Prostate cancer (PCa) is a highly prevalent disease, causing the second largest amount of male cancer deaths worldwide. Currently, the prostate specific antigen (PSA) test remains the standard serum prognostic and diagnostic monitoring biomarker but it lacks specificity and sensitivity. PSA testing can lead to invasive biopsies which can result in under detection of clinically significant disease and potential overtreatment of indolent disease. Promising circulating biomarkers could facilitate less invasive and more accurate tests, but present challenges in robust quantitation and deployment in clinical settings. This work presents the detection of circulating YAP1 nucleic acid, androgen receptor (AR-FL) and AR-V7 mRNA for PCa prognostics in blood plasma from PCa patients. Sensitive detection of circulating YAP1 nucleic acid, AR-FL and AR-V7 mRNA extracted from PCa clinical samples was achieved with a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay. Optimisation of mRNA extraction methodologies for reliable detection of circulating mRNA for RT-LAMP and RT-qPCR detection took place. Multiplex testing of circulating AR-FL mRNA and YAP1 nucleic acid on an ISFET Lab-on-Chip platform was readily achieved with bio-electronic signal detection taking place within 15 min. Detection of AR-V7 and AR-FL mRNA could also be achieved simultaneously with the handheld device. Evaluation of clinical data indicated that circulating YAP1 nucleic acid presence in extracted RNA from the blood plasma of patients correlated with more advanced clinical cancer staging (p = 0.043) and PSA at diagnosis (p = 0.035). The work presents potential for Point-of-Care detection of circulating mRNA from clinical samples for PCa prognostics.

The European Randomized study of screening for prostate cancer (ERSPC) demonstrated a reduction in prostate cancer (PC) mortality via PSA-based screening. We evaluated whether treatments for castration resistant PC vary between the trial arms within the Finnish section (FinRSPC) of the ERSPC.

Clinical data were collected from medical records and national health care databases for all men diagnosed with PC and starting androgen deprivation therapy (ADT) during 1996-2015 at Tampere University Hospital. We evaluated frequencies and durations of treatments for castration resistant PC. Cox regression was used to assess time from ADT initiation to castration resistant PC treatment.

In total, 62 (14.2%) and 116 (15.9%) received at least % cycle of treatment for castration resistant PC in the screening and control-arm, respectively. There were no statistically significant differences in distribution of treatments for castration resistant PC between the study arms at any treatment lines (P-values over 0.05 for first, second and third & later lines of treatment). No difference was found in time to initiation of treatment for castration resistant PC after ADT. (HR: 1.00; 95% [CI], 0.78-1.39; P = 0.998).

Although limited by small sample size and a single-center scope, our findings suggest the mortality result of the FinRSPC is not attributable to differing treatment for castration-resistant PC between the trial arms.

A prostate ultrasound (US) imaging omics model was established to assess its effectiveness in diagnosing prostate cancer (PCa), predicting Gleason score (GS), and determining the likelihood of distant metastasis.

US images of patients with prostate pathology confirmed by biopsy or surgery at our hospital were retrospectively analyzed. Regions of interest (ROI) segmentation, feature extraction, feature screening, and the construction and training of the radiomics model were performed.

Area under the curve (AUC) for the magnetic resonance imaging Prostate Imaging Reporting and Data System (MRI PI-RADS) classification, radiomics alone, and radiomics combined with prostate-specific antigen (PSA) in diagnosing PCa were 70.74%, 71.13%, and 90.47%, respectively. AUCs for the MRI PI-RADS classification, radiomics alone, and radiomics combined with PSA in predicting the GS of PCa were 75.6%, 74.7%, and 88.9%, respectively. Furthermore, AUCs for MRI PI-RADS classification and radiomics alone in predicting distant metastasis of PCa were 66.7% and 90.8%, respectively.

The combination of ultrasonic imaging omics and serum PSA significantly improves the efficiency of PCa diagnosis, GS prediction, and distant metastasis prediction. This method is an important tool for PCa screening and follow-up.

Active surveillance (AS) strategy aims to avoid unnecessary or excessive early treatment in patients at a low risk for prostate cancer (PCa). However, a biomarker that can predict the need for early curative treatment in patients under AS has not been identified to date. In this study, we aimed to investigate the potential of inflammatory biomarkers in predicting the requirement of curative treatment in the early period in patients under AS.

This study included a total of 83 patients with the diagnosis of PCa and under AS. Patient age, prostate-specific antigen (PSA) level, prostate volume (PV), PSA density (PSAD), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic immune-inflammation index (SII) and follow-up period were compared between the groups.

There was a significant difference between the two groups in terms of PSAD, NLR, PLR and SII (p = 0.037, p = 0.046, p = 0.008, p = 0.004 and p = 0.005, respectively). The cut-off value determined by performing ROC analysis to evaluate the levels that predict the need for curative treatment before AS was 0.125 for PSAD (sensitivity: 61.8%, specificity: 61.2%), 2.01 for NLR (sensitivity: 67.6%, specificity: 55.1%), 115.49 for PLR (sensitivity: 73.5%, specificity: 59.2%) and 465.40 for SII (sensitivity: 70.6%, specificity: 59.2%).

The analysis of PSAD, NLR, PLR and SII before making the decision to conduct AS can guide clinicians regarding curative treatment in the early period.

Smoking increases the risk of bladder and kidney cancers and is associated with a poorer prognosis in prostate cancer (PCa) patients, which poses a significant health and socioeconomic burden. Understanding the epidemiologic trends of urological cancers attributable to smoking is critical to developing targeted prevention strategies. This study examines global trends in the three urological cancers attributable to smoking from 1990 to 2021 and projects future trends over the next two decades.

Data were obtained from the Global Burden of Disease (GBD) 2021. Metrics included deaths, disability-adjusted life years (DALYs), age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR), with uncertainty intervals (UIs). Burden comparisons were stratified by sex, age, and sociodemographic index (SDI). Temporal trends were analyzed using Joinpoint regression to calculate annual percentage change (APC) and average annual percentage change (AAPC), with 95% confidence intervals (CIs). Future trends were predicted using the autoregressive integrated moving average (ARIMA) model.

Compared with 1990, the number of deaths of bladder cancer, kidney cancer and PCa attributable to smoking increased by 43%, 67%, and 31%, and the number of DALYs increased by 31%, 52%, and 29% in 2021. However, the corresponding age-standardized rates showed a downward trend (AAPCASMR of bladder cancer, -1.53; AAPCASDR of bladder cancer, -1.68; AAPCASMR of kidney cancer, -0.89; AAPCASDR of kidney cancer, -1.11; AAPCASMR of PCa, -2.10; AAPCASDR of PCa, -1.97). The burden was higher among males than females, with the highest burden observed in high-SDI regions. The ASMR and ASDR were found to have a non-linear positive correlation with SDI (RASMR of bladder cancer=0.574, p<0.001; RASDR of bladder cancer=0.580, p<0.001; RASMR of kidney cancer=0.792, p<0.001; RASDR of kidney cancer=0.783, p<0.001; RASMR of PCa=0.417, p<0.001; RASDR of PCa=0.436, p<0.001), although the greatest improvements over the past three decades were observed in high-SDI regions. Joinpoint regression analysis indicated a downward trend in global deaths and DALYs burden, and the ARIMA model predicted that the burden of related diseases will continue to decline through 2041 (ASMRbladder cancer=0.44; ASDRbladder cancer=8.56; ASMRkidney cancer=0.13; ASDRkidney cancer=2.82; ASMRPCa=0.28; ASDRPCa=4.28).

Smoking has imposed a substantial disease burden on urological cancers over the past three decades. While overall ASDR and ASMR are declining, the disease burden remains high among men, especially those in high-SDI areas. This emphasizes the need for increased tobacco control for these populations or regions.

The objective of this study is to analyse the perspectives of screening candidates and healthcare professionals on shared decision-making (SDM) in prostate cancer (PCa) screening using the prostate-specific antigen (PSA) test.

Descriptive qualitative study (May-December 2022): six face-to-face focus groups and four semistructured interviews were conducted, transcribed verbatim and thematically analysed using ATLAS.ti software.

Data were obtained as part of the project PROSHADE (Decision Aid for Promoting Shared Decision Making in Opportunistic Screening for Prostate Cancer) to develop a tool for SDM in PCa screening with PSA testing in Spain.

A total of 27 screening candidates (three groups of men: 40-50 years old; 51-60 years old and 61-80 years old), 25 primary care professionals (one group of eight nurses and two groups of physicians: one with more and one with less than 10 years of experience), and four urologists. Focus groups for patients and healthcare professionals were conducted separately.

Participants' perceptions of shared decision-making related to PSA opportunistic screening, including their understanding, preferences, and attitudes.

Three themes were generated: (1) perceptions of SDM, (2) perceptions of PSA testing and (3) perceptions of SDM regarding PCa screening. Theme 1: screening candidates valued SDM when it included clear information and empowered them. There was consensus with primary care health professionals on this point, although their knowledge and implementation of SDM varied. Theme 2: candidates were divided on PSA testing; some trusted it for early detection, while others expressed scepticism due to concerns about false positives and invasive procedures, reflecting gaps in accessible information. Theme 3: professionals across primary and specialised care stressed the need for standardised SDM protocols. Primary care physicians were particularly concerned that PSA decisions align with scientific evidence and urologists recognised SDM as valuable in PSA testing only if it was adequately explained to each patient. Barriers to implementing SDM included insufficient coordination across care levels, lack of consensus-driven protocols and limited clinical time.

While patients expect comprehensive information, primarily based on practice to achieve empowerment, healthcare professionals face obstacles such as limited time and insufficient coordination between primary care and urology. All stakeholders agree on the importance of evidence-based tools to reinforce effective SDM and enhance collaboration across urologists and primary care in the context of PSA testing.

Active Surveillance (AS) for Prostate Cancer (PCa) requires regular follow-up, raising concerns that socioeconomic barriers may result in underutilization or decreased adherence to AS guidelines. We examined the relationship between socioeconomic factors, measured by the Area Deprivation Index (ADI), and AS habits in a contemporary North American cohort.

We included all the patients aged ≤ 75 years and diagnosed with low (ISUP GG = 1, PSA ≤ 10 ng/mL and cT1N0M0) and intermediate risk (ISUP GG = 2, PSA 10-20 ng/mL or cT2N0M0) PCa at Henry Ford Health (HFH) between 1995 and 2023. An ADI score was assigned to each patient based on their residential census block group, ranked as a percentile of deprivation relative to the national level. The higher the ADI, the more the area has a socioeconomic disadvantage. Logistic regression analysis tested the impact of ADI on AS utilization and adherence to AS guidelines. Only patients who underwent at least 1 PSA test per year and at least 1 biopsy every 4 years were considered as "adherent to guidelines".

Our final cohort consisted of 4376 patients eligible for AS, 919 of whom actually underwent AS. Older patients (66 vs. 62 years, p < 0.0001) and those diagnosed in more recent years (2017 vs. 2010, p < 0.0001) had higher probability to undergo AS. Moreover, patients in the AS group more likely to be NHB (36% vs. 25%, p < 0.0001), had higher ADI score (61 vs. 55, p < 0.0001), more comorbidities according to Charlson Comorbidity Index (CCI) score, (19.5%% vs. 13.8%, p < 0.0001) and higher probability to harbor low risk PCa (65.7% vs. 26.6%, p < 0.0001), compared to patients who underwent active treatment. Among the 919 patients in AS, only 410 were "adherent to guidelines". Patients following guidelines were more likely to be NHW (64.1% vs. 52.8%, p < 0.003), and had lower ADI percentile (55.5 vs. 66, p < 0.0003). Furthermore, AS patients managed according to the prevailing guidelines received more PSAs tests (1.8 vs. 0.8, p < 0.0001) and prostate biopsies (0.3 vs. 0.0, p < 0.0001) per year, thus reporting both higher upgrading rates during AS (35.6% vs. 23%, p < 0.0001) and an increased probability to undergo active treatment (48% vs. 27%, p < 0.0001). At MVA, patients with a higher ADI score reported higher probability to undergo AS (OR: 1.06, 95% CI: 1.02-1.10, p = 0.004), but at the same time they were less likely to follow AS' guidelines (OR: 0.94, 95% CI: 0.89-0.99, p = 0.02).

Patients in the most deprived areas had a higher likelihood of undergoing AS but were more prone to receive guideline-discordant care. This should be taken into consideration by physicians when recommending AS for those men living in the least advantaged neighborhoods. Our study highlights the need for targeted community reforms to enhance proper and informed AS utilization among socioeconomically disadvantaged populations.

PSA screening remains a pivotal tool for early prostate cancer (PCa) detection. International guidelines rely on evidence from three major randomized clinical trials: ERSPC, PLCO, and CAP. We aim to examine the percentage of patients in real-world practice who get PSA screening as defined by each of the aforementioned trials. Moreover, we seek to evaluate if the different PSA screening patterns have a different impact on PCa incidence and its features at diagnosis.

Our institutional database was queried to identify men aged 55-69 who received at least one PSA test, did not develop PCa or die within 6 years of the initial test, had follow-up within our system at least 6 years after the initial test, and did not have a previous PCa diagnosis. A total of 28,612 patients met our selection criteria. We categorized patients into three distinct PSA screening patterns based on testing frequency (PLCO: 1 PSA test per year for 6 years; ERSPC: 2 or 3 PSA tests over 6 years; CAP: 1 PSA test over 6 years). Our primary outcomes were any PCa incidence and clinically significant PCa (csPCa, defined as ISUP ≥ 3) incidence. Secondary outcome was the rate of cM1 disease. Competing risks cumulative incidence curves were used to depict any PCa and csPCa diagnosis with death before a diagnosis considered a competing risk. Multivariable competing risks regression (CRR) was used to assess the impact of the different screening patterns on any PCa and csPCa incidence, after adjusting for confounding factors.

The most prevalent PSA screening pattern was ERSPC, including 15,530 patients (54.3%), followed by the CAP with 9003 patients (31.5%), and the PLCO with only 4079 patients (14.2%). The median (IQR) follow-up time was 4.8 (1.7-10.8) years. At 10 years, any PCa incidence was 7.4% versus 5.6% versus 2.5% for PLCO versus ERSPC versus CAP, respectively, while for csPCa, the rates were 2.5% versus 2.5% versus 1.2% (both p < 0.001). On multivariable analyses, PLCO and ERSPC patterns were associated with 2.92-fold and 2.31-fold higher risks from 1 year to the next of any PCa diagnosis, respectively, compared to CAP pattern (both p < 0.001). Similarly, patients with PLCO and ERSPC patterns had 2.07-fold and 2.31-fold higher risks, respectively, of csPCa diagnosis compared to CAP pattern (both p < 0.001). In men with PCa diagnosis, the rates of cM1 disease were respectively 1.7% vs 5.6% vs 10.8% for PLCO versus ERSPC versus CAP, respectively (p = 0.0009).

We observed that the most common screening pattern in "real-world" clinical practice is close to what ERSPC recommend, and this pattern seems to achieve a reasonable reduction in the risk of advanced PCa, while limiting overdiagnosis.

We aim to critically assess Microultrasound (mUS) clinical performance in an outpatient setting, focusing on its ability to reduce unnecessary diagnostic procedures, potentially reshape prostate cancer (PCa) diagnostic protocols, and increase the ability to rule out clinically significant (Gleason Score ≥ 3 + 4) PCa (csPCa).

Between November 2018 and April 2022, we conducted a prospective study involving men who underwent mUS examination due to clinical symptoms, PSA elevation, or opportunistic early detection of PCa. Experienced urologists performed mUS assessments in an outpatient setting using the prostate risk identification using micro-ultrasound (PRI-MUS) protocol to identify lesions suspicious of csPCa (PRI-MUS score ≥ 3). Men with negative mUS results were followed through consistent phone follow-up calls and visits until October 2023 to assess their diagnostic and therapeutic pathways. Using Cox regression models adjusted for PSA levels, DRE results, age, and previous biopsy history, we calculated the hazard ratio (HR) for biopsy-free (BFS), defined as the time from mUS to biopsy or last follow-up, cancer-free survival (CFS), and clinically significant cancer-free survival (csCFS) within the cohort based on mUS results.

Overall, 425 men were enrolled. The median (IQR) age was 66 (59-72) years, PSA levels were 5.7 (4.0-7.9) ng/mL, prostate volume was 44 (31.5-62.1) mL, and the median follow-up was 39 months (27-53). mUS identified lesions suggesting csPCa in 201/425 (47.3%) men. Overall, mUS resulted negative in 224/425 (52.7%) men, of whom 207/224 (92.4%) did not undergo subsequent mpMRI, while 22/224 (9.8%) proceeded with mpMRI according to the referring physician's decision. The latter detected suspicious lesions in 12/22 cases (54.5%), but only 2/12 (16.7%) were confirmed by biopsy as csPCa. Among those with negative mUS results, 192/224 (85.7%) men avoided additional biopsies during follow-up. Men with negative mUS results exhibited superior BFS (aHR: 0.17; p < 0.001), CFS (aHR:0.12; p < 0.001), and csCFS (aHR:0.09; p < 0.001) survival rates compared to their mUS-positive counterparts.

Our findings suggest that mUS can potentially refine patient stratification and transform PCa screening and diagnostic protocols. Pending validation by other studies, a wider implementation of mUS could optimize resource allocation, minimize wastage, and reserve additional costly tests.

This meta-analysis aimed to evaluate the predictive value of multiparametric magnetic resonance imaging (mpMRI), specifically T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) maps, in the pathological grading of prostate cancer.

A comprehensive literature search was conducted across multiple databases, including PubMed, the China National Knowledge Infrastructure dataset, Web of Science, Springer Link and Cochrane Library. Studies evaluating the use of mpMRI for prostate cancer grading were included. The quality of the included studies was assessed using the risk of bias tool. Meta-analyses were performed to calculate pooled areas under the curve (AUC) and prostate cancer detection rates.

Seven studies met the inclusion criteria, comprising 843 patients in the experimental group and 962 in the control group. The meta-analysis revealed a significant improvement in diagnostic performance with mpMRI, with a pooled mean difference in AUC of 0.10 (95% confidence interval [CI]: 0.04-0.16, p = 0.002) favouring the mpMRI group. The odds ratio for prostate cancer detection was 2.60 (95% CI: 1.57-4.29, p = 0.0002), indicating a higher detection rate with mpMRI compared with standard techniques. Substantial heterogeneity was observed among the studies (I² = 73% for AUC and 66% for detection rate).

This meta-analysis demonstrates that mpMRI, particularly T2WI and ADC imaging, has a significant predictive value in the pathological grading of prostate cancer. The technique shows improved diagnostic accuracy and higher cancer detection rates compared with conventional methods. However, the substantial heterogeneity among studies suggests that standardisation of mpMRI protocols and interpretation criteria is needed.

Reliable imaging techniques to assist in the diagnosis of prostate cancer (PCa) were not available until the advent of multiparametric magnetic resonance imaging (mpMRI), which has been shown to improve the detection and characterization of prostate lesions. In 2018, the Australian Medicare Benefits Schedule (MBS) extended its coverage to include mpMRI for PCa diagnosis and surveillance.

This retrospective cohort study evaluated the impact of the MBS item expansion on mpMRI referral patterns, sources, yields and patient demographics at a Victorian center. Referrals for prostate mpMRI were analysed over a 30-month period before and after a 54-month period following the MBS update. All indications were considered, without exclusion criteria. Baseline continuous variables (age, PSA, PSA density, prostate volume, PIRADS score) were summarized using medians and interquartile ranges. Categorical variables were expressed as numbers and proportions. Statistical analyses included Mann-Whitney U-tests and T-tests for continuous variables, preceded by a Shapiro-Wilk normality test. GraphPad Prism 6 (San Diego, California, USA) facilitated data analysis.

Following the MBS update, there was a yearly average increase of 13.8% in mpMRI referrals, notably with a 125% surge in urologist referrals. The proportion of diagnostic scans rose from 42% pre-update to 70% post-update. These results highlight enhanced referral pathways and specific clinical applications of mpMRI after the MBS expansion.

In conclusion, federal funding led to a notable rise in mpMRI utilization. Continued monitoring and analysis of the role of mpMRI in PCa diagnostic algorithms are imperative to optimize its benefits and enhance clinical outcomes.

Prostate cancer remains a leading malignancy among men in the United States. While prostate-specific antigen (PSA) screening improves early detection, it also leads to over-diagnosis and over-treatment. Biomarkers offer a promising solution for risk stratification and guiding treatment decisions. This review examines the cost-effectiveness of serum, urine, and tissue-based biomarkers to assess their impact on healthcare expenditures and clinical decision-making.

Serum-based biomarkers like 4Kscore and PHI reduce unnecessary biopsies and healthcare costs. Urine-based biomarkers, including SelectMDx and ExoDx Prostate IntelliScore (EPI), have shown potential to optimize prostate cancer detection while being more cost-effective than some serum-based alternatives. Tissue-based biomarkers, such as OncotypeDx and Decipher, help in treatment selection, though their economic impact varies. Economic analyses suggest that biomarkers can enhance clinical decision-making while reducing healthcare expenditures, but real-world validation remains limited.

Prostate cancer biomarkers improve risk stratification and may lower healthcare costs. However, variations in cost-effectiveness, reimbursement policies, and guideline recommendations limit widespread adoption. Prospective studies are needed to validate real-world cost savings and refine biomarker integration into clinical practice. Addressing financial and policy challenges is essential to ensure equitable access and maximize their impact on prostate cancer management.

Background: The testosterone-to-PSA (T/PSA) ratio has been proposed as a novel biomarker to enhance the diagnostic specificity of prostate-specific antigen (PSA) in prostate cancer (PCa) detection. The objective of this study was to evaluate the diagnostic performance of the T/PSA ratio in distinguishing PCa from benign conditions in men undergoing prostate biopsy. Materials and Methods: Eighty men who underwent systematic and targeted transrectal prostate biopsy were retrospectively studied. Clinical variables included serum PSA, testosterone, prostate volume, PSA density (PSAD), and the T/PSA ratio. Diagnostic accuracy was assessed using Receiver Operating Characteristic (ROC) curve analysis. Optimal cutoffs were determined using Youden's index. Results: PCa was diagnosed in 53 patients (66.3%). Median T/PSA was significantly lower in PCa versus non-PCa patients (0.46 vs. 0.86; p < 0.01). T/PSA showed good diagnostic performance (AUC = 0.75) with an optimal cutoff of 0.81 (sensitivity: 59.3%, specificity: 86.8%). In patients with PSA ≤10 ng/mL, T/PSA retained strong discriminatory ability (AUC = 0.76), with sensitivity and specificity of 82.4% and 72.7%, respectively. Among all parameters, PSAD showed the highest diagnostic accuracy (AUC = 0.813). T/PSA was not significantly associated with Gleason score (p = 0.48). Conclusions: The T/PSA ratio is a clinically accessible and cost-effective biomarker that may improve PCa risk stratification and reduce unnecessary biopsies, particularly in patients with borderline PSA levels. Although it does not correlate with tumor aggressiveness, its combination with PSAD could enhance diagnostic accuracy in routine clinical practice.

Prostate cancer is the most common nonskin cancer in men in the US, with an estimated 299 010 new cases and 35 250 deaths in 2024. Prostate cancer is the second most common cancer in men worldwide, with 1 466 680 new cases and 396 792 deaths in 2022.

The most common type of prostate cancer is adenocarcinoma (≥99%), and the median age at diagnosis is 67 years. More than 50% of prostate cancer risk is attributable to genetic factors; older age and Black race (annual incidence rate, 173.0 cases per 100 000 Black men vs 97.1 cases per 100 000 White men) are also strong risk factors. Recent guidelines encourage shared decision-making for prostate-specific antigen (PSA) screening. At diagnosis, approximately 75% of patients have cancer localized to the prostate, which is associated with a 5-year survival rate of nearly 100%. Based on risk stratification that incorporates life expectancy, tumor grade (Gleason score), tumor size, and PSA level, one-third of patients with localized prostate cancer are appropriate for active surveillance with serial PSA measurements, prostate biopsies, or magnetic resonance imaging, and initiation of treatment if the Gleason score or tumor stage increases. For patients with higher-risk disease, radiation therapy or radical prostatectomy are reasonable options; treatment decision-making should include consideration of adverse events and comorbidities. Despite definitive therapy, 2% to 56% of men with localized disease develop distant metastases, depending on tumor risk factors. At presentation, approximately 14% of patients have metastases to regional lymph nodes. An additional 10% of men have distant metastases that are associated with a 5-year survival rate of 37%. Treatment of metastatic prostate cancer primarily relies on androgen deprivation therapy, most commonly through medical castration with gonadotropin-releasing hormone agonists. For patients with newly diagnosed metastatic prostate cancer, the addition of androgen receptor pathway inhibitors (eg, darolutamide, abiraterone) improves survival. Use of abiraterone improved the median overall survival from 36.5 months to 53.3 months (hazard ratio, 0.66 [95% CI, 0.56-0.78]) compared with medical castration alone. Chemotherapy (docetaxel) may be considered, especially for patients with more extensive disease.

Approximately 1.5 million new cases of prostate cancer are diagnosed annually worldwide. Approximately 75% of patients present with cancer localized to the prostate, which is associated with a 5-year survival rate of nearly 100%. Management includes active surveillance, prostatectomy, or radiation therapy, depending on risk of progression. Approximately 10% of patients present with metastatic prostate cancer, which has a 5-year survival rate of 37%. First-line therapies for metastatic prostate cancer include androgen deprivation and novel androgen receptor pathway inhibitors, and chemotherapy for appropriate patients.

Prostate cancer is one of the most common tumors in men, with its incidence and mortality rates continuing to rise year by year. Prostate-specific antigen (PSA) is the most commonly used screening indicator, but its lack of specificity leads to overdiagnosis and overtreatment. Therefore, identifying new biomarkers related to prostate cancer is crucial for the early diagnosis and treatment of prostate cancer.

This study utilized datasets from the Gene Expression Omnibus (GEO) to screen for differentially expressed genes (DEGs) and employed Weighted Gene Co-expression Network Analysis (WGCNA) to identify driver genes highly associated with prostate cancer within the modules. The intersection of differentially expressed genes and driver genes was taken, and Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed. Furthermore, a machine learning algorithm was used to screen for core genes and construct a diagnostic model, which was then validated in an external validation dataset. The correlation between core genes and immune cell infiltration was analyzed, and Mendelian randomization (MR) analysis was conducted to identify biomarkers closely related to prostate cancer.

This study identified six core biomarkers: SLC14A1, ARHGEF38, NEFH, MSMB, KRT23, and KRT15. MR analysis demonstrated that MSMB may be an important protective factor for prostate cancer. In q-PCR experiments conducted on tumor tissues and adjacent non-cancerous tissues from prostate cancer patients, it was found that: compared to the adjacent non-cancerous tissues, the expression level of ARHGEF38 in prostate cancer tumor tissues significantly increased, while the expression levels of SLC14A1, NEFH, MSMB, KRT23, and KRT15 significantly decreased. To further validate these findings at the protein level, we conducted Western blot analysis, which corroborated the q-PCR results, demonstrating consistent expression patterns for all six biomarkers. IHC results confirmed that ARHGEF38 protein was highly expressed in tumor tissues, while MSMB expression was markedly reduced.

Our study reveals that SLC14A1, ARHGEF38, NEFH, MSMB, KRT23, and KRT15 are potential diagnostic biomarkers for prostate cancer, among which MSMB may play a protective role in prostate cancer.

Urological diseases and their varied forms of management warrant special attention in the setting of climate change. Regarding urological cancers, climate change will probably increase the incidence and severity of cancer diagnoses through exposures to certain environmental risk factors, while simultaneously disrupting cancer care delivery and downstream outcomes. Regarding benign urological diseases, a burgeoning body of work exists on climate-related heat waves, dehydration, urolithiasis, renal injury and infectious and vector-borne diseases. Adding to the potential effect on disease pathogenesis, many patients with urological diseases undergo high-tech, resource-intensive interventions, such as robotic surgery, and entail intensive longitudinal assessments over many years. These features incur a considerable carbon footprint, generate substantial waste, and can introduce vulnerabilities to climate-related weather events. Links exist between planetary health (the health of humans and the natural systems that support our health), climate change and urological disease and urological care providers face many challenges in the era of anthropogenic climate change. The next steps and priorities for research, management, and health care delivery include identification and prioritization of health care delivery strategies to minimize waste and carbon emissions, while supporting climate resilience. Examples include supporting telemedicine, limiting low-value care, and building resilience to minimize impacts of climate-related disasters to prepare for the challenges ahead.

Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles.

Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion.

The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88-0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column.

Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

Fluorine-18 prostate-specific membrane antigen-1007 positron emission tomography/computed tomography (18F-PSMA-1007 PET/CT) has been shown to be superior to multiparametric magnetic resonance imaging (MRI) for the locoregional staging of intermediate-risk and high-risk prostate tumors. This study aims to evaluate whether it is also superior in estimating tumor parameters, such as three-dimensional spatial localization and volume.

134 participants underwent 18F-PSMA-1007 PET/CT and MRI prior to radical prostatectomy as part of the validating paired-cohort Next Generation Trial (NCT05141760). MRI, 18F-PSMA-1007 PET/CT, and final pathology were independently assessed by blinded radiologists, nuclear medicine physicians, and pathologists, respectively. Individual tumor nodules were measured in three dimensions and cognitively registered to 38 segment prostate diagrams as per PI-RADSv2.1. Correct spatial localization was compared using McNemar test and estimation of tumor volumes were compared using linear regression and partial F-test.

286 tumor nodules were identified by final histopathology. 18F-PSMA-1007 PET/CT was superior to MRI for correct localization (186 [65.0%] vs 134 [46.9%], p < 0.001) and tumor volume estimation (R2 = 0.545 vs 0.431, p < 0.001). Larger tumors and higher Gleason Grade Group (GGG) were associated with correct localization by 18F-PSMA-1007 PET/CT (OR = 2.05, p < 0.001 for tumor volume and OR = 4.92, p < 0.01 for ≥ GGG3) and MRI (OR = 1.81, p < 0.001 for tumor volume and OR = 11.67, p < 0.001 for ≥ GGG3).

18F-PSMA-1007 PET/CT outperforms MRI for determination of three-dimensional spatial localization and volume of prostate tumors. These findings support the use of 18F-PSMA-1007 PET/CT prior to definitive treatment of localized prostate cancers.

Recognizing the limitations of prostate-specific antigen (PSA) screening and the morbidity of prostate biopsies, several blood- and urine-based biomarkers have been proposed for pre-biopsy risk stratification. These assays aim to reduce the frequency of unnecessary biopsies (i.e., negative or Grade Group 1 [GG1]) while maintaining highly sensitive detection of clinically significant cancer (GG ≥ 2) prostate cancer.

We reviewed the literature describing the use of currently available blood- and urine-based biomarkers for detection of GG ≥ 2 cancer, including the Prostate Health Index (PHI), 4Kscore, MyProstateScore (MPS), SelectMDx, ExoDx Prostate Intelliscore (EPI), and IsoPSA. To facilitate clinical application, we focused on the use of biomarkers as a post-PSA secondary test prior to biopsy, as proposed in clinical guidelines. Our outcomes included test performance measures-sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV)-as well as clinical outcomes resulting from biomarker use (i.e., unnecessary biopsies avoided, GG ≥ 2 cancers missed).

Contemporary validation data (2015-2023) reveal that currently available biomarkers provide ~15-50% specificity at a sensitivity of 90-95% for GG ≥ 2 PCa. Clinically, this indicates that secondary use of biomarker testing in men with elevated PSA could allow for avoidance of up to 15-50% of unnecessary prostate biopsies, while preserving detection of 90-95% of GG ≥ 2 cancers that would be detected under the traditional "biopsy all" approach.

The contemporary literature further supports the proposed role of post-PSA biomarker testing to reduce the use of invasive biopsy while maintaining highly sensitive detection of GG ≥ 2 cancer. Questions remain regarding the optimal application of biomarkers in combination or in sequence with mpMRI.

To examine the frequency and rate at which transfeminine patients receive prostate-specific antigen testing compared to a matched cisgender cohort.

Patients with prostates who had encounters in our health system, are currently age 46 or older, and who are alive were included in our study. Transfeminine patients were identified through diagnosis codes and chart review. A 1:5 matched cohort was created based on patient age, race, and area deprivation index. Conditional logistic regression was done to compare odds of receiving any testing and Poisson regression was done to compare the total tests.

A total of 275,112 patients were included in the study, of which 315 were confirmed to be transfeminine. A well-matched 1:5 propensity-matched cohort was created. Our results suggest that transfeminine patients were 0.28 (95% CI 0.20-0.38, P <.001) times as likely as cisgender patients to receive at least 1 PSA test at our institution and received only 32% (95% CI 27%-37%, P <.001) as many total PSA tests.

Until more is known about the best practices for PSA testing in the transfeminine population, these patients should receive PSA testing. However, our results suggest that transfeminine patients are significantly less likely to receive any testing and significantly fewer tests in their lifetimes, which may represent a significant healthcare disparity.

The potential oncogenic role of Baculoviral inhibitor of apoptosis (IAP) Repeat-Containing (BIRC) genes in prostate cancer (PCa) has yet to be fully investigated. Two genes associated with disease recurrence, BIRC5 and BIRC7, were identified through survival analysis, and prostate cancer patients were categorized into two subtypes, C1 and C2, based on these genes. We performed survival analyses to assess the relationship between subtypes and the prognosis of PCa. Single-cell dataset analysis was used to identify specific cell types with enriched expression of BIRC family genes. Our findings show that BIRC5 and BIRC7 exhibit higher expression in PCa tissues compared to non-cancerous tissues. High expression of BIRC5 and BIRC7 independently correlates with an adverse prognosis in PCa. The analysis of mechanisms reveals that the differentially expressed genes impact signaling pathways associated with cancer and immunity. BIRC5/BIRC7 correlate with several immune cells infiltrating levels including T cells and macrophages. Furthermore, our research indicates that elevated expression of BIRC5 is associated with immune infiltration in PCa. These findings highlight the potential of BIRC5/BIRC7 or C1 subtype as prognostic biomarkers, offering new insights into possible targets for the development of therapeutic biomarkers and immunotherapeutic for PCa.

Prognostic transcriptomic signatures for prostate cancer (PCa) often overlook the cellular origin of expression changes, an important consideration given the heterogeneity of the disorder. Current clinicopathological factors inadequately predict biochemical recurrence, a critical indicator guiding post-treatment strategies following radical prostatectomy. To address this, we conducted a meta-analysis of four large-scale PCa datasets and found 33 previously reported PCa-associated genes to be consistently up-regulated in prostate tumours. By analysing single-cell RNA-sequencing data, we found these genes predominantly as markers in epithelial cells. Subsequently, we applied 97 advanced machine-learning algorithms across five PCa cohorts and developed an 11-gene epithelial expression signature. This signature robustly predicted biochemical recurrence-free survival (BCRFS) and stratified patients into distinct risk categories, with high-risk patients showing worse survival and altered immune cell populations. The signature outperformed traditional clinical parameters in larger cohorts and was overall superior to published PCa signatures for BCRFS. By analysing peripheral blood data, four of our signature genes showed potential as biomarkers for radiation response in patients with localised cancer and effectively stratified castration-resistant patients for overall survival. In conclusion, this study developed a novel epithelial gene-expression signature that enhanced BCRFS prediction and enabled effective risk stratification compared to existing clinical- and gene-expression-derived prognostic tools. Furthermore, a set of genes from the signature demonstrated potential utility in peripheral blood, a tissue amenable to minimally invasive sampling in a primary care setting, offering significant prognostic value for PCa patients without requiring a tumour biopsy.

Overdiagnosis in PSA-based prostate cancer (PCa) screening is primarily studied in younger, healthier populations from clinical trials. This study aimed to evaluate the probability of overdiagnosis in PCa screening within a clinical practice context, focusing on its relationship with PSA levels, Gleason scores, and subsequent clinical procedures.

We conducted a retrospective cohort analysis of 1,070 asymptomatic men over 40 years old diagnosed with PCa between 2004 and 2022, following a positive PSA test. The patients were followed until December 31, 2022, with a median follow-up time of 5.7 years (IQR 3.2-8.6). The primary outcome was the probability of overdiagnosis, assessed through life expectancy and the Charlson Comorbidity Index, considering lead times of 5, 10, and 15 years.

We found that patients with PSA levels >10 ng/dL and/or Gleason scores ≥8 were generally older and had more comorbidities than those with PSA levels 4-10 ng/dL and/or Gleason scores ≤7. The probability of overdiagnosis was significantly higher in patients with PSA levels >10 ng/dL (41.4%, IQR 21.5-73.9) and Gleason scores ≥8 (42.6%, IQR 14.9-38.9), compared to those with PSA levels 4-10 ng/dL (20.1%, IQR 12.8-30.4) and Gleason scores ≤7 (26.6%, IQR 23.6-68.6). Notably, 71.7% of patients did not receive pharmacological treatment. Patients with higher PSA levels also experienced greater radiation exposure from diagnostic imaging (median 19.9 mSv vs. 14.7 mSv, p = 0.004).

These findings underscore the high likelihood of overdiagnosis in older patients with elevated PSA levels and significant comorbidities, highlighting the need for careful consideration of patient comorbidities before PSA testing.

To validate the use of estimated post-enucleation prostate-specific antigen (EPEPSA) and extra-transitional zone density (EtzD) in predicting clinically significant prostate cancer (csPC) in a Taiwanese cohort.

Between August 2017 and June 2022, patients with PSA levels <20 ng/mL who underwent prostate biopsy at the National Taiwan University Hospital were enrolled. According to a model built by a previous cohort, EPEPSA was calculated using the following formula: 1.068 + 0.016 × PSA +0.004 × prostate volume - 1.02 × adenoma volume/prostate volume. The EtzD was calculated by dividing the EPEPSA value by the peripheral zone volume, and csPC was defined as favorable-intermediate, unfavorable-intermediate, high, very-high-risk or metastatic prostate cancer, according to the National Comprehensive Cancer Network guidelines.

A total of 229 (32.1%) patients with csPC were diagnosed in the enrolled cohort (N = 714). Both EPEPSA and EtzD were statistically associated with csPC prediction (odds ratio [OR]: 29.56, 95% confidence interval [CI]: 5.41-161.6; OR: 4.11, 95% CI: 2.20-7.67, respectively). However, PSA density (PSAD) (area under the curve [AUC]: 0.77) still had the best predictive value compared with PSA, EPEPSA, and EtzD (AUC: 0.68, 0.64, and 0.67, respectively; all p < 0.05). There were no significant differences in the csPC prediction values of EPEPSA, EtzD, and PSA.

Although EPEPSA and EtzD can predict csPC in Taiwan, they failed to outperform PSAD and PSA. Therefore, PSAD is the best predictor for csPC.

Prostate cancer (PCa) is the most common male malignancy in the western world. Many men (40%) are diagnosed with localised low or intermediate-risk PCa, which is suitable for active surveillance (AS). AS affords careful monitoring to identify changes in otherwise non-life-threatening cancers. While AS reduces overtreatment (and quality of life impact), long-term compliance can be poor, with many men undergoing radical treatment after starting AS.

Finasteride in Active Surveillance for men with low and intermediate-risk prostate cancer (FINESSE) is a prospective, open-label, two-arm, phase 3 trial, in which men with low or intermediate PCa are randomised (1:1) to receive AS with or without finasteride (5 mg once a day for 2 years). Randomisation is stratified by age and PCa risk. AS includes regular prostate-specific antigen testing, MRI scans and the offer of repeat biopsy (at 3 years, or if imaging suggests progression). Additional MRI scans and/or biopsies will be performed for biochemical or clinical indications. We aim to recruit 550 men (aged 50 to 75 years) from up to eight sites. Active outpatient follow-up will be for 3-5 years (depending on date recruited), followed by passive registry-based follow-up for up to 10 years. Primary outcome is adherence to AS. Secondary outcomes include rates and type of disease progression, treatments received (for PCa and benign prostatic enlargement), overall and PCa-specific mortality, an understanding of patients/professionals views of this approach and health-related quality of life. An external panel of experts blinded to allocation will review all AS cessation and progression events. Trial pathologist's and radiologist's, blinded to allocation, will review representative cases. Analysis is Intention to Treat.

The study received Health Research Authority and South-Central Oxford Research Ethics Committee (14/12/2021: 21/SC/0349) and CTA/MHRA (29/12/2021: 21304/0274/001-0001) approvals. Results will be made available to providers and researchers via publicly accessible scientific journals.

ISRCTN16867955.

In prostate cancer (PCa), risk calculators have been proposed, relying on clinical parameters and magnetic resonance imaging (MRI) enable early prediction of clinically significant cancer (CsPCa). The prostate imaging-reporting and data system (PI-RADS) is combined with clinical variables predominantly based on logistic regression models. This study explores modeling using regularization techniques such as ridge regression, LASSO, elastic net, classification tree, tree ensemble models like random forest or XGBoost, and neural networks to predict CsPCa in a dataset of 4799 patients in Catalonia (Spain). An 80-20% split was employed for training and validation. We used predictor variables such as age, prostate-specific antigen (PSA), prostate volume, PSA density (PSAD), digital rectal exam (DRE) findings, family history of PCa, a previous negative biopsy, and PI-RADS categories. When considering a sensitivity of 0.9, in the validation set, the XGBoost model outperforms others with a specificity of 0.640, followed closely by random forest (0.638), neural network (0.634), and logistic regression (0.620). In terms of clinical utility, for a 10% missclassification of CsPCa, XGBoost can avoid 41.77% of unnecessary biopsies, followed closely by random forest (41.67%) and neural networks (41.46%), while logistic regression has a lower rate of 40.62%. Using SHAP values for model explainability, PI-RADS emerges as the most influential risk factor, particularly for individuals with PI-RADS 4 and 5. Additionally, a positive digital rectal examination (DRE) or family history of prostate cancer proves highly influential for certain individuals, while a previous negative biopsy serves as a protective factor for others.

Alterations in the prostate cancer (PCa) N-glycome have gained attention as a potential biomarker. This comprehensive review explores the diversity of N-glycosylation patterns observed in PCa-related cell lines, tissue, serum and urine, focusing on prostate-specific antigen (PSA) and the total pool of glycoproteins. Within the context of PCa, altered N-glycosylation patterns are a mechanism of immune escape and a disruption in normal glycoprotein distribution and trafficking. Glycoproteins with PCa-induced N-glycosylation patterns tend to accumulate in prostate tissue and the bloodstream, thereby diminishing N-glycan proportions in urine. Based on literary observations, aberrations in N-glycan branching are probably a characteristic of metabolic reprogramming and (chronic) inflammation. Changes in (core) fucosylation, specific N-glycosylation structures (such as N,N'-diacetyllactosamine) and high-mannose glycans otherwise are more likely indicators of cancer development and progression. Further investigation into these PCa-specific alterations holds promise in the discovery of new diagnostic, prognostic and response prediction biomarkers in PCa.

Multiparametric MRI (mpMRI), interpreted using PI-RADS, improves the initial detection of clinically significant prostate cancer. Prostate MR image quality has increasingly recognized relevance to the use of mpMRI for prostate cancer diagnosis. Additionally, mpMRI is increasingly used in scenarios beyond initial detection, including active surveillance and assessment for local recurrence after prostatectomy, radiation therapy, or focal therapy. In acknowledgment of these evolving demands, specialized prostate MRI scoring systems beyond PI-RADS have emerged to address distinct scenarios and unmet needs. Examples include Prostate Imaging Quality (PIQUAL) for assessment of image quality of mpMRI, Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) recommendations for evaluation of serial mpMRI examinations during active surveillance, Prostate Imaging for Recurrence Reporting (PI-RR) system for assessment for local recurrence after prostatectomy or radiation therapy, and Prostate Imaging after Focal Ablation (PI-FAB) for assessment for local recurrence after focal therapy. These systems' development and early uptake signal a compelling shift toward prostate MRI standardization in different scenarios, and ongoing research will help refine their roles in practice. This AJR Expert Panel Narrative Review critically examines these new prostate MRI scoring systems (PI-QUAL, PRECISE, PI-RR, and PI-FAB), analyzing the available evidence, delineating current limitations, and proposing solutions for improvement.

Overdiagnosis occurs when patients are diagnosed with a disease that would otherwise never have affected the quality or duration of their lives. This often happens unintentionally through well-meaning screening programmes that aim to detect diseases during so-called subclinical stages. Recently, it has been suggested that patients with polymyalgia rheumatica should be screened for giant cell arteritis to identify those at higher risk of relapse or vascular complications. Screening for interstitial lung disease for patients with rheumatoid arthritis has also been recommended to identify patients who could benefit from pulmonary interventions. These potential benefits must be weighed against foreseeable harms. Such harms include the uncovering of incidental findings that necessitate additional medical follow-up, the financial costs associated with screening initiatives, the risk of overtreatment through increased immunosuppression in patients who might not have otherwise required it, and the psychosocial burden of a new diagnosis. Randomised clinical trials and prospective cohort studies of screening interventions should be conducted to establish the risks and benefits and identify patients most likely to benefit from them. This Viewpoint covers risks that overdiagnosis presents to the field of rheumatology, with focus on rheumatoid arthritis and polymyalgia rheumatica.

Prostate cancer (PCa) is highly prevalent among aging men and a significant contributor to global mortality. Balancing early detection and treatment of "clinically significant" disease with avoiding over-detection and overtreatment of slow-growing tumors is challenging, especially for elderly patients with competing health risks and potentially aggressive disease phenotypes. This review emphasizes the importance of individualized approaches for diagnosing and treating PCa in geriatric patients. Active surveillance and watchful waiting are common strategies, while surgical interventions are less frequent but considered based on comorbidities, disease risk, and patient preferences. Radiotherapy, often combined with androgen deprivation therapy, is typical for higher-risk cases, and focal therapy is emerging to reduce morbidity. An inclusive approach combining advanced diagnostics, life expectancy considerations, and minimally invasive interventions can improve decision-making. Integrating multidisciplinary strategies with better risk stratification and less invasive options can significantly enhance care and outcomes for elderly patients with significant PCa.

Anterior prostate cancers (APCs) are a group of impalpable neoplasms located in regions anterior to the urethra, which comprise the transition zone, apical peripheral zone and anterior fibromuscular stroma. These regions are typically undersampled using conventional biopsy schemes, leading to a low detection rate for APC and a high rate of false negatives. Radical prostatectomy series suggest prevalence rates of at least 10-30%, but transperineal systematic biopsy is ideal for diagnosis, particularly where multiparametric MRI is unavailable. Combined MRI-targeted and systematic biopsies demonstrate high concordance with final histopathology and lead to the fewest incidences of upgrading and upstaging at radical prostatectomy. Thus, the use of combined biopsy techniques has important implications for preoperative work-up and surgical planning, as APCs are associated with larger cancer volumes and a higher rate of positive surgical margins than posterior prostate cancer. Nevertheless, anterior tumour location might confer a relative resistance to stage progression, as APCs exhibit lower rates of extraprostatic extension, seminal vesical invasion and lymph node metastases than the more commonly seen posterior neoplasms. Few studies have examined the long-term outcomes of partial gland approaches to APCs, but MRI-targeted techniques have the potential to provide real-time intraoperative guidance and maximize the oncological safety of anterior focal treatment options in patients with APC.

Midlife baseline prostate-specific antigen (MB PSA), defined as a single PSA value measured between 40-59 years of age, has been proposed as a tool that can limit potential harms of PSA screening. This study aimed to examine the ability of MB PSA versus PSA doubling time (PSADT) and PSA velocity (PSAV) in assessing the likelihood of developing of lethal prostate cancer (PCa) in a diverse and contemporary North American population.

Men 40-59 years old, who received their first PSA between the years 1995 and 2019, were included. For MB PSA values, the first PSA test result was included. For PSADT, the first two PSA test results were included. For PSAV, the first three PSA test results within 30 months were included. Selection criteria resulted in a total of 77,594 patients with at least two PSA test results and 11,634 patients with at least three PSA test results. Multivariable Fine-Gray regression was used to examine the impact of the value of the PSA testing methods on the development of lethal PCa (defined as death from PCa or development of metastatic disease either at diagnosis or during follow-up). Time-dependent receiver operating characteristic/area under the curve (AUC) at 5, 10, and 15 years were plotted.

In the main cohort, patients were most frequently in the 50-54 age category (32.8%), had a Charlson comorbidity index of 0 (70.5%), and were White (63.2%). Of these, 9.3% had the midlife baseline PSA in the top 10th percentile, and 0.4% had a PSADT 0-6 months. Lethal PCa was diagnosed in 593 (0.8%) patients. The median (interquartile range) time to lethal PCa was 8.6 (3.2-14.9) years. In the main cohort, MB PSA and PSADT showed significant associations with the occurrence of lethal PCa, with a hazard ratio (HR) of 6.10 (95% confidence interval [CI], 4.85-7.68) and HR of 2.20 (95% CI, 1.07-4.54) for patients in the top 10th percentile MB PSA group and in the PSADT between 0 to <6 months group, respectively. In patients with three PSA results available, MB PSA and PSAV showed significant associations with the occurrence of lethal PCa, with a HR of 3.95 (95% CI, 2.29-6.79) and 3.57 (95% CI, 2.17-5.86) for patients in the top 10th percentile MB PSA group and in the in the PSAV >0.4 ng/mL/year group, respectively. PSADT and PSAV did not exhibit higher AUCs than MB PSA in assessing the likelihood of lethal PCa. Specifically, they were 0.818 and 0.708 at 10 and 15 years, respectively, for the PSADT; 0.862 and 0.756 at 10 and 15 years, respectively, for the PSAV; and 0.868 and 0.762 at 10 and 15 years, respectively, for the MB PSA (all p > .05).

The study findings are that PSAV or PSADT were not superior to midlife baseline in assessing the likelihood of developing lethal PCa. This suggests that these variables may not have practical use in enhancing PSA screening strategies in a clinical setting.

Prostate cancer is the second most diagnosed cancer and the fifth leading cause of cancer death among men worldwide. In the 1980s, the development and implementation of Prostate-Specific Antigen (PSA) testing for diagnosing prostate cancer led to a surge in the number of prostate cancer diagnoses. We explore the trends in recommendations and new innovations in adjunctive testing for prostate cancer screening.

Screening for nasopharyngeal carcinoma (NPC) has shown an improvement in early detection and survival rates of NPC in endemic regions. It is critical to evaluate whether NPC screening can reduce NPC-specific mortality in the population.

Sixteen towns in Sihui and Zhongshan cities, China, were selected; eight were randomly allocated to the screening group and eight to the control group. Residents age 30-69 years with no history of NPC were included from January 1, 2008, to December 31, 2015. Residents in the screening towns were invited to undergo serum Epstein-Barr virus (EBV) viral capsid antigen/nuclear antigen 1-immunoglobulin A antibody tests; others received no intervention. The population was followed until December 31, 2019. Nonparametric tests and Poisson regression models were used to estimate the screening effect on NPC mortality, accounting for the cluster-randomized design. The trial is registered with ClinicalTrials.gov (identifier: NCT00941538).

A total of 174,943 residents in the screening group and 186,263 residents in the control group were included. NPC incidence and overall mortality were similar between the two groups. A total of 52,498 (30.0% of 174,943) residents participated in the serum EBV antibody test. The overall compliance rate for endoscopic examination and/or biopsies among baseline and ever-classified high-risk participants was 65.9% (1,110 of 1,685) and 67.6% (1,703 of 2,518), respectively. A significant 30% reduction in NPC mortality was observed in the screening group compared with the control group (standardized NPC-specific mortality rate of 8.2 NPC deaths per 1,000 person-years versus 12.5; adjusted rate ratio [RR], 0.70 [95% CI, 0.49 to 0.997]; P = .048). This benefit was most evident among individuals age 50 years and older (RR, 0.56 [95% CI, 0.37 to 0.85]; P = .007) compared with those younger than 50 years (RR, 0.96 [95% CI, 0.64 to 1.46]; P = .856).

In this 12-year trial, EBV antibody testing resulted in a significant reduction in NPC mortality.