Prostate-specific Antigen Ratio Research Articles

A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer

Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.536 T > C; Ile163Thr-substitution in PSA) is associated with reduced prostate cancer risk, however, the functional relevance is unknown. Here, we identify that the SNP variant-induced change in PSA biochemical activity mediates prostate cancer pathogenesis. The ‘Thr’ PSA variant leads to small subcutaneous tumours, supporting reduced prostate cancer risk. However, ‘Thr’ PSA also displays higher metastatic potential with pronounced osteolytic activity in an experimental metastasis in-vivo model. Biochemical characterisation of this PSA variant demonstrates markedly reduced proteolytic activity that correlates with differences in in-vivo tumour burden. The SNP is associated with increased risk for aggressive disease and prostate cancer-specific mortality in three independent cohorts, highlighting its critical function in mediating metastasis. Carriers of this SNP allele have reduced serum total PSA and a higher free/total PSA ratio that could contribute to late biopsy decisions and delay in diagnosis. Our results provide a molecular explanation for the prominent 19q13.3 KLK locus, rs17632542 SNP, association with a spectrum of prostate cancer clinical outcomes.

Reply to "Is the Free-to-Total PSA Ratio Less Important Than PSA Density and PSA Velocity in Patients With Negative MRI Examinations?"

Reply to "Is the Free-to-Total PSA Ratio Less Important Than PSA Density and PSA Velocity in Patients With Negative MRI Examinations?"

Is the Free-to-Total PSA Ratio Less Important Than PSA Density and PSA Velocity in Patients With Negative MRI Examinations?

Is the Free-to-Total PSA Ratio Less Important Than PSA Density and PSA Velocity in Patients With Negative MRI Examinations?

B-121 Optimizing Test Ordering: Leveraging Heuristics in Naming Conventions - A PSA Case Study

Abstract Background A common screening test for prostate cancer is the Prostate-Specific Antigen (PSA) test, which may also be referred to as total PSA or total PSA plus free PSA, among other variations. Looking at the test menus of two major reference laboratories, it's apparent that PSA can be ordered under thirteen different test names. From an end-user perspective, the question arises: which of these thirteen tests should be ordered, and why are there so many options? This plethora of choices can lead to confusion and uncertainty for clinicians and patients alike. According to various guidelines, ordering Free PSA is only warranted when PSA values exceed 4 ng/ml. In such cases, the ratio of free PSA to total PSA can aid in further clinical decision-making and patient workup. At Zuckerberg San Francisco General Hospital (ZSFGH), we offer two tests for PSA. The first is named “Prostate Specific Antigen” is total PSA done in house, while the second is labeled “Prostate Spec. Ag. Total and Free.” which is sent out to a reference lab. Upon reviewing our send-out orders, we observed a significant increase (376%) from 2022 to 2023 in the use of the send out order. Methods The ordering data for our providers was collected from February 2022 to January 2024 for both in-house and send-out orders. The data was analyzed using descriptive statistics in Microsoft Excel. Results In our population, we observed an abnormal concentration of send-outs originating from a select group of physicians. Additional we also identified a group of providers who only selected the send out test order. Analysis of in-house assay results for PSA revealed that only 15% (1292 out of 8136) exceeded the cutoff of 4 ng/ml, necessitating further testing to inform clinical decision-making. Yet our send out volume of 4157 test is in discordance with how many PSA would need further evaluation. Based on a cost analysis reducing the send out volume by 80% could result in $53,210 savings. Therefore, to reduce the send out amount and to keep the naming convention similar we decided to implement a new test name that would reflex the PSA to Free PSA if the PSA is above 4 ng/ml. We decided on the name “Prostate Specific Antigen total with reflex to Free Prostate Specific Antigen”. Conclusions Our investigation into the variability in PSA test ordering revealed a significant disparity in the number of send-out orders, particularly originating from a select group of physicians. However, the disproportionately high volume of send-out tests suggested an inefficiency in the current testing approach. To address this issue and align with clinical guidelines, we decided to process a request to our medical executive committee for approval for this reflex test in order to meet reimbursement compliance with the Office of the Inspector General. This change aims to streamline the process, reduce unnecessary send-out tests, and ultimately improve the efficiency and accuracy of prostate cancer screening at our institution.

B-318 Serum PSA in Extracellular Vesicles: Immunoreactivity to Commercial Kits and Elimination Kinetics

Abstract Background Prostate Specific Antigen (PSA) also circulates in blood bound to extracellular vesicles (EVs), and observed higher ratio of PSA in EVs respect total serum PSA when serum concentrations are <4 μg/L, and can represent up to 59% of total circulating PSA. Moreover, this molecular form of PSA (ev-PSA) is recognized and can be quantified with commercial methodologies designed for serum quantification. We aimed to characterize ev-PSA studying its immunoreactivity to different commercial assays and analyzing its presence in international standards used for assays standardization. Serum half-life and elimination kinetics of ev-PSA were also studied. Methods Serum EVs from 32 prostate cancer (PCa) patients were isolated by ultracentrifugation (100,000xg, 90 minutes). PSA was assessed in serum (srm-), serum supernatant free of EVs (sn-) and EVs (ev-) with total PSA (T-PSA) commercial immunoassays (Elecsys® from Roche Diagnostics and Immulite® 2000 from Siemens Healthineers), and Immulite/Elecsys ratio was calculated in all samples. The analysis of the differences between methods was performed with Bland-Altman test, representing the percentage of the difference respect the mean. WHO 96/670 PSA Standard was ultracentrifuged and analyzed by Nanoparticle Tracking Analysis (NTA) in a NanoSight LM20.For half-life estimation, serum samples from 10 localized PCa patients were collected basal and 2 days after radical prostatectomy, and EVs were isolated by Size Exclusion Chromatography using Exo-spinTM kit (Cell Guidance System). The Research Ethic Committee approved the study. Results Significant differences were observed between Elecsys and Immulite immunoassays in ev-T-PSA (p<0.001) concentrations. ev-T-PSA was quantified in all samples with Elecsys (median: 0.134 μg/L; Q1-Q3: 0.033-0.391 μg/L), but only in 22 patients (68.75%) with Immulite (median: 0.206 μg/L; Q1-Q3: 0.074-0.340 μg/L). In those 22 quantifiable patients, the median Immulite/Elecsys ratio was similar (p=0.057) between sn-T-PSA and srm-T-PSA (0.96 and 0.92, respectively), but much lower for ev-T-PSA (0.77; p<0.001). Bland-Altman graphical analysis showed that Elecsys overestimates the concentrations of T-PSA in all samples compared to Immulite, being this overestimation more marked in the case of PSA contained in EVs, and amplified at lower PSA concentrations. Besides, NTA analysis of WHO 96/670 PSA Standard showed that it does not contain EVs, and therefore, ev-PSA. The percentage of remnant PSA calculated in samples obtained post-surgery respect to baseline concentration in prostatectomized patients, was significantly higher for ev-T-PSA compared to soluble srm-T-PSA (p=0.014) and srm-F-PSA (p=0.002). The elimination half-life of ev-T-PSA was 3.99 days, much higher than those estimated for serum T-PSA and F-PSA, that were 1.76 days and 0.64 days, respectively. Conclusions The quantification of ev-PSA is affected by the different immunoreactivity of the diverse commercial assays. Thus, Elecsys T-PSA immunoassay shows higher immunoreactivity compared to Immulite technique, being this different reactivity more marked at lower PSA concentrations. ev-PSA is not considered in the International WHO 96/670 PSA Standard used for methods standardization. PSA bound to EVs remains longer in circulation than soluble serum PSA.

Association of Free-to-Total PSA Ratio and 18F-DCFPyL Prostate-Specific Membrane Antigen PET/CT Findings in Patients with Biochemical Recurrence After Radical Prostatectomy: A Prospective Single-Center Study.

In Canada and across the globe, access to PSMA PET/CT is limited and expensive. For patients with biochemical recurrence (BCR) after treatment for prostate cancer, novel strategies are needed to better stratify patients who may or may not benefit from a PSMA PET scan. The role of the free-to-total prostate-specific antigen (PSA) ratio (FPSAR) in posttreatment prostate cancer, specifically in the PSMA PET/CT era, remains unknown. Our aim in this study was to determine the association of FPSAR in patients referred for 18F-DCFPyL PSMA PET/CT in the BCR setting and assess the correlation between FPSAR and 18F-DCFPyL PSMA PET/CT positivity (local recurrence or distant metastases). Methods: This prospective study included 137 patients who were referred for 18F-DCFPyL PSMA PET/CT and had BCR with a total PSA of less than 1 ng/mL after radical prostatectomy (RP) (including adjuvant or salvage radiotherapy). Blood samples were collected on the day of 18F-DCFPyL PSMA PET/CT. FPSAR was categorized as less than 0.10 or as 0.10 or more. A positive 18F-DCFPyL PSMA PET/CT scan was defined by a PROMISE classification lesion score of 2 or 3, irrespective of the site of increased tracer uptake (e.g., prostate, pelvic nodes, bone, or viscera). Results: Overall, 137 blood samples of patients with BCR after RP were analyzed to calculate FPSAR. The median age at 18F-DCFPyL PSMA PET/CT was 68.6 y (interquartile range, 63.0-72.4 y), and the median PSA at 18F-DCFPyL PSMA PET/CT was 0.3 ng/mL (interquartile range, 0.3-0.6 ng/mL). Eighty-six patients (62.8%) had an FPSAR of less than 0.10, whereas 51 patients (37.2%) had an FPSAR of 0.10 or more. An FPSAR of 0.10 or more was identified as an independent predictor of a positive 18F-DCFPyL PSMA PET/CT scan, with an odds ratio of 6.99 (95% CI, 2.96-16.51; P < 0.001). Conclusion: An FPSAR of 0.10 or more after RP independently correlated with increased odds of a positive 18F-DCFPyL PSMA PET/CT scan among BCR post-RP patients. These findings may offer an inexpensive method by which to triage access to 18F-DCFPyL PSMA PET/CT in jurisdictions where availability is not replete.

Analysis of the Performance and Accuracy of a PSA and PSA Ratio-Based Nomogram to Predict the Probability of Prostate Cancer in a Cohort of Patients with PIRADS 3 Findings at Multiparametric Magnetic Resonance Imaging.

PIRADS score 3 represents a challenge in prostate cancer (PCa) detection with MRI. Our study aimed to evaluate the application of a nomogram on a cohort of patients with PIRADS 3. We analyzed 286 patients undergoing fusion prostate biopsy from January 2020 to February 2024. Only PIRADS 3 patients were included. Two nomograms, previously developed and based on clinical variables such as age, total PSA (specifically 2-10 ng/mL) and PSA ratio were applied to estimate the probability (Nomograms A and B) for PCa Grade Group (GG) > 3 and GG < 3. Out of the 70 patients available for analysis, 14/70 patients (20%) had PCa, 4/14 were GG 1 (28.6%), 1/14 were GG 2 (7.1%), 5/14 were GG 3 (35.8%), 2/14 were GG 4 (14.3%) and 2/14 were GG 5 (14.3%). The median probability of PCa GG > 3 and GG < 3 was 5% and 33%, respectively. A significant difference (p = 0.033) was found between patients with negative versus positive biopsy for Nomogram B. There was a significant difference (p = 0.029) for Nomogram B comparing patients with GG < 3 and GG > 3. Using a cut-off of 40% for Nomogram B, sensitivity and specificity were 70% and 80%, respectively. This cohort has a low probability of harboring PCa especially ISUP > 3. Nomogram B has good accuracy for discriminating patients with PCa from those with negative biopsy.

Investigation of the Relationship Between Prostate-Specific Antigen Levels and Prostate Cancer in Patients Attending a Urology Clinic from 2014 to 2023

Background: Prostate cancer is the second most common neoplasm and the fifth most aggressive cancer among men worldwide, with approximately 1.4 million new cases diagnosed annually. The incidence and mortality of prostate cancer increase with age, with a mean age at diagnosis of 66 years. Prostate cancer may be asymptomatic in its early stages and often has a latent period. The use of the Prostate-Specific Antigen (PSA) Index in the definitive diagnosis of prostate cancer remains a challenge for many urologists, and further research in this area can help to better understand the precise relationship between PSA levels and prostate cancer. Objectives: The present study aimed to investigate the relationship between PSA levels and prostate cancer in patients attending a urology clinic from 2014 to 2023, with the goal of improving diagnosis, developing effective treatments, and enhancing clinical outcomes. Methods: In this cross-sectional study, 242 patients with prostate cancer who attended a urology surgical clinic over a nine-year period from 2014 to 2023 were included. The patients were divided into two groups—youngest and oldest—based on the duration of their disease diagnosis. Demographic and clinical laboratory data were collected and entered into a checklist. Subsequently, the patients underwent a biopsy, and the results were recorded. Upon completion of the study, the collected data were entered into SPSS software for statistical analysis. Multiple regression analysis was used for correlation tests, while nonparametric tests, such as the Kruskal-Wallis test and the Mann-Whitney U test, were applied for nonparametric data analysis. Results: This study included 242 out of 276 samples for analysis. The ages of the participants ranged from 41 to 90 years, with a mean age of 67 ± 9.42 years. The data indicated that at PSA concentrations of 4 - 10 ng/mL, 5% of the samples were healthy, 15.2% had cancer, 46% had benign prostatic hyperplasia (BPH), and 33% had prostate intraepithelial neoplasia (PIN). At PSA concentrations of 10 - 50 ng/mL, 6% of the samples were healthy, 37% had cancer, 26% had BPH, and 29% had PIN. At PSA concentrations greater than 50 ng/mL, 3% of the samples were healthy, 76% had cancer, 14% had BPH, and 7% had PIN. A chi-square test revealed a significant association between PSA levels and pathological response (P &lt; 0.001). Additionally, an analysis of variance (ANOVA) test showed a significant difference between different age and severity groups (P &lt; 0.001). The free PSA-to-total PSA ratio in this study was 0.18, and the PSA-to-prostate volume ratio was 0.15, both of which were significantly associated with biopsy results (P &lt; 0.01). Conclusions: Overall, the data obtained from this study indicated that plasma PSA levels were directly associated with the likelihood of prostate cancer. Additionally, the results showed that plasma PSA levels were not only directly associated with age but also correlated with the severity of trophic disorders, such as cancer, as indicated by biopsy results.

Place de la PSA dans l’exploration des cancers de la prostate Role of PSA in Prostate Cancer Screening

Prostate Cancer (CaP) is a common malignant tumor, particularly among middle-aged and older men. Often dubbed the "invisible killer," it generally remains asymptomatic in its early stages, making early diagnosis crucial. Prostate-Specific Antigen (PSA) is the gold standard biomarker for the screening and monitoring of prostate cancer. This article provides an update on the analytical characteristics of this biomarker, highlighting its advantages and limitations. We will examine the interpretation of PSA results as well as derived indices, such as the free/total PSA ratio and the Prostate Health Index (PHI). These tools are essential in the management and care of prostate cancer. In addition to traditional biomarkers, this article also presents non-classical biomarkers whose potential use for managing this disease could prove interesting.

Technetium-99m-methylene diphosphonate single photon emission computed tomography/computed tomography combined with prostate-specific antigen/free prostate-specific antigen ratio for bone metastasis of prostate cancer.

Prostate cancer (PC) is one of the most common malignant tumors in men, and bone metastasis is one of its common complications, which seriously affects the quality of life and prognosis of patients. To investigate the diagnostic value of technetium-99m-methylene diphosphonate (99mTc-MDP) single photon emission computed tomography (SPECT)/CT imaging combined with the serum prostate-specific antigen (PSA)/free PSA ratio for PC bone metastasis (PCBM). One hundred patients with PC who visited the Hospital of Chengdu University of Traditional Chinese Medicine from January 2020 to January 2022 were recruited as the experimental (Exp) group, while 30 patients with benign prostatic lesions (BPLs) were recruited as the control (Ctrl) group. All patients underwent 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA testing. The SPECT/CT imaging results and serum PSA/fPSA ratios of patients were analyzed to evaluate their diagnostic values for PCBM. The difference in general information of the patients was not obvious, showing comparability. The two methods showed no visible differences in negative predictive value and sensitivity for patients with PCBM, but had great differences in positive predictive value and specificity (P < 0.05). The PSA/fPSA ratio of patients with PC in the Exp group was lower than those with BPLs, and patients with PCBM had a much lower PSA/fPSA ratio than those without PC (P < 0.05). The results confirmed that the combined use of 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA ratio achieved a detection rate of 95% for PCBM. The combination of 99mTc-MDP SPECT/CT and PSA/fPSA ratio is accurate and reliable for the diagnosis of PCBM, which provides an important reference for clinical practice.

Hybrid Machine Learning Algorithms to Evaluate Prostate Cancer

The adequacy and efficacy of simple and hybrid machine learning and Computational Intelligence algorithms were evaluated for the classification of potential prostate cancer patients in two distinct categories, the high- and the low-risk group for PCa. The evaluation is based on randomly generated surrogate data for the biomarker PSA, considering that reported epidemiological data indicated that PSA values follow a lognormal distribution. In addition, four more biomarkers were considered, namely, PSAD (PSA density), PSAV (PSA velocity), PSA ratio, and Digital Rectal Exam evaluation (DRE), as well as patient age. Seven simple classification algorithms, namely, Decision Trees, Random Forests, Support Vector Machines, K-Nearest Neighbors, Logistic Regression, Naïve Bayes, and Artificial Neural Networks, were evaluated in terms of classification accuracy. In addition, three hybrid algorithms were developed and introduced in the present work, where Genetic Algorithms were utilized as a metaheuristic searching technique in order to optimize the training set, in terms of minimizing its size, to give optimal classification accuracy for the simple algorithms including K-Nearest Neighbors, a K-means clustering algorithm, and a genetic clustering algorithm. Results indicated that prostate cancer cases can be classified with high accuracy, even by the use of small training sets, with sizes that could be even smaller than 30% of the dataset. Numerous computer experiments indicated that the proposed training set minimization does not cause overfitting of the hybrid algorithms. Finally, an easy-to-use Graphical User Interface (GUI) was implemented, incorporating all the evaluated algorithms and the decision-making procedure.

Associations of systemic immune‐inflammation index with high risk for prostate cancer in middle‐aged and older US males: A population‐based study

AbstractBackgroundSystemic immune‐inflammation index (SII) provides convincing evaluation of systemic immune and inflammatory condition in human body. Its correlation with prostate cancer (PCa) risk remains uncharted. The principal objective of this investigation was to elucidate the association between SII and the risk for PCa in middle‐aged and elderly males.Materials and MethodsAnalysis entailed multivariate linear and logistic regression, generalized additive model, and smoothing curve fitting using resource from 2007 to 2010 National Health and Nutrition Examination Survey (NHANES). To ascertain robustness and consistency of this association across different demographic strata, we conducted rigorous subgroup analyses and interaction tests.ResultsAmong 3359 participants, those with elevated SII displayed higher total prostate‐specific antigen (tPSA) levels, higher risk for PCa, and lower free/total PSA (f/t PSA) ratio. Specifically, each unit increase of log2 (SII) was associated with a 0.22 ng/mL increase in tPSA (β: 0.22, 95% confidence intervals [CI] 0.05–0.38), a 2.22% decline in f/t PSA ratio (β: −2.22, 95% CI −3.20 to −1.23), and a 52% increased odds of being at high risk for PCa (odds ratio [OR]: 1.52, 95% CI 1.13–2.04). People in the top quartile of log2 (SII) exhibited 0.55 ng/mL increased tPSA (β: 0.55, 95% CI 0.19–0.90), 4.39% reduced f/t PSA ratio (β: −4.39, 95% CI −6.50 to −2.27), and 168% increased odds of being at high risk for PCa (OR: 2.68, 95% CI 1.32–5.46) compared to those in the bottom quartile.ConclusionSystemic immune and inflammatory condition, as represented by SII, is independently and positively associated with tPSA levels and the risk for PCa, as well as independently and negatively associated with f/t PSA ratio among middle‐aged and older US males. These findings may enhance the effectiveness of PCa screening in predicting positive biopsy results.

Is the Serum Prostate-Specific Antigen Level Affected by Urethral Catheterization in Patients with Acute Urinary Retention?

Background: The reason for elevated serum prostate-specific antigen (PSA) levels in patients undergoing urethral catheterization due to acute urinary retention (AUR) remains a significant and controversial issue. Objectives: To assess the serum PSA level in men with AUR and its changes after catheterization. Methods: This prospective quasi-experimental study (reviewer 1 - comment 7) was conducted on 43 patients who underwent transurethral catheterization following AUR caused by benign prostatic hyperplasia (BPH). Total PSA levels and free/total PSA ratios were measured before catheterization and one and three days after catheter insertion. Additionally, prostate volume and urine output after catheterization (UOAC) were recorded. Results: The mean age, prostate volume, and UOAC of the patients were 69.05 ± 9.45 years, 60.51 ± 26.35 g, and 844.04 ± 341.66 mL, respectively. The mean and median baseline total PSA levels were 12.59 ± 17.71 ng/mL and 6.30 ng/mL, respectively. These values changed to 13.73 ± 19.83 ng/mL (median = 4.80 ng/mL) and 11.57 ± 17.70 ng/mL (median = 4.40 ng/mL) after 1 and 3 days of catheterization, respectively. The changes in total PSA and free/total PSA levels during the study period were not statistically significant (P &gt; 0.05). Moreover, the PSA levels showed no statistically significant difference before, 1 day, and 3 days after catheterization in groups with total PSA ≤ 4 and total PSA &gt; 4 (P = 0.37; 0.22, respectively). Conclusions: Our results suggest an initial elevation in PSA levels in patients with AUR before urethral catheterization. Both PSA and free/total PSA ratios showed no statistically significant differences before and after urethral catheter insertion, and initial PSA levels did not affect their changes post-catheterization (reviewer 1 - comment 1).

Unveiling the intricate connection between per- and polyfluoroalkyl substances and prostate hyperplasia

The presence of perfluoroalkyl and polyfluoroalkyl substances (PFAS) in various everyday products has raised concerns about their potential impact on prostate health. This study aimed to investigate the effects of different types of PFAS on prostate health, including PFDeA, PFOA, PFOS, PFHxS, and PFNA. To assess the relationship between PFAS exposure and prostate injury, machine learning algorithms were employed to analyze prostate-specific antigen (PSA) metrics. The analysis revealed a linear and positive dose-dependent association between PFOS and the ratio of free PSA to total PSA (f/tPSA). Non-linear dose-response relationships were observed between the other four types of PFAS and the f/tPSA ratio. Additionally, the analysis showed a positive association between the mixture of PFAS and prostate hyperplasia, with PFNA having the highest impact followed by PFOS. These findings suggest that elevated serum levels of PFDeA, PFOA, PFOS, and PFNA are linked to prostate hyperplasia. Therefore, this study utilized advanced machine learning techniques to uncover potential hazardous effects of PFAS exposure on prostate health, specifically the positive association between PFAS and prostate hyperplasia.

Smartphone-Based Free-to-Total Prostate Specific Antigen Ratio Detection System Using a Colorimetric Reaction Integrated with Proximity-Induced Bio-Barcode and CRISPR/Cas12a Assay.

The free-to-total prostate-specific antigen (f/t-PSA) ratio is of great significance in the accurate diagnosis of prostate cancer. Herein, a smartphone-based detection system is reported using a colorimetric reaction integrated with proximity-induced bio-barcode and the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a assay for f/t-PSA ratio detection. DNA/antibody recognition probes are designed to bind f-PSA or t-PSA and induce the release of the DNA bio-barcode. The CRISPR/Cas12a system is activated by the DNA bio-barcode to release Ag+ from the C-Ag+-C structure of the hairpin DNA. The released Ag+ is used to affect the tetramethylbenzidine (TMB)-H2O2-based colorimetric reaction catalyzed by Pt nanoparticles (NPs), as the peroxidase-like activity of the Pt NPs can be efficiently inhibited by Ag+. A smartphone with a self-developed app is used as an image reader and analyzer to analyze the colorimetric reaction and provide the results. A limit of detection of 0.06 and 0.04 ng mL-1 is achieved for t-PSA and f-PSA, respectively. The smartphone-based method showed a linear response between 0.1 and 100 ng mL-1 of t-PSA or f-PSA. In tests with clinical samples, the smartphone-based method successfully diagnosed prostate cancer patients from benign prostatic hyperplasia patients and healthy cases with high sensitivity and specificity.

Interim analyses from the PROSPET-BX trial: [G8Ga]PSMA PET/CT vs. mpMRI in patients with suspicion of prostate cancer and previous negative biopsy.

282 Background: Herein we present the results of the interim analyses of our prospective trial (Identifier: NCT05297162), designed to compare [68Ga]PSMA PET/CT with mpMRI in men with a high suspicion of prostate cancer (PCa) after at least one previous negative biopsy. Methods: From April 2022 until September 2023, overall, 94 patients were screened, 78 were enrolled and 64 completed all study investigations. Inclusion criteria: PSA&gt;4.0ng/ml; free-to-total PSA ratio &lt;20%; progressive rise of PSA levels in two consecutive samples; at least one previous negative biopsy; negative digital rectal examination. [68Ga]PSMA PET/CT and 3T mpMRI were performed within one month, followed by TRUS-fusion prostate biopsy. Target lesions were defined based on PI-RADS v2.1 for mpMRI and Primary Score, SUVmax and SUVratio for [68Ga]PSMA PET/CT, then correlated to pathology findings. Results: Median age was 64 years (range 51-83) and median PSA 10.4 ng/ml (range 4.3-25,9). Most patients (76.6%) had one previous negative biopsy. According to re-biopsy results, 10 patients presented with clinically significant PCa (csPCa), 4 with GS 6, while the majority had a negative biopsy (78%). mpMRI results were: 40 patients with PI-RADS 2 (62.5%), 3 with PI-RADS 3 (4.7%), 15 with PI-RADS 4 (23.4%), and 6 with PI-RADS 5 (9.4%). Primary scores were: 45 score 1-2 (70%), and 19 score 3-5. PI-RADS and Primary scores were significantly correlated (P=0.0006). Median SUVmax and SUVratio were 3.7 and 1.35 for benign versus 8.9 and 3 for malignancy, respectively (P&lt;0.001). ROC analyses identified optimal cut-off points for csPCA, with SUVmax&gt;7.48 (AUC 0.756; 95%CI 0.633-0.855) and SUVratio&gt;2.79 (AUC 0.748; 95%CI 0.624-0.848). PI-RADS, Primary score, SUVmax and SUVratio proved significantly associated to biopsy results. When combining [68Ga]PSMA PET/CT with mpMRI data, the detection rate was 90% for csPCa, and the combination of both modalities could spare 87.5% of unnecessary re-biopsies. Conclusions: In these interim results, [68Ga]PSMA PET/CT parameters predict biopsy results as mpMRI in patients who are candidates to re-biopsy; the combination of both modalities can spare most unnecessary re-biopsies, by granting a 90% detection rate for csPCa. Clinical trial information: NCT05297162 .

SERS-Temperature Dual-Mode T-type Lateral Flow Strip for Accurate Detection of Free and Total Prostate-Specific Antigens in Blood.

Accurate point-of-care (POC) analysis of cancer markers is the essence in the comprehensive early screening and treatment of cancer. Dual-mode synchronous detection is one of the effective approaches to reduce the probability of false negatives or false positives. As a result, this can greatly improve the accuracy of diagnosis. In this work, a surface-enhanced Raman scattering (SERS)-temperature dual-mode T-type lateral flow strip was fabricated to direct and simultaneous POC detection of total and free prostate-specific antigens (t-PSA and f-PSA) in blood. With the advantage of high stability of T-type lateral flow strip and simultaneous acquirement of assay results for t-PSA and f:t PSA ratio, the proposed method has high accuracy in the diagnosis of prostate cancer, especially in the diagnostic gray zone between 4.0 and 10.0 ng/mL. The SERS-temperature dual-signal has a good linear correlation with either f-PSA or t-PSA. To evaluate the clinical diagnostic performance of the proposed method, spiked human serum samples and the whole blood sample were analyzed. The assay results showed good recovery, and compared with traditional electrochemiluminescence immunoassay (ECLIA) method (t-PSA: 43.151; f/t ratio: 0.08), the results obtained by the proposed method were similar (t-PSA: 40.15 (SERS), 36.21 (temperature); f/t ratio: 0.08 (SERS), 0.08 (temperature), but the detection time (15 min) and cost ($0.05) had been greatly reduced. Therefore, the proposed SERS-temperature synchronous dual-mode T-type lateral flow strip has a strong application potential in the field of accurate large-scale diagnostics of prostate cancer on-site by simultaneous POC detection of t-PSA and f-PSA in blood.

Research of the best screen interval for middle aged and elderly Chinese males with baseline prostate specific antigen levels &lt;2.0 ng/mL in prostate cancer screening

This study aimed to investigate the optimal screening interval of a prostate specific antigen (PSA) screening program for men aged 40–70 with a baseline PSA &lt;2 ng/mL in China. 8-year period clinical data of Chinese males who underwent physical examination annually in our hospital were retrospectively collected. 397 healthy males were included.Total PSA (tPSA) and free PSA (fPSA) were collected, and the free/total PSA ratio (f/t PSA) was calculated. According to the baseline PSA value, study population was divided into 2 groups: 0–0.99 ng/mL and 1–1.99 ng/mL. Prostate biopsy indicates at tPSA &gt;10 ng/mL, or 4–10 ng/mL (gray area) and f/t PSA &lt;0.16. Kaplan-Meier survival analysis was used to calculate the relevant cumulative incidence rate. Over the eight-year screening period, 27 people (6.8%) had abnormal PSA that met prostate biopsy criteria. 7 cases of prostate cancer were detected (detection rate 25.9%) among the 27 patients who performed a biopsy. In the 0–0.99 ng/mL and 1–1.99 ng/mL group, 4.1% (13/317) and 17.5% (14/80) achieved biopsy criteria within 8 years, with a statistically significant difference (p &lt; 0.001). In both groups, abnormal PSA began appearing in the sixth year. According to stratifying the cohort age and PSA, abnormal PSA levels began to appear in all subgroups by the sixth year, except for men aged &lt;50 years plus baseline PSA &lt;1 ng/mL, where they appeared by the seventh year. Furthermore, in the group of baseline 40–49 years and baseline PSA &lt;2 ng/mL, the probability of meeting biopsy indications during eight years was very low (1.4%, 2/143). Chinese men aged 50–70 with baseline PSA &lt;2 ng/mL should undergo for PSA retest in the sixth year, while aged 40–49 with a baseline PSA &lt;2 ng/mL do not need PSA screening within eight years.

Assessment the Ability of Free/Total Ratio of Serum PSA in Diagnosing Prostate Cancer and Benign Prostatic Hyperplasia

Background: The Prostate gland is the male secondary sexual organ most commonly affected by benign or malignant neoplasm. Prostate cancer (Ca-P) is one of the most commonly diagnosed cancers in men and is now the third commonest cause of cancer death in western countries.The aim of the study was to evaluate the use of serum prostate-specific antigen levels in differentiating prostate cancer from benign prostatic hyperplasia. Methods:The present study is a cross-sectional observational study.The study was conducted at the outpatient department and indoor patients at the department of Urology, Rajshahi Medical College Hospital (RMCH), Rajshahi, and different private clinic in Rajshahi City during the period from July 2019 to June 2020.The study population included male patients above 50 years of age, who attended in the department of Urology, Rajshahi Medical College Hospital (RMCH), Rajshahi, and different private clinic in Rajshahi City complaining of irritative or obstructive lower urinary tract symptoms (LUTS) suspected as clinically prostate cancer or benign prostatic hyperplasia (BPHStatistical analysis of the results was obtained by using window-based computer software devised with Statistical Packages for Social Sciences (SPSS-24). Results: The age distribution of the prostatic carcinoma and BPH patients. Prostatic carcinoma was observed to be significantly higher from 80 years onwards, while BPH was common between 60 - 80 years (p = 0.00001). Table 10shows the validity or accuracy of the free/total ratio of serum PSA as a diagnostic test in differentiating prostatic carcinoma from BPH in patientswith total PSA levels between 4-10ng/ml. The percentage of false positives was significantly higher when total PSA ratio was used to diagnose the disease compared to when free to total PSA was used as a diagnostic tool (p&lt;0.000001). The overall accuracy of total PSA was also significantly lower (61.45%) than that of free/total PSA (91.67%) (p&lt; 0.011526). Conclusion: Free and total prostate specific antigen (PSA) is increased significantly in carcinoma prostate than benign prostatic hyperplasia but free/total ratio of serum prostate- specific antigen level significantly decreases in prostatic carcinoma than benign prostatic hyperplasia. TAJ 2023; 36: No-2: 215-230

Ability of Free/Total Serum PSA Ratio in Diagnosing Prostate Cancer and Benign Prostatic Hyperplasia

Ability of Free/Total Serum PSA Ratio in Diagnosing Prostate Cancer and Benign Prostatic Hyperplasia