Folded flexure MOEMS for the detection of PSA and hepatitis DNA as biosensor for prostate cancer and viruses.

Micro-opto-electro-mechanical systems (MOEMS) biosensors are employed in various applications such as disease monitoring, drug investigation, detection of pollutants, and biological fluid studies. In this paper, a novel MOEMS biosensor based on a differential folded-flexure structure is introduced. The designed device is employed to detect prostate-specific antigen (PSA) protein and Hepatitis DNA. The target molecules cause a mechanical deflection in the folded-flexure; subsequently, the transmitted optical power across the finger, attached to the flexure, is modulated in proportion to the input concentration. Then, a photodiode power sensor measures the modulated optical power, where the output of the sensor is simply a current related to the target molecules' concentrations. The employed readout circuit operates at a wavelength of λ = 1550 nm with a laser power of 1 µW. The dimensions of the proposed biosensor are considered to be 365 × 340 × 2 µm³, making this sensor small enough and suitable for integration. The designed biosensor provides notable features of mechanical deflection sensitivities of 0.2053 nm/(ng/ml) and 7.2486 nm/nM, optical transmittance sensitivities of 0.535504 × 10-3 1/(ng/ml) and 18.91 × 10-3 1/nM, total output sensitivities of 0.5398 (mA/W)/(ng/ml) and 19.059 (mA/W)/nM, and measurement ranges of 0-1000 ng/ml and 0-28.33 nM for PSA and Hepatitis DNA, respectively. The proposed system is a sensitive and powerful sensor that can play an important role in diagnosing many diseases.

Outstanding increase in tumor-to-background ratio over time allows tumor localization by [89Zr]Zr-PSMA-617 PET/CT in early biochemical recurrence of prostate cancer.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) using prostate-specific membrane antigen (PSMA)-targeted radiotracers labeled with zirconium-89 (89Zr; half-life ~ 78.41 h) showed promise in localizing biochemical recurrence of prostate cancer (BCR) in pilot studies. METHODS: Retrospective analysis of 38 consecutive men with BCR (median [minimum-maximum] prostate-specific antigen 0.52 (0.12-2.50 ng/mL) undergoing [89Zr]Zr-PSMA-617 PET/CT post-negative [68Ga]Ga-PSMA-11 PET/CT. PET/CT acquisition 1-h, 24-h, and 48-h post-injection of a median (minimum-maximum) [89Zr]Zr-PSMA-617 tracer activity of 123 (84-166) MBq. RESULTS: [89Zr]Zr-PSMA-617 PET/CT detected altogether 57 lesions: 18 local recurrences, 33 lymph node metastases, 6 bone metastases in 30/38 men with BCR (78%) and prior negative conventional PSMA PET/CT. Lesion uptake significantly increased from 1-h to 24-h and, in a majority of cases, from 24-h to 48-h. Tumor-to-background ratios significantly increased over time, with absolute increases of 100 or more. No side effects were noted. After [89Zr]Zr-PSMA-617 PET/CT-based treatment, prostate-specific antigen concentration decreased in all patients, becoming undetectable in a third of patients. LIMITATIONS: retrospective, single center design; infrequent histopathological and imaging verification. CONCLUSION: This large series provides further evidence that [89Zr]Zr-PSMA-617 PET/CT is a beneficial imaging modality to localize early BCR. A remarkable increase in tumor-to-background ratio over time allows localization of tumor unidentified on conventional PSMA PET/CT.

Magnetic microbead-based upconversion immunoassay with laser-induced breakdown spectroscopy readout for the detection of prostate-specific antigen.

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.

Circulating Tumor Cell Count and Overall Survival in Patients With Metastatic Hormone-Sensitive Prostate Cancer.

Importance: In metastatic hormone-sensitive prostate cancer (mHSPC), new first-line combination therapies have enhanced overall survival (OS), but clinical outcomes for individual patients vary greatly and are difficult to predict. Peripheral blood circulating tumor cell (CTC) count is the most extensively validated prognostic liquid biomarker in metastatic castration-resistant prostate cancer (mCRPC), and recent studies have suggested that it may also be informative in mHSPC. Objective: To examine the prognostic value of CTC count in men with mHSPC. Design, Setting, and Participants: In this prognostic study, peripheral blood was drawn at registration (baseline) and at progression to mCRPC in the S1216 study (March 1, 2013, to July 15, 2017), a phase 3, prospective, randomized clinical trial in men with mHSPC. The CTCs were enumerated using a US Food and Drug Administration-cleared isolation platform. Counts were categorized as 0, 1 to 4, or 5 or more CTCs per 7.5 mL based on the prognostic value of these cut points in prior studies. The data analysis was performed between October 28, 2022, and June 15, 2023. Exposure: Metastatic hormone-sensitive prostate cancer. Main Outcomes and Measures: Circulating tumor cell count was evaluated for an association with 3 prespecified trial end points: OS, progression-free survival, and 7-month prostate-specific antigen, after adjusting for other baseline covariates using proportional hazards and logistic regression models. Results: Of 1313 S1216 participants (median [IQR] age, 68 [44-92] years), evaluable samples from 503 (median [IQR] age, 69 [46-90] years) with newly diagnosed mHSPC were collected at baseline, and 93 samples were collected at progression. Baseline counts were 5 or more CTCs per 7.5 mL in 60 samples (11.9%), 1 to 4 CTCs per 7.5 mL in 107 samples (21.3%), and 0 CTCs per 7.5 mL in 336 samples (66.8%). Median OS for men with 5 or more CTCs per 7.5 mL was 27.9 months (95% CI, 24.1-31.2 months) compared with 56.2 months (95% CI, 45.7-69.8 months) for men with 1 to 4 CTCs per 7.5 mL and not reached at 78.0 months follow-up for men with 0 CTCs per 7.5 mL. After adjusting for baseline clinical covariates, men with 5 or more CTCs per 7.5 mL at baseline had a significantly higher hazard of death (hazard ratio, 3.22; 95% CI, 2.22-4.68) and disease progression (hazard ratio, 2.46; 95% CI, 1.76-3.43) and a lower likelihood of prostate-specific antigen complete response (odds ratio, 0.26; 95% CI, 0.12-0.54) compared with men with 0 CTCs per 7.5 mL at baseline. Adding baseline CTC count to other known prognostic factors (covariates only: area under the curve, 0.73; 95% CI, 0.67-0.79) resulted in an increased prognostic value for 3-year survival (area under the curve, 0.79; 95% CI, 0.73-0.84). Conclusions and Relevance: In this prognostic study, the findings validate CTC count as a prognostic biomarker that improved upon existing prognostic factors and estimated vastly divergent survival outcomes regardless of subsequent lines of therapy. As such, baseline CTC count in mHSPC may serve as a valuable noninvasive biomarker to identify men likely to have poor survival who may benefit from clinical trials of intensified or novel regimens.

Serum ACSL4 levels in prostate cancer patients and its relationship between patient prognosis: A prospective observational study.

In this prospective observational study, our objective was to investigate the serum levels of Acyl-CoA synthetase long-chain family member 4 (ACSL4) in prostate cancer (PCa) patients and examine its association with other serum biomarkers, and the clinical outcomes of PCa patients. This prospective observational study was conducted from January 2019 to October 2021, including 103 cases of PCa patients and 101 cases of benign prostate hyperplasia (BPH) patients who received treatment at our hospital. All patients had their serum ACSL4 levels measured using enzyme-linked immunosorbent assay before treatment. The clinical outcomes included age, body mass index, gender, systolic blood pressure, diastolic blood pressure, tumor node metastasis stage, Gleason scores, and prostate volume and serum biomarkers were collected. All patients were followed up for 36 months, the overall survival and disease-free survival were recorded for all patients. All data used SPSS 26.0 for analysis. The phosphorus (P) and serum low-density lipoprotein cholesterol levels were significantly higher in PCa patients compared to BPH patients. Furthermore, compared to the BPH patients, the serum ACSL4 and free prostate-specific antigen levels were significantly decreased while serum total prostate-specific antigen (tPSA) levels were significantly elevated in PCa patients. Pearson correlation analysis showed a positive correlation between ACSL4 levels and free prostate-specific antigen levels, while a negative correlation was observed with P and tPSA levels. ACSL4 might serve as a biomarker for diagnosing PCa with the AUC was 0.747, cutoff value of 33.68 ng/mL, sensitivity of 70.3%, and specificity of 60.2%. Finally, we found that ACSL4, tPSA, and P were identified as risk factors associated with PCa patients. Our findings indicated that the serum levels of ACSL4 were significantly decreased in PCa patients compared to BPH patients. Serum ACSL4 could be used as a potential biomarker for early PCa diagnosis and prognosis.

Association of biological aging with prostate cancer: insights from the National Health and Nutrition Examination Survey.

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.

Long-Term Outcomes of Prostate-Specific Membrane Antigen-PET Imaging of Recurrent Prostate Cancer.

Importance: Although prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown improved sensitivity and specificity compared with conventional imaging for the detection of biochemical recurrent (BCR) prostate cancer, the long-term outcomes of a widespread shift in imaging are unknown. Objective: To estimate long-term outcomes of integrating PSMA-PET into the staging pathway for recurrent prostate cancer. Design, Setting, and Participants: This decision analytic modeling study simulated outcomes for patients with BCR following initial definitive local therapy. Inputs used were from the literature and a retrospective cohort study conducted at 2 institutions. The base case analysis assumed modest benefits of earlier detection and treatment, and scenario analyses considered prostate-specific antigen (PSA) level at imaging and different outcomes of earlier vs delayed treatment. The analysis was performed between April 1, 2023, and May 1, 2024. Exposures: (1) Immediate PSMA-PET imaging, (2) conventional imaging (computed tomography and bone scan [CTBS]) followed by PSMA-PET if CTBS findings were negative or equivocal, and (3) CTBS alone. Main Outcomes and Measures: The main outcomes were detection of metastases, deaths from prostate cancer, and life-years and quality-adjusted life-years (QALYs) gained. Results: The model estimated that per 1000 simulated patients with BCR (assumed median age, 66 years), PSMA-PET is expected to diagnose 611 (95% uncertainty interval [UI], 565-656) patients with metastasis compared with 630 (95% UI, 586-675) patients diagnosed using CTBS followed by PSMA-PET and 297 (95% UI, 202-410) patients diagnosed using CTBS alone. Moreover, the estimated number of prostate cancer deaths was 512 (95% UI, 472-552 deaths) with PSMA-PET, 520 (95% UI, 480-559 deaths) with CTBS followed by PSMA-PET, and 587 (95% UI, 538-632 deaths) with CTBS alone. Imaging with PSMA-PET yielded the highest number of QALYs, which were 824 (95% UI, 698-885) higher than CTBS. These results differed by PSA level at the time of testing, with the highest incremental life-years and QALYs and lowest number of deaths from prostate cancer among patients with PSA levels of at least 5.0 ng/mL. Finally, the estimates were sensitive to the expected benefit of initiating therapy for recurrent prostate cancer earlier in the disease course. Conclusions and Relevance: The results of this decision-analytic model suggest that upfront PSMA-PET imaging for the evaluation of BCR is expected to be associated with reduced cancer mortality and gains in life-years and QALYs compared with the conventional imaging strategy, assuming modest benefits of earlier detection and treatment.

Comparison in prostate cancer diagnosis with PSA 4-10 ng/mL: radiomics-based model VS. PI-RADS v2.1.

BACKGROUND: To evaluate accuracy of MRI-based radiomics in diagnosing prostate cancer (PCa) in patients with PSA levels between 4 and 10 ng/mL and compare it with the latest Prostate Imaging Reporting and Data System (PI-RADS v2.1) score. METHODS: 221 patients with prostate lesions and PSA levels in 4-10 ng/mL, including 154 and 67 cases in the training and validation groups. Pathological confirmation of all patients was accomplished by the use of MRI-TRUS fusion targeted biopsy or systematic transrectal ultrasound (TRUS) guided biopsy. 851 radiomic features were extracted from each lesion of ADC and T2WI images. The least absolute shrinkage and selection operator (LASSO) regression algorithm and logistic regression were employed to select features and build the ADC and T2WI model. The combined model was obtained based on the ADC and T2WI features. The clinical benefit and diagnostic accuracy of the three radiomics models and PI-RADS v2.1 score were evaluated. RESULTS: 10 radiomic features were ultimately selected from the ADC images, 13 from the T2WI images and 7 from the combined models. The ADC, T2WI and combined models achieved satisfactory diagnostic accuracy in the training [AUC:0.945 (ADC), 0.939 (T2WI), 0.979 (combined)] and validation groups [AUC: 0.942 (ADC), 0.943 (T2WI), 0.959 (combined)], which was significantly higher than those in PI-RADS v2.1 model (0.825 for training cohort and 0.853 for validation cohort). Compared with the PI-RADS v2.1 score, the three radiomics models generated superior PCa diagnostic performance in both the training (p = 0.002, p = 0.005, p < 0.001) and validation groups (p = 0.045, p = 0.035, p = 0.015). CONCLUSION: Radiomics based on ADC and T2WI images can better identify PCa in patients with PSA 4-10 ng/mL, and MRI-based radiomics significantly outperforms the PI-RADS v2.1 score. CLINICAL TRIAL NUMBER: Not applicable.

Genetic associations of visfatin polymorphisms with clinicopathologic characteristics of prostate cancer in Taiwanese males.

The most general cancer in men is prostate cancer (PCa), with its risk increasing due to age and obesity. Visfatin, a member of adipokines, is related to cancer progression and metastasis, but its relationship in PCa remains undetermined. In addition, no knowledge is available regarding relations between visfatin polymorphisms and clinicopathological characteristics in PCa. We sought to investigate the functions of four visfatin gene polymorphisms and clinicopathological characteristics on the hazard of developing PCa in 695 Taiwanese males with PCa. Carriers of the GA+AA heterozygote of SNP rs61330082 were at a markedly higher risk of biochemical recurrence than those with the GG genotype. Visfatin rs61330082 and rs11977021 were related with a high risk of perineural invasion, lymphovascular invasion, and biochemical recurrence in prostate-specific antigen (PSA) > 10 PCa patients. The Cancer Genome Atlas database noted that visfatin mRNA level did not prominently differ with pathological T/N stage and overall survival. This finding is the first to document a connection between visfatin polymorphisms and clinicopathological characteristics of PCa in Taiwanese males.

The impact of non-structured PSA testing on prostate cancer-specific mortality on New Zealand Maori men.

OBJECTIVES: To assess the impact of differences in Prostate-Specific Antigen (PSA) testing rates on prostate cancer (PCa) diagnosis and PCa-specific mortality among Maori men in a New Zealand (NZ) population. PATIENTS AND METHODS: Maori 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 Maori 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 Maori men, lower PSA testing rates were associated with a higher risk of PCa-related death. Therefore, regular PSA testing for Maori could improve cancer-specific survival among Maori men. Regular PSA testing should be considered a priority area for improving PCa survival in this population.

Fluorescence Immunoassay of Prostate-Specific Antigen Using 3D Paddle Screw-Type Devices and Their Rotating System.

In this paper, we present a sensitive and highly reproducible fluorescence immunosensor for detecting PSA in human serum. A unique feature of this study is that it uses creatively designed paddle screw-type devices and their custom-made rotating system for PSA immunoassay. The paddle screw devices were designed to maximize the surface-to-volume ratio over which the immunoassay reaction could occur to improve detection sensitivity. This paddle screw-based immunoassay offers an accessible and efficient method with a short analysis time of less than 30 min. Active rotation of the paddle screw plays a crucial role in fast and accurate analysis of PSA. Additionally, a paddle screw-based immunoassay and subsequent fluorescence detection using a custom prototype fluorescence detection system were compared to a typical well plate-based immunoassay system. Results of PSA detection in human serum showed that the detection sensitivity through the paddle screw-based analysis improved about five times compared to that with a well plate-based analysis.

Perspectives and Misconceptions of an Online Adult Male Cohort Regarding Prostate Cancer Screening.

INTRODUCTION: Congruent with most guideline publishers, the Canadian Urological Association (CUA) recommends shared decision-making (SDM) on PSA screening (PSAS) for prostate cancer (PCa) following a discussion of its benefits and harms. However, there are limited data on how the general male population feels about these topics. METHODS: A survey was completed by 906 male-identifying participants (age > 18) recruited via Amazon Mechanical Turk (MTurk), which is a crowdsourcing platform providing minimal compensation. Participants answered questions regarding demographics (15), personal/family history (9), PCa/PSA knowledge (41), and opinions regarding PSAS (45). RESULTS: The median age was 38.2 (SD = 12.0), with 22% reporting a family history of PCa and 20% reporting personally undergoing PSAS. Although most participants had heard of PCa (85%) and that they could be screened for it (81%), they generally did not feel knowledgeable about PCa or PSAS guidelines. Most want to talk to their clinician about PCa and PSAS (74%) and are supportive of SDM (48%) or patient-centered decision-making (25%). In general, participants thought PSAS was still worthwhile, even if it led to additional testing or side effects. Similarly, participants thought higher-risk patients should be screened earlier (p < 0.001). A number of misconceptions were evident in the responses. CONCLUSIONS: Men approaching the age of PSAS do not feel knowledgeable about PCa or PSAS and want their clinician to discuss these topics with them. The majority believe in PSAS and would like to undergo this screening following SDM. Clinicians also have a role in correcting common misconceptions about PCa.

Phase 3 Trial of Stereotactic Body Radiotherapy in Localized Prostate Cancer.

BACKGROUND: Whether stereotactic body radiotherapy (SBRT) is noninferior to conventionally or moderately 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 T1 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). Androgen-deprivation 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 91.6%. At a median follow-up of 74.0 months, the 5-year incidence of freedom from biochemical or clinical failure was 95.8% (95% confidence interval [CI], 93.3 to 97.4) in the SBRT 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 (RTOG) grade 2 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.).

Prospective observational study on the efficacy and tolerability of a complex of phytochemicals versus dutasteride in the treatment of Lower Urinary Tract Symptomps due to Benign Prostatic Hyperplasia.

INTRODUCTION: The aim of our study was to treat 2 similar groups of patients suffering from BPH: one group with a complex based on phycocyanin, PEA and selenium; the other group with dutasteride. So the effectiveness of these treatments was checked, especially regarding the improvement of LUTS and the reduction of PSA and prostate volume. MATERIALS AND METHODS: We included 104 patients in the study. All patients aged between 50 and 70 years, PSA values between 4 and 10 ng/ml, prostate volume calculated by transrectal ultrasound between 50 and 70 cc, flowmetry with maximum flow value greater than or equal to 10 ml/s, no suspicious nodules on DRE, no suspicious lesions on MRI (PI-RADS 1-2), negative previous prostatic biopsies or never bioptied, moreover absence of diabetes mellitus or chronic renal failure (blood creatinine >2 mg/dl). We considered: -Group A of 54 men who used the complex; -Group B of 50 patients treated with dutasteride. Then we controlled all patients 6 months after starting therapy, considering the following parameters: PSA, prostate volume, flowmetry. RESULTS: Our results showed that both dutasteride and complex decreased PSA levels (both had a p<0.0001), with a more significant contribution of dutasteride (mean decrease of -2.743 ng/ml vs -0.971 ng/ml). Uroflowmetry also improved with both ( p<0.0001) with a mean increase in maximum flow of urine of + 3.03 ml/min for the former and + 13.02 ml/min for the latter. Lastly, dutasteride proved to be highly effective on reducing the prostate volume on TRUS (- 22.14 ml, p<0.0001) compared to Ficoxpea, which showed a mean decrease of - 10.04 ml (p<0.0001). Moreover the consistent reduction in prostate volume obtained through the use of dutasteride proved to be more intense than the one obtained by using the complex even in statistical analysis (p<0.0001). CONCLUSIONS: Both Ficoxpea and Dutasteride showed reduction of PSA values after 6 months of treatment. The complex based on phycocyanin, PEA and selenium showed a statistically significant improvement in urinary flow, while dutasteride acts more on the volume of the prostate. However, the natural complex is a product with good efficacy on the phlogistic component and does not have the side effects of dutasteride (e.g. gynecomastia, reduced libido). Therefore, we believe it can be used by a large part of the population, in order to reduce LUTS and PSA and improve urinary flow, without side effects.

The efficacy of different biomarkers and endpoints to refine referrals for suspected prostate cancer: the TARGET study (Tiered integrAted tests for eaRly diaGnosis of clinically significant ProstatE Tumours).

BACKGROUND: The majority of men referred with a raised PSA for suspected prostate cancer will receive unnecessary tertiary investigations including MRI and biopsy. Here, we compared different types of biomarkers to refine tertiary referrals and when different definitions of clinically significant cancer were used. METHODS: Data and samples from 798 men referred for a raised PSA (≥ 3 ng/mL) and investigated through an MRI-guided biopsy pathway were accessed for this study. Bloods were acquired pre-biopsy for liquid biomarkers and germline DNA. Variables explored included PSA + Age (base model), free/total PSA (FTPSA), Prostate Health Index (phi), PSA density (PSAd), polygenic risk score (PRS) and MRI (≥ LIKERT 3). Different diagnostic endpoints for significant cancer (≥ grade group 2 [GG2], ≥ GG3, ≥ Cambridge Prognostic Group 2 [CPG2], ≥ CPG3) were tested. The added value of each biomarker to the base model was evaluated using logistic regression models, AUC and decision curve analysis (DCA) plots. RESULTS: The median age and PSA was 65 years and 7.13 ng/mL respectively. Depending on definition of clinical significance, ≥ grade group 2 (GG2) was detected in 57.0% (455/798), ≥ GG3 in 27.5% (220/798), ≥ CPG2 in 61.6% (492/798) and ≥ CPG3 in 42.6% (340/798). In the pre-MRI context, the PSA + Age (base model) AUC for prediction of ≥ GG2, ≥ GG3, ≥ CPG2 and ≥ CPG3 was 0.66, 0.68, 0.70 and 0.75 respectively. Adding phi and PSAd to base model improved performance across all diagnostic endpoints but was notably better when the composite CPG prognostic score was used: AUC 0.82, 0.82, 0.83, 0.82 and AUC 0.74, 0.73, 0.79, 0.79 respectively. In contrast, neither FTPSA or PRS scores improved performance especially in detection of ≥ GG3 and ≥ CPG3 disease. Combining biomarkers did not alter results. Models using phi and PSAd post-MRI also improved performances but again benefit varied with diagnostic endpoint. In DCA analysis, models which incorporated PSAd and phi in particular were effective at reducing use of MRI and/or biopsies especially for ≥ CPG3 disease. CONCLUSION: Incorporating phi or PSAd can refine and tier who is referred for tertiary imaging and/or biopsy after a raised PSA test. Incremental value however varied depending on the definition of clinical significance and was particularly useful when composite prognostic endpoints are used.

The RECONCILE study protocol: Exploiting image-based risk stratification in early prostate cancer to discriminate progressors from non-progressors (RECONCILE).

INTRODUCTION: RECONCILE (ClinicalTrials.gov:NCT04340245) will identify molecular and radiomic markers associated with clinical progression and radiological progression events in a cohort of localised, newly diagnosed Gleason 3 + 4 tumours. Molecular markers will be correlated against standard of care MRI-targeted histology and oncological outcomes. METHODS: RECONCILE is an ethics approved (20/LO/0366) single centre, prospective, longitudinal, observational cohort study of recently diagnosed (within 12 months), organ-confined Gleason 3 + 4 cancers (MCCL ≤10mm) currently under active surveillance. 60 treatment-naïve participants with a concordant MRI lesion (Likert score 4 or 5) and PSA ≤ 15 ng/ml will be recruited. Blood, urine and targeted prostate tissue cores will be subject to next generation sequencing at baseline and one year in all participants. Semen will be collected from a specified sub-population. Baseline and interval MR images will be extracted from standard of care prostate MRI ahead of radiomic analysis. Data extracted from radiological and biological samples will be used to derive the association of molecular change and radiological progression, the primary outcome of the study. To compensate for spatial intratumoral heterogeneity and inherent sampling bias, a molecular index will be derived for each participant using the molecular profile of tumour tissue at both baseline (MolBL) and one year (MolFU). We will extract a ΔMolBL:MolFU score for each participant. Molecular progression will be defined as a MolBL:MolFU score >95% CI of the combined ΔMolBL scores. Radiological progression is defined as a PRECISE score of 4 or 5. The study is powered to detect an association with a statistical power of 80%. RESULTS: Recruitment began in July 2020 (n = 62). To date, 37 participants have donated tissue for analysis. CONCLUSION: We have designed and implemented a prospective, longitudinal study to evaluate the underlying molecular landscape of intermediate risk, MR-visible prostate tumours. Recruitment is ongoing.

An epitope imprinted electrochemical sensor for highly sensitive and selective determination of prostate-specific antigen.

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.