Molecular targeted therapies, omics, and AI based theranostics approaches for the treatment of prostate cancer.

This study is of an evaluative nature and is based on a retrospective analysis of data from 18 patients of the oncological office of the City Polyclinic No. 1 of the North Kazakhstan region (North Kazakhstan region). PSA levels were compared in patients with various histological diagnoses, including adenocarcinoma, microcarcinoma, benign hyperplasia and inflammatory processes.High PSA levels (> 25 ng/mL) were expected to be a reliable indicator of malignancy, demonstrating a significant difference between gallbladder carcinoma patients and benign changes.Moderate PSA values (4-10 ng/mL) were to include both patients with benign processes and those with precancerous conditions.Low PSA levels (< 4 ng/mL) were expected in patients without evidence of malignancy, which could serve as an additional criterion for exclusion of oncology.The findings confirmed the importance of PSA as a marker for gallbladder carcinoma diagnosis, but also demonstrated its limited specificity. To improve the accuracy of diagnostics, it is recommended to use additional parameters (the ratio of free and bound PSA, the density of the PSA, the rate of change in the PSA level), as well as apply modern methods of visualization and molecular diagnostics.

P505 – The role of prostate-specific antigen after cryotherapy for primary localized prostate cancer

Background: Prostate cancer ranks among the deadliest cancers men develop worldwide. Early diagnosis provides better chances to survive prostate cancer and protect daily activities. Doctors rely on PSA tests as their primary method to identify prostate health problems before treatment becomes more complex. Objectives: to determine how well PSA testing finds early prostate cancer and helps doctors develop better treatment plans. Study Design: A Cross-Sectional Study. Place and duration of study. Department of General Surgery Ziauddin Hospital Karachi from 05 july 2022 to 05 jan 2023 Methods: 100 men between 50 and 75 years old with PSA tests during a year. The data included PSA test values plus findings from physical exams and diagnostic tests when needed. We tested PSA level differences by computing standard deviation and p-values to identify variations that help detect cancer. Results: Out of 100 screened patients 40 showed PSA levels higher than 4 ng/mL. The biopsy reports showed that 25 people among them had prostate cancer. Our research revealed a clearly different PSA pattern between cancer patients who had 10.2 ± 2.5 ng/mL and non-cancer patients who had 3.1 ± 0.8 ng/mL (p < 0.001). PSA velocity and density helped identify cancer patients with aggressive tumors. Conclusion: Testing PSA levels enables doctors to find prostate cancer before symptoms appear. By combining current PSA screening methods with state-of-the-art tests we achieve better results and minimize unwanted procedures. Research teams need to keep studying how to make PSA testing work at its best for healthcare professionals. Keywords: Prostate cancer, PSA testing, Early detection, Biomarkers

Prostate cancer is the only human malignancy that generates predominantly osteoblastic bone metastases, and osteoblastic bone metastases account for more than 90% of osseous metastases of prostate cancer. Prostate-specific antigen (PSA) plays an important role in the osteoblastic bone metastasis of prostate cancer, which can promote osteomimicry of prostate cancer cells, suppress osteoclast differentiation, and facilitate osteoblast proliferation and activation at metastatic sites. In the meantime, it can activate osteogenic factors, including insulin-like growth factor, transforming growth factor β2 and urokinase-type plasminogen activator, and meanwhile suppress osteolytic factors such as parathyroid hormone-related protein. To recapitulate, PSA plays a significant role in the osteoblastic predominance of prostate cancer bone metastasis and bone remodeling by regulating multiple cells and factors involved in osseous metastasis.

This study explores the role of Prostate Specific Antigen (PSA) as a tumour marker in prostate cancer diagnosis and prognosis.A cohort of 120 participants aged 45 to 70 years underwent a cross-sectional analysis of PSA levels and their correlation with tumour characteristics.Data collection involved structured interviews and medical record reviews. Diagnostic assessments, including histopathological analysis and Gleason scores (6 to 9), were performed. PSA levels were correlated with tumour characteristics. Statistical analysis utilized IBM SPSS Statistics.The distribution of PSA levels (mean: 8.52 ng/mL, median: 7.89 ng/mL) reflected variations. A positive correlation (0.67) existed between PSA levels and Gleason scores. Receiver Operating Characteristic analysis yielded an AUC of 0.82, indicating good diagnostic accuracy.The study provides insights into PSA's diagnostic potential and its correlation with tumour characteristics in prostate cancer.Acknowledging limitations, this research prompts validation efforts to bridge research and clinical understanding.

Simple SummaryTargeted cryotherapy is an emerging treatment for prostate cancer (PCa). mpMRI is a powerful tool for image fusion techniques that deliver incremental precision in diagnostic and treatment of PCa. Fusion targeted cryotherapy (FTC) arises from the simultaneous application of both these procedures. Recurrence is a concern after any type of PCa treatment, especially after targeted treatments. In this article we investigate the recurrence rate after FTC and the role of Prostate-Specific Antigen (PSA) as a predictor of recurrences. Our research provides new evidence on the feasibility of FCT by providing new insights on patient management.Targeted therapy (TT) for prostate cancer (PCa) aims to ablate the malignant lesion with an adequate margin of safety in order to obtain similar oncological outcomes, but with less toxicity than radical treatments. The main aim of this study was to evaluate the recurrence rate (RR) in patients with primary localized PCa undergoing mpMRI/US fusion targeted cryotherapy (FTC). A secondary objective was to evaluate prostate-specific antigen (PSA) as a predictor of recurrences. We designed a prospective single-center single-cohort study. Patients with primary localized PCa, mono or multifocal lesions, PSA ≤ 15 ng/mL, and a Gleason score (GS) ≤ 4 + 3 undergoing FTC were enrolled. RR was chosen as the primary outcome. Recurrence was defined as the presence of clinically significant prostate cancer in the treated areas. PSA values measured at different times were tested as predictors of recurrence. Continuous variables were assessed with the Bayesian t-test and categorical assessments with the chix-squared test. Univariate and logistic regression assessment were used for predictions. A total of 75 cases were included in the study. Ten subjects developed a recurrence (RR: 15.2%), while fifty-six (84.8%) patients showed a recurrence-free status. A %PSA drop of 31.5% during the first 12 months after treatment predicted a recurrence with a sensitivity of 53.8% and a specificity of 79.2%. A PSA drop of 55.3% 12 months after treatment predicted a recurrence with a sensitivity of 91.7% and a specificity of 51.9%. FTC for primary localized PCa seems to be associated with a low but not negligible percentage of recurrences. Serum PSA levels may have a role indicating RR.

This study aimed to evaluate the role of serum prostate-specific antigen (PSA) levels and multiparametric magnetic resonance imaging (mpMRI) in the diagnosis of granulomatous prostatitis (GP) induced by intravesical Bacillus Calmette-Guérin vaccine (BCG) therapy in patients with nonmuscle invasive bladder cancer (NMIBC). We retrospectively analyzed eight patients with bladder cancer who underwent intravesical BCG therapy after transurethral resection of bladder tumor (TURBt) cancer. All these eight patients received 12-core transrectal ultrasound-guided prostate systemic biopsies. Clinical data on PSA with T1-weighted imaging (T1WI), T2WI, diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) on mpMRI were enrolled in the study. H and E and acid-fast staining was performed to pathologically prove GP. Four of all eight cases were above 4 ng/ml total PSA (tPSA) levels and four cases were within normal ranges, while free PSA/tPSA levels decreased to lower than 16% in all patients. Every patient had hard prostatic nodules through digital rectal examination (DRE). All characters of prostate mpMRI did not show signal intensity (SI) of prostate cancer before BCG therapy but showed abnormal signals after BCG therapy. All nodular lesions showed equal SI on T1WI, lower SI on T2WI, higher SI on DWI, and lower SI on ADC after BCG therapy. Pathologic results were GP and acid-fast staining outcomes were positive in all biopsies. Perioperative serum PSA levels, prostate magnetic resonance imaging, and DRE may help in the diagnosis of GP induced by intravesical BCG therapy. In general, male patients with middle- and high-risk NMIBC are recommended to undertake DRE, PSA, and prostate mpMRI, if possible, before and after TURBt."

Objective: To evaluate the factors to predict Gleason score upgrading in prostate cancer patients who are suitable for active surveillance (AS) and the role of prostate-specific antigen (PSA) density in the management of these patients. Material and Methods: Seventy seven prostate cancer patients who had active surveillance criteria but preferred radical prostatectomy as the treatment instead of active surveillance protocol were included in the study. In our study, Gleason 3+3≤6 adenocarcinoma, positivity in maximum 2 biopsy cores in ≥12 core transrectal ultrasound guided systematic biopsy, PSA<10 ng/mL, and Clinical T Stage ≤2a were used as active follow-up criteria. Tumor grade in the radical prostate and prostate biopsy specimens were compared. Predictive factors of pathological upgrading after radical prostatectomy have been investigated. Results: There is statistically significant correlation between PSA density (p=0.042), prostate volume (p=0.010), maximum tumor length in a core (p=0.001), maximum percentage of tumor in a core (p=0.002), bladder neck involvement (p=0.023) and postoperative Gleason score upgrading in univariate analysis. The optimal cut-off values of PSA density and prostate volume were 0.12 ng/mL2 and 48 cc, respectively. There isn't statistically significant correlation between PSA, free PSA, free/total PSA, the length of biopsy core, perineural invasion, apical involment and postoperative Gleason score upgrading in univariate analysis. Maximum tumor length in a core and prostate volume were independent predictors of pathological Gleason score upgrading on multivariate regression. Conclusion: Prostate volume and maximum tumor length in a core are independent predictors of pathological Gleason score upgrading in our study. These factors should also be included in current AS criterias in addition to PSA density and tumor percentage.

The role of prostate-specific antigen in light of new scientific evidence: An update in 2020

Introduction: The main aim of our study was to assess the role of prostate specific antigen in Indian males and to determine its correlation with insulin resistance in metabolic syndrome. Materials and Methods: For this study, 62 male subjects of 40-65 years having metabolic syndrome were selected. Body mass index, fasting blood sugar, serum prostate specific antigen, serum fasting insulin and insulin resistance were analyzed using multivariate regression analysis and Annova test. Results and Conclusion: There was no statistically significant difference between body mass index and prostate specific antigen, body mass index and insulin resistance, prostate specific antigen and triglyceride, prostate specific antigen and high density lipoprotein, and prostate specific antigen and fasting blood sugar. Keywords: Body mass index, Insulin resistance and Obesity, Prostate specific antigen.

BackgroundA high prevalence of osteoblastic bone metastases is characteristic of prostate cancer. Prostate‐specific antigen (PSA) is a serine protease uniquely produced by prostate cancer cells and is an important serological marker for prostate cancer. However, whether PSA modulates the osteogenic process remains largely unknown. In this study, we explored the effect of PSA on modulating the osteoblastic differentiation of mesenchymal stem cells (MSCs). In this study, we used flow cytometry, CCK‐8 assay, Alizarin red S (ARS) staining and quantification, alkaline phosphatase (ALP) activity and staining, Western blotting, and quantitative real‐time PCR (qRT‐PCR) to explore the effect of PSA on osteogenic differentiation of MSCs.ResultsWe first demonstrated that although PSA did not affect the proliferation, morphology, or phenotype of MSCs, it significantly promoted the osteogenic differentiation of MSCs in a concentration‐dependent manner. Furthermore, we demonstrated that PSA promoted the osteogenic differentiation of MSCs by elevating the expression of Cadherin 11 in MSCs and, thus, activating the Akt signaling pathway.ConclusionsIn conclusion, we demonstrated that PSA could promote the osteogenesis of MSCs through Akt signaling pathway activation by elevating the expression of cadherin‐11 in MSCs. These findings imply a possible role of PSA in osteoblastic bone metastases in prostate cancer.

Prostate specific antigen and Prostate specific antigen-density are used for the initial evaluation of patient with LUTS due to benign prostatic enlargement in order to discriminate between benign conditions and prostate cancer. Conversely, the role of these markers during the follow up of benign prostatic enlargement patients is still unclear. The aim of our study is to evaluate the role of prostate specific antigen and prostate specific antigen density as outcome parameter for both medical and surgical treatment in patients with male LUTS. We performed a systematic review and meta-analysis based on data from clinical trials evaluating the clinical effect of medical or surgical therapy on LUTS/benign prostatic enlargement. Meta-regression analyses were done to evaluate the effects of several factors on IPSS score improvement. We selected 12 studies out of 433, including data on 1959 patients. Both medical and surgical treatment lead to a significant reduction of PSA levels as compared to baseline (P<0.001). However, after medical treatment, lower PSA values are associated with more significant improvements in lower urinary tract symptoms as measured with the IPSS, while after surgery (P<0.05), the recovery of urinary function does not correlate with the decline in PSA values (P=0.59). After medical treatment, the improvement in LUTS correlate with a decline of PSAD, while the opposite holds true in men treated with surgery (both: P<0.001). PSAD may represent an objective treatment outcome parameter and should be evaluated during the follow up of men treated for LUTS due to BPE as marker of treatment response.

In recent years, several new biomarkers supplementing the role of prostate-specific antigen (PSA) have become available for men with prostate cancer. Although widely used in an ad hoc manner, the role of PSA in screening asymptomatic men for prostate cancer is controversial. Several expert panels, however, have recently recommended limited PSA screening following informed consent in average-risk men, aged 55-69 years. As a screening test for prostate cancer however, PSA has limited specificity and leads to overdiagnosis which in turn results in overtreatment. To increase specificity and reduce the number of unnecessary biopsies, biomarkers such as percent free PSA, prostate health index (PHI) or the 4K score may be used, while Progensa PCA3 may be measured to reduce the number of repeat biopsies in men with a previously negative biopsy. In addition to its role in screening, PSA is also widely used in the management of patients with diagnosed prostate cancer such as in surveillance following diagnosis, monitoring response to therapy and in combination with both clinical and histological criteria in risk stratification for recurrence. For determining aggressiveness and predicting outcome, especially in low- or intermediate-risk men, tissue-based multigene tests such as Decipher, Oncotype DX (Prostate), Prolaris and ProMark, may be used. Emerging therapy predictive biomarkers include AR-V7 for predicting lack of response to specific anti-androgens (enzalutamide, abiraterone), BRAC1/2 mutations for predicting benefit from PARP inhibitor and PORTOS for predicting benefit from radiotherapy. With the increased availability of multiple biomarkers, personalised treatment for men with prostate cancer is finally on the horizon.

The prostate-specific antigen (PSA) blood test is the accepted biomarker of tumor recurrence. PSA levels in serum correlate with disease progression, though its diagnostic accuracy is questionable. As a result, significant progress has been made in developing modified PSA tests such as PSA velocity, PSA density, 4Kscore, PSA glycoprofiling, Prostate Health Index, and the STHLM3 test. PSA, a serine protease, is secreted from the epithelial cells of the prostate. PSA has been suggested as a molecular target for prostate cancer therapy due to the fact that it is not only active in prostate tissue but also has a pivotal role on prostate cancer signaling pathways including proliferation, invasion, metastasis, angiogenesis, apoptosis, immune response, and tumor microenvironment regulation. Here, we summarize the current standing of PSA in prostate cancer progression as well as its utility in prostate cancer therapeutic approaches with an emphasis on the role of PSA in the tumor microenvironment.

Although PSA (prostate-specific antigen)-a tumor marker for prostate cancer-has been reported to be associated with cardiovascular disease (CVD) risk factors, studies on the association of PSA with subclinical and clinical CVD remain limited. We examined the association of total serum PSA within the reference range with coronary artery calcium (CAC) score and CVD mortality. A cross-sectional study was performed in 88 203 Korean men who underwent a health checkup exam including cardiac tomography estimation of CAC score. Logistic regression model was used to calculate odds ratios with 95% CIs for prevalent CAC. PSA levels were inversely associated with the presence of CAC. After adjusting for potential confounders, multivariable-adjusted odds ratio (95% CIs) for prevalent CAC comparing PSA quartiles 2, 3, and 4 to the first quartile were 0.96 (0.90-1.01), 0.88 (0.83-0.93), and 0.85 (0.80-0.90), respectively ( P for trend, <0.001). A cohort study was performed in 243 435 Korean men with a mean age of 39.3 years, PSA values of <4.0 ng/mL, and without known CVD or prostate disease who were followed up with for ≤14 years for CVD mortality (median, 7.3 years). CVD deaths were ascertained through linkage to national death records. Hazard ratios and 95% CIs for CVD mortality were estimated using Cox proportional hazards regression analyses. During 1 829 070.1 person-years of follow-up, 336 CVD deaths were identified. After adjustment for potential confounders, multivariable-adjusted hazard ratios (95% CIs) for CVD mortality comparing PSA quartiles 2, 3, and 4 to the lowest quartile were 0.90 (0.66-1.22), 0.79 (0.58-1.08), and 0.69 (0.51-0.93), respectively. Serum total PSA levels within the reference range showed an inverse association with subclinical atherosclerosis and CVD mortality in young and middle-aged Korean men, indicating a possible role of PSA as a predictive marker for subclinical and clinical CVD.

Introduction: Prostate-Specific Antigen (PSA) is an organ specific rather than cancer specific hormone. It is a single chain glycoprotein produced by epithelial cells of the prostate gland. Role of PSA in carcinoma of prostate is well defined but its role in other diseases of prostate is not very clear. Increased PSA levels are not essentially associated with prostate cancer, but can also be elevated in conditions other than cancerous lesions, such as prostate inflammation, bacterial prostatitis, Benign Prostate Hyperplasia (BPH) and Urinary Tract Infection (UTI). BPH is the most common benign tumours in men with prevalence ranging from 50% for men in their 50s to 90% for men in their 90s. Aim: To find the relation of serum PSA levels with age, Prostate Volume (PV) and PSA density in BPH patients. Materials and Methods: The present hospital-based, crosssectional study was conducted on 162 BPH patients who consulted to the Urology Department of Rajindra Hospital, Patiala and were prescribed to undergo serum PSA evaluation. The serum PSA levels of these patients were estimated by the Enzyme-Linked Immunosorbent Assay (ELISA). Routine investigations included Complete Blood Count (CBC), serum urea, serum creatinine, Fasting Blood Glucose (FBG), serum PSA and ultrasonography of the kidneys, ureter, bladder and prostate. Correlations were evaluated using Pearson correlation coefficient. All the statistical graphs were plotted using Microsoft Excel 2009. The results p-value <0.001 were considered statistically significant. Results: No significant association (p=0.445) between serum PSA and age groups of BPH patients was observed. A significant correlation was observed between serum PSA and PV (r=0.59, p-value <0.001) and PSA density (r=0.56, p-value <0.001) in BPH patients. Conclusion: The present study indicates that there was no association between age specific reference range and serum PSA levels. And PV and PSA density should be considered while interpreting PSA level to improve the diagnostic parameters.

: Prostate cancer management remains a topic of intense debate given favorable disease-specific outcomes for the overwhelming majority of patients. Consensus regarding the role of prostate-specific antigen (PSA) screening among the general male population has been elusive, in part due to questions surrounding the reliability of prostate biopsy results and the difficulty identifying patients with localized disease who will one day progress. Until recently, the Gleason score has been the best prognostic indicator available but issues with interobserver reliability and biopsy sampling error fuel therapeutic indecision and likely lead to over- or under-treatment. Prostate cancer genomic testing takes several forms and offers additional information for predicting the clinical behavior of a tumor. Urine based assays take advantage of the prostate’s anatomic location in the urinary tract to look for genetic material that is associated with finding prostate cancer on a subsequent biopsy. Prostate biopsy tissue samples give direct access to the cancer genome and provide information beyond what is ascertainable using a microscope. If the Gleason score provides a snapshot of the current state of a given prostate tumor, then these tissues based genomic tests offer a window in its future. Several commercially available tests are currently available but only a small number have been FDA-approved thus far. Even the best products have only provided modest gains in prognostic accuracy over existing clinical risk stratification tools, however, this is a key step in the right direction that is nearly a decade behind other malignancies (i.e., breast). There is published data to suggest that these tests can alter physician practice patterns, but to what degree they will ultimately alter clinically significant outcomes remains to be seen.

The clinical and pathological aspects of the Skene's glands have not been addressed in the current scientific literature. To review the current literature to focus on the clinical and pathological aspects of the Skene's glands. The historical perspective including embryology, anatomy, histology, and current role of prostatic specific antigen (PSA) as a tumor marker of lesions which develop from the Skene's glands, 'female prostate.' Medline searches were performed to review the current literature regarding Skene's glands pathology, clinical manifestations, diagnosis, role of PSA, and its treatment options. Anatomical pathology including inflammatory, cystic, solid, benign, and malignant tumors of Skene's glands is emphasized. The unique role of PSA in these lesions is reviewed. Cognizance of periurethral, perimeatal and urethral masses is essential for anatomical pathologists, radiologists, urologists and gynecologists who encounter complex female urethral masses in their clinical practice. Imaging techniques of Skene's glands to diagnose urethral, perimeatal and periurethral masses in female are reviewed. The literature of the interesting scientific concepts related to the Skene's glands are reviewed. The role of PSA in these lesions is expanded for diagnoses and treatment options of pathology of the Skene's glands. Methods of imaging are necessary for radiologist, pathologists, and clinicians alike, for the proper treatment of Skene's gland lesions.

266 Background: ENZ significantly increased OS for men with metastatic castration-resistant prostate cancer (mCRPC) vs. placebo and significantly decreased PSA levels. However, the prognostic significance and role of PSA falls as a surrogate for OS are not established. Methods: Men in the AFFIRM trial were grouped by maximal unconfirmed PSA decline during the 1st 90 days of treatment in a post-hoc analysis. Each PSA decline criterion was assessed for surrogacy for OS by the proportion of treatment effect (PTE)-explained and Prentice criteria. We also assessed the association of PSA decline with OS, progression-free survival (PFS), and pain response. Results: ENZ improved OS (hazard ratio 0.63, p &lt; 0.001) and was associated with higher rates of PSA declines when compared to placebo (odds ratio &gt; 19.0, p &lt; 0.001). Greater declines in PSA were associated with longer OS, PSA PFS, radiographic PFS, and higher pain response when compared with no PSA decline or PSA increase (table). All decline measures from baseline were highly prognostic for OS and several ( &gt; 0%, ≥ 30%, ≥ 50% declines) explained a proportion of the treatment effect (PTE 1.07–1.29, 95% CI lower bounds &gt; 0.63), in which treatment was no longer significant after adjustment for the decline measures (p &gt; 0.20). Full surrogacy was not demonstrated. Conclusions: In AFFIRM, &gt; 0, ≥30%, and ≥50% PSA declines within 90 days of treatment fulfilled Prentice surrogacy criteria 1–3. Prentice 4, equivalency of survival adjusting for PSA decline outcomes, could not be demonstrated. PSA declines are associated with longer PFS and improved pain response. External prospective validation is needed. Clinical trial information: NCT00974311. [Table: see text]