Deep and Durable Prostate-specific Antigen Response to Darolutamide with Androgen Deprivation Therapy and Docetaxel, and Association with Clinical Outcomes for Patients with High- or Low-volume Metastatic Hormone-sensitive Prostate Cancer: Analyses of the Randomized Phase 3 ARASENS Study.

BACKGROUND AND OBJECTIVE: Addition of darolutamide to androgen deprivation therapy (ADT) and docetaxel significantly improved overall survival (OS) in ARASENS (NCT02799602). Here we report on prostate-specific antigen (PSA) responses and their association with outcomes. METHODS: ARASENS is an international, double-blind, phase 3 study in patients with metastatic hormone-sensitive prostate cancer (mHSPC) randomized to darolutamide 600 mg orally twice daily (n = 651) or placebo (n = 654), both with ADT + docetaxel. The proportion of patients with undetectable PSA (<0.2 ng/ml) and time to PSA progression (≥25% relative and ≥2 ng/ml absolute increase from nadir) were compared between groups in prespecified exploratory analyses. PSA outcomes by disease volume and the association of undetectable PSA with OS and times to castration-resistant prostate cancer (CRPC) and PSA progression were assessed in post hoc analyses. KEY FINDINGS AND LIMITATIONS: The proportion of patients with undetectable PSA at any time was more than doubled with darolutamide versus placebo, at 67% versus 29% in the overall population, 62% versus 26% in the high-volume subgroup, and 84% versus 38% in the low-volume subgroup. Darolutamide delayed time to PSA progression versus placebo, with hazard ratios of 0.26 (95% confidence interval [CI] 0.21-0.31) in the overall population, 0.30 (95% CI 0.24-0.37) in the high-volume subgroup, and 0.093 (95% CI 0.047-0.18) in the low-volume subgroup. Undetectable PSA at 24 wk was associated with longer OS, with a hazard ratio of 0.49 (95% CI 0.37-0.65) in the darolutamide group, as well as longer times to CRPC and PSA progression, with similar findings in the disease volume subgroups. CONCLUSIONS AND CLINICAL IMPLICATIONS: Darolutamide + ADT + docetaxel led to deep and durable PSA responses in patients with high- or low-volume mHSPC. Achievement of undetectable PSA (<0.2 ng/ml) was correlated with better clinical outcomes. PATIENT SUMMARY: For patients with metastatic hormone-sensitive prostate cancer being treated with androgen deprivation therapy and docetaxel, PSA (prostate-specific antigen) became undetectable (below 0.2 ng/ml) in 67% of those also receiving darolutamide versus 29% of patients also receiving placebo. On average, patients achieving undetectable PSA lived longer than patients with detectable PSA.

Prostate-Specific Antigen Screening in Smokers: A Comprehensive Analysis Using a National Behavioral Survey.

INTRODUCTION: Cigarette smoking is associated with higher-risk prostate cancer at the time of diagnosis and increased overall and prostate cancer‒specific mortality. Previous studies indicate smokers are less likely to undergo PSA screening. Herein we investigate the association between smoking and PSA screening using a nationally representative US survey. We hypothesize that smokers are less likely to undergo guideline-concordant PSA screening. METHODS: We performed a cross-sectional analysis of men aged 55 to 69 who responded to the cigarette smoking and PSA screening questions of the 2018 Behavioral Risk Factor Surveillance System survey. Adjusted prevalence and adjusted risk differences were calculated using complex weighted multivariable Poisson regression modeling. RESULTS: We identified 58,996 individuals who qualified for analysis. PSA screening prevalence was 39% (95% CI: 39%-40%) nationally, 42% (95% CI: 41%-44%) for never smokers, 42% (95% CI: 39%-40%) for former smokers, and 27% (95% CI: 25%-29%) for current smokers, including 27% (95% CI: 24%-29%) for daily smokers and 29% (95% CI: 24%-33%) for nondaily smokers. Compared to never smokers, the adjusted relative risk for undergoing PSA screening was 0.81 for current smokers (95% CI: 0.75-0.88, P < .01) and 0.99 for former smokers (95% CI: 0.94-1.03, P = .53). CONCLUSIONS: Current smokers are less likely to undergo recommended PSA screening, but former smokers are screened at similar rates as never smokers. As delays in diagnosis may substantially contribute to worse prostate cancer outcomes, targeted interventions to increase screening in this population may yield significant effects.

Interassay Variability and Clinical Implications of Five Different Prostate-specific Antigen Assays.

Background and objective: Prostate-specific antigen (PSA) remains a critical marker for prostate cancer (PCa) detection and monitoring. Recognising historical variability in PSA assays and the evolution of assay technology and calibration, this study aims to reassess interassay variability using the latest generation of five assays in a contemporary cohort of men undergoing prostate biopsy. Methods: Five different commercially available PSA assays were tested in a blood sample of 76 men before undergoing a prostate biopsy. Total PSA (tPSA) and free-to-total PSA ratio (%fPSA) were compared across assays, using Roche (Basel, Switzerland) as the benchmark, and correlated with biopsy outcome to analyse the impact on PCa diagnosis. The statistical analysis included Passing-Bablok regression and Bland-Altman plots, with a p value threshold of <0.05 for significance. Key findings and limitations: Among the 76 men, 28 (36.8%) were diagnosed with significant PCa (defined as International Society of Urological Pathology grade ≥2). A high correlation was observed between tPSA and %fPSA values among the different PSA assays tested (r2 ≥ 0.9). The Passing-Bablok analysis showed that tPSA results varied substantially among the assays, with slopes ranging between 0.78 and 1.04. Compared with the tPSA of Roche, tPSA values were on average 20.7% lower by Beckman (Oststeinbeck, Germany), 15.2% lower by Abbott (Chicago, IL, USA), 6.1% lower by Diasorin (Saluggia, Italy), and 9.6% higher by Brahms (Hennigsdorf, Germany; p < 0.001 for all). The %fPSA values by Abbott and Brahms were higher at 15.7% and 10.6%, respectively (p < 0.001), while the Beckman and Diasorin values had minimal differences of -0.3% and 2.3%, respectively (p > 0.05). The variability across assays would have resulted in discrepancies in both the sensitivity and the specificity for tPSA and %fPSA by at least 14%, depending on the cut-offs applied. Conclusions and clinical implications: Despite the use of the latest PSA assays, relevant variability of tPSA and %fPSA results can be observed among different assays. There is an urgent need for standardised calibration methods and greater awareness among practitioners concerning interassay variability. Clinicians should acknowledge that clinically relevant thresholds may depend on the specific PSA assay and that ideally the same assay is applied over time for better clinical decision-making. Patient summary: Prostate-specific antigen (PSA) is a critical marker for prostate cancer (PCa) detection and monitoring. However, significant variations were observed in the results of the latest PSA assays. Thus, standardised calibration methods and greater awareness among practitioners concerning interassay variability are needed.

Increase of prostate-specific antigen doubling time predicts survival in metastatic castration-resistant prostate cancer patients undergoing radium therapy.

OBJECTIVE: Radium-223 (Ra-223) is an important treatment modality for bone-dominant metastatic castration-resistant prostate cancer (mCRPC). However, there is currently a lack of effective markers to monitor treatment response during treatment. We aim to investigate the response in prostate-specific antigen doubling time (PSADT) as a potential marker for assessing Ra-223 treatment in mCRPC patients. METHODS: We retrospectively collected data from mCRPC patients who underwent radium treatment at our institution between August 2020 and June 2023. Prostate-specific antigen (PSA) measurements prior to treatment and during treatment were collected. Baseline PSADT was calculated from PSA measurements prior to Ra-223 treatment; interim PSADT was calculated from PSA measurements before Ra-223 treatment and prior to the fourth course injection. Overall survival was calculated from the start of treatment to the date of death. Univariable and multivariable analysis using the Cox proportional hazards model were performed to examine the association of factors with overall survival. RESULTS: We included 35 patients from our institution, with a median overall survival of 13.3 months. Eighteen (51.4%) completed all six courses of treatment. PSA dynamic response (interim PSADT > baseline PSADT or decreased PSA) was observed in 20 patients. Overall survival was associated with a PSA dynamic response (HR = 0.318, 95% CI 0.133-0.762, p = 0.010) when compared to patients without response. CONCLUSIONS: Dynamic changes in PSADT were associated with survival in mCRPC patients receiving radium therapy. Comparing interim and baseline PSADT could serve as a valuable marker for determining treatment benefits.

Controlled silver electrodeposition on gold nanoparticle antibody tags for ultrasensitive prostate specific antigen sensing using electrochemical and optical smartphone detection.

One of the current challenges in medicine is to achieve a rapid and unequivocal detection and quantification of extremely low levels of disease biomarkers in complex biological samples. Here, we present the development and analytical evaluation of a low-cost smartphone-based system designed for ultrasensitive detection of the prostate-specific antigen (PSA) using two detection alternatives: electrochemical or optical, by coupling the smartphone with a portable potentiostat or magnifying lenses. An antibody tagged with gold nanoparticles (AuNPs), and indium tin oxide coated polyethylene terephthalate platform (ITO-PET) have been used to develop a sandwich-type immunoassay. Then, a controlled silver electrodeposition on the AuNPs surface is carried out, enhancing their size greatly. Due to such strong nanoparticle-size amplification (from nm to µm), the final detection can be dual, by measuring current intensity or the number of silver-enlarged microstructures generated. The proposed strategies exhibited limit detections (LOD) of 102 and 37 fg/mL for electrochemical and optical detection respectively. The developed immunosensor reaches excellent selectivity and performance characteristics to quantify biomarkers at clinically relevant values without any pretreatment. These proposed procedures could be useful to check and verify possible recurrence after clinical treatment of tumors or even report levels of disease serum biomarkers in early stages.

Predictive Value of Magnetic Resonance Imaging Radiomics Combined with Serum PSA for the Extracapsular Extension of Prostate Cancer Prediction.

OBJECTIVE: We aimed to investigate the value of magnetic resonance imaging (MRI) radiomics combined with serum prostate-specific antigen (PSA) in predicting the extracapsular extension (ECE) of prostate cancer. METHODS: In total, 213 patients with prostate cancer admitted to our hospital from May 2021 to April 2023 were retrospectively enrolled as observation subjects. Based on the presence or absence of extracapsular extension, the patients were divided into occurrence (n = 70) and non-occurrence (n = 143) groups. The clinical data, PSA levels, Prostate Imaging Reporting and Data System (PI-RADS®), and MRI-ECE scores of the two groups were compared. RESULTS: In total, 80 patients were included in the occurrence (n = 40) and non-occurrence groups (n = 40), and no statistical significance was observed in the baseline data of the two groups. Preoperative PSA levels were significantly higher in the occurrence group than in the non-occurrence group, and the PI-RADS and MRI-ECE scores of each group differed significantly (p < 0.05). The area under the curve (AUC) for the combined determination of PSA levels and PI-RADS and MRI-ECE scores was 0.900, which was significantly higher than the AUC for the individual determination of the mentioned indicators (p < 0.05). CONCLUSIONS: The combination of MRI radiomics and PSA can accurately predict the extracapsular extension of prostate cancer; Thus, it is a favorable reference for subsequent precise diagnosis and treatment.

Case report: Prostatic malakoplakia: a rare disease that has a profile mimicking prostate cancer.

Prostatic malakoplakia (PMP) is a rare inflammatory disease, and misdiagnosis on imaging is a major reason for unnecessary punctures; however, information on imaging is even rarer. Five patients with PMP between May 2022 and February 2023 were enrolled in this study to summarize the imaging manifestations. All patients underwent ultrasound (US)-guided prostate biopsy and were confirmed by pathology, and the presence of prostate cancer was also excluded by pathology. The five patients, with a median age of 71 years (range = 58-74 years), had a median total prostate-specific antigen (T-PSA) of 10.40 ng/mL (range = 1.74-63.42 ng/mL). In two patients, chest computed tomography showed pulmonary infections. All patients underwent magnetic resonance imaging (MRI). Of these patients, four had a Prostate Imaging-Reporting and Data System (PIRADS) score of 5, while one had a score of 4. The lesions were mostly distributed in the peripheral zone of the prostate and appeared as a high signal on T1-weighted imaging (T1WI) and a low signal on T2-weighted imaging (T2WI). In the US examination, four patients had abnormal prostate morphology, with an unsmooth envelope and non-uniform parenchymal echogenicity. Four patients had increased prostate volume. US showed a hypoechoic nodule with non-uniform internal echogenicity, and an abundant internal blood flow signal was detected by color Doppler US. PSA, MRI, and US were not specific for PMP in our study, but we found that a history of co-infection may be helpful in an accurate diagnosis and to avoid unnecessary biopsy.

Evaluación del valor predictivo negativo de la resonancia magnética multiparamétrica de próstata al combinar su puntuación con parámetros del antígeno prostático específico en pacientes con PSA en zona gris / The effect of the combination of prostate-specific antigen derivatives with multiparametric prostate magnetic resonance imaging scores on the negative predictive value of it in grey zone patients

Objetivo Calcular el valor predictivo negativo (VPN) de la resonancia magnética multiparamétrica (RMmp) de próstata negativa, definida como la ausencia de lesiones en las imágenes, cuando se combina con la densidad del PSA (DPSA) y el índice PSA libre/total (PSA l/t) en pacientes cuyo PSA se encuentra en la zona gris (4-10mg/ml). Métodos Se analizaron 191 pacientes con niveles de PSA entre 4 y 10mg/ml y RMmp negativa. El VPN de la RMmp negativa se calculó de acuerdo con un nivel de DPSA<0,15ng/ml/ml, un índice PSA l/t>0,15 y una combinación de ambos. Los pacientes se dividieron en 3 grupos de riesgo según estos dos parámetros, de la siguiente manera: • DPSA 0,01-0,07ng/ml/ml e índice PSA l/t≥25 en el grupo de bajo riesgo. • DPSA 0,08-0,15ng/ml/ml e índice PSA l/t 0,15-0,24 en el grupo de riesgo intermedio. • DPSA>0,15ng/ml/ml e índice PSA l/t<15 en el grupo de riesgo alto. Resultados El VPN de la RMmp negativa fue del 92,6% para el carcinoma de próstata clínicamente significativo (CPCS). El VPN aumentó al 97,5% en el grupo de riesgo bajo, y disminuyó al 33,3% en el de riesgo alto. El resultado al combinar la RMmp negativa con la DPSA<0,15ng/ml/ml fue muy similar al de su combinación con el PSA l/t>15. Conclusión el índice PSA l/t también podría utilizarse para aumentar el VPN de la RMmp, al igual que la DPSA. No recomendamos evitar la biopsia de próstata con una DPSA>0,15ng/ml/ml y un índice PSA l/t<0,15. Sin embargo, se requieren estudios controlados aleatorizados con más pacientes para confirmar los hallazgos de nuestro estudio. (AU)

Objective To calculate the negative predictive value (NPV) of negative multiparametric prostate magnetic resonance imaging (mpMRI), accepted as no lesions on images, when combined with prostate-specific antigen density (PSAD) and free/total prostate-specific antigen ratio (f/t PSA) in grey zone patients. Methods One hundred ninety-one patients with PSA levels between 4-10mg/ml and negative mpMRI were analyzed. The NPV of negative mpMRI was calculated according to a PSAD level of <0.15 ng/ml/ml, f/t PSA ratio of >0.15, and a combination of both. Patients were divided into three risk groups according to these two parameters: • PSAD 0.01-0.07 ng/ml/ml and f/t PSA ratio ≥25 in a low-risk group. • PSAD 0.08-0.15 ng/ml/ml, and f/t PSA ratio 0.15-0.24 in an intermediate-risk group and high-risk group. • PSAD>0.15 ng/ml/ml and f/t PSA ratio <15 in high-risk group, Results NPV of negative mpMRI was 92.6% for clinically significant prostate carcinoma (CSPCa). It increased to 97.5% in a low-risk group and decreased to 33.3% for CSPCa in a high-risk group. NPV of negative mpMRI results were so close when combined with PSAD <0.15 ng/ml/ml and f/t PSA>15. Conclusion f/t PSA ratio might also be used to increase the NPV of mpMRI, like PSAD. We advise not to avoid prostate biopsy when PSAD is >0.15 ng/ml/ml and the f/t PSA ratio is <0.15. However, we need randomized controlled studies with more patients to confirm our study. (AU)

Prediagnostic Prostate-specific Antigen Testing and Clinical Characteristics in Men with Lethal Prostate Cancer.

Background and objective: Prostate cancer (PC) is the fifth leading cause of cancer-related mortality in men worldwide. Opportunistic testing with prostate-specific antigen (PSA) has limited impact on PC mortality. Our objective was to assess prediagnostic PSA testing patterns and clinical characteristics at diagnosis in men with lethal PC. Methods: We conducted a population-based observational study of all men dying from PC in Stockholm County, Sweden, from 2015 to 2019. Data were retrieved from the National Prostate Cancer Register and the Stockholm PSA and Biopsy Register. If the first PSA was registered within 1 yr before diagnosis, men were categorised as PSA naïve. If an elevated PSA level was registered >1 yr before diagnosis without leading to prostate biopsy or repeating PSA within 1 yr, men were categorised as having delayed diagnosis. If a normal PSA level was registered within 5 yr before diagnosis, followed by an elevated PSA level that resulted in PC diagnosis within 1 yr, men were categorised as PSA tested. Clinical characteristics at diagnosis were stratified with D'Amico risk group classification. Key findings and limitations: Among 1473 men dying from PC, PSA test history was available for 995. Of these men, 60% (n = 592) were PSA naïve, 25% (n = 250) received delayed diagnosis, and 15% (n = 153) were PSA tested. After examining all 1473 men, 25% (n = 350) were diagnosed with low- or intermediate-risk cancer, 48% (n = 687) with high-risk cancer, and 27% (n = 385) with metastatic disease. Limitations include the retrospective design. Conclusions and clinical implications: Many men with lethal PC lacked PSA testing before diagnosis or had been tested without subsequent follow-up. Nearly half of the study population was diagnosed with high-risk cancer and almost one-third with metastatic disease. These findings suggest further evaluation of the current opportunistic PSA testing approach. Patient summary: Data from a population-based observational study of men dying from prostate cancer showed that many of them did not undergo either prostate-specific antigen (PSA) testing before diagnosis or subsequent follow-up if tested. These findings implicate deficiencies in the current opportunistic PSA testing approach.

A Comprehensive National Survey of Prostate-specific Antigen Testing and Prostate Cancer Management in France: Uncovering Regional and Temporal Disparities.

We report nationwide real-life practice in the management of prostate cancer (PC) in France in a population of 4936750 men. All prostate-specific antigen (PSA) blood tests performed between 2006 and 2018 were recorded in a National Health registry, which allowed to identify 692516 men diagnosed with PC and a control population consisting of 3899509 men without PC. PSA tests, age at diagnosis, treatments, and survival were analysed. Their management was analysed by age range and compared in the different French regions. Disparities were found in age at PSA testing and management approaches (surveillance, and local and systemic therapies). We found that 50% of men had received five PSA blood tests, but the first PSA test was taken late in life, with a peak in the decade between 65 and 75 yr of age. Adoption of monitoring was low (12%). Older men appeared to receive a late diagnosis with reduced chances of curative therapy and a subsequent increase in mortality, but cautious interpretation of our data is warranted in view of competing morbidities and other causes of death. The incidence of metastases at diagnosis, indicated by the use of systemic therapies, increased progressively from 2011 onwards. PATIENT SUMMARY: In this study, we report nationwide real-life practice in the management of prostate cancer (PC) in France in a population of 4936750 men, including 692516 patients with PC. We found that the first prostate-specific antigen test is taken too late in life, leading to a late diagnosis with reduced chances of curative therapy and a subsequent increase in mortality.

BioPrev-C - development and validation of a contemporary prostate cancer risk calculator.

Objectives: To develop a novel biopsy prostate cancer (PCa) prevention calculator (BioPrev-C) using data from a prospective cohort all undergoing mpMRI targeted and transperineal template saturation biopsy. Materials and methods: Data of all men who underwent prostate biopsy in our academic tertiary care center between 11/2016 and 10/2019 was prospectively collected. We developed a clinical prediction model for the detection of high-grade PCa (Gleason score ≥7) based on a multivariable logistic regression model incorporating age, PSA, prostate volume, digital rectal examination, family history, previous negative biopsy, 5-alpha-reductase inhibitor use and MRI PI-RADS score. BioPrev-C performance was externally validated in another prospective Swiss cohort and compared with two other PCa risk-calculators (SWOP-RC and PBCG-RC). Results: Of 391 men in the development cohort, 157 (40.2%) were diagnosed with high-grade PCa. Validation of the BioPrev C revealed good discrimination with an area under the curve for high-grade PCa of 0.88 (95% Confidence Interval 0.82-0.93), which was higher compared to the other two risk calculators (0.71 for PBCG and 0.84 for SWOP). The BioPrev-C revealed good calibration in the low-risk range (0 - 0.25) and moderate overestimation in the intermediate risk range (0.25 - 0.75). The PBCG-RC showed good calibration and the SWOP-RC constant underestimation of high-grade PCa over the whole prediction range. Decision curve analyses revealed a clinical net benefit for the BioPrev-C at a clinical meaningful threshold probability range (≥4%), whereas PBCG and SWOP calculators only showed clinical net benefit above a 30% threshold probability. Conclusion: BiopPrev-C is a novel contemporary risk calculator for the prediction of high-grade PCa. External validation of the BioPrev-C revealed relevant clinical benefit, which was superior compared to other well-known risk calculators. The BioPrev-C has the potential to significantly and safely reduce the number of men who should undergo a prostate biopsy.

Comparative Study of Eclipse and RayStation Multi-Criteria Optimization-Based Prostate Radiotherapy Treatment Planning Quality.

Multi-criteria optimization (MCO) function has been available on commercial radiotherapy (RT) treatment planning systems to improve plan quality; however, no study has compared Eclipse and RayStation MCO functions for prostate RT planning. The purpose of this study was to compare prostate RT MCO plan qualities in terms of discrepancies between Pareto optimal and final deliverable plans, and dosimetric impact of final deliverable plans. In total, 25 computed tomography datasets of prostate cancer patients were used for Eclipse (version 16.1) and RayStation (version 12A) MCO-based plannings with doses received by 98% of planning target volume having 76 Gy prescription (PTV76D98%) and 50% of rectum (rectum D50%) selected as trade-off criteria. Pareto optimal and final deliverable plan discrepancies were determined based on PTV76D98% and rectum D50% percentage differences. Their final deliverable plans were compared in terms of doses received by PTV76 and other structures including rectum, and PTV76 homogeneity index (HI) and conformity index (CI), using a t-test. Both systems showed discrepancies between Pareto optimal and final deliverable plans (Eclipse: -0.89% (PTV76D98%) and -2.49% (Rectum D50%); RayStation: 3.56% (PTV76D98%) and -1.96% (Rectum D50%)). Statistically significantly different average values of PTV76D98%,HI and CI, and mean dose received by rectum (Eclipse: 76.07 Gy, 0.06, 1.05 and 39.36 Gy; RayStation: 70.43 Gy, 0.11, 0.87 and 51.65 Gy) are noted, respectively (p < 0.001). Eclipse MCO-based prostate RT plan quality appears better than that of RayStation.

Incorporating PHI in decision making: external validation of the Rotterdam risk calculators for detection of prostate cancer.

PURPOSE: External validation of existing risk calculators (RC) to assess the individualized risk of detecting prostate cancer (PCa) in prostate biopsies is needed to determine their clinical usefulness. The objective was to externally validate the Rotterdam Prostate Cancer RCs 3 and 4 (RPCRC-3/4) and that incorporating PHI (RPCRC-PHI) in a contemporary Spanish cohort. METHODS: Multicenter prospective study that included patients suspicious of harboring PCa. Men who attended the urology consultation were tested for PHI before prostate biopsy. To evaluate the performance of the prediction models: discrimination (receiver operating characteristic (ROC) curves), calibration and net benefit [decision curve analysis (DCA)] were calculated. These analyses were carried out for detection of any PCa and clinically significant (cs)PCa, defined as ISUP grade ≥ 2. RESULTS: Among the 559 men included, 337 (60.28%) and 194 (34.7%) were diagnosed of PCa and csPCa, respectively. RPCRC-PHI had the best discrimination ability for detection of PCa and csPCa with AUCs of 0.85 (95%CI 0.82-0.88) and 0.82 (95%CI 0.78-0.85), respectively. Calibration plots showed that RPCRC-3/4 underestimates the risk of detecting PCa showing the need for recalibration. In DCA, RPCRC-PHI shows the highest net benefit compared to biopsy all men. CONCLUSIONS: The RPCRC-PHI performed properly in a contemporary clinical setting, especially for prediction of csPCa.

Hypofractionated radiation therapy combined with androgen deprivation therapy for high-risk localized prostate cancer.

INTRODUCTION: This study aimed to analyse the treatment outcomes of moderately hypofractionated radiation therapy (RT) combined with androgen deprivation therapy (ADT) and the prognostic implications of prostate-specific antigen (PSA) kinetics in high-risk localized prostate cancer. METHODS: The medical records of 140 patients who underwent definitive RT (70 Gy in 28 fractions) combined with ADT were retrospectively reviewed. ADT consists of a gonadotropin-releasing hormone agonist and an anti-androgen. Clinical outcomes included the biochemical failure rate (BFR), clinical failure rate (CFR), overall survival (OS) and prostate cancer-specific survival (PCSS). The BFR and CFR were stratified by the PSA nadir and the time to the PSA nadir, respectively. Acute and late genitourinary and gastrointestinal adverse events were also recorded. RESULTS: The 5-year BFR, CFR, OS and PCSS rates were 9.8%, 4.5%, 90.2% and 98.7%, respectively. Ninety-five (67.9%) patients achieved a PSA nadir of 0.01 ng/mL. Patients with a PSA nadir >0.01 ng/mL had a significantly higher BFR and CFR (BFR, P = 0.001; CFR, P = 0.027), even after adjusting for other prognostic factors [per 0.1 ng/mL; BFR, hazard ratio (HR) 4.440, P < 0.001; CFR, HR 4.338, P = 0.001]. However, the time to the PSA nadir and pre-RT PSA were not significantly associated with the BFR and CFR. Six patients (4.3%) reported grade 3 late adverse events, mostly haematuria and haematochezia. CONCLUSION: Definitive RT with moderate hypofractionation combined with long-term ADT showed good efficacy for high-risk localized prostate cancer. The lowest PSA nadir was significantly associated with a low recurrence rate, indicating the importance of PSA follow-up.

A facile electrochemical immunosensor based on EDTA-Pb2+ complexation reaction.

The sensitivity of electrochemical (EC) sensors has been improved through the development of multiple approaches. However, the majority of EC sensors were limited in their practical application by high costs or tedious procedures. Herein, based on ethylenediaminetetraacetic acid (EDTA)-Pb2+ complexation reaction, a facile and affordable immunosensor was designed. Pb2+-magnesium silicate hydrate was served as the sensing substrate. The immunorecognition process was carried out in the Eppendorf tube, and antibody-functionalized Pb2+-polydopamine was utilized as immunoprobe. In the tube, the quantitative and appropriate excess of EDTA was introduced to complex with Pb2+ on the immunoprobes. The remaining EDTA was added to the sensing substrate surface to coordinate with some Pb2+ in it. This leaded to the reduction of the EC signal of Pb2+, which was related to the antigen concentration. Using prostate-specific antigen as the model analyte, the sensitive detection was realized with a low limit of detection (30.49 fg mL-1). Remarkably, the assay results were available within 24 min, sensibly faster than the most existing EC sensors.

Minimally invasive cytoreductive radical prostatectomy, exploring the safety and feasibility of a single-port or multi-port robotic platform.

BACKGROUND: Consolidative resection or cytoreductive radical prostatectomy (CRP) may benefit men with non-organ confined prostate cancer. We report the safety, feasibility, and outcomes of robot-assisted laparoscopic CRP using a single-port (SP) or multi-port (MP) platform. METHODS: We reviewed consecutive men with clinical node positive or metastatic castrate-sensitive prostate cancer who underwent IRB-approved CRP and extended pelvic lymph node dissection using the da Vinci SP or MP Surgical Systems (Intuitive Surgical, Sunnyvale, CA) from 2015-2022. Perioperative data and Clavien-Dindo 90-day complications were recorded. RESULTS: Twenty-four men with a median age of 61 (IQR 56-69) years and prostate-specific antigen of 32.1 (IQR 21.9-62.3) ng/mL were included. Clinical N1, M1, or N1 + M1 disease were detected in 8 (33%), 9 (38%), 7 (29%) patients, respectively. There was no difference in positive margins, 41% vs. 29% (P = 0.67), lymph node yield, 21 (IQR 14-28) vs. 20 (IQR 13.5-21) nodes (P = 0.31), or estimated blood loss, 150 mL (IQR 100-200) vs. 50 mL (IQR 50-125) (P = 0.06), between the MP and SP cohorts, respectively. Hospital length of stay was significantly shorter for the SP group, same-day discharge (IQR 0-0), compared to MP, 1-day (IQR 1-1), P < 0.001. One grade III bowel obstruction and lymphocele occurred in the MP cohort. No major complications occurred in the SP cohort. CONCLUSION: Robot-assisted laparoscopic CRP is safe and feasible for select men with advanced castrate-sensitive prostate cancer.

Factors Influencing Prostate Cancer Screening Intentions in Lebanese Men.

OBJECTIVE: The objective of this study is to investigate the perceived obstacles and willingness of Lebanese men aged 40 and above to undergo screening for prostate cancer. MATERIAL AND METHOD: A cross-sectional research design was employed. The study utilized a survey questionnaire to collect data on various factors influencing screening behaviors. The research instrument consisted of a comprehensive survey questionnaire that incorporated validated scales to assess barriers to prostate cancer screening, intention to screen, and the International Prostate Symptom Score (IPSS). RESULTS: The study found that the 120 participants had an average IPSS score of 7.20 ± 2.23, most people (70%) had mild symptoms of prostate cancer, whereas others had moderate (20%) or severe symptoms (10%). The majority of the men indicated a low to moderate inclination to undergo screening through Prostate-specific antigen testing, or digital rectal examination (DRE) (PSA), with 76% considering DRE and 70% considering PSA. The main barriers to screening included the dread of receiving distressing outcomes (48%) and a lack of understanding about the screening procedure (54%). The study identified key factors affecting the intention to undergo a prostate cancer screening. Regarding DREs, these factors included the perceived danger of the illness and prior information from doctors about prostate conditions. When it came to the intention to undergo screening through the prostate-specific antigen test (PSA), determinants included the perceived threat of the disease, one's general health perception, and prior information from doctors about prostate-related issues. Additionally, a significant proportion of participants believed that prostate cancer was not a serious illness (56%) and 57% thought DRE was embarrassing. CONCLUSIONS: The participants displayed a low willingness to get screened for prostate cancer. Implementing interventions that focus on increasing awareness of the disease and its associated risks could potentially reduce the barriers and boost participation in prostate cancer screening.

Reduction of false positives using zone-specific prostate-specific antigen density for prostate MRI-based biopsy decision strategies.

OBJECTIVES: To develop and test zone-specific prostate-specific antigen density (sPSAD) combined with PI-RADS to guide prostate biopsy decision strategies (BDS). METHODS: This retrospective study included consecutive patients, who underwent prostate MRI and biopsy (01/2012-10/2018). The whole gland and transition zone (TZ) were segmented at MRI using a retrained deep learning system (DLS; nnU-Net) to calculate PSAD and sPSAD, respectively. Additionally, sPSAD and PI-RADS were combined in a BDS, and diagnostic performances to detect Grade Group ≥ 2 (GG ≥ 2) prostate cancer were compared. Patient-based cancer detection using sPSAD was assessed by bootstrapping with 1000 repetitions and reported as area under the curve (AUC). Clinical utility of the BDS was tested in the hold-out test set using decision curve analysis. Statistics included nonparametric DeLong test for AUCs and Fisher-Yates test for remaining performance metrics. RESULTS: A total of 1604 patients aged 67 (interquartile range, 61-73) with 48% GG ≥ 2 prevalence (774/1604) were evaluated. By employing DLS-based prostate and TZ volumes (DICE coefficients of 0.89 (95% confidence interval, 0.80-0.97) and 0.84 (0.70-0.99)), GG ≥ 2 detection using PSAD was inferior to sPSAD (AUC, 0.71 (0.68-0.74)/0.73 (0.70-0.76); p < 0.001). Combining PI-RADS with sPSAD, GG ≥ 2 detection specificity doubled from 18% (10-20%) to 43% (30-44%; p < 0.001) with similar sensitivity (93% (89-96%)/97% (94-99%); p = 0.052), when biopsies were taken in PI-RADS 4-5 and 3 only if sPSAD was ≥ 0.42 ng/mL/cc as compared to all PI-RADS 3-5 cases. Additionally, using the sPSAD-based BDS, false positives were reduced by 25% (123 (104-142)/165 (146-185); p < 0.001). CONCLUSION: Using sPSAD to guide biopsy decisions in PI-RADS 3 lesions can reduce false positives at MRI while maintaining high sensitivity for GG ≥ 2 cancers. CLINICAL RELEVANCE STATEMENT: Transition zone-specific prostate-specific antigen density can improve the accuracy of prostate cancer detection compared to MRI assessments alone, by lowering false-positive cases without significantly missing men with ISUP GG ≥ 2 cancers. KEY POINTS: • Prostate biopsy decision strategies using PI-RADS at MRI are limited by a substantial proportion of false positives, not yielding grade group ≥ 2 prostate cancer. • PI-RADS combined with transition zone (TZ)-specific prostate-specific antigen density (PSAD) decreased the number of unproductive biopsies by 25% compared to PI-RADS only. • TZ-specific PSAD also improved the specificity of MRI-directed biopsies by 9% compared to the whole gland PSAD, while showing identical sensitivity.