Serum Prostate-specific Antigen Levels Research Articles

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.

Possibilities of early diagnosis of localized prostate cancer in outpatient practice of a urologist at the regional level in the stavropol territory

Aim. To develop and implement an algorithm for early diagnosis of a localized form of prostate cancer based on the determination of the specificity of the prostate-specific antigen (PSA) marker in different age groups.Materials and methods. In the framework of a screening program for early detection of diseases of the urogenital system developed at the Stavropol Regional Clinical Specialized Uroandrological Center, middle-aged and elderly men were examined using the following characteristics: IPSS (International Prostate Symptom Score), serum PSA level, digital rectal exam, transrectal prostate ultrasound, urodynamic tests, as well as transrectal ultrasound-guided prostate biopsy in cases of elevated total PSA. The data (for 2010–2021) on the frequency of detection of localized prostate cancer depending on patient age (40–59 years, 60–69 years, ³70 years) and total PSA level were analyzed.Results. With an increase in total blood PSA &gt;4 ng/ml, there is a clear trend towards a decrease in the detection of benign prostatic hyperplasia and an increase in the detection of adenocarcinoma, which is confirmed by the data of histological examinations of biopsy specimens. In 81 % of cases, transrectal multifocal biopsy of the prostate gland (adenocarcinoma and prostatic intraepithelial neoplasia was detected) under transrectal ultrasound control is justified, including when PSA values are in the “gray zone”, which shows a rather high value of this method.Conclusion. Total serum PSA level is a readily available indicator for differential diagnosis of prostate diseases including detection of localized prostate cancer in out-patient conditions. The obtained data points at high specificity of this marker in men over 40 years old. Measurement of serum PSA level at the age of 40–49 years is necessary for early detection of oncological pathology. For total serum PSA level &gt;4 ng/mL, mandatory transrectal multifocal prostate biopsy is recommended at any age.

Investigation of the roles of TGFβ1, CUG2, TGFBI genes, and thiol-disulfide balance on prostate cancer and metastasis

Abstract Objectives Transforming growth factor-beta (TGFβ1) is involved in tumorigenesis and metastasis. It provides this effect both by disrupting the thiol-disulfide balance and through the cancer-upregulated gene (CUG2) and transforming growth factor beta-induced (TGFBI) genes in the signaling pathway. In this study, the roles of TGFβ1 and related genes, as well as thiol-disulfide balance, in the formation of prostate cancer and metastasis were investigated. Methods Tissue samples were taken from 33 benign prostatic hyperplasia (BPH) and 35 prostate cancer (PC) patients to determine the Gleason score and metastasis. TGFβ1, CUG2, and TGFBI gene expression levels were measured by RT-PCR. Serum prostate specific antigen (PSA) levels were measured in patients, and PSA density (PSAD) was calculated. Total thiol and native thiol measurements in serum were performed spectrophotometrically, and disulfide was calculated. Results In patients with prostate cancer and metastases, PSA and PSAD levels were high, while total thiol and native thiol were significantly lower (p&lt;0.05). TGFβ1, CUG2 and TGFBI gene expression levels were higher in patients with prostate cancer and metastases and were negatively correlated with total thiol and native thiol (p&lt;0.001). Conclusions As a result of our study, we determined that the increase in TGFβ1, CUG 2 and TGFBI in prostate cancer plays an important role in cancer formation and metastasis by disrupting the thiol-disulfide balance.

The Change in tPSA, fPSA and f/tPSA Levels in Men Undergoing Hemodialysis Effect of Hemodialysis on Serum PSA Levels

Purpose: This study aimed to assess the impact of hemodialysis treatment and different dialysis membranes with varying surface areas on serum levels of total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), and the fPSA/tPSA ratio in patients undergoing hemodialysis treatment.&#x0D; Material and Methods: The study was conducted at the Central Laboratory of....Hospital in May, June, and July 2020. tPSA, fPSA, and fPSA/tPSA ratios measured in pre-dialysis and post-dialysis samples were determined. Correlation between pre-dialysis and post-dialysis of fPSA and tPSA levels and patients' ultrafiltrates were evaluated. The fPSA, tPSA, and fPSA/tPSA measured in pre-dialysis and post-dialysis samples grouped according to membrane type were compared.&#x0D; Results: The fPSA levels and fPSA/tPSA ratios of pre-dialysis samples were significantly lower than post-dialysis samples. tPSA values were not significantly different in pre-dialysis and post-dialysis samples. According to membrane types, it was found that pre-dialysis and post-dialysis tPSA, fPSA, and fPSA/tPSA were not significantly different. There was a positive correlation between difference in fPSA concentrations measured in pre-dialysis and post-dialysis samples and ultrafiltrate (rho=0.380). A positive correlation was found between difference in tPSA concentrations measured in pre-dialysis and post-dialysis samples and ultrafiltrate (rho=0.562).&#x0D; Conclusion: Post-dialysis fPSA values and fPSA/tPSA ratios were found to be elevated in patients receiving hemodialysis treatment due to hemoconcentration and other potential effects of dialysis. Therefore, interpreting fPSA values and fPSA/tPSA ratios in patients undergoing hemodialysis treatment according to current clinical decision limits may lead to misinterpretation. In this group of patients, the use of tPSA testing is safe as it remains unaffected by dialysis treatment.

Abstract 9: Association Between HMOX1 (GT)n Promoter Microsatellite and Prostate Cancer Prognosis

Abstract Purpose: Heme Oxygenase 1 (HO-1), the rate-limiting enzyme in heme degradation encoded by HMOX1 gene, has a strong anti-tumoral effect in prostate cancer (PCa). HMOX1 expression levels are modulated by the length of a dinucleotide (GT)n microsatellite polymorphism mapping in its promoter region. PCa is the second most frequent cancer and the sixth leading cause of cancer-related deaths in men worldwide. One of the strongest predictors for newly diagnosed PCa is the International Society of Urological Pathology (ISUP) grade, a histopathology-based classification system, which presents diverse limitations due to tumoral heterogeneity. Consequently, the identification of novel biomarkers is important to optimize PCa prognosis. In this study we genotyped the HMOX1 (GT)n promoter polymorphism and analyze its association with PCa clinico-pathological parameters. Methods: We collected 108 peripheral blood samples from PCa patients from Hospital de Clínicas “Jose de San Martín”, Buenos Aires, Argentina. Genomic DNA was isolated and the (GT)n was genotyped by fluorescent PCR and capillary electrophoresis. Randomly selected samples were cloned and sequenced by Sanger to determine the length of the microsatellite and validate the results. We considered a statistically significant difference between groups if p≤0.05. Results: The length of the (GT)n ranged from 11 to 40 repeats. HMOX1 alleles were dichotomized as “Long (l)” (≥30 repeats) or “Short (s)” (&amp;lt;30 repeats) based on the median length; and genotypes were categorized as homozygous “HMOX1ss, homozygous “HMOX1ll”, or heterozygous “HMOX1sl”. We found an association between the “HMOX1ss” genotype and higher serum prostate specific antigen (sPSA) levels among patients with &amp;lt;10 ng/mL sPSA (p&amp;lt;0.01). Furthermore, the proportion of “HMOX1ss” patients increased with the ISUP grade, whereas “HMOX1ll” or “HMOX1sl” genotypes were more frequent in lower ISUP grades (ptrend&amp;lt;0.05). Finally, “HMOX1ss” patients had 4-fold higher risk of biochemical relapse (HR=4.03, p&amp;lt;0.05). Conclusion: “HMOX1ss” patients present more aggressive phenotypes compared with the other genotypes. HMOX1 polymorphism has the potential to classify patients in different groups to predict the severity of PCa tumors, thus evidencing potential to support clinicians on the decision making and improving clinical management of PCa at an early stage through a non-invasive sample. Citation Format: Gaston Pascual, Agustina Sabater, Rocio Seniuk, Ines Achinelli, Pamela Freiria, Carlos Scorticati, Osvaldo Mazza, Ayelen Toro, Elba Vazquez, Geraldine Gueron, Javier Cotignola. Association Between HMOX1 (GT)n Promoter Microsatellite and Prostate Cancer Prognosis [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 9.

Lymphotropic Pattern of Prostate-specific Membrane Antigen–detected Metastases Among Biochemically Recurrent Radical Prostatectomy Patients with Cribriform Disease

BackgroundCribriform morphology portends worse oncologic outcomes, and has unique cellular intrinsic pathway alterations and tumor microenvironments that may impact metastatic spread patterns. ObjectiveTo determine whether the presence of cribriform morphology in prostatectomy specimens of patients with biochemical recurrence after radical prostatectomy (RP) is associated with the presence of metastasis on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and a distinct pattern of spread. Design, setting, and participantsA cross-sectional analysis was conducted of all prostate cancer patients with biochemical recurrence after RP undergoing 18F-DCFPyL-PET/CT between December 2018 and February 2021 at the Princess Margaret Cancer Centre. Outcome measurements and statistical analysisOutcomes were presence of any metastasis in the overall cohort and lymphatic versus bone/visceral metastases among patients with metastatic disease. The associations between the presence of intraductal (IDC) and/or invasive cribriform (ICC) carcinoma on the RP specimen and study outcomes were evaluated using logistic regression analyses. Results and limitationsThe cohort included 176 patients. IDC and ICC were observed in 77 (43.8%) and 80 (45.5%) RP specimens, respectively. The median time from RP to PSMA-PET/CT was 5.0 yr. The median serum prostate-specific antigen level at PSMA-PET/CT was 1.12 ng/ml. Overall, metastasis was observed in 77 patients, of whom 58 were had lymphatic-only metastasis. On a multivariable analysis, presence of IDC on RP was associated with increased odds of overall metastasis (odds ratio [OR]: 2.17; 95% confidence interval [CI]: 1.07–4.45; p = 0.033). Presence of ICC on RP was associated with significantly increased odds of lymphatic versus bone/visceral metastases (OR: 3.13; 95% CI: 1.09–21.7; p = 0.004). ConclusionsPresence of cribriform morphology on RP specimens of patients with biochemical failure after RP is associated with increased odds of PSMA-PET/CT–detected metastases with a lymphatic predominant pattern of spread. These findings have implications for the design and evaluation of post-RP salvage therapies. Patient summaryWe found that microscopic cribriform appearance correlates with disease spread on imaging in prostate cancer patients with recurrence and has a predilection for spread to lymph nodes, as opposed to bone or visceral organs.

Risks of prostate cancer and mortality in the city of Sharjah, United Arab Emirates.

Prostatic hyperplasia (BPH) and prostate cancer (PCa) are common age-related diseases in men. According to World Health Organization (WHO), PCa is the second most common cancer among Emirati men. This study aimed to identify the risk factors associated with PCa and mortality in a cohort diagnosed with PCa between 2012 and 2021 in Sharjah, United Arab Emirates (UAE). The data collected in this retrospective case-control study included patient demographics and comorbidities, as well as PCa markers such as prostate-specific antigen (PSA), prostate volume, prostate-specific antigen density (PSAD), and Gleason scores. Risk factors for PCa were assessed using multivariate logistic regression analysis, and factors associated with all-cause mortality in PCa patients were evaluated using Cox-proportional hazard analysis. Of the 192 cases analyzed in this study, 88 were diagnosed with PCa and 104 were diagnosed with BPH. Regarding risk factors for PCa, a higher risk of PCa was associated with age 65 or older (OR=2.76, 95% confidence interval (CI): 1.04-7.30; P=0.038) and serum PSAD greater than 0.1 ng/mL2 (OR=3.48, 95% CI:1.66-7.32; P=0.001), whereas being of UAE nationals (OR=0.40, 95% CI:0.18-0.88; P=0.029) were associated with lower risk of PCa, after adjusting for patient demographics and comorbidities. Moreover, regarding cancer markers, higher serum PSA level (P=0.003) and smaller prostate volume (P=0.028) were associated with a higher risk of PCa, after adjusting with patients' age and BMI. Additionally, a high-grade Gleason score was associated with an increased risk of all-cause mortality after adjusting for patient's age and BMI (hazard ratio, aHR= 2.3, 95% CI:1.3-4.1; P= 0.016). This study found that age 65 or older and serum PSAD greater than 0.1 ng/mL2 are risk factors for PCa, while UAE nationality is associated with a lower risk. PSAD may be a better screening marker for PCa compared to traditional markers such as PSA and prostate volume.

Ag NC and Ag NP/PorC Film-Based Surface-Enhanced Raman Spectroscopy-Type Immunoassay for Ultrasensitive Prostate-Specific Antigen Detection.

Surface-enhanced Raman scattering (SERS) is a spectral detection technology with high sensitivity and detectivity and can be used to detect the fingerprint information of the molecules with ultralow concentration. Herein, a kind of immunostructure constructed by Ag nanoparticle/porous carbon (Ag NP/PorC) films as the immunosubstrate and Ag NCs as the immunoprobes was presented for ultralow level prostate-specific antigen (PSA) detection. Experimentally, the Ag NP/PorC film was first prepared with a facile method by carbonizing the gelatin-AgNO3 film in air, and Ag NCs were synthesized by the hydrothermal method. Then, the Ag NP/PorC film was modified by PSA antibodies as the substrate, while Ag NCs were decorated by R6G and PSA antibodies for probes. The sandwiched SERS detection embodiment was constructed by the immunoreaction between the PSA and PSA antibody predecorated on the substrate and probes. Our results show that the proposed SERS-type immunoassay is highly sensitive and selective to a wide range of PSA concentrations from 10-5 to 10-12 g/mL. Thereafter, it was also implemented to detect the PSA level in human serum, and the results successfully reproduce the PSA levels as those measured by the chemiluminescence method with a recovery rate above 90%. All in all, this SERS-type immunoassay provides a promising method for the early diagnosis of prostate cancer.