Serum Prostate-specific Antigen Levels Research Articles

Transformation of proteins into reproductive DNA templates for sensitive quantification of PSA

A switch DNA template was designed to transform proteins into linear DNA strands of 97 nt. The linear DNA was subjected to quantitative polymerase chain reaction (qPCR) to determine the initial copy number, which correlated positively with the protein concentration. A restriction endonuclease was used to remove background amplification. Using prostate-specific antigen (PSA) as a protein model, the established method quantified PSA in the range of 10−18-10−13 mol/mL (detection limit = 0.034 pg/mL) with an R2 of 0.974. Good repeatability and specificity of the method were demonstrated. The established method was successfully applied for the quantification of serum PSA levels in women. Significant differences in PSA levels were observed between healthy participants and polycystic ovary syndrome patients.

The Prevalence of Prostate Cancer in Biopsy Samples of Lesions with PI-RADS 2 Score in Multiparametric Magnetic Resonance Imaging: A Cross-sectional Study

Background: Prostate cancer (PC) is one of the most common cancers worldwide. Recently, multiparametric magnetic resonance imaging (mpMRI) has been used to diagnose PC in suspected patients. Prostate Imaging Reporting & Data System (PI-RADS) was developed and applied as a criterion for detecting lesions suspicious of PC. Various studies have been conducted to determine the negative predictive value of non-suspicious mpMRI (PI-RADS 1 or 2). However, the results of these studies have been limited and different. Objectives: This study was conducted to determine the PC rate in patients with PI-RADS 2 lesions in mpMRI and the factors related to clinically significant prostate cancer (CsPC) diagnosis in these lesions. Methods: By referring to the archive department of Shahada-e-Tajrish, Rasul-e-Akram, Treata, and Payambaran hospitals, among the patients suspected of PC who underwent biopsy and had elevated prostate-specific antigen (PSA) serum levels, the prostate biopsy samples of 330 patients were consecutively included in the study. Frequency of samples diagnosed with PC and its histological characteristics, including mass location, Gleason score (GS), Gleason group (GG), percentage of G4 and G5 cells, sample size, percentage of involvement of sample with cancer tissue, and invasion to the surrounding tissues were examined. Adenocarcinoma samples were divided into low-risk, intermediate-to-high-risk groups based on D'Amico criteria and the relationship between age, PSA total (PSAt), PSA density (PSAd), prostate volume, and the presence of a PI-RADS 3 or 4 lesion at the same time with the rate of diagnosed CsPCs were reviewed. Results: The data from 709 tissue samples were collected, among which 249 were from the right inner part, 249 were from the left inner part, and 211 biopsy samples were from the peripheral portion of the prostate. Among these, 390 tissue samples in mpMRI studies were PI-RADS 2, and 319 were PI-RADS 3 or 4. The mean age of the patients was 64.78 ± 37.55. The mean PSAd, PSAt, and prostate volume were 0.15 ± 0.11, 8.73 ± 6.43, and 61.18 ± 25.76, respectively. Seventy-five samples were diagnosed with adenocarcinoma, of which 48% are in PI-RADS group 2, and 52% are in PI-RADS group 3 - 4 (P-value = 0.263). Comparing the histological characteristics of adenocarcinoma samples between the two groups showed that only the amount of GG was significantly higher in the samples with PI-RADS 3 and 4 (P-value = 0.035). Adenocarcinomas diagnosed in 72.2% of cases in PI-RADS 2 samples and 84.6% of PI-RADS 3 and 4 samples were clinically significant, and no significant difference was seen between the two groups (P-value = 0.38). The amount of PSAt in PI-RADS 2 adenocarcinoma samples was significantly higher in clinically significant carcinomas than in low-risk carcinomas (P-value = 0.045). Conclusions: The results of the present study showed that PI-RADS 2 lesions should be considered for biopsy when there is clinical suspicion of PC. PSA levels can effectively determine the need for biopsy in PI-RADS 2 lesions.

Cervi Parvum Cornu complex for men with lower urinary tract symptoms: a multicenter, randomized, double-blind, placebo-controlled trial

BackgroundTo evaluate the efficacy and safety of Cervi Parvum Cornu, Angelicae Gigantis Radix and Glycyrrhizae Radix complex (CAG) in men with moderate lower urinary tract symptoms (LUTS). Materials and methodsFrom November 2020 to January 2022, participants with International Prostate Symptom Score (IPSS) of 12–19 in two centers were recruited and randomize into three groups: a CAG 500 mg/day group (CAG 500), a CAG 1000 mg/day group (CAG 1000), and a placebo group (PG). They were treated for 12 weeks. The primary endpoint was change of IPSS at the end of study from baseline. Secondary end points included change of prostate specific antigen (PSA), testosterone, dihydrotestosterone (DHT), maximum urinary flow rate (Q max), post-void residual volume (PVR), International Index of Erectile Function (IIEF), and drug safety. ResultsA total of 103 patients were able to finish the study according to the study protocol. Total IPSS and sub-scores (residual urine sensation, frequency, weak stream, hesistancy, nocturia, and quality of life) in CAG 500 and CAG 1000 were significantly improved at the 12th week compared to those of the PG. Changes of serum PSA, DHT, and testosterone levels at the 12th week from baseline did not show significant differences among the three groups. Q max and PVR changes did not show significant differences among the three groups either. Total IIEF and sub-scores (erectile function, orgasmic function, sexual desire, intercourse satisfaction) in CAG 1000 were significantly improved at 12th week compared to those in PG. No significant adverse events were found. ConclusionsCAG is well tolerated in patients with moderate LUTS. Treatment with CAG for 12 weeks has a therapeutic effect on moderate LUTS.

Cancer of unknown primary eventually diagnosed as poorly differentiated prostate cancer: a case report

BackgroundProstate cancer has been well known to have a high prevalence among middle-aged and older men, with high incidence of metastases to the bone—the main metastatic site. However, prostate cancer among those less than 50 years of age is extremely rare, and neck swelling is seldom the initial symptom.Case presentationWe herein report case of a 47-year-old Japanese male with poorly differentiated prostate cancer that had been initially diagnosed as a cancer of unknown primary with multiple lymph node and bone metastases before reaching a definitive diagnosis. The patient has been started on endocrine therapy and is currently alive without progression.Discussion and conclusionWhen locating the primary lesion in men with cancer of unknown primary, it is important to consider the possibility of prostate cancer, confirm serum prostate-specific antigen levels, and perform local prostate evaluation.

Association between body mass index and hemoglobin A1c with serum prostate-specific antigen level: A retrospective cohort study.

To assess the association between body mass index (BMI) and hemoglobin A1c (HbA1c) with serum prostate-specific antigen (PSA) level. A retrospective cohort study was carried out at King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, from January 2016 to December 2021. Data were collected from the medical records of patients who visited the family medicine clinics, including demographics, smoking status, BMI value, index PSA level, testosterone level, digital rectal exam findings, prostate biopsy status, fasting blood glucose (FBG), HbA1c, diabetes duration, chronic comorbidities (namely, hypertension, dyslipidemia, or chronic kidney disease), and medication history. The mean PSA level was 1.89±4.02 ng/dL and mean HbA1c was 6.59±2.69%. Of the participants, 41.8% were overweight, 54.3% were non-diabetics, and 85.3% were nonsmokers. Only 11 (1.6%) participants had undergone a prostate biopsy after taking a PSA test. There was a positive correlation between PSA level and age, a negative correlation between PSA level and BMI, and no correlation between PSA level and HbA1c or FBG. Prostate-specific antigen levels were higher in older people and those with low BMIs. No correlations were found between PSA levels and HbA1c or FBG, even after adjusting for other variables. Moreover, no correlations were found between PSA levels and other comorbidities such as dyslipidemia, chronic kidney disease, and hypertension.

Differentiation of patients with and without prostate cancer using urine 1 H NMR metabolomics.

Prostate cancer (PCa) is one of the most prevalent cancers in men worldwide. For its detection, serum prostate-specific antigen (PSA) screening is commonly used, despite its lack of specificity, high false positive rate, and inability to discriminate indolent from aggressive PCa. Following increases in serum PSA levels, clinicians often conduct prostate biopsies with or without advanced imaging. Nuclear magnetic resonance (NMR)-based metabolomics has proven to be promising for advancing early-detection and elucidation of disease progression, through the discovery and characterization of novel biomarkers. This retrospective study of urine-NMR samples, from prostate biopsy patients with and without PCa, identified several metabolites involved in energy metabolism, amino acid metabolism, and the hippuric acid pathway. Of note, lactate and hippurate-key metabolites involved in cellular proliferation and microbiome effects, respectively-were significantly altered, unveiling widespread metabolomic modifications associated with PCa development. These findings support urine metabolomics profiling as a promising strategy to identify new clinical biomarkers for PCa detection and diagnosis.

The role of inflammatory processes and zinc levels in prostatic enlargement among Iraqi samples.

This study aimed to investigate the role of inflammatory processes in benign prostatic enlargement among men with elevated prostate-specific antigen (PSA) levels without a history of prostatic disease. Additionally, we aimed to examine the influence of serum zinc levels on prostate volume. We investigated the associations between systemic inflammatory markers, serum PSA, and serum zinc levels in 48 men without a history of prostatic disease, aged between 60-72 years, and 30 healthy men in the same age range. Data collection occurred between 1/2/2022 to 1/10/2022. The results are presented as mean values ± standard error (SE), and statistical significance was determined at p≤0.05. The levels of sIL-8 (P: 44.295±1.002, C: 1.404±0.2562), IL-6 (P: 7.406±0.5632, C: 4.468±0.830), CRP (P: 14.765±0.565, C: 6.267±0.538), increased significantly in patients with high PSA, while zinc levels (P: 92.305±2.8235, C: 114.565±8.861) decreased in the patient group. Regarding white blood cell (WBC) parameters, patients exhibited a significant increase in WBC total count (P: 12995.00±488.47, C: 7713.333±777.778), neutrophil % (P: 69.450±1.619, C: 51.200±1.826), lymphocyte % (P: 39.50±2.024, C: 30.867±1.268), and NLR (2.013±0.105). Conversely, there were no significant differences in eosinophil % (P: 3.450±0.4558, C: 3.267±0.5297), basophil % (P: 0.300±0.105, C: 0.267±1182), or monocyte % (P: 3.450±0.4558, C: 3.267±0.5297) between the two groups. In men without known prostatic illness, increased PSA was linked to markers of systemic inflammation. The results indicate the role of inflammatory processes in increasing the size of the prostate gland, as evidenced by the increased levels of immune markers like white blood cells and interleukins, along with the influence of zinc. Future research is required to determine how these markers relate to the development and incidence of prostate cancer.

Urine spermine and multiparametric magnetic resonance imaging for prediction of prostate cancer in Japanese men.

To investigate the role of urine spermine and spermine risk score in predicting prostate cancer (PCa) diagnoses in combination with multiparametric magnetic resonance imaging (mpMRI). Three hundred forty seven consecutive men with elevated prostate-specific antigen (PSA) with mpMRI examination were prospectively enrolled in this study. In 265 patients with PSA levels between 4 and20ng/ml, pre-biopsy urine samples were analyzed for spermine levels with ultra-high performance liquid chromatography (UPLC-MS/MS). Transperineal image-guided prostate biopsies with 16-18 cores were performed. Logistic regressions were used to form different models for the prediction of the PCa, and the performances were compared using the area under the curve (AUC). The median serum PSA level and prostate volume were 7.4ng/mL and 33.9mL, respectively. PCa and high-grade PCa (ISUP group ≥2, HGPCa) were diagnosed in 66.0% (175/265) and 132/265 (49.8%) cases, respectively. The urine spermine levels were significantly lower in men with PCa (0.87 vs. 2.20, P<0.001). Multivariate analyses showed that age, PSA, PV, urine spermine level, and Prostate Imaging Reporting and Data System (PI-RADS) findings were independent predictors for PCa. The Spermine Risk Score is a multivariable model including PSA, age, prostate volume, and urine spermine. Adding the Spermine Risk Score to PI-RADS improved the AUC from 0.73 to 0.86 in PCaand from 0.72 to 0.83 in high grade PCa (HGPCa) prediction (both P<0.001). At 90% sensitivity for HGPCa prediction using Spermine Risk Score, 31.1% of unnecessary biopsies could be avoided. In men with equivocal MRI PI-RADS score 3, the AUC for HGPCa prediction was 0.58, 0.79, and 0.87 for PSA, PSA density, and Spermine Risk Score, respectively. Urine Spermine Risk Score, including mpMRI could accurately identify men at high risk of HGPCa and reduce unnecessary prostate biopsies. Spermine Risk Score could more accurately predict HGPCa than PSA density in men with MRI showing equivocal PI-RADS 3 lesions.

Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography-Based Clinical Target Volume Delineation Guideline for Postprostatectomy Salvage Radiation Therapy: The PERYTON Guideline

Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) scan is the standard imaging procedure for biochemical recurrent prostate cancer postprostatectomy because of its high detection rate at low serum prostate-specific antigen levels. However, existing guidelines for clinical target volume (CTV) in prostate bed salvage external beam radiation therapy (sEBRT) are primarily based on experience-based clinical consensus and have been validated using conventional imaging modalities. Therefore, this study aimed to optimize CTV definition in sEBRT by using PSMA PET/CT-detected local recurrences (LRs). Patients with suspected LR on PSMA PET/CT postprostatectomy were retrospectively enrolled in 9 Dutch centers. Anonymized scans were centrally reviewed by an expert nuclear medicine physician. Each boundary of the CTV guideline from the Groupe Francophone de Radiothérapie en Urologie (GFRU) was evaluated and adapted to improve the accuracy and coverage of the area at risk of LR (CTV) on PSMA PET/CT. The proposed CTV adaptation was discussed with the radiation oncologists of the participating centers, and final consensus was reached. To assess reproducibility, the participating centers were asked to delineate 3 new cases according to the new PERYTON-CTV, and the submitted contours were evaluated using the Dice similarity coefficient (DSC). After central review, 93 LRs were identified on 83 PSMA PET/CTs. The proposed CTV definition improved the coverage of PSMA PET/CT-detected LRs from 67% to 96% compared with the GFRU-CTV, while reducing the GFRU-CTV by 25%. The new CTV was highly reproducible, with a mean DSC of 0.82 (range, 0.81-0.83). This study contributes to the optimization of CTV definition in postprostatectomy sEBRT by using the pattern of LR detected on PSMA PET/CT. The PERYTON-CTV is highly reproducible across the participating centers and ensures coverage of 96% LRs while reducing the GFRU-CTV by 25%.

SERUM TESTOSTERONE AS A MARKER OF RESPONSE TO ANDROGEN DEPRIVATION THERAPY IN METASTATIC PROSTATE CANCER

Introduction: Prostate cancer (PCa) is the second most widespread cause of cancer and the sixth foremost cause of cancer death among men worldwide. The sustained presence of particular hormones and growth factors stimulates the prostate, such as other sex accessory tissues, in its growth, maintenance, and secretory function. In the current study, we investigated the association of serum testosterone level and prostate-specific antigen (PSA) level before androgen deprivation therapy in metastatic PCa (mPCa) treated with hormone therapy. Methods: This retrospective cohort was conducted from July 2017 to December 2019 in the Department of Urology, Post Graduate Institute of Medical Education and Research, Chandigarh on patients diagnosed with mPCa of age &gt;40 years. Total serum testosterone was measured by Electro chemiluminescent immune assay before the treatment. PSA in serum specimens was evaluated. Results: The mean age was 67.74±8.12 (55–80) years. Serum PSA levels at baseline, 3 months were 530.98±617.28 (ng/dL), and 56.31±89.04 (ng/dL), respectively. The baseline S. testosterone was 288.89±246.53 (ng/mL). Weak negative correlation between the two (p=0.051) As the serum testosterone levels decrease the PSA levels increase and vice-versa. Positive correlation between baseline testosterone and PSA decline (p&lt;0.05). On histopathology, 58.7% (n=71) of the patients had perineural involvement, while 41.3% (n=50) did not have perineural involvement. Conclusion: We conclude that the effect of testosterone might have a possible role in the assessment of treatment response as assessed by PSA. However, the exact implication and its role in disease assessment need to be examined in a larger prospective cohort.

Comparison of Serum Gamma Glutamyl Transferase Levels between Prostate Cancer Patients and Their Healthy Peers.

Prostate cancer (PCa) is the most common cancer affecting men, apart from cutaneous cancers. Serum prostate specific antigen (PSA) levels are frequently used to predict prostate cancer diagnosis. However, many causes (e.g., prostatitis, benign prostate obstruction, urethral catheterization) may cause elevated PSA, in addition to PCa. We aimed to investigate the gamma glutamyl transferase (GGT) levels, a serum biomarker not affected by situations other than cancer causing elevated PSA. The study evaluated male patients with prostate biopsy due to high serum PSA levels and/or abnormal digital rectal examination (DRE) examined in Ordu University Education and Research Hospital, Ordu/Turkey urology clinic from April 2019 to April 2021. The patient group in the study included 261 men with PCa diagnosis and the control group included 245 healthy men with normal PSA levels, and no PCa and/or benign prostate obstruction (BPO). The two groups were compared in terms of serum GGT levels. GGT was significantly low in the PCa group and might be a predictor in terms of PCa (P=0.000). In the malignant (PCa) group, the GGT cut-off value was identified as 21.5 (sensitivity 68.6%, specificity 54.4%). Serum GGT levels might assist in diagnosis of PCa. However, diagnostic power is weak due to low specificity. There is a need for studies investigating the efficacy of GGT levels for prediction of PCa diagnosis and assessing other parameters alongside GGT.

The Impact of Multiparametric Magnetic Resonance Imaging on Treatment Strategies for Incidental Prostate Cancer after Holmium Laser Enucleation of the Prostate.

To investigate the impact of multiparametric magnetic resonance imaging (mpMRI) on treatment strategies for incidental prostate cancer (iPCa) after holmium enucleation of the prostate (HoLEP); Methods: Data from 1781 men who underwent HoLEP for clinical bladder outlet obstruction between September 2009 and March 2022 were reviewed retrospectively. Among patients with confirmed iPCa, those with prostate-specific antigen (PSA) levels < 10 ng/mL and who underwent mpMRI 3 months after HoLEP were included. Pathologic results, including Gleason grade (GG) and tumor volume, were identified. mpMRI was interpreted using the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2). Treatment strategies for iPCa according to GG alone, or according to a combination of Gleason grade and mpMRI, were analyzed and compared. Of 1764 men with serum PSA levels < 10 ng/mL, iPCa was confirmed in 64 (3.6%) after HoLEP. Of the 62 men who underwent mpMRI, the median (IQR) age at the time of HoLEP was 72.5 (66.5-78.0) years. The median PSA level and prostate volume were 3.49 (1.82-5.03) ng/mL and 49.6 (38.5-85.4) cm3, respectively. The pathologic results of iPCa were as follows: GG1 = 42 (67.7%), GG2 = 13 (21.0%), GG3 = 2 (3.2%), GG4 = 1 (1.6%), and GG5 = 4 (6.5%). Of the patients with GG1 and GG2, 78.6% (33/42) and 53.8% (7/13), respectively, underwent active surveillance (AS). However, of 42 patients with GG1, 27 (64.3%) had a PI-RADSv2 score of 2, and 24 (88.9%) of them underwent AS. Of the 13 patients with GG2, 4 (80%) with a PI-RADSv2 score of 2 underwent AS. All patients with GG 3-5 were clinically expected to have locally advanced PCa and be treated with radiotherapy and/or ADT. For patients with iPCa of GG 1-2 after HoLEP, mpMRI helps to establish a treatment strategy by allowing risk stratification to select those who should be considered for AS or active treatment.

Long-term survival outcomes of salvage [225Ac]Ac-PSMA-617 targeted alpha therapy in patients with PSMA-expressing end-stage metastatic castration-resistant prostate cancer: a real-world study.

Despite the existence of various treatment options, the prognosis for patients with metastatic castration-resistant prostate cancer (mCRPC) remains unfavorable. One potential therapeutic approach is the use of [225Ac]Ac-PSMA-617, a targeted alpha therapy (TAT) that administers alpha-particle radiation specifically to prostate cancer cells expressing PSMA. In this study, we report the long-term survival outcomes of this novel therapy in a series of patients with mCRPC who have exhausted all standard treatment options. The study enrolled patients with mCRPC who had shown resistance to standard lines of therapies, including next-generation anti-androgen therapies and taxane-based chemotherapies. These eligible patients received treatment with [225Ac]Ac-PSMA-617 at 100-150 kBq/kg doses administered every 8 weeks. The primary objective of the study was to assess overall survival (OS), while secondary objectives included evaluating radiological progression-free survival (rPFS), monitoring serum prostate-specific antigen (PSA) levels as a measure of biochemical response, and assessing adverse events using the CTCAE v5.0 grading system. Among the 63 initially enrolled patients, a total of 56 patients who had completed at least two cycles of [225Ac]Ac-PSMA-617 were included in this study. The mean age was 67 years (range, 39-87) and patients received a total of 204 cycles of [225Ac]Ac-PSMA-617 TAT. 91% of patients exhibited any PSA decline, with 67.8% experiencing a decline of 50% or more. The median follow-up was of 22 months (range: 6-59 months). Imaging-based disease progression was observed in 68% of patients, and 66% of patients succumbed to the disease. The median OS was 15 months (95% CI: 10-19). In univariate analysis, factors such as lack of >50% PSA decline (P=0.031), Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher (P=0.048), and radiological progression (rPD) (P<0.001) were found to be predictors of poor OS. However, in multivariate analysis, only rPD emerged as an independent prognostic factor with a hazard ratio (HR) of 8.264 (95% CI: 1.429-16.497, P=0.004). The estimated median rPFS was 9 months (95% CI: 7-15). Moreover, patients who demonstrated any PSA decline had a median rPFS of 10 months compared to only 3 months in patients without any PSA decline (multivariate HR: 6.749; 95% CI: 1.949-23.370; P=0.002). Fatigue was one of the most common treatment-emergent adverse events, with grades 1/2 occurring in 70% of patients and grades 3 or higher in 3.5% of patients. This fatigue was transient and resolved before the next treatment cycle. Additionally, approximately one-third of patients experienced xerostomia (grades 1/2: 32.1%). [225Ac]Ac-PSMA-617 targeted alpha therapy, was found to be well-tolerated with acceptable adverse events and effective in the treatment of patients with end-stage mCRPC.

Establishment and validation of serum lipid-based nomogram for predicting the risk of prostate cancer

BackgroundThis study aimed to explore the value of combined serum lipids with clinical symptoms to diagnose prostate cancer (PCa), and to develop and validate a Nomogram and prediction model to better select patients at risk of PCa for prostate biopsy.MethodsRetrospective analysis of 548 patients who underwent prostate biopsies as a result of high serum prostate-specific antigen (PSA) levels or irregular digital rectal examinations (DRE) was conducted. The enrolled patients were randomly assigned to the training groups (n = 384, 70%) and validation groups (n = 164, 30%). To identify independent variables for PCa, serum lipids (TC, TG, HDL, LDL, apoA-1, and apoB) were taken into account in the multivariable logistic regression analyses of the training group, and established predictive models. After that, we evaluated prediction models with clinical markers using decision curves and the area under the curve (AUC). Based on training group data, a Nomogram was developed to predict PCa.Results210 (54.70%) of the patients in the training group were diagnosed with PCa. Multivariate regression analysis showed that total PSA, f/tPSA, PSA density (PSAD), TG, LDL, DRE, and TRUS were independent risk predictors of PCa. A prediction model utilizing a Nomogram was constructed with a cut-off value of 0.502. The training and validation groups achieved area under the curve (AUC) values of 0.846 and 0.814 respectively. According to the decision curve analysis (DCA), the prediction model yielded optimal overall net benefits in both the training and validation groups, which is better than the optimal net benefit of PSA alone. After comparing our developed prediction model with two domestic models and PCPT-RC, we found that our prediction model exhibited significantly superior predictive performance. Furthermore, in comparison with clinical indicators, our Nomogram’s ability to predict prostate cancer showed good estimation, suggesting its potential as a reliable tool for prognostication.ConclusionsThe prediction model and Nomogram, which utilize both blood lipid levels and clinical signs, demonstrated improved accuracy in predicting the risk of prostate cancer, and consequently can guide the selection of appropriate diagnostic strategies for each patient in a more personalized manner.

Flotufolastat F 18: Diagnostic First Approval.

Flotufolastat F 18 (POSLUMA®) is an 18F-labelled radiohybrid (rh) prostate-specific membrane antigen (PSMA)-targeted imaging agent being developed by Blue Earth Diagnostics, a subsidiary of Bracco Imaging, for prostate cancer imaging. In May 2023, flotufolastat F 18 received its first approval in the USA as a radioactive diagnostic agent for positron emission tomography (PET) of PSMA positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level. This article summarizes the milestones in the development of flotufolastat F 18 leading to this first approval.

Correlation of expression of Cyclin D1 and E-cadherin with gleason grade, serum prostate specific antigen levels and prostatic volume in prostatic carcinoma

Background: Prostate cancer is increasingly being diagnosed early due to easy access and availability of better diagnostic modalities. Gleason scoring is important for prognosis and is used to determine the management protocol. As the behavior of these tumors is unpredictable, many markers are being investigated. Cyclin D1 and E-Cadherin have been linked to the development, progression, and aggressiveness in some studies. We studied the expression of E cadherin and cyclin D1 in various grades to understand their relationship with clinicopathologic features, PSA, and prostatic volume. Material &amp; methods: 52 patients diagnosed with prostatic adenocarcinoma on core biopsy after ethical clearance in our tertiary care center were included in the study and their records were retrieved. Hematoxylin and Eosin stained sections were used for Gleason scoring as well as Gleason grade group as per existing protocols. Immunohistochemistry using antibodies against Cyclin D1 and E-Cadherin along with appropriate controls was performed. Studied parameters were correlated with E-Cadherin and cyclin D1. We used a statistical software package (version 22, IBM, US). Results: Cyclin D1 showed increasing immunoexpression with an increase in Gleason score and Gleason grade group emphasizing a significant correlation between these parameters (p= 0.001). There was a significant negative association between E-cadherin score, Gleason score, and Gleason grade group (p=0.001). No correlation was obtained with serum PSA or prostatic volume. Conclusions: E-cadherin and Cyclin D1 dysregulation could be used as prognostic and predictive markers in prostatic carcinoma.

Disease-related complications in patients with metastatic hormone-sensitive prostate cancer.

Prostate-specific antigen-based screening for prostate cancer reportedly does not improve cancer-specific survival. However, there remain concerns about the increasing incidence of advanced disease at initial presentation. Here, we investigated the incidences and types of complications that occur during the course of disease in patients with metastatic hormone-sensitive prostate cancer (mHSPC). This study included 100 consecutive patients who were diagnosed with mHSPC at five hospitals from January 2016 to August 2017. Analyses were conducted using patient data extracted from a prospectively collected database, along with information about complications and readmission obtained from electronic medical records. The median patient age was 74 years and the median serum prostate-specific antigen level at diagnosis was 202.5 ng/mL. Ninety-nine patients received androgen deprivation therapy; 17 of these patients also received chemotherapy. During a mean follow-up period of 32.9 months, 41 patients reported bone pain; of these patients, 21 developed pathologic fractures and eight had cord compression. Twenty-eight patients developed retention of urine; of these patients, 10 (36%) required surgery and 11 (39%) required long-term urethral catheter use. Among 15 patients who developed ureteral obstruction, four (27%) required ureteral stenting and four (27%) required long-term nephrostomy drainage. Other complications included anaemia (41%) and deep vein thrombosis (4%). Fifty-nine (59%) patients had ≥1 unplanned hospital admission during the course of disease; 16% of such patients had >5 episodes of readmission. Among patients with mHSPC, 70% experienced disease-related complications and unplanned hospital admissions, which substantially burdened both patients and the healthcare system.

Role of Pelvic Ischemia in Human Lower Urinary Tract Symptoms and Sexual Function Among Patients With Common Iliac Artery Obstruction Undergoing Revascularization Surgery.

In this case-control study, we explored the relationships among pelvic ischemia, lower urinary tract symptoms (LUTS), and sexual function in patients with common iliac artery steno-occlusive disease, along with the potential therapeutic role of revascularization. We recruited 33 men diagnosed with radiologically documented common iliac artery stenosis (>80%) who underwent endovascular revascularization, and 33 healthy controls. Five patients had obstruction of the abdominal aorta (Leriche syndrome). The International Prostate Symptom Score (IPSS), Overactive Bladder Questionnaire, and International Index of Erectile Function were used to evaluate LUTS and erectile function. Medical history, anthropometrics, urinalysis, and blood tests, including levels of serum prostate-specific antigen, urea, creatinine, triglycerides, cholesterol, low-density lipoprotein, high-density lipoprotein, and hemoglobin A1c, were recorded. Uroflow (maximum flow, average flow, voided volume, and voiding time) and ultrasound parameters (prostate volume and postvoid residual [PVR]) were also measured. Patients with moderate-to-severe LUTS (IPSS>7) underwent complete urodynamic investigation. Patients were examined at baseline and 6 months postoperatively. Patients exhibited poorer total IPSS (P<0.001), storage (P=0.001) and voiding symptom (P<0.001) subscores, as well as worse OAB-bother (P=0.015), OAB-sleep (P<0.001), OAB-coping (P<0.001), and OAB-total (P<0.001) scores than control participants. Additionally, erectile function (P=0.002), sexual desire (P<0.001), and satisfaction from intercourse (P=0.016) deteriorated in the patient group. Six months postoperatively, significant improvements were observed in erectile function (P=0.008), orgasm (P=0.021), and desire (P=0.014). Similarly, PVR significantly improved (P=0.012), while fewer patients experienced increased bladder sensation (P=0.035) and detrusor overactivity (P=0.035) upon postoperative urodynamic study. No significant differences were found between patients with bilateral and unilateral obstruction or between either of those groups and Leriche syndrome patients. Patients with steno-occlusive disease of the common iliac artery experienced more severe LUTS and sexual dysfunction than healthy controls. Endovascular revascularization alleviated LUTS in patients with moderate-to-severe symptoms and improved bladder and erectile function.

Dose-Volume Histogram Parameters and Quality of Life in Patients with Prostate Cancer Treated with Surgery and High-Dose Volumetric-Intensity-Modulated Arc Therapy to the Prostate Bed.

Prostate bed radiotherapy (RT) is a major affecter of patients' long-term quality of life (QoL). To ensure the best possible outcome of these patients, dose constraints are key for optimal RT planning and delivery. However, establishing refined dose constraints requires access to patient-level data. Therefore, we aimed to provide such data on the relationship between OAR and gastrointestinal (GI) as well as genitourinary (GU) QoL outcomes of a homogenous patient cohort who received dose-intensified post-operative RT to the prostate bed. Furthermore, we aimed to conduct an exploratory analysis of the resulting data. Patients who were treated with prostate bed RT between 2010 and 2020 were inquired about their QoL based on the Expanded Prostate Cancer Index Composite (EPIC). Those (n = 99) who received volumetric arc therapy (VMAT) of at least 70 Gy to the prostate bed were included. Dose-volume histogram (DVH) parameters were gathered and correlated with the EPIC scores. The median age at the time of prostate bed RT was 68.9 years, and patients were inquired about their QoL in the median 2.3 years after RT. The median pre-RT prostate-specific antigen (PSA) serum level was 0.35 ng/mL. The median duration between surgery and RT was 1.5 years. The median prescribed dose to the prostate bed was 72 Gy. A total of 61.6% received prostate bed RT only. For the bladder, the highest level of statistical correlation (p < 0.01) was seen for V10-20Gy, Dmean and Dmedian with urinary QoL. For bladder wall, the highest level of statistically significant correlation (p < 0.01) was seen for V5-25Gy, Dmean and Dmedian with urinary QoL. Penile bulb V70Gy was statistically significantly correlated with sexual QoL (p < 0.05). A larger rectal volume was significantly correlated with improved bowel QoL (p < 0.05). Sigmoid and urethral DVH parameters as well as the surgical approach were not statistically significantly correlated with QoL. Specific dose constraints for bladder volumes receiving low doses seem desirable for the further optimization of prostate bed RT. This may be particularly relevant in the context of the aspiration of establishing focal RT of prostate cancer and its local recurrences. Our comprehensive dataset may aid future researchers in achieving these goals.

Early Detection of Prostate Cancer: The Role of Scent

Prostate cancer (PCa) represents the cause of the second highest number of cancer-related deaths worldwide, and its clinical presentation can range from slow-growing to rapidly spreading metastatic disease. As the characteristics of most cases of PCa remains incompletely understood, it is crucial to identify new biomarkers that can aid in early detection. Despite the prostate-specific antigen serum (PSA) levels, prostate biopsy, and imaging representing the actual gold-standard for diagnosing PCa, analyzing volatile organic compounds (VOCs) has emerged as a promising new frontier. We and other authors have reported that highly trained dogs can recognize specific VOCs associated with PCa with high accuracy. However, using dogs in clinical practice has several limitations. To exploit the potential of VOCs, an electronic nose (eNose) that mimics the dog olfactory system and can potentially be used in clinical practice was designed. To explore the eNose as an alternative to dogs in diagnosing PCa, we conducted a systematic literature review and meta-analysis of available studies. PRISMA guidelines were used for the identification, screening, eligibility, and selection process. We included six studies that employed trained dogs and found that the pooled diagnostic sensitivity was 0.87 (95% CI 0.86–0.89; I2, 98.6%), the diagnostic specificity was 0.83 (95% CI 0.80–0.85; I2, 98.1%), and the area under the summary receiver operating characteristic curve (sROC) was 0.64 (standard error, 0.25). We also analyzed five studies that used an eNose to diagnose PCa and found that the pooled diagnostic sensitivity was 0.84 (95% CI, 0.80–0.88; I2, 57.1%), the diagnostic specificity was 0.88 (95% CI, 0.84–0.91; I2, 66%), and the area under the sROC was 0.93 (standard error, 0.03). These pooled results suggest that while highly trained dogs have the potentiality to diagnose PCa, the ability is primarily related to olfactory physiology and training methodology. The adoption of advanced analytical techniques, such as eNose, poses a significant challenge in the field of clinical practice due to their growing effectiveness. Nevertheless, the presence of limitations and the requirement for meticulous study design continue to present challenges when employing eNoses for the diagnosis of PCa.