Comparison of digital and analog [68Ga]Ga-PSMA-11 PET/CT for detecting post-prostatectomy biochemical recurrence in prostate cancer patients: a prospective study.

Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study compared the diagnostic performance of digital and analog PET/CT with [68Ga]Ga-PSMA-11 in prostate cancer patients who experienced biochemical recurrence (BCR) after prostatectomy. Forty prostate cancer patients who experienced BCR, defined as serum prostate-specific antigen (PSA) concentrations exceeding 0.2 ng/mL after prostatectomy, were prospectively recruited. These patients were stratified into three groups based on their serum PSA levels. [68Ga]Ga-PSMA-11 was injected into each patient, and images were acquired using both analog and digital PET/CT scanners. Analog and digital PET/CT showed comparable lesion detection rate (71.8% vs. 74.4%), sensitivity (85.0% vs. 90.0%), and positive predictive value (PPV, 100.0% vs. 100.0%). However, digital PET/CT detected more lesions (139 vs. 111) and had higher maximum standardized uptake values (SUVmax, 14.3 vs. 10.3) and higher kappa index (0.657 vs. 0.502) than analog PET/CT, regardless of serum PSA levels. On both analog and digital PET/CT, lesion detection rates and interrater agreement increased with increasing serum PSA levels. Compared with analog PET/CT, digital PET/CT detected more lesions with a higher SUVmax and better interrater agreement in prostate cancer patients who experienced BCR after prostatectomy.

Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomics and transcriptomic evolution.

Extracellular vesicles (EVs) secreted by tumors are abundant in plasma, but their potential for interrogating the molecular features of tumors through multi-omic profiling remains widely unexplored. Genomic and transcriptomic profiling of circulating EV-DNA and EV-RNA isolated from in vitro and in vivo models of metastatic prostate cancer (mPC) reveal a high contribution of tumor material to EV-loaded DNA/RNA, validating the findings in two cohorts of longitudinal plasma samples collected from patients during androgen receptor signaling inhibitor (ARSI) or taxane-based therapy. EV-DNA genomic features recapitulate matched-patient biopsies and circulating tumor DNA (ctDNA) and associate with clinical progression. We develop a novel approach to enable transcriptomic profiling of EV-RNA (RExCuE). We report how the transcriptome of circulating EVs is enriched for tumor-associated transcripts, captures certain patient and tumor features, and reflects on-therapy tumor adaptation changes. Altogether, we show that EV profiling enables longitudinal transcriptomic and genomic profiling of mPC in liquid biopsy.

Predictive Value of Preoperative PSA Levels Combined with MRI Features for BCR after Radical Prostatectomy: A Retrospective Study.

BACKGROUND: Existing models for predicting that biochemical recurrence (BCR) will occur in patients after radical prostatectomy (RP) vary in their predictive results from magnetic resonance imaging (MRI). This study aimed to assess the predictive value of preoperative prostate-specific antigen (PSA) levels combined with MRI features in determining BCR following radical prostatectomy. METHODS: A retrospective analysis was conducted on a cohort comprising 102 patients who underwent radical prostatectomy at our hospital between January 2019 and December 2019. On the basis of the outcomes observed during a 4-year follow-up after surgery, the patients were categorised into BCR group (n = 52) and non-BCR group (n = 50). Differences in preoperative PSA levels and MRI characteristics between the two groups were compared, and factors influencing postoperative BCR were analysed. The receiver operating characteristic curve was drawn, and the sensitivity, specificity, area under the curve (AUC) and Youden index were calculated to observe the predictive value of the combination of preoperative PSA level and MRI features for BCR following radical prostatectomy. RESULTS: Logistic regression analysis showed that preoperative PSA level, postoperative Gleason score, data system (Prostate Imaging-Reporting and Data System (PI-RADS)) score and clinical T stage were independent risk factors for BCR in patients following radical prostatectomy, with odds ratio (OR) greater than 1. The AUC value of preoperative PSA level combined with PI-RADS score was 0.921, surpassing the AUC values of 0.783, 0.822, 0.617 and 0.608 predicted by preoperative PSA level, postoperative Gleason score, PI-RADS score and clinical T stage alone, respectively. CONCLUSIONS: Postoperative BCR in patients with prostate cancer undergoing radical prostatectomy is associated with preoperative PSA level, postoperative Gleason score, PI-RADS score and clinical T stage. The combination of preoperative PSA level and MRI features can improve the predictive efficiency for postoperative BCR.

Relationship between prostate-specific antigen, alkaline phosphatase levels, and time-to-tumor shrinkage: understanding the progression of prostate cancer in a longitudinal study.

BACKGROUND: This study delves into the complex interplay among prostate-specific antigen, alkaline phosphatase, and the temporal dynamics of tumor shrinkage in prostate cancer. By investigating the longitudinal trajectories and time-to-prostate cancer tumor shrinkage, we aim to untangle the intricate patterns of these biomarkers. This understanding is pivotal for gaining profound insights into the multifaceted aspects of prostate cancer progression. The joint model approach serves as a comprehensive framework, facilitating the elucidation of intricate interactions among these pivotal elements within the context of prostate cancer . METHODS: A new joint model under a shared parameters strategy is proposed for mixed bivariate longitudinal biomarkers and event time data, for obtaining accurate estimates in the presence of missing covariate data. The primary innovation of our model resides in its effective management of covariates with missing observations. Built upon established frameworks, our joint model extends its capabilities by integrating mixed longitudinal responses and accounting for missingness in covariates, thus confronting this particular challenge. We posit that these enhancements bolster the model's utility and dependability in real-world contexts characterized by prevalent missing data. The main objective of this research is to provide a model-based approach to get full information from prostate cancer data collected with patients' baseline characteristics ( Age , body mass index ( BMI ), GleasonScore , Grade , and Drug ) and two longitudinal endogenous covariates ( Platelets and Bilirubin ). RESULTS: The results reveal a clear association between prostate-specific antigen and alkaline phosphatase biomarkers in the context of time-to-prostate cancer tumor shrinkage. This underscores the interconnected dynamics of these key indicators in gauging disease progression. CONCLUSIONS: The analysis of the prostate cancer dataset, incorporating a joint evaluation of mixed longitudinal prostate-specific antigen and alkaline phosphatase biomarkers alongside tumor status, has provided valuable insights into disease progression. The results demonstrate the effectiveness of the proposed joint model, as evidenced by accurate estimates. The shared variables associated with both longitudinal biomarkers and event times consistently deviate from zero, highlighting the robustness and reliability of the model in capturing the complex dynamics of prostate cancer progression. This approach holds promise for enhancing our understanding and predictive capabilities in the clinical assessment of prostate cancer.

Comparative analysis of genetic risk scores for predicting biochemical recurrence in prostate cancer patients after radical prostatectomy.

BACKGROUND: In recent years, Genome-Wide Association Studies (GWAS) has identified risk variants related to complex diseases, but most genetic variants have less impact on phenotypes. To solve the above problems, methods that can use variants with low genetic effects, such as genetic risk score (GRS), have been developed to predict disease risk. METHODS: As the GRS model with the most incredible prediction power for complex diseases has not been determined, our study used simulation data and prostate cancer data to explore the disease prediction power of three GRS models, including the simple count genetic risk score (SC-GRS), the direct logistic regression genetic risk score (DL-GRS), and the explained variance weighted GRS based on directed logistic regression (EVDL-GRS). RESULTS AND CONCLUSIONS: We used 26 SNPs to establish GRS models to predict the risk of biochemical recurrence (BCR) after radical prostatectomy. Combining clinical variables such as age at diagnosis, body mass index, prostate-specific antigen, Gleason score, pathologic T stage, and surgical margin and GRS models has better predictive power for BCR. The results of simulation data (statistical power = 0.707) and prostate cancer data (area under curve = 0.8462) show that DL-GRS has the best prediction performance. The rs455192 was the most relevant locus for BCR (p = 2.496 × 10-6) in our study.

Single-molecule microfluidic assay for prostate-specific antigen based on magnetic beads and upconversion nanoparticles.

Early-stage diagnosis of prostatic carcinoma is essential for successful treatment and, thus, significant prognosis improvement. In laboratory practice, the standard non-invasive diagnostic approach is the immunochemical detection of the associated biomarker, prostate-specific antigen (PSA). Ultrasensitive detection of PSA is essential for both diagnostic and recurrence monitoring purposes. To achieve exceptional sensitivity, we have developed a microfluidic device with a flow-through cell for single-molecule analysis using photon-upconversion nanoparticles (UCNPs) as a detection label. For this purpose, magnetic microparticles (MBs) were first optimized for the capture and preconcentration of PSA and then used to implement a bead-based upconversion-linked immunoassay (ULISA) in the microfluidic device. The digital readout based on counting single nanoparticle-labeled PSA molecules on MBs enabled a detection limit of 1.04 pg mL-1 (36 fM) in 50% fetal bovine serum, which is an 11-fold improvement over the respective analog MB-based ULISA. The microfluidic technique conferred several other advantages, such as easy implementation and the potential for achieving high-throughput analysis. Finally, it was proven that the microfluidic setup is suitable for clinical sample analysis, showing a good correlation with a reference electrochemiluminescence assay (recovery rates between 97% and 105%).

Association between lymphocyte-to-monocyte ratio and prostate cancer in men: A population-based study.

Using the novel inflammatory biomarker lymphocyte-to-monocyte ratio (LMR), this work aimed to look into any potential connections between LMR and prostate cancer (PCa). A cross-sectional research investigation was conducted on 7706 male participants involved in the National Health and Nutrition Examination Survey from 2001 to 2010. Multivariate logistic regression modeling investigated the relationship between LMR levels and PCa risk. Furthermore, threshold analysis, subgroup analysis, interaction testing, and smoothed curve fitting were carried out. A significant negative correlation was seen between LMR and PCa risk (OR = 0.79, 95% CI: 0.65-0.97, P = .0002), even after controlling for potential confounding factors. A significant nonlinear negative correlation with a threshold effect and a breakpoint of 4.86 was found by smooth curve fitting between LMR and PCa. Subgroup analysis revealed a significant interaction (P for interaction = 0.0448) between the negative correlation between PCa and LMR about hypertension. Moreover, additional stratified smoothed curve fitting demonstrated a statistically significant inverse relationship between PCa risk and LMR. According to our findings, there is a substantial inverse relationship between PCa risk and LMR level. The inflammatory response-related index is quick, easy to use, and offers some clinical references. However, more extensive prospective investigations are required to confirm the involvement of LMR levels in PCa.

ProsTAV, a clinically useful test in prostate cancer: an extension study.

PURPOSE: To assess the clinical performance of ProsTAV®, a blood-based test based on telomere associate variables (TAV) measurement, to support biopsy decision-making when diagnosing suspicious prostate cancer (PCa). METHODS: Preliminary data of a prospective observational pragmatic study of patients with prostate-specific antigen (PSA) levels 3-10 ng/ml and suspicious PCa. Results were combined with other clinical data, and all patients underwent prostate biopsies according to each center's routine clinical practice, while magnetic resonance imaging (MRI) before the prostate biopsy was optional. Sensitivity, specificity, positive and negative predicted values, and subjects where biopsies could have been avoided using ProsTAV were determined. RESULTS: The mean age of the participants (n = 251) was 67.4 years, with a mean PSA of 5.90 ng/ml, a mean free PSA of 18.9%, and a PSA density of 0.14 ng/ml. Digital rectal examination was abnormal in 21.1% of the subjects, and according to biopsy, the prevalence of significant PCa was 47.8%. The area under the ROC curve of ProsTAV was 0.7, with a sensitivity of 0.90 (95% CI, 0.85-0.95) and specificity of 0.27 (95% CI, 0.19-0.34). The positive and negative predictive values were 0.53 (95% CI, 0.46-0.60) and 0.74 (95% CI, 0.62-0.87), respectively. ProsTAV could have reduced the biopsies performed by 27% and showed some initial evidence of a putative benefit in the diagnosis pathway combined with MRI. CONCLUSIONS: ProsTAV increases the prediction capacity of significant PCa in patients with PSA between 3 and 10 ng/ml and could be considered a complementary tool to improve the patient diagnosis pathway.

External validation of the barcelona magnetic resonance imaging predictive model for detecting significant prostate cancer including men receiving 5-alpha reductase inhibitors.

PURPOSE: To validate the Barcelona-magnetic resonance imaging predictive model (BCN-MRI PM) for clinically significant prostate cancer (csPCa) in Catalonia, a Spanish region with 7.9 million inhabitants. Additionally, the BCN-MRI PM is validated in men receiving 5-alpha reductase inhibitors (5-ARI). MATERIALS AND METHODS: A population of 2,212 men with prostate-specific antigen serum level > 3.0 ng/ml and/or a suspicious digital rectal examination who underwent multiparametric MRI and targeted and/or systematic biopsies in the year 2022, at ten participant centers of the Catalonian csPCa early detection program, were selected. 120 individuals (5.7%) were identified as receiving 5-ARI treatment for longer than a year. The risk of csPCa was retrospectively assessed with the Barcelona-risk calculator 2 (BCN-RC 2). Men undergoing 5-ARI treatment for less than a year were excluded. CsPCa was defined when the grade group was ≥ 2. RESULTS: The area under the curve of the BCN-MRI PM in 5-ARI naïve men was 0.824 (95% CI 0.783-0.842) and 0.849 (0.806-0.916) in those receiving 5-ARI treatment, p 0.475. Specificities at 100, 97.5, and 95% sensitivity thresholds were to 2.7, 29.3, and 39% in 5-ARI naïve men, while 43.5, 46.4, and 47.8%, respectively in 5-ARI users. The application of BCN-MRI PM would result in a reduction of 23.8% of prostate biopsies missing 5% of csPCa in 5-ARI naïve men, while reducing 25% of prostate biopsies without missing csPCa in 5-ARI users. CONCLUSIONS: The BCN-MRI PM has achieved successful validation in Catalonia and, notably, for the first time, in men undergoing 5-ARI treatment.

Biomolecule-regulation of fluorescent probe signaling: Homogeneous rapid portable protease sensing in serum.

BACKGROUND: As is well documented, prostate cancer (PCa) being the second most prevalent cancer in men worldwide, emphasizing the importance of early diagnosis for prognosis. However, conventional prostate-specific antigen (PSA) testing lacks sufficient diagnostic efficiency due to its relatively low sensitivity and limited detection range. Mounting evidence suggests that matrix metalloproteinase 9 (MMP-9) expression increases with the aggressive behavior of PCa, highlighting the significance of detecting the serum level of MMP-9 in patients. Developing a non-immune rapid, portable MMP-9 detection strategy and investigating its representativeness of PCa serum markers hold considerable implications. RESULTS: Herein, our study developed a simple, homogeneous dual fluorescence and smartphone-assisted red-green-blue (RGB) visualization peptide sensor of MMP-9, utilizing cadmium telluride quantum dots (CdTe QDs) and calcein as signal reporters. The essence of our approach revolves around the proteolytic ability of MMP-9, exploiting the selective recognition of molecule-Cu2+ complexes with different molecular weights by CdTe QDs and calcein. Under optimized conditions, the limits of detection (LODs) for MMP-9 were 0.5 pg/mL and 6 pg/mL using fluorescence and RGB values readouts, respectively. Indeed, this strategy exhibited robust specificity and anti-interference ability. MMP-9 was quantified in 42 clinical serum samples via dual-fluorescence analysis, with 12 samples being visually identified with a smartphone. According to receiver operating characteristic curve (ROC) analysis, its sensitivity and specificity were 90 % and 100 %, respectively, with an area under curve (AUC) value of 0.903. SIGNIFICANCE AND NOVELTY: Of note, the results of the aforementioned analysis were highly consistent with the serum level of PSA, clinical color Doppler flow imaging (CDFI), and histopathological results. Therefore, this simple, rapid, homogeneous fluorescence and visualization strategy can reliably measure MMP-9 levels and exhibit promising potential in point-of-care testing (POCT) applications for PCa patients.

Digital Rectal Exam in Prostate Cancer Screening and Elevated PSA Work-up-Is there a role anymore?

PURPOSE OF REVIEW: Prostate cancer (PCa) screening tools, particularly digital rectal examination (DRE), are under scrutiny. This review assesses the utility of DRE in PCa screening. RECENT FINDINGS: Recent studies reaffirm the DRE's sensitivity and specificity, a higher PCa detection rate with PSA in conjunction with DRE, and a slightly elevated risk of clinically significant PCa (CSPC) in those with elevated PSA and suspicious DRE. Studies confirm high accuracy of MRI in identifying CSPC, with ongoing research exploring its screening potential. DRE alone lacks accuracy for PCa screening, often resulting in missed diagnoses and unnecessary biopsies. Its supplementary use with PSA marginally increases detection rates of identifying a small percentage of CSPC, but the benefit remains questionable. Emerging evidence suggests MRI has the potential as a superior screening tool compared to DRE, although direct comparative studies are lacking. Overall, the DRE has a limited role in current PCa screening.

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

BACKGROUND: Systemic 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 METHODS: Analysis 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. RESULTS: Among 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 (ß: 0.22, 95% confidence intervals [CI] 0.05-0.38), a 2.22% decline in f/t PSA ratio (ß: -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 (ß: 0.55, 95% CI 0.19-0.90), 4.39% reduced f/t PSA ratio (ß: -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. CONCLUSION: Systemic 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.

Tumour-specific activation of a tumour-blood transport improves the diagnostic accuracy of blood tumour markers in mice.

BACKGROUND: The accuracy of blood-based early tumour recognition is compromised by signal production at non-tumoral sites, low amount of signal produced by small tumours, and variable tumour production. Here we examined whether tumour-specific enhancement of vascular permeability by the particular tumour homing peptide, iRGD, which carries dual function of binding to integrin receptors overexpressed in the tumour vasculature and is known to promote extravasation via neuropilin-1 receptor upon site-specific cleavage, might be useful to improve blood-based tumour detection by inducing a yet unrecognised vice versa tumour-to-blood transport. METHODS: To detect an iRGD-induced tumour-to-blood transport, we examined the effect of intravenously injected iRGD on blood levels of α-fetoprotein (AFP) and autotaxin in several mouse models of hepatocellular carcinoma (HCC) or in mice with chronic liver injury without HCC, and on prostate-specific antigen (PSA) levels in mice with prostate cancer. FINDINGS: Intravenously injected iRGD rapidly and robustly elevated the blood levels of AFP in several mouse models of HCC, but not in mice with chronic liver injury. The effect was primarily seen in mice with small tumours and normal basal blood AFP levels, was attenuated by an anti-neuropilin-1 antibody, and depended on the concentration gradient between tumour and blood. iRGD treatment was also able to increase blood levels of autotaxin in HCC mice, and of PSA in mice with prostate cancer. INTERPRETATION: We conclude that iRGD induces a tumour-to-blood transport in a tumour-specific fashion that has potential of improving diagnosis of early stage cancer. FUNDING: Deutsche Krebshilfe, DKTK, LOEWE-Frankfurt Cancer Institute.

Predictive Factors for Early Biochemical Recurrence Following Robot-assisted Radical Prostatectomy.

BACKGROUND/AIM: The primary objective of this study was to identify predictors for biochemical recurrence (BCR) within 2 years following robot-assisted radical prostatectomy (RARP). Identifying predictors will enable insights that enhance personalized patient management and facilitate the ongoing refinement of postoperative therapy strategies. PATIENTS AND METHODS: This retrospective study included patients undergoing RARP from September 2014 to January 2021. Exclusion criteria were preoperative endocrine therapy, BCR beyond 2 years post-surgery, and incomplete postoperative data. Multivariate analyses were conducted to evaluate predictors of BCR, focusing on preoperative prostate-specific antigen (PSA) level, pathological tumor (pT) stage, Gleason score (GS), extraprostatic extension (EPE), and surgical margin status. RESULTS: Among 374 patients, 40 experienced BCR within 2 years. Significant predictors of early BCR included initial PSA level ≥10 ng/ml, pT3 or greater, GS ≥8, EPE, and positive surgical margins (RM1). Multivariate analysis identified pT3 or higher, GS ≥8, and RM1 as independent risk factors for early BCR. CONCLUSION: Early BCR after RARP is significantly associated with advanced pathological stage, high GS, and positive surgical margins. These findings emphasize the need for tailored postoperative management strategies and highlight the importance of precision in surgical technique to improve patient outcomes.

Blood metabolites mediate the causal relationship between circulating CX3CL1 levels and prostate cancer: A 2-step Mendelian randomization study.

Chemokines influence the progression of prostate cancer (PCa) through multiple mechanisms. However, the effect of C-X3-C chemokine ligand 1 (CX3CL1) on PCa risk remains controversial. Our study aimed to investigate whether circulating CX3CL1 is causally associated with PCa and to identify metabolites that have mediating effects using the 2-step bidirectional Mendelian randomization (MR) analysis process. Inverse variance weighting (IVW) results were used as the primary observations, while additional sensitivity analyses were conducted. For each standard deviation increase exhibited by the circulating CX3CL1 levels, the risk of PCa was reduced by 0.4% (IVW: OR = 0.996, [95% CI = 0.994-0.998], P < .001), and blood alliin levels increased by 19% (IVW: OR = 1.185, [95% CI = 1.01-1.54], P = .003). For each standard deviation increase in the blood alliin levels, the risk of PCa was reduced by 0.1% (IVW: OR = 0.999, [95% CI = 0.997-0.999], P = .03). Therefore, the protective effect of circulating CX3CL1 on PCa may be mediated by blood alliin levels (mediated proportion = 6.7%). The results supported the notion that high levels of circulating CX3CL1 indicate a lower PCa risk and the idea that the food-derived antioxidant alliin may mediate this association. We emphasize that the use of CX3CL1 as a protective factor against PCa may provide new strategies for PCa prevention and care in the future.

Circulating free insulin-like growth factor-I and prostate cancer: a case-control study nested in the European prospective investigation into cancer and nutrition.

BACKGROUND: Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk. METHODS: We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics. RESULTS: Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade. CONCLUSIONS: Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.

Evaluation of the clinical application value of cytokine expression profiles in the differential diagnosis of prostate cancer.

BACKGROUND: The significance of tumor-secreted cytokines in tumor development has gained substantial attention. Nevertheless, the precise role of tumor-related inflammatory cytokines in prostate cancer (PCa) remains ambiguous. OBJECTIVES: To gain deeper insights into the inflammatory response in the process of PCa. METHODS: A total of 233 cases were collected, including 80 cases of prostate hyperplasia as disease control, 65 cases of postoperative prostate cancer and 36 cases of prostate cancer as PCa group. Additionally, 52 patients undergoing physical examinations during the same period were collected as the healthy control. The levels of 12 inflammatory cytokines in peripheral blood samples were analyzed using flow cytometric bead array technology. The levels of total prostate-specific antigen (TPSA) and free prostate-specific antigen (FPSA) in peripheral blood samples were analyzed using electrochemiluminescence technology. RESULTS: Our findings revealed significant increases in serum IL-8 levels in PCa group compared to the healthy control group. Additionally, IL-6, IL-10, IFN-γ and IL-12p70 levels were markedly elevated in the PCa group compared to the disease control group (all p < 0.05). Conversely, the level of IL-4, TNF-α, IL-1ß, IL-17A and IFN-α were lower in the PCa group compared to those in control group. Following surgery, the concentration of IL-6 decreased; whereas, the concentrations of IL-4, TNF-α, IL-17A, IL-1ß, IL-12p70, and IFN-α increased, demonstrating significant differences (p < 0.05). The differential upregulation of IL-6 or downregulation of IL-17A in peripheral blood exhibited diagnostic efficacy in PCa patients. Moreover, we observed a significant increase in IL-17A levels, accompanied by decreased of IL-2, IL-4, IL-10, TNF-a, IFN-γ, IL-1ß, and IL-12P70 in patients with distant metastasis. CONCLUSION: The peripheral blood cytokines are closely associated with the occurrence and development of prostate cancer, especially the serum levels of IL-6 and IL-17A may be useful as potential predictors of PCa diagnosis.

Access to Prostate-Specific Antigen Testing and Mortality Among Men With Prostate Cancer.

Importance: Prostate-specific antigen (PSA) screening for prostate cancer is controversial but may be associated with benefit for certain high-risk groups. Objectives: To evaluate associations of county-level PSA screening prevalence with prostate cancer outcomes, as well as variation by sociodemographic and clinical factors. Design, Setting, and Participants: This cohort study used data from cancer registries based in 8 US states on Hispanic, non-Hispanic Black, and non-Hispanic White men aged 40 to 99 years who received a diagnosis of prostate cancer between January 1, 2000, and December 31, 2015. Participants were followed up until death or censored after 10 years or December 31, 2018, whichever end point came first. Data were analyzed between September 2023 and January 2024. Exposure: County-level PSA screening prevalence was estimated using the Behavior Risk Factor Surveillance System survey data from 2004, 2006, 2008, 2010, and 2012 and weighted by population characteristics. Main Outcomes and Measures: Multivariable logistic, Cox proportional hazards regression, and competing risks models were fit to estimate adjusted odds ratios (AOR) and adjusted hazard ratios (AHR) for associations of county-level PSA screening prevalence at diagnosis with advanced stage (regional or distant), as well as all-cause and prostate cancer-specific survival. Results: Of 814 987 men with prostate cancer, the mean (SD) age was 67.3 (9.8) years, 7.8% were Hispanic, 12.2% were non-Hispanic Black, and 80.0% were non-Hispanic White; 17.0% had advanced disease. There were 247 570 deaths over 5 716 703 person-years of follow-up. Men in the highest compared with lowest quintile of county-level PSA screening prevalence at diagnosis had lower odds of advanced vs localized stage (AOR, 0.86; 95% CI, 0.85-0.88), lower all-cause mortality (AHR, 0.86; 95% CI, 0.85-0.87), and lower prostate cancer-specific mortality (AHR, 0.83; 95% CI, 0.81-0.85). Inverse associations between PSA screening prevalence and advanced cancer were strongest among men of Hispanic ethnicity vs other ethnicities (AOR, 0.82; 95% CI, 0.78-0.87), older vs younger men (aged ≥70 years: AOR, 0.77; 95% CI, 0.75-0.79), and those in the Northeast vs other US Census regions (AOR, 0.81; 95% CI, 0.79-0.84). Inverse associations with all-cause mortality were strongest among men of Hispanic ethnicity vs other ethnicities (AHR, 0.82; 95% CI, 0.78-0.85), younger vs older men (AHR, 0.81; 95% CI, 0.77-0.85), those with advanced vs localized disease (AHR, 0.80; 95% CI, 0.78-0.82), and those in the West vs other US Census regions (AHR, 0.89; 95% CI, 0.87-0.90). Conclusions and Relevance: This population-based cohort study of men with prostate cancer suggests that higher county-level prevalence of PSA screening was associated with lower odds of advanced disease, all-cause mortality, and prostate cancer-specific mortality. Associations varied by age, race and ethnicity, and US Census region.

Insights into polycrystalline microstructure of blood films with 3D Mueller matrix imaging approach.

This study introduces a novel approach in the realm of liquid biopsies, employing a 3D Mueller-matrix (MM) image reconstruction technique to analyze dehydrated blood smear polycrystalline structures. Our research centers on exploiting the unique optical anisotropy properties of blood proteins, which undergo structural alterations at the quaternary and tertiary levels in the early stages of diseases such as cancer. These alterations manifest as distinct patterns in the polycrystalline microstructure of dried blood droplets, offering a minimally invasive yet highly effective method for early disease detection. We utilized a groundbreaking 3D MM mapping technique, integrated with digital holographic reconstruction, to perform a detailed layer-by-layer analysis of partially depolarizing dry blood smears. This method allows us to extract critical optical anisotropy parameters, enabling the differentiation of blood films from healthy individuals and prostate cancer patients. Our technique uniquely combines polarization-holographic and differential MM methodologies to spatially characterize the 3D polycrystalline structures within blood films. A key advancement in our study is the quantitative evaluation of optical anisotropy maps using statistical moments (first to fourth orders) of linear and circular birefringence and dichroism distributions. This analysis provides a comprehensive characterization of the mean, variance, skewness, and kurtosis of these distributions, crucial for identifying significant differences between healthy and cancerous samples. Our findings demonstrate an exceptional accuracy rate of over 90 % for the early diagnosis and staging of cancer, surpassing existing screening methods. This high level of precision and the non-invasive nature of our technique mark a significant advancement in the field of liquid biopsies. It holds immense potential for revolutionizing cancer diagnosis, early detection, patient stratification, and monitoring, thereby greatly enhancing patient care and treatment outcomes. In conclusion, our study contributes a pioneering technique to the liquid biopsy domain, aligning with the ongoing quest for non-invasive, reliable, and efficient diagnostic methods. It opens new avenues for cancer diagnosis and monitoring, representing a substantial leap forward in personalized medicine and oncology.