Prostate-Specific Antigen (PSA) based screening of prostate cancer (PCa) needs refinement. The aim of this study was the identification of urinary biomarkers to predict the Prostate Imaging-Reporting and Data System (PI-RADS) score and the presence of PCa prior to prostate biopsy. Urine samples from patients with elevated PSA were collected prior to prostate biopsy (cohort = 99). The re-analysis of mass spectrometry data from 45 samples was performed to identify urinary biomarkers to predict the PI-RADS score and the presence of PCa. The most promising candidates, i.e. SPARC-like protein 1 (SPARCL1), Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), Alpha-1-microglobulin/bikunin precursor (AMBP), keratin 13 (KRT13), cluster of differentiation 99 (CD99) and hornerin (HRNR), were quantified by ELISA and validated in an independent cohort of 54 samples. Various biomarker combinations showed the ability to predict the PI-RADS score (AUC = 0.79). In combination with the PI-RADS score, the biomarkers improve the detection of prostate carcinoma-free men (AUC = 0.89) and of those with clinically significant PCa (AUC = 0.93). We have uncovered the potential of urinary biomarkers for a test that allows a more stringent prioritization of mpMRI use and improves the decision criteria for prostate biopsy, minimizing patient burden by decreasing the number of unnecessary prostate biopsies.

UNASSIGNED: The aim of our study was to investigate whether repeat prostate-specific antigen (PSA) testing as currently recommended improves risk stratification for men undergoing magnetic resonance imaging (MRI) and targeted biopsy for suspected prostate cancer (PCa).
UNASSIGNED: Consecutive men undergoing MRI and prostate biopsy who had at least two PSA tests before prostate biopsy were retrospectively registered and assigned to a development cohort (n = 427) or a validation (n = 174) cohort. Change in PSA level was assessed as a predictor of clinically significant PCa (csPCa; Gleason score ≥3 + 4, grade group ≥2) by multivariable logistic regression analysis. We developed a multivariable prediction model (MRI-RC) and a dichotomous biopsy decision strategy incorporating the PSA change. The performance of the MRI-RC model and dichotomous decision strategy was assessed in the validation cohort and compared to prediction models and decision strategies not including PSA change in terms of discriminative ability and decision curve analysis.
UNASSIGNED: Men who had a decrease on repeat PSA testing had significantly lower risk of csPCa than men without a decrease (odds ratio [OR] 0.3, 95% confidence interval [CI] 0.16-0.54; p < 0.001). Men with an increased repeat PSA had a significantly higher risk of csPCa than men without an increase (OR 2.97, 95% CI 1.62-5.45; p < 0.001). Risk stratification using both the MRI-RC model and the dichotomous decision strategy was improved by incorporating change in PSA as a parameter.
UNASSIGNED: Repeat PSA testing gives predictive information regarding men undergoing MRI and targeted prostate biopsy. Inclusion of PSA change as a parameter in an MRI-RC model and a dichotomous biopsy decision strategy improves their predictive performance and clinical utility without requiring additional investigations.
UNASSIGNED: For men with a suspicion of prostate cancer, repeat PSA (prostate-specific antigen) testing after an MRI (magnetic resonance imaging) scan can help in identifying patients who can safely avoid prostate biopsy.

BACKGROUND: Many people struggle with the choice in a series of processes, from prostate cancer (PCa) diagnosis to treatment. We investigated the degree of regret after the prostate biopsy (PBx) and relevant factors in patients recommended for biopsy for suspected PCa.
METHODS: From 06/2020 to 05/2022, 198 people who performed PBx at three institutions were enrolled and analyzed through a questionnaire before and after biopsy. Before the biopsy, a questionnaire was conducted to evaluate the sociodemographic information, anxiety scale, and health literacy, and after PBx, another questionnaire was conducted to evaluate the decision regret scale. For patients diagnosed as PCa after biopsy, a questionnaire was conducted when additional tests were performed at PCa staging work-up.
RESULTS: 190 patients answered the questionnaire before and after PBx. The mean age was 66.2 ± 7.8 years. Overall, 5.5% of men regretted biopsy, but there was no significant difference between groups according to the PCa presence. Multivariate analysis, to identify predictors for regret, revealed that the case when physicians did not properly explain what the prostate-specific antigen (PSA) test was like and what PSA elevation means (OR 20.57, [95% CI 2.45-172.70], p = 0.005), low media literacy (OR 10.01, [95% CI 1.09-92.29], p = 0.042), and when nobody to rely on (OR 8.49, [95% CI 1.66-43.34], p = 0.010) were significantly related.
CONCLUSIONS: Overall regret related to PBx was low. Decision regret was more significantly related to media literacy rather than to educational level. For patients with relatively low media literacy and fewer people to rely on in case of serious diseases, more careful attention and counseling on PBx, including a well-informed explanation on PSA test, is helpful.

Objective: Due to inconsistent results in earlier investigations regarding the relationship between vitamin D and prostate-specific antigen (PSA), this study was conducted to gain a deeper understanding of the association between vitamin D and PSA. Methods: A total of 7174 male samples with 25(OH)D, PSA, and other variables were obtained from the National Health and Nutrition Examination Survey (NHANES) database. Three models, created through stepwise logistic regression, were employed to examine the dose-response association between PSA and 25(OH)D. Subsequently, restricted cubic spline analysis (RCS) was used to explore the nonlinear association between 25(OH)D and PSA. The study also compared the performance of four machine learning models in predicting PSA levels. Results: The dose-response relationship indicated a negative impact of high 25(OH)D levels on PSA (p for trend 0.05). The odds ratio (OR) of Q4 (7.73 with 95% CI (0.26, 15.76)) was significantly higher than Q1 (6.23 with 95% CI (0.24, 12.57)). OR values in Q2 and Q3 were less than 1 (Q2= 0.57 with 95% CI (-6.37, 8.04) and Q3= 0.26 with 95% CI (-5.94, 6.86)), suggesting a potential protective effect of 25(OH)D on PSA. RCS analysis revealed a U-shaped relationship between blood 25(OH)D levels and PSA, with serum 25(OH)D in the range of 20-134 ng/ml showing a potential decrease in PSA levels. Above this range, an increase in 25(OH)D might elevate PSA levels. Age (2.67 with 95% CI 2.24 to 3.1) and BMI (17.52 with 95% CI 7.65 to 26.32), along with the OR of obesity (10.36 with 95% CI 0.68 to 20.18), were identified as potential PSA risk factors. Among the machine learning models, the random forest algorithm performed the best in predicting PSA levels. Conclusion: This study revealed a U-shaped relationship between 25(OH)D and PSA, with PSA potentially declining when 25(OH)D is between 20 and 134 ng/mL and possibly rising above this range. The random forest method proved effective in both predicting PSA levels and guiding vitamin D dosage.

Serum carbohydrate antigen 19-9 (CA19-9) is used for recurrence surveillance in patients with resected pancreatic ductal adenocarcinoma (PDAC). This report describes the association of increasing CA19-9 in a male PDAC survivor with presence of prostatic hyperplasia. Unexplained elevation of CA19-9 in male PDAC survivors might be attributable to benign prostatic conditions.

UNASSIGNED: Large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of prostate cancer. The pathogenesis, clinical manifestation, treatment options, and prognosis are uncertain and underreported.
UNASSIGNED: A systematic search was conducted in April 2022 through PubMed, Embase, and Cochrane. We reviewed cases of LCNEC developed either from de novo or transformation from prostate adenocarcinoma and summarized the relevant pathophysiological course, treatment options, and outcomes.
UNASSIGNED: A total of 25 patients with a mean age of 70.4 (range 43 87 years old) from 18 studies were included in this review. 13 patients were diagnosed with de novo LCNEC of the prostate. 12 patients were from the transformation of adenocarcinoma post-hormonal therapy treatment. Upon initial diagnosis, patients diagnosed with de novo prostatic LCNEC had a mean serum PSA value of 24.6 ng/ml (range: 0.09-170 ng/ml, median 5.5 ng/ml), while transformation cases were significantly lower at 3.3 ng/ml (range: 0-9.3 ng/ml, median 0.05 ng/ml). The pattern of metastasis closely resembles prostate adenocarcinoma. Six out of twenty-three cases displayed brain metastasis matching the correlation between neuroendocrine tumors and brain metastasis. Three notable paraneoplastic syndromes included Cushings syndrome, dermatomyositis, and polycythemia. Most patients with advanced metastatic disease received conventional platinum-based chemotherapy with a mean survival of 5 months. There was one exception in the transformation cohort with a somatic BRCA2 mutation who was treated with a combination of M6620 and platinum-based chemotherapy with an impressive PFS of 20 months. Patients with pure LCNEC phenotype have worse survival outcomes when compared to those with mixed LCNEC and adenocarcinoma phenotypes. It is unclear whether there is a survival benefit to administering ADT in pure pathologies.
UNASSIGNED: LCNEC of the prostate is a rare disease that can occur de novo or transformation from prostatic adenocarcinoma. Most patients present at an advanced stage with poor prognosis and are treated with conventional chemotherapy regimens. Patients who had better outcomes were those who were diagnosed at an early stage and received treatment with surgery or radiation and androgen deprivation therapy (ADT). There was one case with an exceptional outcome that included a treatment regimen of M6620 and chemotherapy.

Prostate cancer represents a significant health risk to aging men, in which diagnostic challenges to the identification of aggressive cancers remain unmet. Prostate cancer screening is driven by the prostate-specific antigen (PSA); however, in men with benign prostatic hyperplasia (BPH) due to an enlarged prostate and elevated PSA, PSA\'s screening utility is diminished, resulting in many unnecessary biopsies. To address this issue, we previously identified a cleaved fragment of Filamin A (FLNA) protein (as measured with IP-MRM mass spectrometry assessment as a prognostic biomarker for stratifying BPH from prostate cancer and subsequently evaluated its expanded utility in Caucasian (CA) and African American (AA) men. All men had a negative digital rectal examination (DRE) and PSA between 4 and 10 ng/mL and underwent prostate biopsy. In AA men, FLNA serum levels exhibited diagnostic utility for stratifying BPH from patients with aggressive prostate cancer (0.71 AUC and 12.2 OR in 48 men with BPH and 60 men with PCa) and outperformed PSA (0.50 AUC, 2.2 OR). In CA men, FLNA serum levels also exhibited diagnostic utility for stratifying BPH from patients with aggressive prostate cancer (0.74 AUC and 19.4 OR in 191 men with BPH and 109 men with PCa) and outperformed PSA (0.46 AUC, 0.32 OR). Herein, we established FLNA alone as a serum biomarker for stratifying men with BPH vs. those with high Gleason (7-10) prostate cancers compared to the current diagnostic paradigm of using PSA. This approach demonstrates clinical actionability of FLNA alone without the requirement of prostate volume measurement as a test with utility in AA and CA men and represents a significant opportunity to decrease the number of unnecessary biopsies in aggressive prostate cancer diagnoses.

Oxidative Balance Score (OBS) is an index affecting the oxidative stress of dietary and lifestyle factors. We aimed to explore the association of OBS with prostate specific antigen (PSA) among older males.
A total of 5,136 samples were collected in this study to investigate the relationship between OBS and PSA from the National Health and Nutrition Examination Survey. Logistic regression models and restricted cubic spline were used to assess the associations between OBS and PSA.
Compared with the Q1 group, the odds ratios for the association between OBS and PSA were 1.005 (1.003, 1.009), 1.003 (1.001, 1.006), and 1.001 (0.978, 1.022) for Q2, Q3, and Q4, respectively. In the age-specific analyses, the association was significant among individuals aged 65 years old and over: the odds ratios for the association between OBS and PSA were 1.019 (1.005, 1.028), 1.028 (1.018, 1.039), and 1.038 (1.022, 1.049) for Q2, Q3, and Q4, respectively. But it was not significant among individuals aged less than 65 years old: the odds ratios for the association between OBS and PSA were 1.016 (0.995, 1.026), 1.015 (0.985, 1.022), and 0.988 (0.978, 1.016) for Q2, Q3, and Q4, respectively. The restricted cubic splines also indicated a nonlinear relationship between OBS and PSA among individuals aged 65 years old and over (Poverall = 0.006, Pnonlinear = 0.021).
Our findings provide evidence that OBS is positively associated with higher levels of PSA among older adults. Further large-scale prospective cohort studies are needed to verify our findings.

UNASSIGNED: An increasing number of studies have demonstrated that gastrointestinal inflammation may increase prostate cancer risk and raise the prostate-specific antigen (PSA) level. However, the association between ulcerative colitis (UC) and acute gastroenteritis (AGE) with PSA remains unclear and complicated. Herein, we evaluated the relationship between UC and AGE with PSA concentration using the National Health and Nutrition Examination Survey (NHANES) database and Mendelian randomization (MR) analyses.
UNASSIGNED: A total of 1,234 participants fit into the study after conducting the screening based on the NHANES survey conducted from 2009 to 2010. UC and AGE were the independent variables, and PSA was the dependent variable. Weighted multiple linear regressions were utilized to estimate the association of UC and AGE with PSA concentration. To detect the causal relationship between UC and AGE with PSA, a two-sample Mendelian randomized analysis was conducted.
UNASSIGNED: After controlling for all covariates, PSA (log2 transform) concentrations in the UC group were increased by 0.64 (0.07, 1.21). AGE was not independently associated with PSA levels after adjusting potential confounders. In patients with coronary artery disease, AGE promotes elevated PSA (log2 transform) concentrations (β = 1.20, 95% CI: 0.21-2.20, p < 0.001). Moreover, an IVW MR analysis indicated that genetically predicted UC was associated with increased PSA, and that AGE was not associated with PSA.
UNASSIGNED: This study indicated that a positive causal association exists between UC and the PSA level. However, there is no evidence to support the relationship between AGE and the PSA level.

BACKGROUND: Prostate cancer is one of the most common cancers among men worldwide and the fourth most common cause of death. The number of prostate cancer cases and deaths is increasing every year because of population aging. This study aimed to clarify the risk of developing prostate cancer due to fluctuations in Prostate Specific Antigen (PSA) levels in patients without a history of prostate cancer using large medical information data.
RESULTS: This retrospective cohort included 1707 male patients aged 60 years or older who had a PSA level measurement date (2-PSA) within 3 months or more and 2 years from the first PSA level measurement date (1-PSA) in the database between 2008 and 2019. We subtracted 1-PSA from 2-PSA and designated patients with a higher 2-PSA than 1-PSA to the \"up\" group (n = 967) and patients with a lower 2-PSA than 1-PSA to the \"down\" group (n = 740). By using Cox proportional hazards model, a significant increase in prostate cancer risk was observed in the up group compared with the down group (adjusted hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.21-2.72; adjusted for patient background factors). Subgroup analysis showed that patients with PSA levels < 4 ng/mL had a significantly increased risk of developing prostate cancer if the next PSA level increases by approximately 20% (adjusted HR = 2.94, 95% CI = 1.14-7.58), and patients with PSA levels of 4 ng/mL or higher if the next PSA level is decreased by approximately 20% had a significantly reduced risk of developing prostate cancer (adjusted HR = 0.36, 95% CI = 0.18-0.74), compared to that with no change.
CONCLUSIONS: This is the first study to clarify the association between PSA variability and risk of developing prostate cancer in patients without a history of prostate cancer. These results suggest that the suppression of elevated PSA levels may lead to the prevention of prostate cancer and that it would be better to perform a biopsy because the risk of developing prostate cancer may increase in the future if the PSA value increases above a certain level.