Fe-single-atom catalysts boosting electrochemiluminescence via bipolar electrode integrated with its peroxidase-like activity for bioanalysis.

Multifunctional single-atom catalysts (SACs) have been extensively investigated as outstanding signal amplifiers in bioanalysis field. Herein, a type of Fe single-atom catalysts with Fe-nitrogen coordination sites in nitrogen-doped carbon (Fe-N/C SACs) was synthesized and demonstrated to possess both catalase and peroxidase-like activity. Utilizing Fe-N/C SACs as dual signal amplifier, an efficient bipolar electrode (BPE)-based electrochemiluminescence (ECL) immunoassay was presented for determination of prostate-specific antigen (PSA). The cathode pole of the BPE-ECL platform modified with Fe-N/C SACs is served as the sensing side and luminol at the anode as signal output side. Fe-N/C SACs could catalyze decomposition of H2O2 via their high catalase-like activity and then increase the Faraday current, which can boost the ECL of luminol due to the electroneutrality in a closed BPE system. Meanwhile, in the presence of the target, glucose oxidase (GOx)-Au NPs-Ab2 was introduced through specific immunoreaction, which catalyzes the formation of H2O2. Subsequently, Fe-N/C SACs with peroxidase-like activity catalyze the reaction of H2O2 and 4-chloro-1-naphthol (4-CN) to generate insoluble precipitates, which hinders electron transfer and then inhibits the ECL at the anode. Thus, dual signal amplification of Fe-N/C SACs was achieved by increasing the initial ECL and inhibiting the ECL in the presence of target. The assay exhibits sensitive detection of PSA linearly from 1.0 pg/mL to 100 ng/mL with a detection limit of 0.62 pg/mL. The work demonstrated a new ECL enhancement strategy of SACs via BPE system and expands the application of SACs in bioanalysis field.

Colorimetric and Photothermal Dual-Modal Switching Lateral Flow Immunoassay Based on a Forced Dispersion Prussian Blue Nanocomposite for the Sensitive Detection of Prostate-Specific Antigen.

Prostate-specific antigen (PSA) is a key marker for a prostate cancer diagnosis. The low sensitivity of traditional lateral flow immunoassay (LFIA) methods makes them unsuitable for point-of-care testing. Herein, we designed a nanozyme by in situ growth of Prussian blue (PB) within the pores of dendritic mesoporous silica (DMSN). The PB was forcibly dispersed into the pores of DMSN, leading to an increase in exposed active sites. Consequently, the atom utilization is enhanced, resulting in superior peroxidase (POD)-like activity compared to that of cubic PB. Antibody-modified DMSN@PB nanozymes serve as immunological probes in an enzymatic-enhanced colorimetric and photothermal dual-signal LFIA for PSA detection. After systematic optimization, the LFIA based on DMSN@PB successfully achieves a 4-fold amplification of the colorimetric signal within 7 min through catalytic oxidation of the chromogenic substrate by POD-like activity. Moreover, DMSN@PB exhibits an excellent photothermal conversion ability under 808 nm laser irradiation. Accordingly, photothermal signals are introduced to improve the anti-interference ability and sensitivity of LFIA, exhibiting a wide linear range (1-40 ng mL-1) and a low PSA detection limit (0.202 ng mL-1), which satisfies the early detection level of prostate cancer. This research provides a more accurate and reliable visualization analysis methodology for the early diagnosis of prostate cancer.

Dual-mode photoelectrochemical radar based on CdS quantum dot and Ce-MOF for detection of low-abundance disease-associated proteins.

Herein, we developed a convenient and versatile dual-mode electrochemiluminescence (ECL) and photoelectrochemistry (PEC) sensing radar for the detection of Prostate-specific antigen (PSA), which has important implications for detection of low-abundance disease-associated proteins. Cerium-based metal-organic framework (Ce-MOFs) were firstly modified on the electrode, showing well ECL and PEC property. In particular, a unique multifunctional Au@CdS quantum dots (QDs) probe loaded numerous QDs and antibody was fabricated, not only displaying strong ECL and PEC signals, but also having specific recognition to PSA. After the signal probe was linked to the electrode by immune reaction, much amplified signals of ECL and PEC were generated for double-mode detection of PSA. Therefore, this work proposed a multifunctional Au@CdS QDs signal probe with excellent ECL and PEC performance, and developed an ultrasensitive photoelectric biosensing platform for dual-mode detection, which provides an effective method for health monitoring of cancer patients.

Multiplexed Opto-Microfluidic Biosensing: Advanced Platform for Prostate Cancer Detection.

Cancer stands as a prominent global cause of mortality, necessitating early detection to augment survival rates and alleviate economic burdens on healthcare systems. In particular, prostate cancer (PCa), impacting 1.41 million men globally in 2020, accentuates the demand for sensitive and cost-effective detection methods beyond traditional prostate-specific antigen (PSA) testing. While clinical techniques exhibit limitations, biosensors emerge as compact, user-friendly alternatives to traditional laboratory approaches. However, existing biosensors predominantly concentrate on PSA detection, prompting the necessity for advancing toward multiplex sensing platforms. This study introduces a compact opto-microfluidic sensor featuring a substrate of gold nanospikes, fabricated via electrodeposition, for enhanced sensitivity. Embedded within a microfluidic chip, this nanomaterial enables the precise and concurrent measurement of PSA, alongside two complementary PCa biomarkers, matrix metalloproteinase-2 (MMP-2) and anti-α-methylacyl-CoA racemase (anti-AMACR) in diluted human plasma, offering a comprehensive approach to PSA analysis. Taking advantage of the localized surface plasmon resonance principle, this biosensor offers robustness and sensitivity in real sample analysis without the need for labeling agents. With the limit of detection at 0.22, 0.37, and 0.18 ng/mL for PSA, MMP-2, and anti-AMACR, respectively, this biosensing platform holds promise for point-of-care analysis, underscoring its potential impact on medical diagnostics.

Controlled-Release Electrochemiluminescence Biosensor with Strong Self-On Effect by a Multiple Signal Amplification Strategy for Trace Detection of Prostate-Specific Antigen.

The enhancement of sensitivity in biological analysis detection can reduce the probability of false positives of the biosensor. In this work, a novel self-on controlled-release electrochemiluminescence (CRE) biosensor was designed by multiple signal amplification and framework-enhanced stability strategies. As a result, the changes of the ECL signal were enhanced before and after the controlled-release process, achieving sensitive detection of prostate-specific antigen (PSA). Specifically, for one thing, Fe3O4@CeO2-NH2 with two paths for enhancing the generation of coreactant radicals was used as the coreaction accelerator to boost ECL performance. For another, due to the framework stability, zeolitic imidazolate framework-8-NH2 (ZIF-8-NH2) was combined with luminol to make the ECL signal more stable. Based on these strategies, the constructed CRE biosensor showed a strong self-on effect in the presence of PSA and high sensitivity in a series of tests. The detection range and limit of detection (LOD) were 5 fg/mL to 10 ng/mL and 2.8 fg/mL (S/N = 3), respectively, providing a feasible approach for clinical detection of PSA.

PSA-density, DRE, and PI-RADS 5: potential surrogates for omitting biopsy?

OBJECTIVE: In contrast to other malignancies, histologic confirmation prior treatment in patients with a high suspicion of clinically significant prostate cancer (csPCA) is common. To analyze the impact of extracapsular extension (ECE), cT-stage defined by digital rectal examination (DRE), and PSA-density (PSA-D) on detection of csPCA in patients with at least one PI-RADS 5 lesion (hereinafter, "PI-RADS 5 patients"). MATERIALS AND METHODS: PI-RADS 5 patients who underwent MRI/Ultrasound fusion biopsy (Bx) between 2016 and 2020 were identified in our institutional database. Uni- and multivariable logistic-regression models were used to identify predictors of csPCA-detection (GGG ≥ 2). Risk models were adjusted for ECE, PSA-D, and cT-stage. Corresponding Receiver Operating Characteristic (ROC) curves and areas under the curve (AUC) were calculated. RESULTS: Among 493 consecutive PI-RADS 5 patients, the median age and PSA was 69 years (IQR 63-74) and 8.9 ng/ml (IQR 6.0-13.7), respectively. CsPCA (GGG ≥ 2) was detected in 405/493 (82%); 36/493 patients (7%) had no cancer. When tabulating for PSA-D of > 0.2 ng/ml/cc and > 0.5 ng/ml/cc, csPCA was found in 228/253 (90%, PI-RADS5 + PSA-D > 0.2 ng/ml/cc) and 54/54 (100%, PI-RADS5 + PSA-D > 0.5 ng/ml/cc). Finally, a model incorporating PSA-D and cT-stage achieved an AUC of 0.79 (CI 0.74-0.83). CONCLUSION: In PI-RADS 5 patients, PSA-D and cT-stage emerged as strong predictors of csPCA at biopsy. Moreover, when adding the threshold of PSA-D > 0,5 ng/ml/cc, all PI-RADS 5 patients were diagnosed with csPCA. Therefore, straight treatment for PCA can be considered, especially if risk-factors for biopsy-related complications such as obligatory dual platelet inhibition are present.

NIR-II-Absorbing TMB Derivative for 1064 nm-Excited Photothermal Immunoassay.

Materials exhibiting strong absorption in the NIR-II region are appealing for photothermal conversion-based imaging, diagnosis, and therapy, due to better thermal effect and decreased absorption of water in such a region. 3,3',5,5'-Tetramethylbenzidine (TMB), the typical substrate in ELISA, has been explored in photothermal immunoassay, since its oxidation product (oxTMB) is photothermally active in the NIR region. However, its absorption at 1064 nm (the most often used laser wavelength in photothermal studies) is not appreciable, thus limiting the assay sensitivity. Here, we proposed a derivative of TMB (3,3'-dimethoxy-5,5'-dimethylbenzidine, 2-OCH3) bearing higher NIR-II absorption for 1064 nm-excited photothermal immunoassay. Since electron-donating groups can help decrease the energy gap of molecules (here -CH3 → -OCH3), the oxidation product of 2-OCH3 exhibited substantially red-shifted absorption as compared with oxTMB, leading to a more than twofold higher absorption coefficient at 1064 nm. As a result, 2-OCH3 showed enhanced sensitivity over TMB in a photothermal immunoassay (PTIA), yielding a limit of detection (LOD) of 0.1 ng/mL for prostate-specific antigen (PSA). The feasibility of 2-OCH3-based PTIA for diagnosis was further validated by analyzing PSA in 61 serum samples. Considering its superior photothermal performance, 2-OCH3 can be explored for a broad range of photothermal applications.

A sensitive immunosensing platform based on the high cathodic photoelectrochemical activity of Zr-MOF and dual-signal amplification of peroxidase-mimetic Fe-MOF.

Cathodic photoelectrochemical (PEC) analysis has received special concerns because of its outstanding anti-interference capability toward reductive substances in samples, so it is highly desirable to develop high-performance photocathodic materials for PEC analysis. Herein, a Zr-based metal-organic framework (Zr-MOF), MOF-525, is explored as a photoactive material in aqueous solution for the first time, which shows a narrow band-gap of 1.82 eV, excellent visible-light absorption, and high cathodic PEC activity. A sandwiched-type PEC immunosensor for detecting prostate-specific antigen (PSA) is fabricated by using MIL-101-NH2(Fe) label and MOF-525 photoactive material. MIL-101-NH2(Fe) as a typical Fe-MOF can serve as a peroxidase mimic to catalyze the production of precipitates on the photoelectrode. Both the produced precipitates and the MIL-101-NH2(Fe) labels can quench the photocathodic current, enabling "signal-off" immunosensing of PSA. The detection limit is 3 fg mL-1, and the linear range is between 10 fg mL-1 and 100 ng mL-1 for detecting PSA. The present study not only develops a high-performance Zr-MOF photoactive material for cathodic PEC analysis but also constructs a sensitive PEC immunosensing platform based on the dual-signal amplification of peroxidase-mimetic Fe-MOF.

Carbon quantum dots(CQDs)-sensitized CdS/CuInS2 heterojunction as a photoelectrochemical biosensing platform for highly sensitive detection of prostate-specific antigen.

Sensitive and quantitative detection of prostate-specific antigen (PSA) has been determined to be indispensable for clinical diagnostics of prostate cancer, whereas such detection is quite challenging due to the extremely low concentration of biomarkers in human serum samples. In this study, a photoelectrochemical (PEC) sensor was effectively developed for the high-sensitivity analysis of prostate-specific antigen (PSA) using a signal amplification method utilizing sensitized carbon quantum dots (CQDs). In this experiment, cadmium sulfide quantum dots were employed as the substrate materials, and indium copper sulfide quantum dots were loaded on their surfaces. Moreover, the efficient matching of energy levels in these two materials contributed to the generation of photocurrents. The aforementioned heterojunction semiconductor QDs were thus combined with CQDs to produce CQDs on their surfaces. As a result of the presence of CQDs, the ability of heterojunction materials to absorb light was remarkably enhanced, increasing the photocurrent by over ten times. Consequently, in this study, CQDs were combined with PEC sensors, and the developed PEC biosensors exhibited excellent optical performance, sensitivity, repeatability, and stability. The results obtained from the analysis of actual samples were satisfactory and have promising application prospects.

Bio-conjugated carbon dots for the bimodal detection of prostate cancer biomarkers via sandwich fluorescence and electrochemical immunoassays.

Bimodal detection facilitates the accurate and reliable detection of cancer biomarkers, which can assist in the early diagnosis of cancer. Herein, S-doped carbon dots (OCDs) with a size of 3 nm and blue emission were synthesized by the hydrothermal treatment of onion extract. The S-doped carbon dots were bioconjugated with an antibody (OCDs@PSAAbHRP) to design a nanoprobe for the detection of prostate specific antigen (PSA), an important serum based prostate cancer biomarker. The detection probe enabled the biomodal assay of PSA via fluorescence immunoassay (FIA) and electrochemical immunoassay (ECIA). In both assays, polyethylenimine stabilized polyaniline nanoparticles (PNPs) were used as the immobilization matrix, which played a major role in widening the linear range of biosensors (0.1 to 100 ng ml-1 for ECIA and 5 to 120 ng ml-1 for FIA). Paper-based and smartphone-integrated fluorescence immuno-array developed using the OCDs@PSAAbHRP detection probe provided cost-effective and rapid detection, while the electrochemical immunoassay provided a high sensitivity (7.8 µA ng-1 ml-1 cm-2) and low detection limit (38 pg ml-1) for PSA detection. The role of OCDs in enhancing the sensor performance was deciphered by carrying out detailed electrochemical studies with HRP enzyme-loaded OCDs. The biosensor was used to detect PSA in human blood serum samples and the results were consistent with conventional techniques. Owing to its analytical properties coupled with simplicity, cost-effectiveness, and portability, the bimodal sensor system has potential for application in clinical analysis.

Construction of Multi-Mode Photoelectrochemical Immunoassays for Accurate Detection of Cancer Markers: Assisted with MOF-Confined Plasmonic Nanozyme.

In clinical diagnostics, sensitive and accurate biomarker monitoring is greatly challenged by the limitations of false positive/negative errors in single-modal photoelectrochemical analysis. Herein, we propose a multimode immunoassay by integrating photoelectrochemical, colorimetric, and photothermal imaging analysis into one electrode. The immunosensors could simultaneously achieve three detection modes at one electrode, which provided a new pathway for the accurate detection of the target prostate-specific antigen (PSA) and circumvented false-positive or negative errors during the detection process. To this end, an integrated multifunctional chip (TiO2/ZIF-8/Cu(II)) was first constructed via in situ embedding of Cu(II) in the Metal-organic framework growth process. Then, an alkaline phosphatase-labeled magnetic probe was designed to achieve split-type detection for PSA. In a sodium thiophosphate solution, the in situ generated H2S could react with Cu(II) to form small-size CuS due to the nanoconfinement of ZIF-8 and thus result in the formation of p-n heterojunctions (TiO2/ZIF-8/CuS). The TiO2/ZIF-8/CuS could efficiently improve the light-harvesting ability and facilitate the charge separation efficiency, thus finally resulting in an increased photocurrent in the PEC mode. Furthermore, by constructing the portable colorimetric and photothermal sensors based on the Arduino microcontroller and photothermal imager, the TiO2/ZIF-8/CuS also provided point-of-care and visual detection modes, as the in situ-formed CuS exhibited peroxidase-mimicking activity and outstanding photothermal properties. The work had important prospects for establishing multimode immunoassays for the accurate detection of cancer markers in early disease diagnosis.

SERS-Temperature Dual-Mode T-type Lateral Flow Strip for Accurate Detection of Free and Total Prostate-Specific Antigens in Blood.

Accurate point-of-care (POC) analysis of cancer markers is the essence in the comprehensive early screening and treatment of cancer. Dual-mode synchronous detection is one of the effective approaches to reduce the probability of false negatives or false positives. As a result, this can greatly improve the accuracy of diagnosis. In this work, a surface-enhanced Raman scattering (SERS)-temperature dual-mode T-type lateral flow strip was fabricated to direct and simultaneous POC detection of total and free prostate-specific antigens (t-PSA and f-PSA) in blood. With the advantage of high stability of T-type lateral flow strip and simultaneous acquirement of assay results for t-PSA and f:t PSA ratio, the proposed method has high accuracy in the diagnosis of prostate cancer, especially in the diagnostic gray zone between 4.0 and 10.0 ng/mL. The SERS-temperature dual-signal has a good linear correlation with either f-PSA or t-PSA. To evaluate the clinical diagnostic performance of the proposed method, spiked human serum samples and the whole blood sample were analyzed. The assay results showed good recovery, and compared with traditional electrochemiluminescence immunoassay (ECLIA) method (t-PSA: 43.151; f/t ratio: 0.08), the results obtained by the proposed method were similar (t-PSA: 40.15 (SERS), 36.21 (temperature); f/t ratio: 0.08 (SERS), 0.08 (temperature), but the detection time (15 min) and cost ($0.05) had been greatly reduced. Therefore, the proposed SERS-temperature synchronous dual-mode T-type lateral flow strip has a strong application potential in the field of accurate large-scale diagnostics of prostate cancer on-site by simultaneous POC detection of t-PSA and f-PSA in blood.

Magnetically-assisted electrochemical immunoplatform for simultaneous detection of active and total prostate-specific antigen based on proteolytic reaction and sandwich affinity analysis.

Simultaneous detection of active and inactive proteases is clinically meaningful for improving diagnostic specificity. In this work, we reported an electrochemical method for simultaneous immunoassays of active and total proteases. Magnetic beads (MBs) were used as the solid supports for immobilization of capture antibodies and enrichment of targets. For the detection of active protease, the proteolytic-reaction-based analysis was carried out by the generation of Cu2+-binding peptide, in which a label-free peptide was used as the proteolytic substrate. The redox potential of the resulting peptide-Cu2+ complex was intrinsically distinguished from that of free Cu2+, thus allowing the "signal-on" detection of active protease. For the immunoassay of total protease in a sandwich-like format, electroactive metal-organic frameworks (Cu-MOFs) were used as the signal tags. The captured Cu-MOFs could directly produce a well-defined electrochemical signal from the reduction of Cu2+ ions. The analytical performances of the immunoplatform were evaluated by determining the model analytes of free and total prostate-specific antigen (fPSA and tPSA) in buffer and serum. The detection limits were found to be 0.3 pM for fPSA and 2 pM for tPSA. This work proposed a new strategy for simultaneous detection of active and total proteases, which should be evaluable for clinical diagnosis and treatment of protease-relative diseases.

European Association of Urology Biochemical Recurrence Risk Classification as a Decision Tool for Salvage Radiotherapy-A Multicenter Study.

BACKGROUND: The European Association of Urology (EAU) has proposed a risk stratification for patients harboring biochemical recurrence (BCR) after radical prostatectomy (RP). OBJECTIVE: To assess whether this risk stratification helps in choosing patients for salvage radiotherapy (SRT). DESIGN, SETTING, AND PARTICIPANTS: Analyses of 2379 patients who developed BCR after RP (1989-2020), within ten European high-volume centers, were conducted. Early and late SRT were defined as SRT delivered at prostate-specific antigen values <0.5 and ≥0.5 ng/ml, respectively. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable Cox models tested the effect of SRT versus no SRT on death and cancer-specific death. The Simon-Makuch method tested for survival differences within each risk group. RESULTS AND LIMITATIONS: Overall, 805 and 1574 patients were classified as having EAU low- and high-risk BCR. The median follow-up was 54 mo after BCR for survivors. For low-risk BCR, 12-yr overall survival was 87% versus 78% (p = 0.2) and cancer-specific survival was 100% versus 96% (p = 0.2) for early versus no SRT. For high-risk BCR, 12-yr overall survival was 81% versus 66% (p < 0.001) and cancer-specific survival was 98% versus 82% (p < 0.001) for early versus no SRT. In multivariable analyses, early SRT decreased the risk for death (hazard ratio [HR]: 0.55, p < 0.01) and cancer-specific death (HR: 0.08, p < 0.001). Late SRT was a predictor of cancer-specific death (HR: 0.17, p < 0.01) but not death (p = 0.1). CONCLUSIONS: Improved survival was recorded within the high-risk BCR group for patients treated with early SRT compared with those under observation. Our results suggest recommending early SRT for high-risk BCR men. Conversely, surveillance might be suitable for low-risk BCR, since only nine patients with low-risk BCR died from prostate cancer during follow-up. PATIENT SUMMARY: The impact of salvage radiotherapy (SRT) on cancer-specific outcomes stratified according to the European Association of Urology biochemical recurrence (BCR) risk classification was assessed. While men with high-risk BCR should be offered SRT, surveillance might be a suitable option for those with low-risk BCR.

Racial Disparities in Prostate Cancer Screening: The Role of Shared Decision Making.

INTRODUCTION: The 2018 U.S. Preventive Services Task Force recommendations endorsed shared decision making for men aged 55-69 years, encouraging consideration of patient race/ethnicity for prostate-specific antigen screening. This study aimed to assess whether a proxy shared decision-making variable modified the impact of race/ethnicity on the likelihood of prostate-specific antigen screening. METHODS: A cross-sectional analysis of men aged between 55 and 69 years, who responded to the prostate-specific antigen screening portions of the 2020 U.S.-based Behavioral Risk Factor Surveillance System survey, was performed between September and December 2022. Complex sample multivariable logistic regression models with an interaction term combining race and estimated shared decision making were used to test whether shared decision making modified the impact of race/ethnicity on screening. RESULTS: Of a weighted sample of 26.8 million men eligible for prostate-specific antigen screening, 25.7% (6.9 million) reported for prostate-specific antigen screening. In adjusted analysis, estimated shared decision making was a significant predictor of prostate-specific antigen screening (AOR=2.65, 95% CI=2.36, 2.98, p<0.001). The interaction between race/ethnicity and estimated shared decision making on the receipt of prostate-specific antigen screening was significant (pint=0.001). Among those who did not report estimated shared decision making, both non-Hispanic Black (OR=0.77, 95% CI=0.61, 0.97, p=0.026) and Hispanic (OR=0.51, 95% CI=0.39, 0.68, p<0.001) men were significantly less likely to undergo prostate-specific antigen screening than non-Hispanic White men. On the contrary, among respondents who reported estimated shared decision making, no race-based differences in prostate-specific antigen screening were found. CONCLUSIONS: Although much disparities research focuses on race-based differences in prostate-specific antigen screening, research on strategies to mitigate these disparities is needed. Shared decision making might attenuate the impact of race/ethnic disparities on the likelihood of prostate-specific antigen screening.

A pilot study of an organised population-based testing programme for prostate cancer.

OBJECTIVE: To determine the feasibility of a digitally automated population-based programme for organised prostate cancer testing (OPT) in Southern Sweden. PATIENTS AND METHODS: A pilot project for a regional OPT was conducted between September 2020 and February 2021, inviting 999 randomly selected men aged 50, 56, or 62 years. Risk stratification was based on prostate-specific antigen (PSA) level, PSA density (PSAD), and bi-parametric prostate magnetic resonance imaging (MRI). Men with a PSA level of 3-99 ng/mL had an MRI, and men with elevated PSA level (≥3 ng/mL) had a urological check-up, including a digital rectal examination and transrectal ultrasonography (TRUS). Indications for targeted and/or systematic transrectal prostate biopsies were suspicious lesions on MRI (Prostate Imaging-Reporting and Data System [PI-RADS] 4-5) and/or PSAD > 0.15 ng/mL/mL. Additional indications for prostate biopsies were palpable tumours, PSA ratio < 0.1, or cancer suspicion on TRUS. Patient selection, mail correspondence, data collection, and algorithm processing were performed by an automated digital management system. Feasibility is reported descriptively. RESULTS: A total of 418 men had a PSA test (42%), with increasing participation rates by age (50 years, 38%; 56 years, 44%; and 62 years, 45%). Among these, 35 men (8%) had elevated PSA levels (≥3 ng/mL: one of 139, aged 50 years; 10/143, aged 56 years; and 24/146, aged 62 years). On MRI, 16 men (48%) had a negative scan (PI-RADS < 3), seven men (21%) had PI-RADS 3, nine men (27%) had PI-RADS 4, and one man (3%) had PI-RADS 5. All men with PI-RADS 4 or 5 underwent prostate biopsies, as well as two men with PI-RADS 3 due to PSAD > 0.15 ng/mL/mL or a suspicious finding on TRUS. Prostate cancer was diagnosed in 10 men. Six men underwent active treatment, whereas four men were assigned to active surveillance. CONCLUSION: Our OPT model is feasible from an operational point of view, but due to the limited scale of this study no conclusions can be made regarding the efficacy of the diagnostic model or outcome.

Focal therapy with high-intensity focused ultrasound for prostate cancer: 3-year outcomes from a prospective trial.

OBJECTIVE: To assess the oncological and functional outcomes of focal high-intensity focused ultrasound (HIFU) in treating localised prostate cancer (PCa), a 3-year prospective study was undertaken using periodic post-ablation saturation biopsies. PATIENTS AND METHODS: Men with two or fewer lesions of grade group (GG) ≤3 PCa were eligible for participation. Additional criteria included a prostate-specific antigen (PSA) level of ≤15 ng/mL, clinical T1c-T2, and a life expectancy of ≥10 years. The primary endpoint was failure-free survival (FFS), defined as absence of clinically significant PCa (csPCa) in- or out-of-field on protocol-mandated saturation biopsy, no whole-gland or systemic salvage treatment, PCa metastasis, or PCa-related death. Results are reported using two distinct definitions of csPCa: (i) the presence of any GG ≥2 and (ii) any GG ≥3 or core involvement of ≥6 mm. Secondary endpoints were functional patient-reported outcome measures addressing urinary, sexual, and bowel function. RESULTS: A total of 91 patients were included: six (7%) with GG1 and 85 (93%) with GG ≥2. In all, 83 (91%) underwent at least one follow-up biopsy. Biopsy attendance at 6, 12, and 36 months was 84%, 67%, and 51%, respectively. The FFS at these time points for any GG ≥2 PCa was 79% (95% confidence interval [CI] 80-88%), 57% (95% CI 48-69%) and 44% (95% CI 34-56%), respectively. Using the second definition, FFS were 88% (95% CI 81-95%), 70% (95% CI 61-81%) and 65% (95% CI 55-77%), respectively. The 3-year cancer-specific survival was 100%, and freedom from metastasis was 99%. Magnetic resonance imaging (MRI) (negative predictive value of up to 89%, 95% CI 84-93%) and relative decrease of PSA values (P = 0.4) performed poorly in detecting residual disease. Urinary and bowel assessment returned to baseline questionnaire scores within 3 months. In all, 17 (21%) patients reported meaningful worsening in erectile function. A significant decrease of PCa related anxiety was observed. CONCLUSIONS: Focal HIFU treatment for localised PCa shows excellent functional outcomes with half of the patients remaining cancer-free after 3 years. Whole-gland treatment was avoided in 81%. Early follow-up biopsies are crucial to change or continue the treatment modality at the right time, while the use of MRI and PSA in detecting PCa recurrence is uncertain.

Prospective study of HDR brachytherapy (BT), external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT): 10-years experience of an MRI-guided approach.

OBJECTIVES: To evaluate the predictive factors for biochemical failure and distant metastases in a prospective cohort of patients with localized prostate cancer treated with the combination of HDR BT and EBRT. METHODS AND MATERIALS: Patients with intermediate (IR) or high-risk (HR) prostate adenocarcinoma received a single fraction of HDR of 15 Gy combined with RT of 37.5 Gy in 15 fractions. ADT duration was used depending on risk-group. Descriptive analyses were performed. Univariate and multivariate Hazard Ratios were obtained. Finally, the Kaplan-Meier model was used to describe the survival of the events of interest. RESULTS: 309 patients were treated prospectively (199 were IR and 110 HR). Median age was 72 years; 58.3 % were MRI stage ≤ T2c, 34.1 % T3a and 7.6 % T3b; ISUP-grade 1-3 in 78.9 % and ISUP 4-5 in 21.1 %. 71.8 % of patients had ≤ 50 % positive-cores in biopsy and 28.2 % had > 50 %. Median pre-treatment PSA was 9.9 ng/mL. After a median follow-up of 88 months, 41 patients presented biochemical failure and 18 developed distant metastases. Multivariate cox-regression analyses found that MR-T3b Stage (HR 3.88, p = 0.001) and ADT use (HR 3.99, p = 0.03) were the only predictive factors for biochemical failure and the number of positive cores (>50 %) the only independent predictive factor of distant metastases (HR 4.36, p = 0.002). CONCLUSIONS: Patients with mpMRI evidence of invasion of the SV and involvement of more than 50% of the cores in the prostate biopsy are patients with a higher risk of presenting a biochemical recurrence or developing metastasis due to their prostate cancer, respectively.

Based on PI-RADS v2.1 combining PHI and ADC values to guide prostate biopsy in patients with PSA 4-20 ng/mL.

PURPOSE: The study aimed to investigate the diagnostic accuracy of prostate health index (PHI) and apparent diffusion coefficient (ADC) values in predicting prostate cancer (PCa) and construct a nomogram for the prediction of PCa and clinically significant PCa (CSPCa) in Prostate Imaging-Reporting and Data System (PI-RADS) three lesions cohort. METHODS: This study prospectively enrolled 301 patients who underwent multiparametric magnetic resonance (mpMRI) and were scheduled for prostate biopsy. The receiver operating characteristic curve (ROC) was performed to estimate the diagnostic accuracy of each predictor. Univariable and multivariable logistic regression analysis was conducted to ascertain hidden risk factors and constructed nomograms in PI-RADS three lesions cohort. RESULTS: In the whole cohort, the area under the ROC curve (AUC) of PHI is relatively high, which is 0.779. As radiographic parameters, the AUC of PI-RADS and ADC values was 0.702 and 0.756, respectively. The utilization of PHI and ADC values either individually or in combination significantly improved the diagnostic accuracy of the basic model. In PI-RADS three lesions cohort, the AUC for PCa was 0.817 in the training cohort and 0.904 in the validation cohort. The AUC for CSPCa was 0.856 in the training cohort and 0.871 in the validation cohort. When applying the nomogram for predicting PCa, 50.0% of biopsies could be saved, supplemented by 6.9% of CSPCa being missed. CONCLUSION: PHI and ADC values can be used as predictors of CSPCa. The nomogram included PHI, ADC values and other clinical predictors demonstrated an enhanced capability in detecting PCa and CSPCa within PI-RADS three lesions cohort.

Biparametric Quantitative MRI for Prostate Cancer Detection.

OBJECTIVES: This study sought to prospectively investigate a novel quantitative biparametric prostate magnetic resonance imaging (MRI) protocol to detect prostate cancer (PCa) in biopsy-naïve men. Secondarily, this study reports the accuracy of fractional order calculus (FROC) diffusion and quantitative T2 compared with the Prostate Imaging Reporting & Data System (PI-RADS). METHODS: This prospective pilot study (NCT04175730) enrolled 50 prostate biopsy-naïve men who met eligibility criteria. All men received 3T MRI with T2 and diffusion-weighted imaging (DWI) (b-values: 50-4,000 s/mm2). Men with PI-RADS lesions ≥3 underwent targeted and systematic prostate biopsy, omitting systematic biopsy cores in peripheral zone lesions. DWI series images were fit to signal decay to calculate ADC (mm2/s) and the FROC model for coefficient DF (mm2/s). The primary end point was detection of Gleason grade group ≥2 (GG≥2) PCa. Receiver operating characteristic regression and area under the curve (AUC) were reported. RESULTS: Forty-eight men underwent MRI and biopsy. Mean age was 61.5 years (56-68), 29% were White, 52% were African American, mean PSA was 6.0 ng/mL (4.9-8.0), and mean PSA density was 0.14 ng/mL2. In total, 61 PI-RADS ≥3 lesions were targeted for biopsy. GG≥2 PC was found in 7% (1/14) of PI-RADS 3 lesions, 28% (10/36) of PI-RADS 4 lesions, and 36% (4/11) of PI-RADS 5 lesions. The AUC for detection of GG≥2 PC was 0.63 (0.5-0.76) for PI-RADS, 0.82 (0.68-0.96) for ADC, and 0.87 (0.77-0.97) for the FROC model. CONCLUSION: This small prospective pilot study demonstrates the feasibility of a novel quantitative biparametic MRI protocol to detect prostate cancer in biopsy-naïve men.