt diagnosis of cancer of prostate. Irrespective of the prostate size or patient’s age, 25% cut off value is set or less free PSA level in percentage is suggested for cases with values of PSA amid 4.1 and 10 ng/ml; This helps in detecting prostate cancers in 95% of cases and prevent 20% of unnecessary biopsies. The greater the free PSA percentage, the less jeopardy of cancer. This analysis was designed to evaluate the incidence of prostate cancer in patients with a low percentage of free PSA. If the scale is found to be higher, aggressive strategies and early treatment can lead to good progress. Aim: To determine the frequency of prostate cancer in males with a low percentage of serum free PSA. Study Design: This is a descriptive, cross-sectional study lasting 6 months from July 2020 to December 2020 at the Urology Department of the Sindh Institute of Urology and Transplantation. Subject and method: 149 total individuals with symptoms of lower urinary tract were included in the research. All patients who came to the urology clinic (OPD); free PSA were examined with the same technique as the surgical patient and the result was recorded as proforma. Results: - The prostate cancer Incidence in males with decreased free serum PSA in percentage is noted in 128(85.91%) patients. Conclusions: Our study showed that prostate-specific free antigen plays an important role in the analysis of cancer of prostate. Keywords: Serum prostate specific antigen, Prostate cancer, percentage of free PSA

Gri Zondaki Prostat Spesifik Antijen Düzeyleri Olan Erkeklerde Prostat Kanseri Tahmininde Bazı Kan Bazlı Parametrelerin Serum Prostat Spesifik Antijen ve Türevlerine Yardımcı Rolü: Prospektif Klinik Çalışma

Objective: To investigate the adjunctive role of some peripheral blood parameters to serum prostate specific antigen (PSA) in predicting the patients with prostate cancer (PCa) prior to prostate biopsy, and clinically significant PCa among those. Material and Methods: This prospective study included men aged ≥45 years, who were scheduled to undergo a prostate biopsy due to gray-zone PSA levels. The levels of free and total PSA (fPSA and tPSA), total testosterone (TT), PSA density (PSAD), C-reactive protein (CRP), De Ritis ratio (aspartate aminotransferase/alanine transaminase) and hemograms were recorded. Patients were divided into 2 groups as benign prostatic hyperplasia (Group 1) and PCa (Group 2) groups. The PCa group was further divided into 2 subgroups as clinically significant and clinically insignificant PCa. The pre-biopsy values of the variables were compared between the groups. Results: A total of 210 patients were included in the study (Group 1, n=105; Group 2, n=105). The mean age was 65.1±7.4 years, the mean tPSA level was 6.14±2.05 ng/mL, and the mean TT level was 15.46±5.47 nmol/L. Age, prostate volume, the values of fPSA, PSAD, CRP, and the ratios of fPSA/tPSA, CRP/albumin and De Ritis were statistically different between the groups. In the PCa group, only the tPSA level was significantly different between the subgroups (p=0.005). The area under curve and the cut-off value for tPSA to predict clinically significant PCa were 0.669 and 5.8 ng/mL, respectively. Conclusion: CRP, the CRP/albumin ratio and De Ritis ratio may further help predict a diagnosis of PCa.

Effects of Psychological Intervention on Perioperative Quality of Life and Serum PSA and FPSA Levels of Patients with Prostate Cancer Treated with Integrated Traditional Chinese and Western Medicine.

Objective To observe the effects of psychological intervention on the perioperative quality of life and serum prostate-specific antigen (PSA) and free PSA (FPSA) levels in patients with prostate cancer treated with integrated traditional Chinese and Western medicine. Method A total of 208 prostate cancer patients were selected and randomly divided into a study group with 104 cases and a control group with 104 cases. The control group received a plan of basic nursing combined with integrated traditional Chinese and Western medicine, and the study group received psychological intervention on the basis of the control group. Negative emotion, pain degree, quality of life, maximum urine flow rate, residual urine volume, International Prostate Symptom Score (IPSS), and incidence of adverse reactions were compared between the two groups before and after the treatment. The levels of PSA and FPSA and the long-term efficacy of the two groups of patients before and after treatment were compared. Results After nursing, Hamilton Anxiety Scale (HAMA) score, Hamilton Depression Scale (HAMD) score, pain degree, maximum urine flow rate, residual urine volume, IPSS score, emotional function, social function, role function, and physical function scores of patients in two groups were decreased, and the decrease was more significant in the study group. After treatment, serum PSA and FPSA levels in the study group were obviously lower than those in the control group. The two-year cumulative survival rate of the study group was higher than that of the control group. There was no significant difference in the cognitive function score and incidence of adverse reactions between the two groups. Conclusion Psychological intervention combined with traditional Chinese and Western medicine in the treatment of prostate cancer can effectively improve the patient's psychological state, reduce the degree of pain in patients, improve the therapeutic effect and the quality of life of patients, and significantly reduce serum PSA and FPSA levels, which could lead to a prolonged life.

SIGNIFICANCE OF DETECTION OF FREE/TOTAL PSA RATIO AND OTHER BIOCHEMICAL PARAMETERS IN PATIENTS WITH BPH, CARCINOMA PROSTATE AND ITS CLINICOPATHOLOGIC CORRELATION

Background. Benign prostatic hyperplasia (BPH) can raise prostate-specific antigen (PSA) levels two to three times higher than the normal level. An increased PSA level does not indicate Prostate Cancer (PCa), but the higher the PSA level, the higher the chance of having PCa. Detection and treatment have been profoundly affected by the advent of Free/Total PSA ratio testing. Objectives. The aim of the study was to estimate free, total PSA levels and its ratio for serum levels of calcium, acid phosphatase and alkaline phosphatase in patients with BPH and PCa; to correlate clinical, biochemical and histopathological findings in the above patients. Methods. PSA levels were detected by Chemiluminescent assay; serum calcium – by Modified Arsenazo method; serum acid phosphatase – by Doumas et al method; and Alkaline phosphatase – by Lowry et al method. Results. Present study found high levels of total PSA in BPH and PCa. Levels of free PSA were high in BPH as compared to PCa rate. Free/Total PSA ratio is reduced considerably in PCa as compared to BPH. Serum acid phosphatase and alkaline phosphatase were considerably higher in PCa as compared to BPH. Serum calcium levels did not show significant difference in control and study groups. Conclusions. It was established that patients with PCa have a greater fraction of bound PSA and a lower percentage of free PSA than in those without PCa. Therefore, in clinical practice Free/Total PSA ratio helps clinicians to decide if a biopsy is necessary. Objectives: The study was carried out with the following objectives: to estimate free, total PSA levels and calculate Free/Total PSA ratio in patients with BPH and Carcinoma Prostate, to study the serum levels of calcium, acid phosphates, and alkaline phosphatase in patients with BPH and PCa. and to correlate clinical, biochemical and histopathological findings in the above patients. Methods. Free and total PSA levels were detected by Chemiluminescent assay; Serum Calcium was detected by Modified Arsenazo method. Serum acid phosphatase was detected by Doumas et al method and Alkaline phosphatase were detected by Lowry et al method Results: Present study found high levels of Total PSA in BPH and PCa. Levels of free PSA were high in BPH as compared to PCa ate. Free /Total PSA ratio is reduced considerably in PCa as compared to BPH. Serum acid phosphatase and alkaline phosphatase were slightly raised in PCa as compared to BPH. Serum calcium levels did not show a significant difference in control and study groups. Conclusion: We concluded that patients with PCa have a greater fraction of bound PSA and a lower percentage of free PSA than in men without PCa. There was a negative correlation found between the free/total PSA ratio and the histopathologic findings. The lower the ratio higher is the grade of malignancy. Therefore in clinical practice Free/Total PSA ratio helps clinicians to decide if a biopsy is necessary

Evaluation of endocrine therapy combined with intensity modulated radiation therapy in patients with advanced prostate cancer

Abstract Objective The aim of this study was to study the effect of endocrine therapy combined with intensity-modulated radiation therapy in patients with advanced prostate cancer. Methods The clinical data of 231 patients with advanced prostate cancer treated with radiotherapy in our hospital from May 2010 to March 2018 were collected. A total of 135 patients were treated with endocrine therapy combined with intensity-modulated radiotherapy, and 96 patients were treated with intensity-modulated radiotherapy only because of drug allergy, serious adverse reactions, and economic reasons. Two months after the end of the treatment, the short-term curative effect was evaluated using imaging reexamination. The total prostate-specific antigen (TPSA) and free prostate-specific antigen (FPSA) were detected before and 2 months after the end of the treatment. All patients were followed up for at least 3 years, and the metastasis-free survival rate and cumulative survival rate of the two groups were calculated. Results The remission rates (RRs) of the observation and control groups were 64.45% and 46.87%, respectively; the difference was not statistically significant (P &gt; 0.05); however, the efficacy distribution of the endocrine therapy combined with intensity-modulated radiotherapy group was significantly better than that of the intensity-modulated radiotherapy group (P &lt; 0.05). There was no significant difference in clinical efficacy between the two groups in different TNM stages and Gleason grades. After treatment, the levels of TPSA and FPSA were significantly decreased compared with those before treatment; however, the decrease in the endocrine therapy combined with the intensity-modulated radiation therapy (IMRT) group was significantly higher than that in the IMRT group (P &lt; 0.05). Although there were no significant differences in the 1-year and 3-year cumulative survival rates between the two groups, the 1-year and 3-year metastasis-free survival rates of the endocrine therapy combined with the IMRT group were 60% and 38.17%, respectively, which were significantly higher than those of the IMRT group (37.5% and 20.83%, P &lt; 0.05). Conclusion Endocrine therapy combined with IMRT significantly improved the clinical efficacy of advanced prostate cancer, reduced PSA (prostate specific antigen) levels, and improved the metastasis-free survival rates.

Study on individualized prostate biopsy guided by prostate specific antigen at different ranges

Background: Prostate specific antigen (PSA) is the most commonly used indicator for screening of prostate cancer(PCa), and the studies on PSA in PCa are very extensive at present. How to effectively use this indicator is worth for further study which this article wish to address. Objective: The aim of this study is to explore how PSA in different ranges can better guide the individualized prostate biopsy. Methods: A total of 117 patients with suspected PCa admitted to the Affiliated Hospital of Chengde Medical College from October 2018 to July 2020 were selected as the research subjects. PSA level and ratio of free and total PSA (F/TPSA) value of each patient were measured, and ultrasound-guided transrectal prostate biopsy was conducted for each patient, and then the PSA measurement results were compared with the prostate biopsy results. Results: The result of biopsy was PCa in 40 cases, BPH in 77 cases. The positive expression rates of Group I in BPH and PCa patients were 25.97% and 87.50%, respectively, and the difference was statistically significant (P &lt; 0.05).The positive expression rates of Group II in BPH and PCa patients were 10.39% and 75.00%, respectively, and the difference was statistically significant (P &lt; 0.05). The sensitivity, specificity, positive predictive value and diagnostic coincidence rates of Group I and Group II were 87.50%, 74.03%, 63.63%, 78.63% and 75.00%, 89.61%, 78.94% and 84.62%, respectively. Conclusion: Under different TPSA intervals, F/T &lt; 0.16 has different diagnostic efficacy for PCa. Group I is more sensitive and suitable for early screening. Group II has stronger specificity in the diagnosis of PCa, Higher diagnostic coincidence rate, and has more diagnostic advantages before biopsy. Selecting Group II can help clinicians make more patient-friendly decisions and reduce the incidence of complications related to biopsy. According to patients’ aspiration for biopsy, auxiliary examinations such as magnetic resonance scan of prostate and bone scan should be performed actively for patients who meet the criteria I if they refuse to undergo biopsy. On the premise of not affecting PCa secondary prevention as much as possible, a more individualized biopsy plan was developed for patients.

Impact of Prostate Specific Antigen and Testosterone Hormone Levels in Patients of Benign Prostatic Hyperplasia in Khartoum State-Sudan

Lower Urinary Tract Symptoms (LUTS) and Benign Prostatic Hyperplasia (BPH) are progressive ailments resulting from androgenic imbalances and aging that can lead to serious long term complications. Objective of this study was to determine the relationship between prostate-specific antigens and testosterone hormone levels in patients with BPH before transurethral surgery. This case control study was done on 112 serum samples collected from two secondary care centres in Khartoum, Sudan. Collected serum samples were analyzed by ELISA and fluorescence enzymes immunoassay to measure testosterone, total PSA level and free PSA levels, respectively. Out of 112 patients, 56 BPH diagnosed patients were included in the study with mean age 67.10±7.90 years. Total PSA (T. PSA) levels were higher in patients (14.1±10.6 ng mL-1) than the control group (2.21±1.01 ng mL-1). Total 52% of patients had total PSA level in the gray zone (4-10 ng mL-1) and 33% had total PSA more than 10 ng mL-1. Testosterone levels were low in patients 3.97±2.84 ng mL-1 when compared to the control group 4.95±0.59 ng mL-1. The present study revealed that, there was a strong association between T. PSA level and testosterone hormone in BPH patients, which suggested that monitoring of testosterone level is useful in patients with prostate enlargement.

PSMA whole-body tumor burden in primary staging and biochemical recurrence of prostate cancer.

The objective of this study was to evaluate whether 68Ga-PSMA PET/CT whole-body tumor burden (PSMAwbtb) is associated with clinical parameters and laboratory parameters in prostate cancer patients. We retrospectively evaluated prostate cancer patients submitted to PSMA PET/CT for primary staging purposes or due to biochemical recurrence (BR). PSMAwbtb metrics (total volume of PSMA-avid tumor (PSMA-TV)) and total uptake of PSMA-avid lesions (PSMA-TL) were calculated semi-automatically. Spearman's rank correlations between PSMAwbtb metrics and clinical, laboratory parameters (age, time-to-BR, years of diagnosis of prostate cancer, free and total serum PSA levels, and the Gleason score) and with the highest SUVmax of a lesion (hSUVmax) were analyzed. Among the 257 PSMA PET/CT studies, there were 46 scans (17.9%) performed for primary staging and 211 (82.1%) for BR. PSMA-TV and PSMA-TL were calculated for the 157 positive scans (58.8%), which were 43 patients (93.5%) in the primary staging group and 114 patients (54.0%) in the BR group. In the primary staging group, we observed a significant correlation between PSMA-TL and hSUVmax (p = 0.0021). In the BR group, there was a significant direct correlation between PSMA-TL and the variables age (p = 0.0031), total serum PSA values (p = < 0.0001), free serum PSA values (p= < 0.0001), and the hSUVmax (p = < 0.0001). Similar results were obtained for PSMA-TV. PSMAwbtb has a direct and positive correlation with serum PSA values and age in prostate cancer patients with BR.

Development and validation of an explainable artificial intelligence-based decision-supporting tool for prostate biopsy.

To develop and validate a risk calculator for prostate cancer (PCa) and clinically significant PCa (csPCa) using explainable artificial intelligence (XAI). We used data of 3791 patients to develop and validate the risk calculator. We initially divided the data into development and validation sets. An extreme gradient-boosting algorithm was applied to the development calculator using five-fold cross-validation with hyperparameter tuning following feature selection in the development set. The model feature importance was determined based on the Shapley value. The area under the curve (AUC) of the receiver operating characteristic curve was analysed for each validation set of the calculator. Approximately 1216 (32.7%) and 562 (14.8%) patients were diagnosed with PCa and csPCa. The data of 2843 patients were used for development, whereas the data of 948 patients were used as a test set. We selected the variables for each PCa and csPCa risk calculation according to the least absolute shrinkage and selection operator regression. The AUC of the final PCa model was 0.869 (95% confidence interval [CI] 0.844-0.893), whereas that of the csPCa model was 0.945 (95% CI 0.927-0.963). The prostate-specific antigen (PSA) level, free PSA level, age, prostate volume (both the transitional zone and total), hypoechoic lesions on ultrasonography, and testosterone level were found to be important parameters in the PCa model. The number of previous biopsies was not associated with the risk of csPCa, but was negatively associated with the risk of PCa. We successfully developed and validated a decision-supporting tool using XAI for calculating the probability of PCa and csPCa prior to prostate biopsy.

The Influences of Metformin on Prostate in Terms of PSA Level and Prostate Volume.

The effects of metformin on prostate volume and prostate-specific antigen (PSA) were investigated. We enrolled 384 newly diagnosed diabetes mellitus (DM) patients and 152 controls all of whom were >50 years into our prospective cross-sectional observational study. The first group contained patients receiving metformin only, the second group patients were taking a mixture of medications, including metformin plus other oral anti-diabetics, and the third was the control group. Before beginning treatment, body mass indices (BMI) of all cases were obtained. Prostate volumes were evaluated using transabdominal ultrasonography at the sixth and twelfth months. Insulin, glycosylated hemoglobin (HbA1C), insulin sensitivity index (ISI), insulin-rich growth factor (IGF-1), PSA, free PSA, and total testosterone levels were measured. The differences in BMI between the first and third groups were statistically significant (P < 0.05). There were no statistical differences among the groups in terms of prostate volumes (P > 0.05). The differences between the groups for insulin, HbA1C, ISI, IGF-1 (somatomedin), PSA, free PSA, and total testosterone levels were not statistically significant (P > 0.05). Free PSA and total testosterone levels in groups 1 and 2 were not statistically different at the beginning of treatment and the sixth month (p >0.05), but within groups 1 and 2, only PSA levels were different at the start of the study until completion. No differences were seen in the third group. Metformin appears to cause a decrease in PSA levels. The mechanism and any effects on prostate tissue will be studied in future randomized, prospective studies.

The Four-Kallikrein Panel Is Effective in Identifying Aggressive Prostate Cancer in a Multiethnic Population.

The four-kallikrein (4K) panel has been demonstrated to improve prediction of aggressive prostate cancer compared with prostate-specific antigen (PSA) among men with moderately elevated PSA levels. However, the development and testing of the 4K panel has been conducted primarily in White men, with limited data in African Americans and no studies in other racial and ethnic groups. We evaluated the 4K panel in a nested case-control study among African American, Latino, Japanese, Native Hawaiian, and White men in the Multiethnic Cohort. Prediagnostic blood levels of free, intact, and total PSA and human kallikrein-related peptidase 2 were measured among 1,667 incident prostate cancer cases and 691 controls with PSA ≥2 ng/mL. We evaluated the discriminative ability of the 4K panel within and across all racial/ethnic groups. The 4K panel enhanced discrimination of overall prostate cancer compared with free plus total PSA and total PSA alone (AUC 0.748 vs. 0.711 and 0.669, respectively). Discrimination was further enhanced for Gleason 8+ prostate cancer, aggressive prostate cancer, and death due to prostate cancer, and to a lesser degree for nonaggressive prostate cancer. Improvement of the 4K panel over PSA was observed in each population. Adding a prostate cancer polygenic risk score slightly improved upon the discriminative ability of the 4K panel. The superior discriminative ability of the 4K panel over PSA for overall and aggressive prostate cancer across multiethnic populations indicates the broad clinical applicability of the 4K panel. Our multiethnic investigation suggests potential for the 4K panel to improve current prostate cancer screening practices.

Abstract PR01: The four-kallikrein panel discriminates prostate cancer and aggressive disease in a multiethnic population

Abstract Purpose: The four-kallikrein (4K) panel, commercially available as the 4Kscore, has been demonstrated to improve prediction of aggressive prostate cancer (PCa) compared to prostate-specific antigen (PSA) alone or PSA in combination with free PSA. However, the development and testing of the 4K panel has been limited to studies conducted primarily in White men. Methods: We prospectively evaluated the 4K panel in a nested case-control study among African American (AA), Latino (LA), Japanese (JA), Native Hawaiian (NH), and White (WH) men in the Multiethnic Cohort (MEC). Prediagnostic blood levels of free, intact, and total PSA and human kallikrein-related peptidase 2 (hK2) were measured among 2,227 incident PCa cases and 2,189 controls. We used area under the curve (AUC) calculations to compare the discriminative ability of the 4K panel to PSA for overall PCa, Gleason-Grade Group (GGG) 2 or higher, aggressive PCa (Gleason&amp;gt;7, non-localized disease, or death from PCa), and death due to PCa within and across all racial/ethnic groups. Results: The mean ages of the cases and controls at blood draw were 68 (range 47–86) and 69 (range 47–87), respectively, and for cases, samples were drawn an average of 4.9 years prior to their PCa diagnosis (range &amp;lt;1–18 years). For men with elevated PSA (≥2.0 ng/ml; 1,669 cases and 663 controls), the AUC for overall PCa was 0.76 (95% CI 0.74–0.78) for the 4K panel compared to 0.72 (95% CI 0.70–0.74) for free plus total PSA and 0.67 (95% CI 0.65–0.70) for total PSA alone. Discrimination was slightly enhanced for the 4K panel for GGG≥2 (1,067 cases; 0.78 for panel versus 0.74 for free plus total PSA and 0.68 for total PSA only) and aggressive PCa (542 cases; 0.79 for panel versus 0.74 for free plus total PSA and 0.68 for total PSA only). Improvement of the 4K panel over total PSA alone was observed in each racial/ethnic group for all four PCa outcomes, most notably for GGG≥2 (AA, 0.71 vs. 0.66; LA, 0.82 vs. 0.71; JA, 0.80 vs. 0.69; NH, 0.90 vs. 0.77; WH, 0.77 vs. 0.69) and aggressive PCa (AA, 0.72 vs. 0.67; LA, 0.81 vs. 0.70; JA, 0.81 vs. 0.69; NH, 0.91 vs. 0.73; WH, 0.77 vs. 0.67). Conclusion: The superior predictive ability of the 4K panel over PSA for overall and aggressive PCa across multiethnic populations indicates the broad clinical applicability of the 4K panel. This abstract is also being presented as Poster A068. Citation Format: Burcu F. Darst, Peggy Wan, Alisha Chou, Emily Vertosick, David V. Conti, Lynne Wilkens, Loic Le Marchand, Andrew Vickers, Hans Lilja, Christopher A. Haiman. The four-kallikrein panel discriminates prostate cancer and aggressive disease in a multiethnic population [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr PR01.

Serum Levels of Matrix Metalloproteinase-1 in Brazilian Patients with Benign Prostatic Hyperplasia or Prostate Cancer.

Metalloproteinases (MMPs) are involved in metastatic tumor processes, with changes in circulating levels detected in several cancer types. Here, we compare serum concentrations of metalloproteinase-1 (MMP-1) across individuals clinically diagnosed with prostate cancer (PCa) or benign prostatic hyperplasia (BPH), correcting results for the rs495366 single nucleotide polymorphism (SNP) that predisposes to differential MMP-1 levels. 196 men aged ≥50 years were followed at a university hospital urology outpatient clinic, with clinical, anthropometric, and rectal examinations performed by one urologist. Blood samples obtained prior to any clinical intervention provided baseline MMP-1 and total/free PSA levels as well as metabolic, hormonal, and inflammatory markers. The SNP was genotyped by real-time PCR. Participants with medical and/or laboratory profile compatible with malignancy composed the PCa group when confirmed by the Gleason scale. As expected, A-allele homozygotes showed reduced levels of MMP-1. Genotype-adjusted analyses revealed the mean MMP-1 level as 2-fold higher in PCa carriers compared to BPH patients. No other differences were found according to the prostatic condition or genotypic distribution, except for the expected raise in total and free PSA levels in PCa. In conclusion, increased serum levels of MMP-1 were observed in this context of prostatic malignancy compared to a benign phenotype, regardless of a genetic influence.

Assessment of testosterone and its fraction in patients with locally advanced prostate cancer and in patients with primary metastatic disease

Introduction: The assessment of serum concentration testosterone in patients with localized prostate cancer in the aspect of the development of aggressive features raises a number of controversies, remains still an unresolved research area with the results of studies trying to assess the importance of circulating androgens in prostate cancer are still not clear. The aim of the study was to determine whether preoperative levels of circulating androgens (testosterone and its free and bioavailable fractions) are correlated with tumor aggressiveness in patients with localized prostate cancer and metastatic disease Materials and Methods: The study involved 40 asymptomatic men, 98 men with benign prostatic hyperplasia and 129 male patients diagnosed with prostate cancer (PCa) (T1 – T2, irrespective of N and M). All patients had total PSA (tPSA), free PSA (fPSA), testosterone (TEST), SHBG and albumin levels measured before the treatment begun. For each of the subjects, the percentage of free PSA (f/tPSA), free (fTEST) and bioavailable testosterone (bioTEST) concentration, percentage of free (% fTEST) and bioavailable (% bioTEST) testosterone were calculated. Results: In patients with prostate cancer the significantly higher tPSA levels (p = 0.0001 and p = 0.0001), significantly lower albumin concentration (p = 0.0001 and p = 0.0001), and levels f/tPSA (p = 0.0001 and p = 0.0001) were found, compared to the group of asymptomatic men and BPH . In addition, in the group of patients with PCa, the lower levels of fTEST (p = 0.0004) and bioTEST (p = 0.0001), and their percentages (p = 0.0013 and p = 0.0001), as well as higher SHBG concentration (p = 0.0002) were observed compared to the asymptomatic males. Significantly higher fTEST (p = 0.0377) and bioTEST (p = 0.0447) concentration were found in patients with cT2c stage as compared to the cT2b stage. There were no significant differences in the levels of the parameters studied depending on the grade of malignancy according to Gleason score. The presence of distant and / or regional node metastases is associated with the significantly higher tPSA (p = 0.0001), and SHBG (p = 0.0039) concentrations and significantly lower levels of %fTEST (p = 0.0346) and %bioTEST (p = 0.0030). Patients who died within the five years (since diagnosis) had significantly higher tPSA (p = 0.0001) and SHBG (p = 0.0002), and significantly lower levels of %fTEST (p = 0.0018) and %bioTEST (p = 0.0003). The percentages of free and bioavailable testosterone and the bioTEST concentration showed a statistically significant downward trend and the SHBG concentration significantly increased with the increase of tPSA concentration in PCa patients. In patients in the cT2a + cT2b group, tPSA concentrations inversely correlated with %bioTEST (r = – 0.2633). There were no significant correlations between the studied hormones and tPSA in the group of patients with the worse prognosis (cT2c). Patients with GS &lt; 7 presented also a significant correlation between tPSA concentration and the %bioTEST levels (r = – 0.2548). Conclusions: Significantly lower percentages of free and bioavailable testosterone are observed in prostate cancer patients with PSA concentration higher than 100 ng/ml, distant and/or regional node metastases and shorter overall survival. Lower percentages of free and bioavailable testosterone are associated with the elevated serum hormone binding globulin (SHBG) levels (up to 5 years).