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For prostate cancer patients who experience biochemical progression during androgen deprivation therapy (ADT), prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has not been prospectively compared to planar bone scan plus CT. This was a single-arm, head-to-head, prospective phase II trial (NCT04928820) designed to enroll 102 men with prostate cancer who experienced biochemical progression (rising prostate-specific antigen [PSA] ≥ 1 ng/mL) during ADT. All patients received 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scans. Each scan was interpreted by three central independent readers. The primary endpoint was the per-patient bone metastasis detection rate of PSMA PET/CT versus planar bone scan and CT. Secondary endpoints compared the number of bone metastases detected per patient and the inter-reader agreement of each imaging modality. Twenty-two men were enrolled between July 2021 and June 2022. Due to slow accrual following approval of PSMA PET radiotracers in the U.S. and a lack of a statistical signal between the two imaging modalities on interim analysis, this trial was closed early on October 2022. Median PSA was 8.5 ng/mL (interquartile range: 1.6-77.6). There was 100% agreement between the two scans. Six patients (27%) had negative findings and 16 patients (73%) had positive findings on both scans. PSMA PET/CT and bone scan plus CT detected an equal number of bone lesions for 14 patients (64%), PSMA PET/CT detected more bone lesions for six patients (27%), and bone scan plus CT detected more bone lesions for two patients (9.1%) (p = 0.092). The inter-reader agreement rates of PSMA PET/CT and bone scan plus CT were 96% and 82%, respectively (p = 0.25). In men with biochemical progression during ADT, 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scan plus CT had identical bone metastasis detection rates. Bone scan plus CT can continue to serve as a cost-effective and readily accessible restaging modality in patients with biochemical progression. ClinicalTrials.gov NCT04928820. Registered 16/06/2021.

Deciphering the genetic basis of prostate-specific antigen (PSA) levels may improve their utility for prostate cancer (PCa) screening. Using genome-wide association study (GWAS) summary statistics from 95,768 PCa-free men, we conducted a transcriptome-wide association study (TWAS) to examine impacts of genetically predicted gene expression on PSA. Analyses identified 41 statistically significant (p 0.5: CCNA2 and HIST1H2BN. Six of the 20 identified genes are not known to impact PCa risk. Fine-mapping based on whole blood and prostate tissue revealed five protein-coding genes with evidence of causal relationships with PSA levels. Of these five genes, four exhibited evidence of colocalization and one was conditionally independent of previous GWAS findings. These results yield hypotheses that should be further explored to improve understanding of genetic factors underlying PSA levels.

Nearly all men with metastatic hormone-sensitive prostate cancer treated with intermittent androgen deprivation therapy (ADT) experience recurrence within 6 mo of testosterone recovery. We conducted a single-arm phase 2 trial to evaluate whether addition of dual androgen receptor pathway inhibitors (ARPIs) and metastasis-directed stereotactic body radiotherapy (SBRT) to intermittent ADT improves recurrence rates for men with between one and five nonvisceral, extrapelvic metastases on prostate-specific membrane antigen positron emission tomography/computed tomography after prior radical prostatectomy. Patients received 6 mo of androgen annihilation therapy (AAT; leuprolide, abiraterone acetate plus prednisone, and apalutamide) and metastasis-directed SBRT. The primary endpoint was the percentage of patients with prostate-specific antigen (PSA)

BACKGROUND: Nearly one-third of patients with prostate cancer (PCa) experience biochemical recurrence (BCR) after primary definitive treatment. BCR increases the risk of distant metastasis and mortality in patients with prognostically unfavorable features. These patients are best managed with a tailored treatment strategy incorporating risk stratification using clinicopathological factors, next-generation imaging, and genomic testing. OBJECTIVE: This narrative review examines the utility of risk stratification for the management of patients with BCR in the context of clinical trial data, referencing the latest recommendations by European and US medical societies. METHODS: PubMed was searched for relevant studies published through May 21 2023 on treatment of patients with BCR after radical prostatectomy (RP) or external beam radiotherapy (EBRT). RESULTS: European and US guidelines support the risk-stratified management of BCR. Post-RP, salvage EBRT (with or without androgen deprivation therapy [ADT]) is an accepted treatment option for patients with BCR. Post-EBRT, local salvage therapies (RP, cryotherapy, high-intensity focused ultrasound, stereotactic body radiotherapy, and low-dose-rate and high-dose-rate brachytherapy) have demonstrated comparable relapse-free survival rates but differing adverse event profiles, short and long term. Local salvage therapies should be used for local-only relapses while ADT should be considered for regional or distant relapses. In practice, patients often receive ADT, with varying guidance for intermittent ADT vs. continuous ADT, due to consideration of quality-of-life effects. CONCLUSIONS: Despite a lack of consensus for BCR treatment among guideline associations and medical societies, risk stratification of patients is essential for personalized treatment approaches, as it allows for an informed selection of therapeutic strategies and estimation of adverse events. In lower-risk disease, observation is recommended while in higher-risk disease, after failed repeat local therapy, ADT and/or clinical trial enrollment may be appropriate. Results from ongoing clinical studies of patients with BCR should provide consensus for management.

BACKGROUND: Biochemical recurrence (BCR) following primary interventional treatment occurs in approximately one-third of patients with prostate cancer (PCa). Next-generation imaging (NGI) can identify local and metastatic recurrence with greater sensitivity than conventional imaging, potentially allowing for more effective interventions. This narrative review examines the current clinical evidence on the utility of NGI for patients with BCR. METHODS: A search of PubMed was conducted to identify relevant publications on NGI applied to BCR. Given other relevant recent reviews on the topic, this review focused on papers published between January 2018 to May 2023. RESULTS: NGI technologies, including positron emission tomography (PET) radiotracers and multiparametric magnetic resonance imaging, have demonstrated increased sensitivity and selectivity for diagnosing BCR at prostate-specific antigen (PSA) concentrations

We report our initial real-world experience with 177Lu-PSMA-617 radioligand therapy. Methods: We performed a retrospective review of patients treated with 177Lu-PSMA-617. Pretreatment PSMA PET, laboratory findings, overall survival, a fall in prostate-specific antigen by 50% (PSA50), and toxicities were evaluated. Results: Ninety-nine patients were included. Sixty patients achieved a PSA50. Seven of 18 (39%) patients who did not meet the TheraP PSMA imaging criteria achieved a PSA50. Nineteen of 31 (61%) patients who did not meet the VISION laboratory criteria achieved a PSA50. Sixty-three patients had a delay or stoppage in therapy, which was due to a good response in 19 patients and progressive disease in 14 patients. Of 10 patients with a good response who restarted treatment, 9 subsequently achieved a PSA50 on retreatment. The most common toxicities were anemia (33%) and thrombocytopenia (21%). Conclusion: At our center, patients who did not meet the TheraP PSMA imaging criteria or the VISION laboratory criteria benefited from 177Lu-PSMA-617 radioligand therapy.

Opinion statementPSMA-PET has been a practice-changing imaging biomarker for the management of men with PCa. Research suggests improved accuracy over conventional imaging and other PET radiotracers in many contexts. With multiple approved PSMA-targeting radiotracers, PSMA PET will become even more available in clinical practice. Its increased use requires an understanding of the prospective data available and caution when extrapolating from prior trial data that utilized other imaging modalities. Future trials leveraging PSMA PET for treatment optimization and management decision-making will ultimately drive its clinical utility.

PURPOSE: To assess the diagnostic performance and utility of the ExoDx IntelliScore and an OPKO4K score to predict prostate cancer in men presenting with elevated PSA-both as independent predictors and in combination with clinical/MRI characteristics. METHODS: Patients with elevated PSA were retrospectively reviewed. Abnormal tests were defined as an OPKO4K score ≥ 7.5% and an ExoDx IntelliScore ≥ 15.6. Four regression models and ROC curves were generated based on: (1) age, PSA, and DRE, (2) model 1 + OPKO4K 4Kscore ≥ 7.5%, (3) model 2 + ExoDx IntelliScore ≥ 15.6, and (4) model 3 + MRI PIRADS 4-5. RESULTS: 359 men received an OPKO4K test, 307 had MRI and 113 had ExoDx tests. 163 men proceeded to prostate biopsy and 196 (55%) were saved from biopsy. Mean age was 65.0 ± 8.7 years and mean PSA was 7.1 ± 6.1 ng/mL. Positive biopsies were found in 84 (51.5%) men. The sensitivity and negative predictive value of an OPKO4K score were 86.7% and 72.3%; values for an ExoDx test were 76.5% and 77.1%, respectively. On regression analysis, clinical markers (Age, PSA, DRE) generated an AUC of 0.559. The addition of an OPKO4K score raised the AUC to 0.653. The stepwise addition of an ExoDx score raised the AUC to 0.766. The combined use of both biomarkers, patient characteristics, and MRI yielded an AUC of 0.825. CONCLUSION: This analysis demonstrates the high negative predictive value of both the OPKO4K score and ExoDX IntelliScore independently while demonstrating that the combination of an OPKO4K score, an ExoDX IntelliScore, and MRI increases predictive capability for biopsy confirmed prostate cancer.

Distinguishing indolent from clinically significant localized prostate cancer is a major clinical challenge and influences clinical decision-making between treatment and active surveillance. The development of novel predictive biomarkers will help with risk stratification, and clinical decision-making, leading to a decrease in over or under-treatment of patients with prostate cancer. Here, we report that Trop2 is a prognostic tissue biomarker for clinically significant prostate cancer by utilizing the Canary Prostate Cancer Tissue Microarray (CPCTA) cohort composed of over 1100 patients from a multi-institutional study. We demonstrate that elevated Trop2 expression is correlated with worse clinical features including Gleason score, age, and pre-operative PSA levels. More importantly, we demonstrate that elevated Trop2 expression at radical prostatectomy predicts worse overall survival in men undergoing radical prostatectomy. Additionally, we detect shed Trop2 in urine from men with clinically significant prostate cancer. Our study identifies Trop2 as a novel tissue prognostic biomarker and a candidate non-invasive marker for prostate cancer.

A ratiometric electrochemiluminescence (ECL) aptamer-based sensing platform was fabricated for prostate-specific antigen (PSA) determination. Activated CdS nanocrystals/multi-walled carbon nanotubes (CdS/MCNTs) and luminol-Pt/PAMAM nanocomposites (L-Pt/PAMAM NCs) were synthesized and used as cathodic and anodic ECL emitters, respectively. Amino group–modified aptamers were assembled on carboxylated magnetic beads, followed by hybridization with probe DNA functionalized L-Pt/PAMAM NCs. In the presence of PSA, the aptamer would bind specifically to the target PSA, thereby releasing L-Pt/PAMAM NCs. After magnetic separation, the separated L-Pt/PAMAM NCs would hybridize with capture DNA on CdS/MCNTs coated on glassy carbon electrode. This binding would lead to a decrease in cathodic ECL signal of CdS/MCNTs, due to the efficient energy transfer from CdS/MCNTs to L-Pt/PAMAM NCs. Meanwhile, L-Pt/PAMAM brought the anodic ECL signal from luminol. With the increase of PSA concentration, the ECL emission from luminol increased and the ECL emission from CdS/MCNTs decreased. The ratio of ECL intensity of luminol at 0.55 V and CdS/MCNTs at − 1.25 V could be used to quantify the concentration of PSA. This method enables sensitive and reliable detection of PSA over a wide range from 0.05 to 200 ng mL−1, and the detection limit is 0.02 ng mL−1. [ABSTRACT FROM AUTHOR]

In this study, a novel aptasensor based on a transition metal oxide–modified pencil graphite electrode (PGE) was developed for the diagnosis of early-stage prostate cancer (PCa) via monitoring the prostate-specific antigen (PSA), which is the main biomarker for PCa. Single-use PGEs modified with pulsed deposited manganese oxide (MnOx) film were used to attach the amino-terminated aptamer specific to the PSA via carbodiimide chemistry. The designed aptasensor was placed in an electrochemical cell containing ferri/ferrocyanide ions as a redox probe to measure the charge transfer resistances (Rct) of the electrode surface by electrochemical impedance spectroscopy (EIS) to follow the response of each modification step. The effect of the medium pH on the ionic structure of the aptamer molecule according to its pI value and, thus, the reversing of the direction of the response (ΔRct) by the pH change was also discussed. The level of PSA secreted from PCa cells was investigated using impedimetric transduction. The specificity of the aptasensor was validated through selectivity studies against non-specific tumor markers like VEGF and different cancer cell lines including breast cancer and androgen-insensitive prostate cancer. The developed system showcases a label-free, fast, specific, and cost-effective approach for PSA detection, highlighting the importance of medium pH and the electrostatic environment on the aptamer's response. Our work emphasizes the potential for such aptasensors in clinical diagnostics and paves the way for further exploration into using transition metal oxides in biosensing applications. [ABSTRACT FROM AUTHOR]

This study examined the comparability of venous and capillary blood samples with regard to routine chemistry analytes.Venous and capillary blood samples were collected from adult patients to assess comparability of alanine transaminase, albumin, alkaline phosphatase, apolipoprotein B, aspartate aminotransferase, total bilirubin, calcium, chloride, creatin kinase, creatinine, C-reactive protein, ferritin, folic acid, free T4, gamma glutamyltransferase, glucose, high density lipoprotein cholesterol, iron, lipase, lipoprotein a, magnesium, phosphate, postassium, prostate specific antigen, sodium, total cholesterol, total protein, transferrin, triglycerides, thyroid stimulating hormone, urate, urea, vitamin B12 and 25-hydroxyvitamin-D3. Furthermore, hemolysis-icterus-lipemia Index (HIL-Index) was measured for all samples. All measurements were performed using the Siemens Atellica® CH or IH Analyzer. Deming regression analysis and mean relative differences between venous and capillary measurements of each analyte were contrasted with the desirable total allowable error (TEa) and Clinical Laboratory Improvement Amendments (CLIA) 2024 proposed acceptance limits for proficiency testing.Deming regression and mean relative differences demonstrated excellent comparability between venous and capillary samples for most measured analytes.Capillary and venous samples showed comparable results for almost all studied chemistry analytes. Of the 33 studied analytes for which TEa criteria where available, 30 met TEa criteria. CLIA 2024 criteria where available for 29 of the studied analytes of which only glucose did not meet the criteria. In conclusion, capillary blood draw is a suitable alternative for venous blood sampling for measuring most of the investigated analytes. This benefits patients with fear of needles and might pave the way for remote self-sampling. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Approximately 10%–20% of prostate cancers progress to metastatic and castration‐resistant forms (mCRPC). Radioligand (RLT) therapy with [177Lu]Lu‐prostate‐specific membrane antigen (PSMA) is an approved treatment for metastasized mCRPC. Moreover, Actinium‐225 (225Ac), an alpha‐emitter isotope, has also been used to label PSMA and, recently, to treat mCRPC patients with encouraging results. However, robust clinical data on [225Ac]Ac‐PSMA therapy and its comparison with [177Lu]Lu‐PSMA are still limited. Our aim was to evaluate the role of [225Ac]Ac‐PSMA in treating mCRPC and compare it with conventional [177Lu]Lu‐PSMA therapy.A systematic search was performed in PubMed, Web of Science, Scopus and the Cochrane Register of Controlled Trials from June 2023 to January 2024. This work was conducted in accordance with PRISMA guidelines.After screening and study selection according to PRISMA guidelines, 11 studies were included, 9 of which focused on [225Ac]Ac‐PSMA only and two on tandem therapy ([225Ac]Ac‐PSMA/[177Lu]Lu‐PSMA). Overall, the pooled proportion of PSA decline in patients was .85 (95% CI: .79–.91, p < .001); patients pretreated with [177Lu]Lu‐PSMA achieved a pooled proportion of PSA decline of .90 (95% CI: .82–.97, p < .001). In patients treated with tandem therapy, PSA decline was observed in approximately 90% of them, while PSA response rates above 50% ranged from 53.3% to 65%. Xerostomia was the most frequently reported side effect, along with anaemia, thrombocytopenia and nephrotoxicity.Overall, the main results of our study showed that [225Ac]Ac‐PSMA‐617 had a significant therapeutic effect on mCRPC with an acceptable toxicity level. The latter, however, appears greater than with [177Lu]Lu‐PSMA‐617. In future studies, an adequate analysis of the incidence of side effects associated with [225Ac]Ac‐PSMA should be performed to evaluate the role of cumulative toxicity of earlier treatments and the higher frailty of heavily pretreated patients. [ABSTRACT FROM AUTHOR]

For men with intermediate-risk prostate cancer treated with definitive therapy, the addition of androgen deprivation therapy (ADT) reduces the risk of distant metastasis and cancer-related mortality. However, the absolute benefit of ADT varies by baseline cancer risk. Estimates of prognosis have improved over time, and little is known about ADT decision making in the modern era. We sought to characterize variability and identify factors associated with intended ADT use within the Michigan Radiation Oncology Quality Consoritum (MROQC). Patients with localized prostate cancer undergoing definitive radiation therapy were enrolled from June 9, 2020, to June 26, 2023 (n = 815). Prospective data were collected using standardized patient, physician, and physicist forms. Intended ADT use was prospectively defined and was the primary outcome. Associations with patient, tumor, and practice-related factors were tested with multivariable analyses. Random intercept modeling was used to estimate facility-level variability. Five hundred seventy patients across 26 facilities were enrolled with intermediate-risk disease. ADT was intended for 46% of men (n = 262/570), which differed by National Comprehensive Cancer Network favorable intermediate-risk (23.5%, n = 38/172) versus unfavorable intermediate-risk disease (56.3%, n = 224/398; P <.001). After adjusting for the statewide case mix, the predicted probability of intended ADT use varied significantly across facilities, ranging from 15.4% (95% CI, 5.4%-37.0%) to 71.7% (95% CI, 57.0%-82.9%), with P <.01. Multivariable analyses showed that grade group 3 (OR, 4.60 [3.20-6.67]), ≥50% positive cores (OR, 2.15 [1.43-3.25]), and prostate-specific antigen 10 to 20 (OR, 1.87 [1.24-2.84]) were associated with ADT use. Area under the curve was improved when incorporating MRI adverse features (0.76) or radiation treatment variables (0.76), but there remained significant facility-level heterogeneity in all models evaluated (P <.05). Within a state-wide consortium, there is substantial facility-level heterogeneity in intended ADT use for men with intermediate-risk prostate cancer. Future efforts are necessary to identify patients who will benefit most from ADT and to develop strategies to standardize appropriate use. [ABSTRACT FROM AUTHOR]

Background: Anabolic androgenic steroids (AAS) are synthetic forms of testosterone frequently used as performance enhancing drugs among gay, bisexual, and queer (GBQ) men. Despite widespread use, associated harms, and the likely existence of an AAS use disorder, there is no medical consensus on standards of care for people who use AAS, with most medical providers focusing exclusively on abstinence. Individuals using AAS have developed community-based harm reduction strategies to mitigate these harms. Methods: This paper is a sub-analysis of qualitative data obtained through semi-structured interviews with GBQ men using AAS for 8 or more weeks recruited through convenience and snowball sampling from clinical sites and LGBTQ + venues in New York City as well as through social media. Interviews were coded with themes developed using reflexive thematic analysis. Data related to harm reduction techniques were then re-analyzed through a prevention strategies framework lens of primary, secondary, and tertiary harm prevention. Results: Thematic saturation was reached at twelve interviews in the primary analysis, with men reporting frequent use of multiple harm reduction techniques. For primary prevention, men avoided oral steroids and simultaneous substance use, tried to obtain AAS from reputable sources, used "cycling" to dose steroids, and practiced sterile injection techniques. Secondary prevention methods included patient-directed lab testing for hematocrit, liver and kidney function, cholesterol, prostate specific antigen, testosterone, and self-performed blood pressure checks. Tertiary prevention included donating blood and the use of medications without a prescription, including aromatase inhibitors, selective estrogen receptor blockers, aspirin, statins, angiotensin receptor blockers, clomiphene, and human chorionic gonadotropin. Conclusions: Despite many GBQ men experiencing harms from anabolic androgenic steroids, community members have often sought harm reduction techniques in lieu of abstinence. Though many of these techniques embrace clinical reasoning and may be more broadly applicable, additional research is needed to understand the impact of each intervention on the overall health of individuals using AAS. [ABSTRACT FROM AUTHOR]

Primary seminal vesicle lymphoma is a remarkably rare condition, predominantly manifesting as diffuse large B-cell lymphoma. Due to its rarity and nonspecific clinical presentations, it is often misdiagnosed or overlooked. Here, we report a case of a 68-year-old male diagnosed with primary seminal vesicle lymphoma, coinciding with prostate cancer. The diagnosis followed initial findings of elevated prostate-specific antigen levels and abnormal magnetic resonance imaging of the prostate and left seminal vesicle. Suspicion of prostate cancer led to a radical resection of both the prostate and seminal vesicle. Subsequent pathological examination and next-generation sequencing post-surgery confirmed the diagnosis of primary seminal vesicle diffuse large B-cell lymphoma, characterized by CD79B mutation type (MCD type). The patient was treated with six cycles of the R-CHOP regimen (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone), achieving complete metabolic remission as confirmed by positron emission tomography-computed tomography. Fifteen months post-treatment, the patient's condition remains favorable. Through our literature review of additional six cases of primary seminal vesicle lymphoma, we aim to elucidate the typical clinical presentations, imaging features, pathological characteristics, genetic mutations, and therapeutic strategies, aiming to contribute to better detection and management of this rare malignancy. This case underscores the diagnostic challenges and emphasizes the necessity for heightened clinical suspicion and definitive pathological examination in the management of primary seminal vesicle lymphoma. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a major world-wide health concern. Current diagnostic methods involve Prostate-Specific Antigen (PSA) blood tests, biopsies, and Magnetic Resonance Imaging (MRI) to assess cancer aggressiveness and guide treatment decisions. MRI aligns with in silico medicine, as patient-specific image biomarkers can be obtained, contributing towards the development of digital twins for clinical practice. This work presents a novel framework to create a personalized PCa model by integrating clinical MRI data, such as the prostate and tumour geometry, the initial distribution of cells and the vasculature, so a full representation of the whole prostate is obtained. On top of the personalized model construction, our approach simulates and predicts temporal tumour growth in the prostate through the Finite Element Method, coupling the dynamics of tumour growth and the transport of oxygen, and incorporating cellular processes such as proliferation, differentiation, and apoptosis. In addition, our approach includes the simulation of the PSA dynamics, which allows to evaluate tumour growth through the PSA patient's levels. To obtain the model parameters, a multi-objective optimization process is performed to adjust the best parameters for two patients simultaneously. This framework is validated by means of data from four patients with several MRI follow-ups. The diagnosis MRI allows the model creation and initialization, while subsequent MRI-based data provide additional information to validate computational predictions. The model predicts prostate and tumour volumes growth, along with serum PSA levels. This work represents a preliminary step towards the creation of digital twins for PCa patients, providing personalized insights into tumour growth. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence suggests that serum urea nitrogen may be a risk factor for prostate cancer (PCa) and influence serum prostate-specific antigen (PSA) concentrations, but direct evidence of a relationship between PSA and serum urea nitrogen levels in the general population is still lacking. The aim of this study was to demonstrate the relationship between serum urea nitrogen levels and prostate-specific antigen (PSA) and prostate cancer. Methods: We conducted a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES, 2003–2010) database. We performed a multifactorial regression analysis of the association between serum urea nitrogen levels and PSA and PCa, followed by subgroup analyses. Results: A total of 5256 subjects were included in this study, and after adjusting for demographic, biological, and immunologic variables, we found that there was a threshold for blood urea nitrogen concentration below which every 1 ng/mL increase in serum urea nitrogen was associated with a 0.0325 ng/mL increase in PSA concentration (log2 transformed) (95% CI: 0.0064, 0.0586), and the P trend was was less than 0.05 and the difference was statistically significant. Sensitivity analyses using the generalized additive model (GAM) showed a linear relationship between serum urea nitrogen and serum PSA concentrations when blood urea nitrogen concentrations ranged from 0 ng/ml to 6.78 ng/ml. Conclusion: Serum urea nitrogen was independently and positively correlated with serum PSA concentration when the concentration of serum urea nitrogen ranged from 0 ng/ml to 6.78 ng/ml. [ABSTRACT FROM AUTHOR]

Background: Androgen receptor signaling inhibitors (ARSis), when administered sequentially or in combination with docetaxel and androgen deprivation therapy (ADT), have been shown to enhance overall survival (OS) and progression-free survival (PFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Nonetheless, the optimal sequence for administering chemotherapy and ARSis remains to be determined. Objective: To compare the efficacy of ARSis sequential therapy with ARSis combined therapy for mHSPC, and to evaluate the efficacy and safety of different combination regimens. Methods: The PubMed, Embase, Cochrane Central, and ClinicalTrials.gov databases were searched from their inception through 14 July 2024, to identify eligible phase III randomized clinical trials (RCTs) evaluating the combination or sequential use of docetaxel + ADT with abiraterone, enzalutamide, apalutamide, or darolutamide. The outcomes of interest included OS, PFS, time to prostate-specific antigen (PSA) progression, grade 3–5 adverse events (AEs), and serious adverse events (SAEs). Results: Five RCTs involving 2836 patients were included in the analysis. When comparing ARSis sequential therapy to ARSis combined therapy, no significant differences were observed in OS (Hazard Ratio (HR): 1.17, 95% Confidence Interval (CI): 0.69–1.96), PFS (HR: 1.03, 95% CI: 0.47–2.22), or time to PSA progression (HR: 0.48, 95% CI: 0.03–7.69). Within the different ARSis combined regimens, the triple therapies involving enzalutamide, abiraterone, and darolutamide demonstrated comparable efficacy and safety profiles in the overall population, and their efficacy in patients with high-volume disease or low-volume disease was also similar. Conclusion: ARSis sequential therapy did not significantly differ from ARSis combined therapy in improving OS and PFS among patients with mHSPC, and thus can be considered as a viable treatment option. [ABSTRACT FROM AUTHOR]

Background: Nodes are the second site for prostate cancer recurrence. Whole-pelvic radiotherapy (WPRT) has shown superiority over nodal stereotactic body radiotherapy (SBRT) in two retrospective cohorts. We aimed to compare both modalities and assess factors associated with treatment outcomes. Materials and methods: This retrospective multicentric cohort study included patients from five institutions spanning from 2010 to 2022. Patients had a history of prostatic adenocarcinoma classified as N0 M0 at diagnosis with a first nodal-only pelvic castration-sensitive recurrence. Failure-free survival (FFS) was defined as the time from the end of RT to the first failure event–biochemical or imaging recurrence, or death. Results: A total of 147 patients (pts) were analyzed, mainly treated for a recurrence after initial prostatectomy (87%), with 64 (43.5%) undergoing SBRT and 83 (56.5%) undergoing WPRT. SBRT was chosen mainly for dosimetric constraints (67%) and was associated with a lower rate of concomitant androgen deprivation therapy (ADT) prescription. With a median follow-up of 68 months [inter-quartile range (IQR) = 51], FFS was significantly lower in the SBRT group (p < 0.0001). In multivariable analysis, WPRT and ADT were associated with a longer FFS. Factors associated with a longer FFS after SBRT included associated ADT, lower prostate-specific antigen (PSA) levels, a PSA doubling time >6 months, and a Gleason score <8. SBRT was associated with a lower rate of genitourinary and gastrointestinal grade ≥2 complications. Discussion: For an isolated pelvic nodal prostate cancer recurrence, SBRT is associated with a shorter FFS compared to WPRT. SBRT is often more convenient for patients and leaves further pelvic salvage options available, so it can be explored as an option for well-informed patients. [ABSTRACT FROM AUTHOR]

Objectives: To assess the impact of differences in Prostate-Specific Antigen (PSA) testing rates on prostate cancer (PCa) diagnosis and PCa-specific mortality among Māori men in a New Zealand (NZ) population. Patients and Methods: Māori men aged 40 years or older, without a history of PCa, with a PSA test between 2006 and 2018 were included. The cohort was divided into two groups; the “screened group” (ScG) consisting of men who had at least one PSA test every four years or less, and the “non-screened group” (non-SG). We measured the rate of cancer diagnoses and used competing risk analysis to assess survival. Results: The study cohort included 63,939 Māori men, with 37,048 (58%) in the ScG. PCa was more frequently diagnosed in the ScG (3.7% vs. 3.0%, P < 0.001). A higher proportion of high-grade cancers were found in the non-SG (32.7% vs. 25.6%, P = 0.001). The 10-year cancer-specific survival was significantly higher in the ScG (99.4% vs. 98.5%, P < 0.001). In a multivariable risk model, PSA testing frequency was an independent predictor of PCa mortality. (HR 2.43, [95% CI 1.97–3.01], P < 0.001). Conclusions: In a cohort of only Māori men, lower PSA testing rates were associated with a higher risk of PCa-related death. Therefore, regular PSA testing for Māori could improve cancer-specific survival among Māori men. Regular PSA testing should be considered a priority area for improving PCa survival in this population. [ABSTRACT FROM AUTHOR]

The prognostic value of prostate-specific antigen (PSA) kinetics in primary high-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with novel hormonal therapy agents is still unclear. Here, we retrospectively reviewed the data of 102 patients with primary high-volume mHSPC who received novel hormonal therapy agents. The median follow-up was 32.25 ± 14.51 months and the median nadir PSA (nPSA) was 0.20 (0.06, 11.71) ng/mL after treatment. The mean time to nPSA was 10.82 ± 7.27 months and 55 patients (53.9%) had a PSA-density (PSA-D) ≤ 0.08 at 3-months. Univariate and multivariate Cox regression analyses showed that the absence of visceral metastases, nPSA ≤ 0.2 and PSA-D ≤ 0.08 were independent prognostic factors for better PFS and OS (all P < 0.05). Moreover, patients with nPSA ≤ 0.2 and PSA-D ≤ 0.08 had the best PFS and OS, and the combination of the nPSA and PSA-D had a better predictive accuracy for PFS and OS than nPSA and PSA-D alone. Thus, Visceral metastases, nPSA and PSA-D were independent prognostic factors for primary high-volume mHSPC patients treated with novel hormonal therapy agents. Patients with lower nPSA and PSA-D had a best survival outcome, and the combination of nPSA and PSA-D had a better effect on prognosis predicting. [ABSTRACT FROM AUTHOR]

This study aimed to assess if prostate-specific antigen (PSA) threshold and PSA bounce are associated with oncological control after low-dose-rate brachytherapy (LDR-BT) alone or with external beam radiotherapy (EBRT), with or without androgen deprivation therapy (ADT), considering serum testosterone levels. This study enrolled 944 prostate cancer patients treated at a single institution with LDR-BT alone or LDR-BT combined with EBRT, with or without ADT. The Fine-Gray hazard model was used to evaluate factors related to clinical failure, including experience of PSA bounce between baseline and 2, 4, or 7 years after LDR-BT and PSA value (0.1, 0.2, or 0.5 ng/mL) with normal testosterone levels at 2, 4, and 7 years after LDR-BT, respectively. Patients with normal testosterone levels and a PSA of 0.2 or 0.5 ng/mL at 2, 4, and 7 years after LDR-BT had a significantly better clinical failure free rate (CFFR) than those with PSA levels >0.2 or >0.5 ng/mL or low testosterone levels. Multivariate analysis revealed that PSA <0.1, 0.2, or 0.5 ng/mL with normal testosterone levels at 2, 4, and 7 years and experience of PSA bounce between baseline and 2 or 4 years after LDR-BT were significantly related to better CFFR. Patients with normal serum testosterone levels who reached PSA of <0.1, 0.2, or 0.5 ng/mL after LDR-BT, or those who experienced PSA bounce, showed better oncological control. [ABSTRACT FROM AUTHOR]

Laser-induced breakdown spectroscopy (LIBS) is a promising technique for the readout of immunochemical assays utilizing indirect detection of labels (Tag-LIBS), typically based on nanoparticles. We have previously demonstrated that Tag-LIBS immunoassay employing yttrium-based photon-upconversion nanoparticles (UCNPs) can reach sensitivity similar to commonly used enzyme and fluorescence immunoassays. In this study, we report on further increasing the sensitivity of UCNP-based Tag-LIBS immunoassay by employing magnetic microbeads (MBs) as the solid phase in the determination of cancer biomarker prostate-specific antigen. Due to the possibility of analyte preconcentration, MBs enabled achieving a limit of detection (LOD) of 4.0 pg·mL−1, representing two orders of magnitude improvement compared with equivalent microtiter plate-based assay (LOD of 460 pg·mL−1). In addition, utilizing MBs opens up the possibility of an internal standardization of the LIBS readout by employing iron spectral lines, which improves the assay robustness by compensating for LIBS signal fluctuations and bead-bound immunocomplexes lost throughout the washing steps. Finally, the practical applicability of the technique was confirmed by the successful analysis of clinical samples, showing a strong correlation with the standard electrochemiluminescence immunoassay. Overall, MB-based Tag-LIBS was confirmed as a promising immunoassay approach, combining fast readout, multiplexing possibilities, and high sensitivity approaching upconversion luminescence scanning while avoiding the requirement of luminescence properties of labels. [ABSTRACT FROM AUTHOR]

A simple method for highly selective and sensitive prostate-specific antigen (PSA) detection using a molecularly imprinted electrochemical sensor is presented. The sensor was developed through an epitope imprinted strategy combined with electrochemical measurement techniques. An epitope molecularly imprinted polymer (EMIP) film was constructed on a AuNPs-coated gold electrode surface through electropolymerization, utilizing the C-terminus epitope of PSA (KWIKDTIVANP) as the template molecular and o-phenylenediamine as the functional monomer. The characteristics of EMIP film were investigated by using a scanning electron microscope and electrochemical test methods, including electrochemical impedance spectroscopy and cyclic voltammetry. Key parameters such as electropolymerization cycles, elution and rebinding times, and the molar ratio of template molecular to functional monomer were systematically optimized. The sensor demonstrated a detection limit (LOD) of 0.31 fg/mL and exhibited an excellent linear response towards PSA concentration ranging from 1.0 fg/mL to 0.1 µg/mL. Furthermore, the EMIP sensor showed excellent selectivity against other biological macromolecules, such as bovine serum albumin, human serum albumin, alpha-fetoprotein, and carcinoembryonic antigen. With recoveries between 95.89 and 106.04% for PSA detection in human serums the EMIP/AuNPs/AuE electrochemical sensor showed great potential in real sample analysis. [ABSTRACT FROM AUTHOR]

Background: Rising metastatic prostate cancer incidence has renewed debate regarding benefits of prostate‐specific antigen (PSA) screening. Identifying barriers to accessing screening for individuals at high risk of lethal prostate cancer may slow this rise. We examined associations of access barriers with receipt of PSA testing, stratified by sociodemographic factors. Methods: We pooled data from male respondents to Behavior Risk Factor Surveillance Systems (BRFSS) surveys from 2006 to 2020. Questions related to affordability (insurance, cost of visits) and accommodation (regular primary care provider (PCP), physician recommending a PSA test) were considered as individual‐level barriers. For availability, we linked provider density from the 2012 Area Health Resource File and estimated driving times to closest health facility within Micropolitan and Metropolitan Statistical Area (MMSA) using Google Earth Engine. These measures were used to compute a spatial accessibility index. We fit survey‐weighted, covariate‐adjusted logistic regression models to estimate associations of barriers with receipt of PSA within the past 2 years and examined effect modification by sociodemographic factors. Results: There were 185,643 participants, of whom 73% were White, 11% were Black, 4% were Asian, and 11% were Hispanic. Physician recommendation was the strongest predictor of having a PSA test (aOR: 14.5, 95% CI: 13.6, 15.6). Not having a regular PCP (aOR: 0.29, 95% CI: 0.27, 0.31), insurance (aOR: 0.64, 95% CI: 0.58, 0.71), and prohibitive cost of care (aOR: 0.82, 95% CI: 0.75, 0.90) were associated with lower PSA testing. Access barriers were stronger predictors of PSA testing for Asian and White participants compared to other groups (Phet < 0.004 for insurance and regular PCP) and for those with college education compared to those without (Phet < 0.05 for insurance, perceived unaffordability). Discussion: Physician recommendation was the strongest predictor of receipt of PSA testing, regardless of sociodemographic grouping. Future studies should consider access barriers jointly and across sociodemographic strata. Understanding barriers to accessing appropriate prostate‐specific antigen screening is important in light of concerning increases in metastatic prostate cancer incidence. While insurance, regular contact with a primary care provider, and high cost were barriers to accessing screening in a panel study using Behavior Risk Factor Surveillance System data, physician's recommendation was the strongest predictor of screening. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer (PCa) is a heterogeneous disease and the second most diagnosticated cancer in men. Epidemiological information is essential to adopt the strategy of early detection. In Mexico there is paucity of epidemiological data. We observed that Mexican men present aggressive disease at diagnosis with metastatic symptoms. Seems the Mexican race is a risk factor for PCa, as African men. "OPUS program " is the actual screening protocol for Mexican men. We describe the concernment of early detection of PCa in the Mexican population to reduce the rate of metastases. Introduction: Epidemiological data are crucial for adopting primary and secondary prevention strategies and to develop screening protocols against prostate cancer (PCa). Despite the comprehensive characterization of PCa across White and Black men, there is a lack of data from the Mexican population. This manuscript presents data from the Can.Prost registry that captures PCa trends over the past two decades in Mexico City; furthermore, we aimed to compare clinical differences and oncological outcomes before and after the promotion of early detection actions through a campaign against PCa that occurred in 2014. Methods: A retrospective observational study on newly diagnosed Mexican PCa patients was carried out at the Instituto Nacional de Cancerología (INCan) in Mexico City. During 2014 and 2015, a project for the early diagnosis of PCa ("OPUS program") was launched in the aforementioned tertiary hospital. Starting at the age of 45 years, all men were invited for a PSA measurement and a specialist urologist consultation. All individuals with clinical or biochemical suspicion of PCa (PSA > 4 ng/mL), in the context of age and prostate volume, underwent ultrasound-guided transrectal prostate biopsy. Then, patients with pathologically confirmed prostate cancer were stratified according to the year of diagnosis: Group A accounted for those diagnosed between 2000 and 2014 and Group B for those patients diagnosed in the timeframe of 2015–2021. Comparisons of PCa characteristics, treatment modalities and oncologic outcomes between Group A and B were performed. Results: Overall, we collected data from 2759 PCa patients from 2000 to 2021. The median PSA at baseline was 32 ng/mL, and 25% had a family history of PCa. Overall, 25.8% were asymptomatic and 46% had a non-metastatic presentation. After the OPUS campaign, PSA at diagnosis was significantly lower across all age groups. The incidence of PCa diagnosis in asymptomatic men was higher (31.4% vs. 19.9%) and a higher proportion of men were diagnosed with organ-confined, palpable disease (46% vs. 28%) (p < 0.001). The rate of patients eligible for active/radical treatment was higher after the OPUS campaign (patients who received surgery increased from 12.78% to 32.41%; patients who underwent radiation increased from 28.38% to 49.61%). The proportion of patients diagnosed with non-clinically significant disease was negligible and remained stable across time. Conclusions: PCa in Mexican patients displays aggressive features at diagnosis, whereas the rate of non-significant disease is negligible. The introduction of early detection strategies may lead to lower symptomatic and metastatic PCa and higher opportunities for radical treatment. This emphasizes the need for public awareness and for adjustment of screening strategies to the peculiarities of the Mexican population. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is the second most common cancer diagnosed in men and yet is the second leading cause of cancer-related deaths worldwide. This is often due to the cancer being misdiagnosed as benign prostatic hyperplasia or missed entirely due to the limited nature of the most popular detection method, prostate-specific antigen levels. The aim of this study was to assess the potential of G-protein-coupled receptor-associated sorting protein 1 (GASP-1) as a valid prostate cancer biomarker. Prostate tissue samples from healthy, benign prostatic hyperplasia, and prostate cancer patients were subjected to anti-GASP-1 polyclonal antibodies in immunohistochemical staining and enzyme-linked immunosorbent assay analyses, showing that GASP-1 levels were significantly greater in prostate cancer patients when compared to benign prostatic hyperplasia and healthy patients. Specifically in prostate cancer patients, there was a positive correlation between GASP-1 overexpression and the severity of the prostate cancer. Background/Objectives: Prostate cancer (PCa) is a prevalent malignancy, necessitating accurate diagnostic methods to distinguish it from benign conditions such as benign prostatic hyperplasia (BPH). Current diagnostic tools, relying primarily on serum prostate-specific antigen (PSA) levels, lack specificity, leading to an over-diagnosis and unnecessary treatment of patients with benign conditions. This study explores G-protein-coupled receptor-associated sorting protein 1 (GASP-1) as a more sensitive biomarker for PCa detection. Methods: Prostate tissue microarrays of healthy, BPH, and prostate cancer patients with different Gleason scores were studied. Polyclonal antibodies targeted against GASP-1 were used for routine immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) analyses. Results: The results indicated a 5-fold difference in serum GASP-1 levels between BPH and PCa, which was validated through GASP-1 IHC. Furthermore, a novel scoring system, the H-score, assesses GASP-1 granules' intensity and size, revealing a clear distinction between BPH and PCa. An additional analysis of GASP-1 expression between PCa cases with different Gleason scores reveals that GASP-1 overexpression correlates with PCa severity, providing insights into disease progression. Conclusions: The study supports GASP-1′s role as a promising diagnostic marker, supplementing PSA testing, and offering improved risk stratification for PCa. Additionally, an open-source software system is introduced for an efficient GASP-1 granule color analysis, enhancing diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Simple Summary: Many beneficial mechanisms of action are known from soy isoflavones, including in prostate and prostate cancer. Previous research was able to demonstrate a clear effect of PSA modulation, and this could potentially lead to better selection of patients at increased risk of occult prostate carcinoma. In low-grade localized prostate cancer, more and more active surveillance is being proposed and a lot of research is being carried out to see if certain factors or treatments may also act in this regard. This formed the basis to study the effect of soy isoflavones in patients under active surveillance. In this study, we were able to observe PSA modulation in a large proportion of patients, resulting in fewer follow-up examinations and fewer positive control biopsies. Potentially, in active surveillance, a soy supplement could be useful to help select patients who could continue to be followed up or who should be treated earlier. Background/Objectives: To investigate the effect of a fermented soy supplement during 18 months in patients under active surveillance (AS) for low-risk and selected favorable intermediate-risk prostate cancer (PCa), with an emphasis on PSA modulation. Methods: Low-risk patients with ISUP grade 1, clinical stage cT1 or cT2a, PSA < 10 ng/mL and favorable intermediate-risk patients with ISUP grade 2 (<10% pattern 4), clinical stage T2b-c, PSA 10–20 ng/mL. The primary outcome was PSA response defined as maximum PSA rise less than or equal to 0.87 ng/mL after 1 year, based on the weighted average of PSA velocity (PSAV) in previous studies in similar populations. Secondary outcomes were disease progression, adverse histology on repeat biopsy or switch to active therapy. In addition, primary and secondary outcomes with imputed data were also determined as sensitivity analyses, using Mann–Whitney U or Chi-squared tests. Results: Overall, 92 (61.3%) of 150 patients showed a PSA level response. This was more evident in ISUP 1 patients and resulted in fewer follow-up MRIs and fewer control biopsies, as well as a fewer number of positive control biopsies with statistical significance in the imputed dataset. Obtaining a PSA response was numerically associated with less initiated therapy. Conclusions: a fermented soy supplement in patients under AS for low-risk and selected favorable intermediate-risk PCa could be useful in selecting patients who may remain under AS or who may need to switch to active therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Biochemical recurrence (BCR) of prostate cancer (PCa) after surgery is marked by an increase in prostate-specific antigen. BCR is associated with the risk of metastatic disease and/or death. This review evaluates the ability of artificial intelligence (AI) to predict BCR in PCa post-operatively. AI demonstrated high accuracy, especially when radiological features are utilised in its development. AI occasionally outperforms traditional methods of BCR prediction. However, due to the limited number of high-quality studies and insufficient external validation, further research is necessary to confirm the reliability and effectiveness of these AI techniques before they can be widely used in clinical practice. Background/Objectives: Biochemical recurrence (BCR) after radical prostatectomy (RP) is a significant predictor of distal metastases and mortality in prostate cancer (PCa) patients. This systematic review aims to evaluate the accuracy of artificial intelligence (AI) in predicting BCR post-RP. Methods: Adhering to PRISMA guidelines, a comprehensive literature search was conducted across Medline, Embase, Web of Science, and IEEE Xplore. Studies were included if they utilised AI to predict BCR in patients post-RP. Studies involving patients who underwent radiotherapy or salvage RP were excluded. This systematic review was registered on PROSPERO (International prospective register of systematic reviews) under the ID CRD42023482392. Results: After screening 9764 articles, 24 met the inclusion criteria. The included studies involved 27,216 patients, of whom 7267 developed BCR. AI algorithms developed using radiological parameters demonstrated higher predictive accuracy (median AUROC of 0.90) compared to algorithms based solely on pathological variables (median AUROC of 0.74) or clinicopathological variables (median AUROC of 0.81). According to the Prediction Model Risk of Bias Assessment Tool (PROBAST), the overall risk of bias was unclear in three studies due to ambiguous inclusion criteria and the exclusion of many patients because of missing follow-up data. In seven studies, the developed AI outperformed or was at least equivocal to traditional methods of BCR prediction. Conclusions: AI shows promise in predicting BCR post-RP, particularly when radiological data were used in its development. However, the significant variability in AI performance and study methodologies highlights the need for larger, standardised prospective studies with external validation prior to clinical application. [ABSTRACT FROM AUTHOR]

To compare appointment availability and wait times between private equity-owned and non-private equity-owned urology clinics for 2 common urologic complaints. We identified all PE-owned urology clinic locations as of June 2022 (n = 390). For each PE-owned location, a geographically matched, non-PE-owned clinic was identified. Each office was called using a "secret shopper" method with a standardized script, requesting an appointment on behalf of their Medicare-aged father for evaluation of gross hematuria or elevated prostate-specific antigen (PSA). The primary outcome was appointment availability, and the secondary outcome was wait time until soonest appointment. PE-owned and non-PE-owned clinics treated the presenting complaints with similar frequency (gross hematuria: 85% vs 88%, P =.3, elevated PSA: 93% vs 94%, P =.5). Wait time in days until the next available appointment was similar for PE-owned clinics compared to non-PE clinics for both complaints (gross hematuria: 16 vs 13, P =.06, elevated PSA: 18 vs 19, P =.7). If available, the time in days until the soonest next appointment with an advanced practice provider was also similar between PE-owned and non-PE clinics (gross hematuria: 13 vs 11, P =.07, elevated PSA: 13 vs 12, P =.6). Overall, there were no large-scale differences in access to outpatient urologic care between PE-owned clinics and non-PE-owned clinics. Access to care in PE-owned clinics is likely clinically similar to geographic-matched controls for Medicare patients with gross hematuria or elevated PSA. [ABSTRACT FROM AUTHOR]

To evaluate predictors of contralateral clinically significant prostate cancer (csPCa) in men with biopsy-proven unilateral lesions on magnetic resonance imaging (MRI). We retrospectively identified men with no prior diagnosis of PCa with unilateral biopsy-confirmed csPCa within PI-RADS 2-5 lesions within our institutional biopsy database. Multivariate logistic regression was used to identify clinical predictors of contralateral disease. Four hundred ninety men met study inclusion criteria, of which 385 men (78.6%) had no contralateral csPCa and 105 men (21.4%) had contralateral csPCa (Fig. 1). Prior negative biopsy (OR 0.34 [0.14, 0.75], P =.012), prostate-specific antigen density (OR 18.8 [2.77, 249], P =.017), and tumor location in the transverse plane ("Posterior": OR 1.93 [1.02, 3.87], P =.048; "Throughout Transverse Plane": OR 6.56 [2.26, 19.6], P <.001) were significantly associated with contralateral csPCa in multivariate logistic regression models. However, there appear to be no attributes within the MRI-targeted tumor that reliably predict contralateral csPCa (Table 2). Approximately 20% of men with unilateral MRI findings and csPCa on targeted biopsy were found to have contralateral csPCa on systematic biopsy (SB). Prior negative biopsy was associated with a decreased odds of contralateral csPCa. Prostate-specific antigen density and tumor in the posterior aspect of or throughout the transverse plane were associated with increased odds of contralateral csPCA. Consideration of these clinical factors may afford an opportunity to only use SB in cases in which the odds of contralateral csPCa are high. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We aimed to compare the detection rate of prostate cancer (PCa) and clinically significant (cs) PCa by magnetic resonance imaging-guided targeted biopsy (MTBx) alone and MTBx plus systematic biopsy (SBx) using an outpatient transperineal (TP) approach under local anesthesia. METHODS: A retrospective study of patients who underwent outpatient TP prostate biopsy under local anesthesia at our tertiary institution between 2019 and 2022 was performed. To compare the proportions of PCa and csPCa in both pathways, McNemar's tests were used. Multivariable logistic regression model was fitted to determine the predictors of csPCa. RESULTS: Of 255 men included, 177 (69%) underwent MTBx alone. MTBx had similar detection rate for PCa (56%) and csPCa (47%) compared to the combination of MTBx and SBx (PCa 61%; csPCa 49%; p=0.1 and p=0.3, respectively). MTBx had lower median number of biopsy cores compared to the combination of MTBx and SBx (6 vs. 11, p<0.001). At multivariable logistic regression analysis, age (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.04-1.13, p<0.001), prior negative biopsy (OR 0.19, 95% CI 0.09-0.44, p<0.001), prostate-specific antigen density cutoff =0.15 (OR 3.17, 95% CI 1.67-6.01, p<0.001), and prostate imaging reporting and data system =4 (OR 12.2, 95% CI 4.21-35.6, p<0.001) were independent predictors of csPCa. CONCLUSIONS: MTBx showed similar diagnostic performance to the combination of MTBx and SBx in patients undergoing outpatient TP prostate biopsy. Future studies are needed to evaluate the role of MTBx in avoiding unnecessary biopsies. [ABSTRACT FROM AUTHOR]

Aim: Rechallenge of [177Lu]Lu-PSMA-617 radioligand therapy (RLT) was proposed for patients who initially responded to PSMA-RLT experiencing partial remission, but relapsed into progression after a certain period of remission. However, only limited data is available regarding this approach. In this study, we analyzed the efficacy and safety profile of one or more series of [177Lu]Lu-PSMA-617 RLT rechallenge in patients from a prospective registry (REALITY Study, NCT 04833517) after they initially benefited from PSMA-RLT. Methods: Forty-seven patients with metastatic castration-resistant prostate cancer (mCRPC) who had biochemical response to initial [177Lu]Lu-PSMA-617 RLT followed by disease progression received at least one (up to three) series of [177Lu]Lu-PSMA-617 RLT rechallenge. Biochemical response rates based on prostate-specific antigen (PSA) serum value, PSA-based progression-free survival (PFS) and overall survival (OS) were calculated. Adverse events of the treatment were assessed according to 'common terminology criteria for adverse events' (CTCAE). Results: After one series of RLT rechallenge, a PSA decline of at least 50% was achieved in 27/47 patients (57.4%). The median PFS of all patients was 8.7 mo and the median OS was 22.7 mo, each calculated from the administration of the first rechallenge series. Patients who responded (PSA decline > 50%) to the rechallenge showed a median OS of 27.3 mo. Regarding PFS, a significant correlation (r = 0.4128, p = 0.0323) was found for these patients comparing initial and rechallenge RLT. Ten patients received a second and 3 patients received a third rechallenge series with 8/10 and 3/3 patients responding to repeated RLT rechallenge. No severe deterioration of adverse events rated by CTCAE criteria was observed. Conclusion: [177Lu]Lu-PSMA-617 RLT rechallenge is associated with significant PSA response and encouraging survival outcome as well as a very favourable safety profile and should therefore be considered as a straight-forward treatment option in mCRPC patients, who previously benefited from PSMA-RLT. [ABSTRACT FROM AUTHOR]

Background Ceftolozane/tazobactam and ceftazidime/avibactam are commonly used in patients with MDR- Pseudomonas aeruginosa (PSA) pneumonia (PNA). This study compared outcomes between non-COVID-19 hospitalized patients with MDR-PSA PNA who received ceftolozane/tazobactam or ceftazidime/avibactam. Methods The study included non-COVID-19 adult hospitalized patients with MDR-PSA PNA in the PINC AI Healthcare Database (2016–22) who received ceftolozane/tazobactam or ceftazidime/avibactam within 3 days of index culture for ≥2 days. Outcomes were mortality, recurrent MDR-PSA PNA, discharge destination, post-index culture day length of stay (LOS) and costs (in US dollars, USD), and hospital readmission. Results The final sample included 197 patients (117 ceftolozane/tazobactam, 80 ceftazidime/avibactam). No significant differences were observed in mortality and post-index culture LOS and costs between groups. In the multivariable analyses, patients who received ceftolozane/tazobactam versus ceftazidime/avibactam had lower recurrent MDR-PSA PNA (7.9% versus 18.0%, P  = 0.03) and 60 day PNA-related readmissions (11.1% versus 28.5%, P  = 0.03) and were more likely to be discharged home (25.8% versus 9.8%, P  = 0.03). Compared with ceftazidime/avibactam patients, ceftolozane/tazobactam patients had lower adjusted median total antibiotic costs (5052 USD versus 8099 USD, P  = 0.003) and lower adjusted median comparator (ceftolozane/tazobactam or ceftazidime/avibactam) antibiotic costs (3938 USD versus 6441 USD, P  = 0.005). In the desirability of outcome ranking (DOOR) analysis, a ceftolozane/tazobactam-treated patient was more likely to have a more favourable outcome than a ceftazidime/avibactam-treated patient [DOOR probability: 59.6% (95% CI: 52.5%–66.8%)]. Conclusions Early treatment with ceftolozane/tazobactam may offer some clinical and cost benefits over ceftazidime/avibactam in patients with MDR-PSA PNA. Further large-scale studies are necessary to comprehensively understand the outcomes associated with these treatments for MDR-PSA PNA. [ABSTRACT FROM AUTHOR]

AbstractOne of the undesirable complications of diabetes is sexual dysfunctions in males which may affect their fertility. This research aims to study the effect of C-peptide administration on the prostate of diabetic rats and focusing on exploring the role of the autophagy pathway in diabetic prostate and whether it is involved in C-peptide action. Forty adult male Wistar albino rats were separated into control group, diabetic group, diabetic + C-peptide and diabetic + C-peptide + 3-Methyladenine (autophagy inhibitor). Serum metabolic parameters and prostatic specific antigen (PSA) were measured. Markers of oxidative stress, inflammation, fibrosis, cell proliferation and cell autophagy were evaluated in prostate tissues using biochemical, western blotting and immunohistochemical techniques. C-peptide administration ameliorated the effects of diabetes on the prostate through its hypoglycaemic, antioxidant, anti-inflammatory, and antiproliferative effects which were reversed with autophagy inhibition. Thus, we concluded that C-peptide prevented the effects of diabetes on the prostate through stimulation of the autophagy pathway. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the results of the prostate-specific antigen (PSA) test used in prostate cancer screening. Methods: This retrospective study was conducted on a total of 1106 male individuals, including 615 people (55.6%) aged 40-54, 379 people (34.3%) aged 55-69, and 112 individuals (10.1%) aged 70 and over. In the study, prostate-specific antigen (PSA) blood test results were performed on a total of 1106 male individuals aged 40 and over registered in the Uludag University Family Health Center, Bursa, Turkey during the 5-years between June 1, 2018, and May 31, 2023, were taken from the database and analyzed. Relationships with sociodemographic characteristics, comorbidities, and risk factors were examined. Data was analyzed using SPSS 25. Results: About 15.5% of the participants were married, 78.4% were single, and 6% were separated from their spouses or widows. The PSA values of the patients referred to the urologist were found to be significantly different between the ages of 55 and 69. It was determined that the PSA levels of the patients with benign prostatic hypertrophy and prostate cancer were higher than the patients without any finding, and the mean was 6.81±4.39 (p=0.01). Conclusion: In our study, it is important to diagnose benign prostatic hypertrophy or prostate cancer in patients aged 55-69 years, whose mean PSA levels were 6.81±4.39, and referred to a urologist. As a contribution to the discussions in the literature, we recommend that the patient with symptoms be referred to the urologist after the test request and the joint decision with the family physician. [ABSTRACT FROM AUTHOR]

Introduction: Benign prostatic hyperplasia (BPH) mainly leads to lower urinary tract symptoms (LUTS) in aging men. The present study investigates the role of cholecalciferol, Silymarin, and their combined administration in patients with BPH suffering from LUTS. Methods: This double-blind, randomized, controlled trial enrolled 80 participants (50–80 years) diagnosed with BPH, from March 2019 to March 2020. Based on serum 25-(OH) vitamin D levels we formed subgroups, each receiving specific interventions. Measurements of International Prostate Symptom Score (IPSS), Maximal Urinary Flow Rate (Q-max), Prostate Volume (PV), Post-Void Residual (PVR), and Prostate-Specific Antigen (PSA) were recorded at baseline and following 3 months of follow-up. Results: Participants with serum concentration of 25-(OH) vitamin D below 20 ng/ml simultaneously received cholecalciferol and Silymarin that significantly improved IPSS, irritation, obstruction, PV, and PVR. In those with concentrations ⩾20 ng/ml, a single use of Silymarin significantly reduced IPSS, irritation, obstruction, and PVR. Adjustment of confounding variables revealed independent and significant effects of both cholecalciferol and Silymarin on PVR, IPSS, and obstruction. Cholecalciferol also improved irritation, while Silymarin reduced prostate volume. These findings highlight potential therapeutic benefits for BPH-associated LUTS, encouraging further exploration and clinical consideration. Conclusions: In this investigation, combination therapy with cholecalciferol at 50,000 IU/w for 8 weeks and Silymarin at a dosage of 480 mg for 3 months resulted in a notable improvement in the IPSS score, PV, and PVR, as well as both irritative and obstructive symptoms. However, the total PSA and free PSA amounts did not reach a significant difference. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the predictive values and relationships of serum prostate-specific antigen (PSA) levels, delta neutrophil index (DNI), neutrophil-lymphocyte ratio (NLR), and other hematological parameters in patients diagnosed with acute prostatitis. Methods: Serum PSA levels and hemogram parameters of patients diagnosed with acute prostatitis were retrospectively analyzed. Healthy patients of the same age group were assigned to the control group. WBC, neutrophil, lymphocyte, thrombocyte (PLT), mean platelet volume (MPV), plateletcrit (PCT), NLR, and DNI were determined. Serum total PSA and C-reactive protein (CRP) levels were also assessed. Results: Total PSA levels (3.48 [1.11–6.66]) in the acute prostatitis (AP) group were significantly higher than those of healthy men (0.82 [0.47–1.39]) (p < 0.001). Total CRP levels (3.88 [1.50–22.03]) in the AP group were significantly higher than those in healthy men (1.15 [0.89–2.00]) (p < 0.001). The sensitivity and specificity of PSA at a cutoff value of 1.52 were 68.4% and 79.7%, respectively. The NLR value in the AP group was 2.62 (1.87–4.42), compared to 1.63 (1.18–2.20) in the healthy group (p < 0.001). Differences in WBC, neutrophil, and lymphocyte counts were also statistically significant (p < 0.001). There were no significant differences in PLT, PCT, or DNI values. Significant positive correlations were observed between PSA, CRP, and DNI values (all p < 0.001). Conclusion: This study demonstrated the usefulness of NLR, PSA, CRP, and WBC as predictors of acute prostatitis. NLR is a simple, inexpensive inflammation parameter that correlates well with CRP levels. [ABSTRACT FROM AUTHOR]

Studies have reported lower incidence of prostate cancer in men living with HIV compared with men without HIV for reasons that remain unclear. Lower prostate cancer screening in men living with HIV could explain these findings. We describe receipt of prostate-specific antigen (PSA) test each calendar year by HIV status in Medicaid beneficiaries enrolled in 14 U.S. states, 2001–2015. A total of 15,299,991 Medicaid beneficiaries aged 18–64 with ≥7 months of continuous enrollment were included in analyses. HIV diagnosis and PSA tests were identified using non-drug claims. Incidence rate ratios comparing receipt of PSA test by HIV status adjusted for age, race/ethnicity, state of residence, calendar year, comorbid conditions, benign prostatic conditions, and receipt of testosterone-replacement therapy were estimated using Poisson regression. Models were also stratified by state, and estimates were pooled using random-effects meta-analysis to account for heterogeneity by state. Models were additionally stratified by age and race/ethnicity. There were 42,503 PSA tests over 314,273 person-years and 1,669,835 PSA tests over 22,023,530 person-years observed in beneficiaries with and without HIV, respectively. The incidence of PSA test was slightly lower in men living with HIV than men without HIV (incidence rate ratio [IRR] = 0.98; 95% confidence interval [CI]: 0.97, 0.99) when adjusting for state. In the pooled estimate, the rate was higher among men living with HIV (IRR = 1.11; 95% CI: 0.97, 1.27). Pooled estimates indicated approximately equal or higher rates of PSA test in men living with HIV compared with men without HIV across models stratified by age and race/ethnicity groups. Findings do not support the hypothesis that differences in prostate cancer screening explain differences in incidence by HIV status. [ABSTRACT FROM AUTHOR]

Prostate cancer is a prevalent and debilitating disease that necessitates effective prevention and treatment strategies. Green tea, a well-known beverage derived from the Camellia sinensis plant, contains bioactive compounds with potential health benefits, including catechins and polyphenols. This comprehensive review aims to explore the potential benefits of green tea in prostate cancer prevention and treatment by examining existing literature. Green tea possesses antioxidant, anti-inflammatory, and anti-carcinogenic properties attributed to its catechins, particularly epigallocatechin gallate. Epidemiological studies have reported an inverse association between green tea consumption and prostate cancer risk, with potential protection against aggressive forms of the disease. Laboratory studies demonstrate that green tea components inhibit tumor growth, induce apoptosis, and modulate signaling pathways critical to prostate cancer development and progression. Clinical trials and human studies further support the potential benefits of green tea. Green tea consumption has been found to be associated with a reduction in prostate-specific antigen levels, tumor markers, and played a potential role in slowing disease progression. However, challenges remain, including optimal dosage determination, formulation standardization, and conducting large-scale, long-term clinical trials. The review suggests future research should focus on combinatorial approaches with conventional therapies and personalized medicine strategies to identify patient subgroups most likely to benefit from green tea interventions. [ABSTRACT FROM AUTHOR]

Background: In recent decades, the analytical quality of clinical laboratory results has substantially increased because of collaborative efforts. To effectively utilize laboratory results in applications, such as machine learning through big data, understanding the level of harmonization for each test would be beneficial. We aimed to develop a quantitative harmonization index that reflects the harmonization status of real-world laboratory tests. Methods: We collected 2021–2022 external quality assessment (EQA) results for eight tests (HbA1c, creatinine, total cholesterol, HDL-cholesterol, triglyceride, alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], and prostate-specific antigen [PSA]). This EQA was conducted by the Korean Association of External Quality Assessment Service, using commutable materials. The total analytical error of each test was determined according to the bias% and CV% within peer groups. The values were divided by the total allowable error from biological variation (minimum, desirable, and optimal) to establish a real-world harmonization index (RWHI) at each level (minimum, desirable, and optimal). Good harmonization was arbitrarily defined as an RWHI value ≤1 for the three levels. Results: Total cholesterol, triglyceride, and CEA had an optimal RWHI of ≤1, indicating an optimal harmonization level. Tests with a desirable harmonization level included HDL-cholesterol, AFP, and PSA. Creatinine had a minimum harmonization level, and HbA1c did not reach the minimum harmonization level. Conclusions: We developed a quantitative RWHI using regional EQA data. This index may help reflect the actual harmonization level of laboratory tests in the field. [ABSTRACT FROM AUTHOR]

Purpose: Following treatment for localized prostate cancer, a subset of men will develop recurrent disease in the abdominopelvic nodes. For radiation therapy (RT), the optimal treatment volume, fractionation schedule, and dose remain unanswered questions. We report early outcomes for patients treated with involved-field stereotactic body radiation therapy (SBRT) (IF-SBRT) for nodal oligo-recurrent (NOR) prostate cancer. Methods: Between January 2018 and October 2023, 67 patients with a median age of 75 with NOR prostate cancer treated with 74 courses of IF-SBRT at Georgetown were eligible for this analysis. NOR was defined as any volume of disease that could be safely treated within an IF. All patients were treated with five-fraction IF-SBRT (27.5-35 Gy). The IF treatment volume was defined as the nodal basin containing the gross disease as well as the immediately adjacent basins. Disease progression was defined as a prostate-specific antigen (PSA) rise above the pretreatment baseline or initiation of a second treatment. Local control and progression-free survival were calculated using the Kaplan-Meier method. Results: Detection of pre-SBRT NOR was ascertained by prostate-specific membrane antigen (PSMA) (38%), fluciclovine (50%), or MRI/CT (12%). Median follow-up was 50 months (1-262). The median pre-salvage PSA was 6.5 ng/mL (range, 0.1-335). The median number of involved nodes was 3 (range, 1-16). The local control at 1 and 2 years was 98% and 93%, respectively. The 1- and 2-year progression-free survival was 78% and 50%, respectively. Twenty percent of treatment courses were followed by acute Grade 2 gastrointestinal (GI) toxicity: diarrhea (9%) and/or nausea (14%). Two patients (3%) experienced late Grade 2 nausea. On univariate analysis, measures of disease volume such as hormone sensitivity (p = 0.03), increasing involved node number (p = 0.008), and abdominal treatment (p = 0.03) were significantly associated with GI toxicity. Conclusions: With the widespread adoption of PSMA agents, NORs are likely to increase. The optimal combination of local and systemic therapy in this population is unknown. With a favorable toxicity profile, IF-SBRT represents a safe and convenient local therapy treatment option for an elderly patient population. Patient- and treatment-related factors such as a large number of involved nodes and/or abdominal treatment may be associated with an increased risk of GI toxicity. [ABSTRACT FROM AUTHOR]

Purpose: No study has compared cancer regression (d) and growth (g) rates in patients with advanced castration-sensitive prostate cancer (CSPC) treated with androgen deprivation therapy. The comparison of d and g rates provides insight into the differential impact of ADT regimens on tumor dynamics, potentially guiding more personalized treatment strategies. Therefore, we aimed to estimate these rates and evaluate their impact on survival outcomes. Methods: Sequential prostate-specific antigen (PSA) data was obtained from the KYUCOG-1401 trial including patients with advanced CSPC randomized to gonadotropin-releasing hormone (GnRH) antagonist (group A) and GnRH agonist plus bicalutamide (group B). d and g rates were estimated by applying mathematical models and were compared in subgroups. PSA-progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS) were compared by lower and higher than the median of these rates. Results: Patients with higher PSA and higher extent of disease score at enrollment presented higher d rates (0.03965 vs. 0.03546, p = 0.0006) and (0.03947 vs. 0.03587, p = 0.0113) for groups A and B, respectively. The median d rate was lower for group A than group B (0.03306 vs. 0.039965, respectively [p = 0.0002]). The median g rate was higher for group A than group B (0.00016 vs. 0.00002, respectively [p = 0.0014]). The g rate, but not the d rate discriminated PSA-PFS, rPFS, and OS. Conclusion: Our results suggest that GnRH agonist plus bicalutamide reduced PSA level faster and suppressed PSA rising longer than GnRH antagonist. Moreover, measuring the g rate can predict PSA-PFS, rPFS, and OS in patients with advanced CPSC treated with androgen deprivation therapy. These findings suggest that incorporating g rate measurements into clinical practice could improve prognostic accuracy and guide treatment decisions in advanced CSPC. [ABSTRACT FROM AUTHOR]

The article published in EJNMMI Research explores the intra- and interobserver variability of PSMA-expression scores in patients with primary prostate cancer undergoing PSMA PET/CT staging. The study highlights the importance of standardized interpretation and reporting of PSMA-targeted imaging studies using the PROMISE framework. Results show that consensus training and quantification-based assessment using SUVmax significantly improved interobserver agreement rates. The study emphasizes the need for clear interpretation criteria and the impact of different PSMA PET tracers on observer agreement rates. [Extracted from the article]

Background Methods Results Conclusions Prostate and breast cancer screening are prevalent among older adults, even among those unlikely to benefit. We aimed to evaluate why older adults stop cancer screening, including the role of physician recommendations.We used nationally representative data from the 2019 Medicare Current Beneficiary Survey (MCBS). We included women aged 76 and older without a history of breast cancer and men aged 71 and older without a history of prostate cancer. The primary outcome was reason for discontinuing screening, categorized as follows: (1) physician recommendation against screening; (2) absence of a recommendation to screen; and (3) patient‐driven reason, such as patient preferences or beliefs. We evaluated reasons for screening discontinuation by health status and educational attainment using age‐stratified multinomial logistic regression.The sample included 7350 participants representing a weighted population of 22,498,715. Overall, 53% of women underwent screening mammography in the past year or intended to continue screening. Among those who stopped screening, 5% reported a recommendation to stop screening from their doctor, 48% reported no recommendation, and 32% reported a patient‐driven reason for cessation. Findings did not differ by educational attainment or health status, including among the oldest patients. For men, 61% were screened with PSA in the past year or intended to continue. Among those who stopped, 3% reported a recommendation against screening, 54% reported no recommendation, and 27% reported a patient‐driven reason for cessation. Men with higher educational attainment were more likely to report that their physician recommended against screening (4% vs. 1%, p = 0.01) and that their doctor did not recommend screening (58% vs. 47%, p = 0.01). Reasons for screening cessation did not differ by health status, including among the oldest patients.Cancer screening remains common, even among those with limited potential for benefit, but discussions around screening cessation are rare. Improving communication between patients and physicians may improve screening decision quality. [ABSTRACT FROM AUTHOR]

Background: Due to the limitations of clinical trials, some delayed and rare adverse events (AEs) may remain undetected, and safety information can be supplemented through post-market data analysis. This study aims to comprehensively analyze the AEs associated with Relugolix (Orgovyx®) using data from the FAERS database, and gain a better understanding of the potential risks and side effects of Relugolix (Orgovyx®) therapy. Methods: Data of Relugolix (Orgovyx®) were collected from the FAERS database covering the period from the fourth quarter of 2020 to the third quarter of 2023. Disproportionality analysis was performed by calculating the reporting odds ratios (ROR), proportional reporting ratio (PRR), Bayesian analysis confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) to detect positive signals. Results: Totally, 5,382,189 reports were collected from the FAERS database, 4,397 reports of Relugolix (Orgovyx®) were identified as the 'primary suspected (PS)' AEs. Relugolix (Orgovyx®) induced AEs occurred in 26 organ systems. 58 significant disproportionality preferred terms (PTs) satisfying with the four algorithms were retained at the same time. Unexpected significant AEs such as Pollakiuria, and Prostatic specific antigen increased also occur. The median time of onset was 60 days. The majority of the AEs occurred within the first 30 days after Relugolix (Orgovyx®) initiation. Conclusion: Common AEs included Hot flush, Fatigue, Asthenia, Constipation, and Myalgia. These AEs should be focused on when using the drug to avoid serious consequences. In addition, the study results also suggested that the drug may exist Pollakiuria, Prostatic specific antigen increased and other AEs not mentioned in the manual, to supplement the AEs in the manual. This study is helpful for clinicians and pharmacists to improve their understanding of Relugolix (Orgovyx®) related AEs, and take timely prevention and treatment measures to ensure drug safety for patients. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is one of the most prevalent and deadly cancers among men, particularly affecting men of African descent and contributing significantly to cancer-related morbidity and mortality worldwide. The disease varies widely, from slow-developing forms to highly aggressive or potentially fatal variants. Accurate risk stratification is crucial for making therapeutic decisions and designing adequate clinical trials. This review assesses a broad spectrum of diagnostic and prognostic biomarkers, many of which are incorporated into clinical guidelines, including the Prostate Health Index (PHI), 4Kscore, STHLM3, PCA3, SelectMDx, ExoDx Prostate Intelliscore (EPI), and MiPS. It also highlights emerging biomarkers with preclinical support, such as urinary non-coding RNAs and DNA methylation patterns. Additionally, the review explores the role of tumor-associated microbiota in PCa, offering new insights into its potential contributions to disease understanding. By examining the latest advancements in PCa biomarkers, this review enhances understanding their roles in disease management. [ABSTRACT FROM AUTHOR]

The link between biological aging and prostate cancer (PCa) risk, particularly as indicated by elevated prostate-specific antigen (PSA) levels, remains uncertain. This study utilized data from the National Health and Nutrition Examination Survey (2001–2010) to explore this association. Biological age was assessed using Klemera-Doubal method age (KDMAge) and phenotypic age (PhenoAge). PCa was identified through self-reported diagnoses, and highly probable PCa was determined by PSA levels. We analyzed the prevalence of PCa and PSA-defined highly probable PCa across quartiles of biological age measures using weighted chi-square and linear trend tests. Associations were evaluated using weighted multiple logistic regression models. Among 7,209 and 6,682 males analyzed, the overall weighted prevalence of PCa was 2.86%, increasing to 9.60% in those aged 65 and above. A significant rise in PCa prevalence was observed with higher quartiles of KDMAge or PhenoAge (P for trend < 0.001), particularly in those under 65. In this younger group, higher PhenoAge acceleration quartiles were linked to increased PCa prevalence and higher risk of PCa (OR = 1.50, P = 0.015) as well as highly probable PCa in those without a diagnosis (OR = 1.28, P = 0.031). These findings suggest that accelerated biological aging is associated with an increased risk of PCa and may indicate early risk as signaled by PSA levels, even in those without a PCa diagnosis. [ABSTRACT FROM AUTHOR]

BACKGROUND Whether stereotactic body radiotherapy (SBRT) is noninferior to conventionally demoderately hypofractionated regimens with respect to biochemical or clinical failure in patients with localized prostate cancer is unclear. METHODS We conducted a phase 3, international, open-label, randomized, controlled trial. Men with stage Tl or T2 prostate cancer, a Gleason score of 3+4 Or less, and a prostate-specific antigen (PSA) level of no more than 20 ng per milliliter were randomly assigned (in a 1:1 ratio) to receive SBRT (36.25 Gy in 5 fractions over a period of 1 or 2 weeks) or control radiotherapy (78 Gy in 39 fractions over a period of 7.5 weeks or 62 Gy in 20 fractions over a period of 4 weeks). Androgendeprivation therapy was not permitted. The primary end point was freedom from biochemical or clinical failure, with a critical hazard ratio for noninferiority of 1.45. The analysis was performed in the intention-to-treat population. RESULTS A total of 874 patients underwent randomization at 38 centers (433 patients in the SBRT group and 441 in the control radiotherapy group) between August 2012 and January 2018. The median age of the patients was 69.8 years, and the median PSA level was 8.0 ng per milliliter; the National Comprehensive Cancer Network risk category was low for 8.4% of the patients and intermediate for 91.696. At a median follow-up of 74.0 months, the 5-year incidence of freedom from biochemical or clinical failure was 95.8% (9596 confidence interval ICI], 93.3 to 97.4) in the SBRI group and 94.6% (95% CI, 91.9 to 96.4) in the control radiotherapy group (unadjusted hazard ratio for biochemical or clinical failure, 0.73; 90% CI, 0.48 to 1.12; P=0.004 for noninferiority), which indicated the noninferiority of SBRT. At 5 years, the cumulative incidence of late Radiation Therapy Oncology Group (RIOG) grade or higher genitourinary toxic effects was 26.9% (95% CI, 22.8 to 31.5) with SBRT and 18.3% (95% CI, 14.8 to 22.5) with control radiotherapy (P<0.001), and the cumulative incidence of late RTOG grade 2 or higher gastrointestinal toxic effects was 10.7% (95% CI, 8.1 to 14.2) and 10.2% (95% CI, 7.7 to 13.5), respectively (P-0.94). CONCLUSIONS Five-fraction SBRT was noninferior to control radiotherapy with respect to biochemical or clinical failure and may be an efficacious treatment option for patients with low-to-intermediate-risk localized prostate cancer as defined in this trial. (Funded by Accuray and others; PACE-B ClinicalTrials.gov number, NCT01584258.). [ABSTRACT FROM AUTHOR]