Background: Prostate cancer is the most frequently diagnosed malignancy among men. Screening strategies aimed at reducing prostate cancer–related mortality have raised concerns about overdiagnosis—defined as the detection of cancers that would not cause symptoms or death during a patient’s lifetime—and subsequent overtreatment. This review systematically evaluates whether PSA-based screening primarily enables early detection or contributes to clinically relevant overdiagnosis. Methods: Following PRISMA guidelines, randomized controlled trials and cohort studies enrolling men aged ≥ 40 years without prior prostate cancer were included. Studies compared PSA-based screening with no screening or alternative strategies. PubMed, Web of Science, and Scopus were searched from 2015 onward. Risk of bias was assessed using RoB2 for randomized trials and the Newcastle–Ottawa Scale for cohort studies. Primary outcomes included prostate cancer diagnosis, overdiagnosis, prostate cancer–specific mortality, and overall mortality. Results: Thirteen studies enrolling men aged 45–74 years, with follow-up ranging from 2 to 22 years and sample sizes from 4,276 to 415,357, were included. Biopsy-related complications were infrequent (≤2%), and MRI-guided biopsy was associated with fewer infectious complications compared with standard transrectal biopsy. Overdiagnosis estimates varied widely across studies; however, the pooled estimate was not statistically significant (RR 1.56 [95% CI 0.65–3.79]). PSA screening did not reduce overall mortality (RR 0.99 [95% CI 0.88–1.11]). Prostate cancer–specific mortality was modestly reduced, with pooled results borderline significant (IRR 0.87 [95% CI 0.76–1.00]). Substantial heterogeneity and risk of bias across studies limited the certainty and generalizability of pooled estimates. Conclusion: PSA-based screening is associated with a modest reduction in prostate cancer–specific mortality without an improvement in overall survival. Lower overdiagnosis rates observed in more recent, risk-adapted screening strategies highlight the importance of shared decision-making and support the integration of modern diagnostic tools to minimize harms. Further well-designed, representative trials are needed to define optimal screening pathways across diverse populations

Multimodal urinary biomarker panel achieves superior prostate cancer detection accuracy and reduces unnecessary biopsies.

A novel PPtNPs/rGO@Cu(BDC-NH2) MOF/PEDOT@PB/SPCE platform for ultra-sensitive label-free electrochemical immunosensor for prostate-specific antigen.

Enzalutamide with or without leuprolide in patients with high-risk biochemically recurrent prostate cancer: EMBARK post hoc analysis by age.

Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and contrast-enhanced magnetic resonance imaging (MRI) are extensively used for the clinical diagnosis of prostate cancer (PCa). However, both modalities are prone to misdiagnoses or missed lesions. Fusing these complementary data sources, specifically the combined CT-PET image data from PSMA PET/CT scans and contrast-enhanced MRI, may improve diagnostic accuracy, with precise spatial registration being a crucial prerequisite for effective image fusion. While previous studies have used software tools for MRI-PSMA PET/CT fusion, most rely on MRI-CT-based anatomical registration and treat PET as a secondary overlay, thereby underutilizing PSMA's tumor-specific metabolicinformation. To propose a global and local information-based registration network (GLNet) that integrates PSMA PET/CT's functional-semantic features with MRI's high-resolution soft-tissue details to improve PCa lesiondiagnosis. To improve prostate image registration, GLNet was designed using semantic gating convolutional (SGC) modules and a convolutional long short-term memory network based on a U-shaped channel (U-CLSTM). Specifically, SGC modules enhance perception of the prostate gland using global information, while U-CLSTM improves attention to local tumor regions. The dataset comprised 77 clinical cases, each verified by two experienced physicians through clinical biopsy. After data augmentation, 244 cases were used for training and validation, and 64 cases for testing. GLNet's performance was compared against state-of-the-art methods: symmetric normalization (SyN), VoxelMorph (VM), volume tweening network (VTN), and recursive deformable pyramid (RDP). Statistical analyses were conducted using the Kruskal-Wallis test with Bonferroni correction for pairwise comparisons, and effect sizes were assessed using Cohen'sd. GLNet achieved Dice similarity coefficient (DSC) of 0.76 0.11, HD95 of 9.32 3.13 mm, average symmetric surface distance (ASD) of 1.69 0.65 mm, and a near-zero negative Jacobian proportion of for prostate gland registration. In contrast to other networks, GLNet demonstrated significant improvements (p 0.001), with DSC increasing by - , 5th-percentile Hausdorff distance (HD95) decreasing by 1.69-30.03 mm, and ASD reducing by 0.24-15.44 mm. Cohen's d values indicated large effect sizes. For local lesion detection, GLNet achieved precision, recall, and an F1-score of 0.86, which outperformed other methods by - in precision, - in recall, and 0.21-0.37F1-score. This study presents GLNet, a deep learning-based non-rigid registration network that fuses PSMA PET/CT and contrast-enhanced MRI. GLNet outperforms existing methods in registration accuracy and lesion detection, thereby offering a promising approach for integrating structural and functional imaging in clinical PCadiagnosis.

Amyloid bodies (corpora amylacea) are found in the prostate and other organs, and their abnormal accumulation can lead to amyloidosis. However, it remains unclear how the constituents and pathological significance of amyloid bodies differ between tissues. We performed pathological, proteomic, and biochemical analyzes of prostatic amyloid bodies isolated from 53 consecutive patients who underwent pathological autopsy at Kumamoto University from 2006 to 2017. Amyloid bodies were isolated using laser microdissection, and their constituents were analyzed by liquid chromatography-tandem mass spectrometry, immunohistochemistry, and immunoblotting. Prostatic amyloid bodies were found in samples from 47 of the 53 patients (89%). The most frequently detected proteins were lactoferrin (100%), S100-A9 (90.9%), prostate-specific antigen (90.9%), and cytoskeleton-associated protein 2-like (90.9%). Amyloid-associated proteins, such as apolipoprotein E (72.7%), vitronectin (54.5%), and serum amyloid P component (36.4%), were also present but were less prevalent. Prostatic amyloid bodies were more common in patients with benign prostatic hyperplasia (N = 25) than in other patients (N = 28). These results suggest that amyloid bodies from different tissues may share some constituents. Our findings support further investigation to determine the relationship between the constituents of prostatic amyloid bodies and the pathophysiology of prostatic diseases.

Multimodal magnetic modulation QCM for motion-based detection of biomolecule concentration and base liquid viscosity.

Clinical and MRI variables in decision support systems for prostate MRI: A systematic review of decision support tools, nomograms, and risk models.

A 72-year-old man was referred for the evaluation of multiple hepatic lesions incidentally detected on contrast-enhanced computed tomography during prostate cancer staging. Imaging could not exclude malignancy, but the tumor markers were within the normal limits, except for prostate-specific antigen (PSA), and endoscopic examinations revealed no primary malignancy. A percutaneous biopsy was not feasible because of the lesion size and location. Endoscopic ultrasound (EUS) revealed a 25-mm caudate lobe lesion, from which fine-needle biopsy (FNB) was performed without complications. A histopathological examination confirmed a diagnosis of hepatic sarcoidosis. This case highlights the utility of EUS-FNB for the diagnosis of hepatic sarcoidosis, especially when a conventional biopsy is impractical.

Machine learning-based optimization of the prostate health index for prostate cancer detection.

Impact of Negative Prostate-specific Membrane Antigen Positron Emission Tomography on the Decision to Perform a Pelvic Lymph Node Dissection During Radical Prostatectomy for Intermediate- to High-risk Prostate Cancer Patients: Results of an International Survey

Prostate-specific antigen (PSA) is indispensable but not cancer specific; inflammation, benign prostatic hyperplasia, urinary retention, ejaculation, and instrumentation can all elevate PSA and complicate cancer risk assessment. This review synthesizes current evidence and guidelines to support clinicians in interpreting PSA elevations when inflammation is present or suspected. Acute febrile urinary tract infection and acute bacterial prostatitis may produce very high PSA values, sometimes exceeding 100 ng/mL, and normalization can be slow; therefore, PSA testing during active infection is discouraged. When PSA is only mildly to moderately elevated, standardized repeat testing is essential because a meaningful proportion of results normalize on retesting. A magnetic resonance imaging (MRI)-first pathway improves detection of clinically significant prostate cancer while reducing overdiagnosis and enables biopsy deferral after a negative MRI under structured monitoring. PSA density (PSAD) further refines triage alongside MRI, with practical working thresholds of roughly 0.10–0.20 ng/mL/cm<sup>3</sup> calibrated to MRI quality and pretest risk. However, asymptomatic histologic prostatitis (National Institutes of Health category IV) is common and may raise PSA without reliably altering PSAD, which means that PSAD alone cannot confirm that an elevation is attributable solely to inflammation. Validated secondary biomarkers (e.g., Prostate Health Index, 4Kscore, IsoPSA [isoform PSA], Stockholm3, Proclarix, PCA3 [prostate cancer gene 3], SelectMDx [select molecular diagnostics], ExoDx [exosome diagnostics], MPS/MPS2 [MyProstateScore/MyProstateScore 2.0]) are best used selectively when MRI is negative or equivocal and clinical risk remains uncertain. A pragmatic sequence—confirm, image, and refine—helps minimize missed clinically significant cancer while reducing unnecessary antibiotics and biopsies when inflammation is the predominant driver of PSA elevation.

Benign prostatic hyperplasia (BPH) is a nonmalignant enlargement of the prostate has been associated with an increased prostate cancer risk. Spontaneous BPH rarely occurs outside humans, dogs, and chimpanzees, limiting suitable animal models. Researchers have developed induction protocols, but conflicting data on optimal duration affects consistency. This study compared protocols for inducing BPH in albino Wistar rats to determine the most effective method. Fifty-four mature male rats (11–12 weeks old) were randomly assigned to six groups (n=9). Group I was the control; groups IV and V underwent bilateral orchiectomy; and Group VI was the sham control. BPH induction used testosterone propionate (6 mg/kg, subcutaneously) in groups II and IV, or testosterone plus oestradiol valerate (0.6 mg/kg, subcutaneously) in groups III and V, every other day for 28 days. Sacrifices occurred on days 14, 21, and 28. Assessments included relative prostate weight, serum prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), and histology. Non-castrated rats showed higher induction rates with both testosterone alone and hormone combination from day 14, with the non-castrated testosterone-oestradiol group (NCTE) producing the strongest response—relative prostate weight 0.26±0.01 vs. 0.16±0.02 in controls (p<0.05). PAP rose in all induction groups and peaked in non-castrated testosterone-treated animals. Histology revealed glandular hyperplasia, enlarged acini, and congestion in intact rats given hormones; castrated rats showed minimal changes. The testosterone-oestradiol protocol in intact rats was most effective, producing significant hyperplasia within 14 days, providing a reliable model for BPH research.

The high kidney uptake of prostate-specific membrane antigen (PSMA) radiotracers remains a significant challenge in the clinical diagnosis and treatment of prostate cancer (PCa). The aim of this study was to reduce the absolute kidney uptake of PSMA tracers by modifying targeting groups, thereby increasing the tumor-to-kidney (T/K) ratio. [99mTc]Tc-AuK-NapLPRO-HYNIC-EDDA demonstrated the most prominent imaging potential. It bound stably within the active cavity of the PSMA protein with nanomolar affinity (Kd = 14.73 nM). Density functional theory (DFT) and molecular dynamics provide a theoretical framework for understanding tracer coordination structures and ligand-protein interactions. [99mTc]Tc-AuK-NapLPRO-HYNIC-EDDA effectively reduced kidney uptake (1.19 ± 0.19% ID/g, 4 h) and resulted in good tumor retention, with rapid clearance from nontarget organs resulting in a high target-to-background ratios (TBRs). High-contrast SPECT/CT images were obtained within 2 to 4 h postinjection, indicating that [99mTc]Tc-AuK-NapLPRO-HYNIC-EDDA holds great potential for both standard and time-lapse imaging in PCa.

It is still unclear if curcumin's therapeutic effect in benign prostatic hyperplasia (BPH) is linked to microRNA regulation. This study explored the potential role of miR-21-3p in curcumin-induced anti-inflammatory and antiproliferative effects in BPH. Twenty-four male adult rats were grouped randomly into four groups: normal control group, BPH group, BPH group treated with curcumin and BPH group treated with finasteride as a reference drug. The BPH model was experimentally induced by s.c. injection of testosterone enanthate (3mg/ Kg) five times a week for two weeks, curcumin and finasteride were given orally, parallel to testosterone injection. The results showed that curcumin-induced decrease in prostate index and prostate-specific antigen (PSA)-like protein expression were associated with downregulation of miR-21-3p compared with the BPH untreated group. Immunohistochemical staining revealed increased SIRT1 expression and decreased NF-κB and TNF-α expression in the curcumin-treated group compared to the BPH untreated group. In addition, β-catenin protein expression, measured by Western blotting, as well as β-catenin-linked signaling proteins, LRP6 and c-Myc, were suppressed in the curcumin group. The results obtained with curcumin treatment were comparable to those with finasteride treatment. Our data were supported by histopathological findings. The current study demonstrated that curcumin alleviated the inflammatory manifestations of BPH by targeting the pro-inflammatory microRNA miR-21-3p, thereby upregulating SIRT1 and downregulating the pro-inflammatory mediators NF-κB and TNF-α. Furthermore, the anti-proliferative effect of curcumin may be attributed to the inhibition of the β-catenin signaling pathway.

Background: Improved clinical outcomes have been observed in patients with metastatic castration-sensitive prostate cancer (mCSPC) who experience deep prostate-specific antigen (PSA) responses after treatment with androgen receptor pathway inhibitors (ARPIs). Objective: This retrospective longitudinal study aimed to compare real-world PSA90 response (≥90% reduction from pretreatment levels) in Black patients with mCSPC treated with apalutamide vs abiraterone acetate. Methods: Electronic medical record (EMR) data from Precision Point Specialty Analytics were linked to claims data from the Komodo Research Database. Black adult patients with mCSPC who initiated apalutamide or abiraterone acetate on or after 9/17/2019 were included. Inverse probability of treatment weighting was used to balance patient characteristics between treatment cohorts. PSA90 was evaluated during the on-treatment period, defined as the time from index date to the earliest of treatment discontinuation, initiation of a new ARPI or radiopharmaceutical, or end of insurance claims activity or clinical activity. Weighted Kaplan-Meier curves and hazard ratios (HRs) were used to compare PSA90 responses between treatment cohorts. Results: This study included 363 patients, of which 236 initiated apalutamide and 127 initiated abiraterone acetate. At 6 months following treatment initiation, a greater proportion of patients treated with apalutamide (65.4%) vs abiraterone acetate (49.0%) achieved a PSA90 response. Patients who initiated apalutamide vs abiraterone acetate were 66% more likely to achieve a PSA90 response within 6 months of treatment initiation (HR, 1.66; 95% confidence interval, 1.18-2.35; P = .004). The median time-to-PSA90 response was approximately 6 months earlier for patients treated with apalutamide (3.3 months) compared with abiraterone acetate (9.1 months). Discussion: This study leveraged robust information from combined insurance claims and routinely collected EMR data to evaluate PSA90, a clinically relevant biomarker of treatment response, among Black patients with mCSPC. These results are among the first in this understudied patient population and suggest that a deeper and earlier PSA response achieved with apalutamide relative to abiraterone acetate can extend to Black patients in a real-world US clinical setting. Conclusion: Black patients treated with apalutamide experienced significantly higher PSA90 response rates than those treated with abiraterone acetate, suggesting possible clinical benefits from early treatment response in this population.

Background. The growing epidemiological burden of prostate cancer, projected for 2025, combined with the diagnostic limitations of prostate-specific antigen (PSA), necessitates the search for new strategies in precision oncology. Aim. This review article analyzes the evolution of diagnostic methods, pointing to the need to move from traditional serum markers to non-invasive liquid biopsy. Material and methods. We synthesize the current state of knowledge on established urinary biomarkers and present a novel approach using saliva as a source of information on cancer status. Results. The paper discusses the potential of metabolic profiling (sialic acid, citrate), identification of new protein biomarkers (S100P), analysis of specific microRNA signatures depending on the stage of the disease, and the role of the oral microbiome in pathogenesis and risk stratification. Conclusions. We conclude that salivary and urinary biomarkers represent a rapidly developing experimental direction in prostate cancer diagnostics. Preliminary studies indicate promising diagnostic performance; however, the majority of available evidence is based on pilot and case–control studies and requires further large-scale validation before clinical implementation.

Identification of prostate cancer by urinary DLX1/HOXC6 expression in Chinese population with prostate-specific antigen levels of 4-10ng/mL.

Actinium-225 (²²⁵Ac)-labeled prostate-specific membrane antigen (PSMA) radiopharmaceuticals represent a promising therapeutic approach for metastatic castration-resistant prostate cancer (mCRPC), yet clinical implementation remains limited by the absence of accurate dosimetric assessment methods. The complex decay chain and non-imaging alpha emissions of ²²⁵Ac pose substantial challenges for quantitative imaging. We aimed to evaluate the feasibility of quantitative single photon emission computed tomography (SPECT)-based dosimetry for ²²⁵Ac-PSMA-CY313 therapy by exploiting gamma emissions from daughter radionuclides francium-221 (²²¹Fr) and bismuth-213 (²¹³Bi). Four mCRPC patients received 185.8 ± 11.7 µCi ²²⁵Ac-PSMA-CY313 and underwent multi-timepoint SPECT/CT and whole-body planar imaging at 6, 24, 48, and 96h post-injection. Quantitative SPECT reconstruction used ordered-subsets expectation-maximization with comprehensive corrections for attenuation, scatter, resolution blur, and crosstalk. Volume of interest were defined using co-registered ¹⁸F-PSMA-CY313 positron emission tomography /computed tomography (PET/CT). Time-activity curves were fitted with mono- or bi-exponential models, and absorbed doses were calculated using validated Monte Carlo-based software and International Commission on Radiological Protection reference phantoms. High-quality quantitative imaging was successfully achieved across all timepoints. Among normal organs, kidneys and liver exhibited the highest absorbed doses (1.55 ± 0.38Gy and 1.07 ± 0.19Gy, respectively), corresponding to dose coefficients of 0.23 ± 0.07Gy/MBq and 0.16 ± 0.03Gy/MBq. Soft-tissue lesions exhibited higher absorbed doses than bone metastases (5.03 ± 5.51Gy versus 1.61 ± 2.28Gy), with corresponding dose coefficients of 0.73 ± 0.80Gy/MBq and 0.25 ± 0.33Gy/MBq. Tumor-to-critical organ dose ratios indicated favorable therapeutic windows, with red marrow showing the highest ratio (14.84), followed by adrenal glands (6.35) and salivary glands (4.96), while the dose-limiting kidneys demonstrated a ratio of 1.55. Quantitative SPECT-based dosimetry for ²²⁵Ac-PSMA-CY313 therapy is clinically feasible using standard imaging systems. This methodology demonstrates preferential tumor targeting with acceptable organ-at-risk dose distributions, supporting the therapeutic potential of ²²⁵Ac-PSMA-CY313 for mCRPC and providing a practical framework for personalized dosimetry in targeted alpha therapy.

[211At]PSMA-5 is a novel α-emitting therapeutic agent designed to target prostate-specific membrane antigen (PSMA), which is overexpressed in metastatic castration-resistant prostate cancer (mCRPC). Unlike β-emitting radioligands, [211At]PSMA-5 delivers highly localized cytotoxicity while minimizing damage to surrounding normal tissues. To enable clinical application, the objective of this study is to scale up the lab-scale synthesis to an automated manufacturing process that ensures high reproducibility and sufficient radioactivity for human administration. We developed and optimized a scalable automated synthesis method for [211At]PSMA-5 using the COSMiC-Mini VTRSC2 automated synthesizer. Optimization involved evaluating the recovery efficiency of 211At from the cold trap and reaction conditions, followed by automated synthesis under investigational new drug Good Manufacturing Practice conditions. Quality control of the synthesized [211At]PSMA-5 included assessment of radiochemical purity, radionuclide identity, impurity profile and sterility. Optimization with sodium hydrogen carbonate (7%) achieved over 90% recovery of 211At from the cold trap, and labeling rate of up to 93% were obtained using glass reaction vessels with stirring at 95°C. Three automated syntheses were conducted using irradiated Bi targets containing 211At produced at two different facilities. Consistent radiochemical yield (approximately 30%) and high radiochemical purity (96 ± 1%) were achieved. Additional quality control confirmed the absence of impurities such as 210At, Bi residues, and iodide, as well as sterility and chemical stability suitable for intravenous administration. This study successfully established an automated, scalable production process for [211At]PSMA-5 that meets clinical-grade quality requirements, enabling stable and reproducible manufacturing for investigator-initiated clinical trials in mCRPC. Equivalent radiochemical yields and consistent quality were obtained using irradiated Bi targets from two cyclotron facilities (RCNP and RIKEN), demonstrating site-independent robustness. This flexible system ensures a reliable supply and resilience to unexpected cyclotron downtime, representing a significant step toward clinical application of 211At-based PSMA-targeted alpha therapy.