CRISPR-Cas9 genome and long non-coding RNAs as a novel diagnostic index for prostate cancer therapy via liposomal-coated compounds.

CRISPR/Cas9 is a recently discovered genomic editing technique that altered scientist's sight in studying genes function. Cas9 is controlled via guide (g) RNAs, which match the DNA targeted in cleavage to modify the respective gene. The development in prostate cancer (PC) modeling directed not only to novel resources for recognizing the signaling pathways overriding prostate cell carcinoma, but it has also created a vast reservoir for complementary tools to examine therapies counteracting this type of cancer. Various cultured somatic rat models for prostate cancer have been developed that nearly mimic human prostate cancer. Nano-medicine can passively target cancer cells via increasing bioavailability and conjugation via specific legend, contributing to reduced systemic side-effects and increased efficacy. This article highlights liposomal loaded Nano-medicine as a potential treatment for prostate cancer and clarifies the CRISPR/Cas9 variation accompanied with prostate cancer. PC is induced experimentally in western rat model via ethinyl estradiol for 4 weeks and SC. dose of 3, 2'- dimethyl-4-aminobiphenyl estradiol (DAE) (50mg/kg) followed by treatment via targeted liposomal-coated compounds such as liposomal dexamethasone (DXM), liposomal doxorubicin (DOX) and liposomal Turmeric (TUR) (3mg/kg IP) for four weeks in a comparative study to their non-targeted analogue dexamethasone, doxorubicin and Turmeric. 3, 2'- dimethyl-4-aminobiphenylestradiol elicit prostate cancer in western rats within 5 months. Simultaneous supplementations with these liposomal compounds influence on prostate cancer; tumor markers were investigated via prostate-specific antigen (PSA), Nitric oxide (NOX) and CRISPR/Cas9 gene editing. Several long non-coding RNAs were reported to be deregulated in prostate cell carcinoma, including MALAT1. On the other hand, gene expression of apoptotic biomarkers focal adhesion kinase (AKT-1), phosphatidylinistol kinase (PI3K) and glycogen synthase kinase-3 (GSK-3) was also investigated and further confirming these results via histopathological examination. Liposomal loaded dexamethasone; doxorubicin and Turmeric can be considered as promising therapeutic agents for prostate cancer via modulating CRISPR/Cas9 gene editing and long non coding gene MALAT1.

CYP7B1 as a Biomarker for Prostate Cancer Risk and Progression: Metabolic and Oncogenic Signatures (Diagnostic Immunohistochemistry Analysis by Tissue Microarray in Prostate Cancer Patients-Diamond Study).

We aimed to analyze the association between CYP7B1 and prostate cancer, along with its association with proteins involved in cancer and metabolic processes. A retrospective analysis was performed on 390 patients with prostate cancer (PC) or benign prostatic hyperplasia (BPH). We investigated the interactions between CYP7B1 expression and proteins associated with PC and metabolic processes, followed by an analysis of the risk of biochemical recurrence based on CYP7B1 expression. Of the 139 patients with elevated CYP7B1 expression, 92.8% had prostate cancer. Overall, no increased risk of biochemical recurrence was associated with CYP7B1 expression. However, in a non-diabetic subgroup analysis, higher CYP7B1 expression indicated a higher risk of biochemical recurrence, with an HR of 1.78 (CI: 1.0-3.2, p = 0.05). PC is associated with elevated CYP7B1 expression. In a subgroup analysis of non-diabetic patients, elevated CYP7B1 expression was associated with an increased risk of biochemical recurrence, suggesting increased cancer aggressiveness.

Associations between knowledge of health issues and health care satisfaction and propensity to complain: a cross-sectional survey of adult men in Denmark.

OBJECTIVES: The objective of this study was to investigate associations between knowledge of health issues and healthcare satisfaction and propensity to complain including the association between knowledge and greater patient involvement. DESIGN: The present study is a secondary analysis of a larger cross-sectional case vignette survey. SETTING: Survey conducted in adult Danish men. PARTICIPANTS: Participants included 6755 men aged 45-70 years. INTERVENTIONS: Participants responded to a survey with scenarios illustrating prostate-specific antigen (PSA) testing and different information provision. PRIMARY AND SECONDARY OUTCOME MEASURES: Using Likert scales (scored 1-5), participants rated their satisfaction with the care described and their inclination to complain and responded to a short quiz (scored 0-3) assessing their knowledge about the PSA test. RESULTS: Satisfaction with healthcare increased with better quiz performance (Likert difference 0.13 (95% CI .07 to 0.20), p <0.001, totally correct vs totally incorrect responders) and correspondingly, the desire to complain significantly decreased (Likert difference -0.34 (95% CI 0.40 to -0.27), p <0.001). Respondents with higher education performed better (mean quiz score difference 0.59 (95% CI 0.50 to 0.67), p <0.001, most educated vs least educated). Responders who received information about the PSA test generally performed better (quiz score difference 0.41 (95% CI 0.35 to 0.47), p<0.001, neutral vs no information). Overestimation of PSA merits was more common than underestimation (7.9% vs 3.8%). CONCLUSIONS: Mens' knowledge of the benefits of screening varies with education, predicts satisfaction with care and the desire to complain, and may be improved through greater involvement in decision-making.

Active surveillance of low-grade prostate cancer using the SurACaP Criteria: A multi-institutional series with a median follow-up of 10years.

PURPOSE: To report on the oncological outcomes of active surveillance (AS) in low-grade prostate cancer (PCa) patients using the French SurACaP protocol, with a focus on long-term outcomes. METHODS: This multicenter study recruited patients with low-grade PCa between 2007 and 2013 in four referral centers in France. The cohort included patients meeting the SurACaP inclusion criteria, i.e., aged ≤75years, with low-grade PCa (i.e., ISUP 1), clinical stage T1c/T2a, PSA ≤10ng/mL and ≤3 positive cores and tumor length ≤3mm per core. The SurACaP protocol included a digital rectal examination every six months, PSA level measurement every three months for the first two years after inclusion and twice a year thereafter, a confirmatory biopsy in the first year after inclusion, and then follow-up biopsy every two years or if disease progression was suspected. Multiparametric magnetic resonance imaging (mpMRI) was progressively included over the study period. RESULTS: A total of 86 consecutive patients were included, with a median follow-up of 10.6 years. Only one patient developed metastases and died of PCa. The estimated rates of grade reclassification and treatment-free survival at 15 years were 53.4% and 21.2%, respectively. A negative mpMRI at baseline and a negative confirmatory biopsy were significantly associated with a lower risk of disease progression (P<0.05). CONCLUSIONS: AS using the French SurACaP protocol is a safe and valuable strategy for patients with low-risk PCa, with excellent oncological outcomes after more than 10 years' follow-up. Future studies are crucial to broaden the inclusion criteria and develop a personalized, risk based AS protocol with the aim of de-escalating follow-up examinations. LEVEL OF EVIDENCE: Grade 4.

Predicting clinically significant prostate cancer following suspicious mpMRI: analyses from a high-volume center.

PURPOSE: mpMRI is routinely used to stratify the risk of clinically significant prostate cancer (csPCa) in men with elevated PSA values before biopsy. This study aimed to calculate a multivariable risk model incorporating standard risk factors and mpMRI findings for predicting csPCa on subsequent prostate biopsy. METHODS: Data from 677 patients undergoing mpMRI ultrasound fusion biopsy of the prostate at the TUM University Hospital tertiary urological center between 2019 and 2023 were analyzed. Patient age at biopsy (67 (median); 33-88 (range) (years)), PSA (7.2; 0.3-439 (ng/ml)), prostate volume (45; 10-300 (ml)), PSA density (0.15; 0.01-8.4), PI-RADS (V.2.0 protocol) score of index lesion (92.2% ≥3), prior negative biopsy (12.9%), suspicious digital rectal examination (31.2%), biopsy cores taken (12; 2-22), and pathological biopsy outcome were analyzed with multivariable logistic regression for independent associations with the detection of csPCa defined as ISUP ≥ 3 (n = 212 (35.2%)) and ISUP ≥ 2 (n = 459 (67.8%) performed on 603 patients with complete information. RESULTS: Older age (OR: 1.64 for a 10-year increase; p < 0.001), higher PSA density (OR: 1.60 for a doubling; p < 0.001), higher PI-RADS score of the index lesion (OR: 2.35 for an increase of 1; p < 0.001), and a prior negative biopsy (OR: 0.43; p = 0.01) were associated with csPCa. CONCLUSION: mpMRI findings are the dominant predictor for csPCa on follow-up prostate biopsy. However, PSA density, age, and prior negative biopsy history are independent predictors. They must be considered when discussing the individual risk for csPCa following suspicious mpMRI and may help facilitate the further diagnostical approach.

Survival benefit of radical prostatectomy in patients with advanced TURP-diagnosed prostate cancer: a population-based real-world study.

OBJECTIVES: A considerable number of patients are diagnosed with prostate cancer (PCa) by transurethral resection of the prostate (TURP). We aimed to evaluate whether radical prostatectomy (RP) brings survival benefits for these patients, especially in the elderly with advanced PCa. PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to obtain PCa cases diagnosed with TURP. After the propensity matching score (PSM) for case matching, univariate, multivariate, and subgroup analyses were performed to investigate whether RP impacts the survival benefit. RESULTS: 4,677 cases diagnosed with PCa by TURP from 2010 to 2019 were obtained, including 1,313 RP patients and 3,364 patients with no RP (nRP). 9.6% of RP patients had advanced PCa. With or without PSM, cancer-specific mortality (CSM) and overall mortality (OM) were significantly reduced in the RP patients compared to the nRP patients, even for older (> 75 ys.) patients with advanced stages (all p < 0.05). Except for RP, younger age (≤ 75 ys.), being married, and earlier stage (localized) contributed to a significant reduction of CSM risk (all p < 0.05). These survival benefits had no significant differences among patients of different ages, married or single, and at different stages (all p for interaction > 0.05). CONCLUSIONS: Based on this retrospective population-matched study, we first found that in patients diagnosed with PCa by TURP, RP treatment may lead to a survival benefit, especially a reduction in CSM, even in old aged patients (> 75 ys.) with advanced PCa.

Trial of Electronic Medical Record Integrated Next-Generation Sequencing Ordering in Veterans Affairs Cancer Care.

PURPOSE: Previous studies document underuse of next-generation sequencing (NGS). We examined the impact to oncology care for veterans of incorporating NGS ordering into the Veterans Affairs (VA) electronic medical record (EMR) at two New York City VA Medical Centers. METHODS: We identified patients with non-small cell lung cancer and prostate cancer with oncology clinic visits and NGS testing indications between January and December 2021. Patients were divided into external ordering (EO) with visits before we implemented an EMR ordering system for NGS in July 2021, and internal ordering (IO) with visits after this date. The primary outcome was proportion of NGS testing performed in EO versus IO groups. Secondary outcomes were time between metastatic disease diagnosis to receipt of test by vendor, time of metastatic diagnosis to result, and proportion of testing by race. RESULTS: A total of 168 patients were identified, 116 EO and 52 IO patients. Between IO and EO periods, testing significantly increased from 52% to 87% (P ≤ .01); it was conducted more quickly, with time from metastatic diagnosis to sample receipt by the NGS vendor improving to median 37 days from 299 days (P = .03); and the time from documented metastatic disease to a test result improved to median 56 days from 309 days (P = .03). The proportion of tissue received by the vendor was not significantly different between the two groups. There were no significant differences in testing according to self-reported race. CONCLUSION: Integration of NGS ordering in the EMR led to increased proportion and speed of testing for a vulnerable patient population served by the country's largest health system.

Dual-mode fluorescence and colorimetric smartphone-based sensing platform with oxidation-induced self-assembled nanoflowers for sarcosine detection.

BACKGROUND: Early prostatic cancer (PCa) diagnosis significantly improves the chances of successful treatment and enhances patient survival rates. Traditional enzyme cascade-based early cancer detection methods offer efficiency and signal amplification but are limited by cost, complexity, and enzyme dependency, affecting stability and practicality. Meanwhile, sarcosine (Sar) is commonly considered a biomarker for PCa development. It is essential to develop a Sar detection method based on cascade reactions, which should be efficient, low skill requirement, and suitable for on-site testing. RESULTS: To address this, our study introduces the synthesis of organic-inorganic self-assembled nanoflowers to optimize existing detection methods. The Sar oxidase (SOX)-inorganic hybrid nanoflowers (Cu3(PO4)2:Ce@SOX) possess inherent fluorescent properties and excellent peroxidase activity, coupled with efficient enzyme loading. Based on this, we have developed a dual-mode multi-enzyme cascade nanoplatform combining fluorescence and colorimetric methods for the detection of Sar. The encapsulation yield of Cu3(PO4)2:Ce@SOX reaches 84.5 %, exhibiting a remarkable enhancement in catalytic activity by 1.26-1.29 fold compared to free SOX. The present study employing a dual-signal mechanism encompasses 'turn-off' fluorescence signals ranging from 0.5 µM to 60 µM, with a detection limit of 0.226 µM, and 'turn-on' colorimetric signals ranging from 0.18 µM to 60 µM, with a detection limit of 0.120 µM. SIGNIFICANCE: Furthermore, our study developed an intelligent smartphone sensor system utilizing cotton swabs for real-time analysis of Sar without additional instruments. The nano-platform exhibits exceptional repeatability and stability, rendering it well-suited for detecting Sar in authentic human urine samples. This innovation allows for immediate analysis, offering valuable insights for portable and efficient biosensors applicable to Sar and other analytes.

Prostate MRI Was Negative-What's Next?

The primary benefit of prostate MRI in the modern diagnostic pathway for prostate cancer is that many men with elevated serum PSA can safely avoid an immediate biopsy if the MRI is nonsuspicious. It is less clear, though, how these patients should be followed thereafter. Are they to be followed the same as the general population, or do they warrant more attention because of the risk of a cancer missed on MRI? In this issue, Pylväläinen and colleagues report on incidence of clinically significant prostate cancer (csPCa) and clinically insignificant PCa (ciPCa) among patients who were referred for prostate MRI for clinical suspicion of csPCa in Helsinki but had a nonsuspicious MRI (nMRI). Compared with the general population in Finland, patients who had nMRI were approximately 3.4 times more likely to be diagnosed with csPCa and 8.2 times more likely to be diagnosed with ciPCa. Balancing the competing risks of a missed csPCa versus overdiagnosis in patients after nMRI requires integration of MRI and other risk factors, especially age and PSA density. This integration may be facilitated by multivariable models and quantitative pathology and imaging. See related article by Pylväläinen et al., p. 749.

AAT resistance-related AC007405.2 and AL354989.1 as novel diagnostic and prognostic markers in prostate cancer.

OBJECTIVE: Prostate cancer (PCa) is the second disease threatening men's health, and anti-androgen therapy (AAT) is a primary approach for treating this condition. Increasing evidence suggests that long non-coding RNAs (lncRNAs) play crucial roles in the development of PCa and the process of AAT resistance. The objective of this study is to utilize bioinformatics methods to excavate lncRNAs association with AAT resistance and investigate their biological functions. METHODS: AAT resistance-related risk score model (ARR-RSM) was established by multivariate Cox analysis. Paired clinical tissue samples of 36 PCa patients and 42 blood samples from patients with PSA over 4 ng/ml were collected to verify the ARR-RSM. In vitro, RT-qPCR, CCK-8 and clone formation assays were displayed to verify the expression and function of AL354989.1 and AC007405.2. RESULTS: Pearson correlation analysis identified 996 lncRNAs were associated with AAT resistance (ARR-LncRs). ARR-RSM was established using multivariate Cox regression analysis, and PCa patients were divided into high-risk and low-risk groups. High-risk patients showed increased expression of AL354989.1 and AC007405.2 had poorer prognoses. The high-risk score correlated with advanced T-stage and N-stage. The AUC of ARR-RSM outperformed tPSA in diagnosing PCa. Silencing of AC007405.2 and AL354989.1 inhibited PCa cells proliferation and AAT resistance. CONCLUSIONS: In this study, we have discovered the clinical significance of AC007405.2 and AL354989.1 in predicting the prognosis and diagnosing PCa patients. Furthermore, we have confirmed their correlation with various clinical features. These findings provide potential targets for PCa treatment and a novel diagnostic and predictive indicator for precise PCa diagnosis.

Development of a multigenomic liquid biopsy (PROSTest) for prostate cancer in whole blood.

INTRODUCTION: We describe the development of a molecular assay from publicly available tumor tissue mRNA databases using machine learning and present preliminary evidence of functionality as a diagnostic and monitoring tool for prostate cancer (PCa) in whole blood. MATERIALS AND METHODS: We assessed 1055 PCas (public microarray data sets) to identify putative mRNA biomarkers. Specificity was confirmed against 32 different solid and hematological cancers from The Cancer Genome Atlas (n = 10,990). This defined a 27-gene panel which was validated by qPCR in 50 histologically confirmed PCa surgical specimens and matched blood. An ensemble classifier (Random Forest, Support Vector Machines, XGBoost) was trained in age-matched PCas (n = 294), and in 72 controls and 64 BPH. Classifier performance was validated in two independent sets (n = 263 PCas; n = 99 controls). We assessed the panel as a postoperative disease monitor in a radical prostatectomy cohort (RPC: n = 47). RESULTS: A PCa-specific 27-gene panel was identified. Matched blood and tumor gene expression levels were concordant (r = 0.72, p < 0.0001). The ensemble classifier ("PROSTest") was scaled 0%-100% and the industry-standard operating point of ≥50% used to define a PCa. Using this, the PROSTest exhibited an 85% sensitivity and 95% specificity for PCa versus controls. In two independent sets, the metrics were 92%-95% sensitivity and 100% specificity. In the RPCs (n = 47), PROSTest scores decreased from 72% ± 7% to 33% ± 16% (p < 0.0001, Mann-Whitney test). PROSTest was 26% ± 8% in 37 with normal postoperative PSA levels (<0.1 ng/mL). In 10 with elevated postoperative PSA, PROSTest was 60% ± 4%. CONCLUSION: A 27-gene whole blood signature for PCa is concordant with tissue mRNA levels. Measuring blood expression provides a minimally invasive genomic tool that may facilitate prostate cancer management.

Development and validation of an imageless machine-learning algorithm for the initial screening of prostate cancer.

PURPOSE: Prostate specific antigen (PSA) testing is a low-cost screening method for prostate cancer (PCa). However, its accuracy is limited. While progress is being made using medical imaging for PCa screening, PSA testing can still be improved as an easily accessible first step in the screening process. We aimed to develop and validate a new model by further personalizing the analysis of PSA with demographic, medical history, lifestyle parameters, and digital rectal examination (DRE) results. METHODS: Using data from 34,224 patients in the screening arm of the PLCO trial (22,188 for the training set and 12,036 for the validation set), we applied a gradient-boosting model whose features (Model 1) were one PSA value and the personal variables available in the PLCO trial except those that signaled an ex-ante assumption of PCa. A second algorithm (Model 2) included a DRE result. The primary outcome was the occurrence of PCa, while the aggressiveness of PCa was a secondary outcome. ROC analyses were used to compare both models to other initial screening tests. RESULTS: The areas under the curve (AUC) for Model 2 was 0.894 overall and 0.908 for patients with a suspicious DRE, compared to 0.808 for PSA for patients with a suspicious DRE. The AUC for Model 1 was 0.814 compared to 0.821 for PSA. Model 2 predicted 58% more high-risk PCa than PSA ≥4 combined with an abnormal DRE and had a positive predictive value of 74.7% (vs. 50.6%). CONCLUSION: Personalizing the interpretation of PSA values and DRE results with a gradient-boosting model showed promising results as a potential novel, low-cost method for the initial screening of PCa. The importance of DRE, when included in such a model, was also highlighted.

Comprehensive Prostate Fluid-Based Spectral Libraries for Enhanced Protein Detection in Urine.

Biofluids contain molecules in circulation and from nearby organs that can be indicative of disease states. Characterizing the proteome of biofluids with DIA-MS is an emerging area of interest for biomarker discovery; yet, there is limited consensus on DIA-MS data analysis approaches for analyzing large numbers of biofluids. To evaluate various DIA-MS workflows, we collected urine from a clinically heterogeneous cohort of prostate cancer patients and acquired data in DDA and DIA scan modes. We then searched the DIA data against urine spectral libraries generated using common library generation approaches or a library-free method. We show that DIA-MS doubles the sample throughput compared to standard DDA-MS with minimal losses to peptide detection. We further demonstrate that using a sample-specific spectral library generated from individual urines maximizes peptide detection compared to a library-free approach, a pan-human library, or libraries generated from pooled, fractionated urines. Adding urine subproteomes, such as the urinary extracellular vesicular proteome, to the urine spectral library further improves the detection of prostate proteins in unfractionated urine. Altogether, we present an optimized DIA-MS workflow and provide several high-quality, comprehensive prostate cancer urine spectral libraries that can streamline future biomarker discovery studies of prostate cancer using DIA-MS.

Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial.

Importance: Prostate-specific antigen (PSA) screening has potential to reduce prostate cancer mortality but frequently detects prostate cancer that is not clinically important. Objective: To describe rates of low-grade (grade group 1) and high-grade (grade groups 2-5) prostate cancer identified among men invited to participate in a prostate cancer screening protocol consisting of a PSA test, a 4-kallikrein panel, and a magnetic resonance imaging (MRI) scan. Design, Setting, and Participants: The ProScreen trial is a clinical trial conducted in Helsinki and Tampere, Finland, that randomized 61 193 men aged 50 through 63 years who were free of prostate cancer in a 1:3 ratio to either be invited or not be invited to undergo screening for prostate cancer between February 2018 and July 2020. Interventions: Participating men randomized to the intervention underwent PSA testing. Those with a PSA level of 3.0 ng/mL or higher underwent additional testing for high-grade prostate cancer with a 4-kallikrein panel risk score. Those with a kallikrein panel score of 7.5% or higher underwent an MRI of the prostate gland, followed by targeted biopsies for those with abnormal prostate gland MRI findings. Final data collection occurred through June 31, 2023. Main Outcomes and Measures: In descriptive exploratory analyses, the cumulative incidence of low-grade and high-grade prostate cancer after the first screening round were compared between the group invited to undergo prostate cancer screening and the control group. Results: Of 60 745 eligible men (mean [SD] age, 57.2 [4.0] years), 15 201 were randomized to be invited and 45 544 were randomized not to be invited to undergo prostate cancer screening. Of 15 201 eligible males invited to undergo screening, 7744 (51%) participated. Among them, 32 low-grade prostate cancers (cumulative incidence, 0.41%) and 128 high-grade prostate cancers (cumulative incidence, 1.65%) were detected, with 1 cancer grade group result missing. Among the 7457 invited men (49%) who refused participation, 7 low-grade prostate cancers (cumulative incidence, 0.1%) and 44 high-grade prostate cancers (cumulative incidence, 0.6%) were detected, with 7 cancer grade groups missing. For the entire invited screening group, 39 low-grade prostate cancers (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected. During a median follow-up of 3.2 years, in the group not invited to undergo screening, 65 low-grade prostate cancers (cumulative incidence, 0.14%) and 282 high-grade prostate cancers (cumulative incidence, 0.62%) were detected. The risk difference for the entire group randomized to the screening invitation vs the control group was 0.11% (95% CI, 0.03%-0.20%) for low-grade and 0.51% (95% CI, 0.33%-0.70%) for high-grade cancer. Conclusions and Relevance: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT03423303.

Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial.

Importance: The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear. Objective: To evaluate the effect of a single invitation for PSA screening on prostate cancer-specific mortality at a median 15-year follow-up compared with no invitation for screening. Design, Setting, and Participants: This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021. Intervention: Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation). Main Outcomes and Measures: The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis. Results: Of 415 357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P = .03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] ≤6: 2.2% vs 1.6%; P < .001) and localized (T1/T2: 3.6% vs 3.1%; P < .001) disease but not intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45 084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50 336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P = .11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small. Trial Registration: isrctn.org Identifier: ISRCTN92187251.

Advantage of whole-mount histopathology in prostate cancer: current applications and future prospects.

BACKGROUND: Whole-mount histopathology (WMH) has been a powerful tool to investigate the characteristics of prostate cancer. However, the latest advancement of WMH was yet under summarization. In this review, we offer a comprehensive exposition of current research utilizing WMH in diagnosing and treating prostate cancer (PCa), and summarize the clinical advantages of WMH and outlines potential on future prospects. METHODS: An extensive PubMed search was conducted until February 26, 2023, with the search term "prostate", "whole-mount", "large format histology", which was limited to the last 4 years. Publications included were restricted to those in English. Other papers were also cited to contribute a better understanding. RESULTS: WMH exhibits an enhanced legibility for pathologists, which improved the efficacy of pathologic examination and provide educational value. It simplifies the histopathological registration with medical images, which serves as a convincing reference standard for imaging indicator investigation and medical image-based artificial intelligence (AI). Additionally, WMH provides comprehensive histopathological information for tumor volume estimation, post-treatment evaluation, and provides direct pathological data for AI readers. It also offers complete spatial context for the location estimation of both intraprostatic and extraprostatic cancerous region. CONCLUSIONS: WMH provides unique benefits in several aspects of clinical diagnosis and treatment of PCa. The utilization of WMH technique facilitates the development and refinement of various clinical technologies. We believe that WMH will play an important role in future clinical applications.

[Prostate cancer - from the patients' perspective]. / Prostatacancer ur patienternas perspektiv.

Prostate cancer is the most common cancer among Swedish men. To get this diagnose is not only a threat to the men's lives but also to their quality of life because the treatment often affects sexuality, bladder function and bowel function. It is therefore particularly problematic that the rehabilitation of men after treatment for prostate cancer often does not reach the standards set out in the national guidelines. Despite the past years' promotion of standardized cancer care pathways to speed up the process of investigating and treating cancer, the lead times for men who are being investigated for a suspicion of prostate cancer, or are waiting for a planned prostate cancer treatment, are the longest in Swedish cancer care. Patients' organisations are currently active in all 21 Swedish regions to support men with prostate cancer and their near ones. Their national umbrella organisation is increasingly involved in various healthcare organisations, such as the National Prostate Cancer Guidelines Group, and supports clinical prostate cancer research.