Prostate-specific Antigen Level Research Articles

DNA Repair Capacity and Clinicopathological Characteristics in Puerto Rican Hispanic/Latino Patients with Metastatic Castration-Resistant Prostate Cancer

Background: Prostate cancer (PCa) accounts for 22% of the new cases diagnosed in Hispanic/Latino (H/L) men in the US. PCa has the highest incidence (38.3%) and mortality (16.4%) among all types of cancer diagnosed in Puerto Rico. We previously showed that PCa patients (n = 41) have a significant reduction of 59% in their levels of DNA repair capacity (DRC) when compared to controls (n = 14). This study aimed to evaluate DRC levels through the nucleotide excision repair (NER) pathway for the first time in 16 Puerto Rican H/L men with metastatic castration-resistant PCa (mCRPCa) while establishing comparisons with controls and PCa patients with indolent and aggressive disease. Methods: Blood samples and clinicopathological data from PCa cases (n = 71) and controls (n = 25) were evaluated. PCa cases were stratified into mCRPCa (n = 16), aggressive (n = 31), and indolent (n = 24). DRC levels through NER were measured in lymphocytes with the CometChip assay. The stratification by Gleason score (GS) was GS6 (n = 7), GS7 (n = 23), GS ≥ 8 (n = 20), and mCRPCa patients (n = 16). Results: Significant statistical differences were found when comparing the DRC values of the controls with any other of the four PCa patient groups. mCRPCa patients had the lowest mean DRC level of all four patient groups studied. The mean DRC level of mCRPCa patients was 6.65%, and compared to the controls, this represented a statistically significant reduction of 62% (p < 0.0001). Further analysis was performed to evaluate the contributions of age, anthropometric measurements, and prostate-specific antigen (PSA) levels to the DRC. Kaplan–Meier curves of mCRPCa revealed that survival probability decreased by approximately 50% by 30 months. This pilot study uses a blood-based phenotypic assay to present the first report of mCRPCa in Puerto Rican men and at a global level of DRC levels of mCRPCa patients. Conclusions: This study evaluated DRC levels through the NER pathway for the first time in 16 Puerto Rican H/L men with mCRPCa. Significant differences in DRC values were found between the controls and the three PCa patient groups. Kaplan–Meier curves revealed that survival probability decreased by approximately 50% by 30 months, and only 20% of the cohort was alive at 50 months, confirming the lethality of mCRPCa in this H/L population. This pilot study represents the first report of metastatic PCa in Puerto Rican men at a global level of DRC levels of mCRPCa patients using a blood-based phenotypic assay.

Development of Novel Nomograms to Predict 5- and 7-Year Biochemical-Recurrence-Free Survival in High-Risk Prostate Cancer Patients After Carbon-Ion Radiotherapy and Androgen Deprivation Therapy

Background: The aim of this study was to develop nomograms predicting 5- and 7-year biochemical-recurrence (BCR)-free survival in high-risk prostate cancer (PCa) patients treated with carbon-ion radiotherapy (CIRT) and androgen deprivation therapy (ADT). Methods: We retrospectively evaluated 785 high-risk PCa patients treated with CIRT and ADT. Based on the least absolute shrinkage and selection operator model, two nomograms predicting 5- and 7-year BCR-free survival were developed and internally validated. The ability of each nomogram to predict BCR-free survival was determined by calculating the area under the survival curve (AUC). Results: The 5- and 7-year BCR-free survival rates were 92.1% and 89.3%, respectively. Age, prostate-specific antigen level, clinical T stage, and Gleason score were incorporated into the nomogram predicting 5-year BCR-free survival. In addition to these variables, the percentage of positive biopsy cores was also added to the nomogram predicting 7-year BCR-free survival. The AUC value of each nomogram showed suboptimal-to-good discrimination. Conclusions: We developed the first nomograms accurately predicting BCR-free survival in high-risk PCa patients treated with CIRT and ADT. These nomograms will enable adequate understanding and explanation of BCR-free survival to patients when clinicians use them.

Rethinking prostate cancer screening in transgender women

Introduction: Over the years, the number of people openly identifying as transgender has steadily increased, leading to a greater need for transgender-specific healthcare information. Among transgender women (TW), there remains a risk of prostate cancer since the prostate is not removed during gender-affirming hormone therapy (GAHT) or surgery; however, there is limited knowledge about prostate cancer screening in the transgender population. Although there are few reported cases of prostate cancer screening or prostate-specific antigen (PSA) testing in TW, the impact of hormone therapies on PSA levels is well-documented. Notably, GAHT for TW and hormone therapy for treating prostate cancer share similarities. Drawing on these similarities, we aimed to develop guidelines for baseline PSA levels and prostate cancer screening in TW. Methods: Through a systematic review, we examined the existing PubMed publications on PSA levels and prostate cancer screening in TW, as well as expected PSA levels in patients with prostate cancer undergoing hormone therapies. We also investigated other aspects considered for the diagnosis of prostate cancer. Given the limited research on TW, we also included relevant case studies. These publications and case reports were reviewed and analyzed to create a comprehensive overview of expected baseline PSA levels and prostate cancer screening guidelines for TW. Results: Currently, there are no established guidelines for PSA or prostate cancer screening in TW; however, these case studies indicated a range of PSA values from 3.3 to <100 ng/ml. Existing literature on expected PSA levels in prostate cancer patients undergoing hormone therapy shows a reduction in PSA of over 50% post-therapy. This evidence suggests that PSA values in TW presenting with prostate cancer may be lower than those observed in cisgender males with the disease. Conclusions: While TW exhibit lower prostate cancer incidence compared to cisgender men, the impact of hormone therapy on PSA levels presents significant challenges for screening and diagnosis. The parallels between PSA level reductions in TG women and cisgender men undergoing estrogen therapy highlight the need for revised screening protocols. Addressing these challenges through targeted research and personalized care approaches will be vital for improving prostate cancer management in transgender individuals.

Prospective validation study of a combined urine and plasma test for predicting high-grade prostate cancer in biopsy naïve men.

Early and accurate diagnosis of prostate cancer (PC) is crucial for effective treatment. Diagnosing clinically insignificant cancers can lead to overdiagnosis and overtreatment, highlighting the importance of accurately selecting patients for further evaluation based on improved risk prediction tools. Novel biomarkers offer promise for enhancing this diagnostic process. In this study, we aimed to externally validate a previously developed urine and plasma biomarker test in a biopsy-naïve population. Urine and blood samples were prospectively collected from 362 biopsy-naïve men with suspected PC before they underwent transrectal prostate biopsies. The expression levels of a 10-gene mRNA panel were quantified using reverse transcription/quantitative polymerase chain reaction of both urine and plasma. These gene expression levels, combined with clinical features and plasma prostate-specific antigen (PSA) levels, were used to predict the presence of International Society of Urological Pathology grade group ≥ 2 PC. Complete data were available for 314 patients. The sensitivity and specificity of the biomarker test were 87% (95% CI: 79-93%) and 42% (95% CI: 36-49%), respectively. The area under the curve was 0.76 (95% CI: 0.7-0.82) for the biomarker test probability and 0.65 (95% CI: 0.59-0.72) for PSA (p = 0.02). The test's negative predictive value was 89% (CI: 81-94%). This study did not replicate the previously reported high accuracy of the biomarker test, highlighting the need for further refinement and robust external validation to ensure reliable performance across diverse patient populations.

Prognostic Testing for Prostate Cancer-A Cost-Effectiveness Analysis Comparing a Prostatype P-Score Biomarker Approach to Standard Clinical Practice.

The Prostatype score (P-score) is a prognostic biomarker that integrates a three-gene (IGFBP3, F3, and VGLL3) signature derived from prostate biopsy samples, with key clinical parameters, including prostate-specific antigen (PSA) levels, Gleason grade, and tumor stage at diagnosis. The test has demonstrated superior predictive accuracy for prostate cancer outcomes compared with traditional risk categorization systems such as D'Amico. Notably, it reclassifies a higher proportion of patients into the low-risk category, making them eligible for active surveillance. This study assessed the cost-effectiveness of the P-score in comparison with D'Amico and the Swedish National Prostate Cancer Register (NPCR) risk categorization systems. A two-step decision analytic model was developed. The model consisted of a decision tree-informed Markov structure estimating the lifetime outcomes of 60-year-old men with diagnosed prostate cancer. Prostate cancer was classified as low-risk, intermediate-risk, or high-risk using either the P-score or D'Amico. Initial therapy was based on observed treatment patterns from the Swedish NPCR. Costs (SEK, year 2022) and quality-adjusted life years (QALYs) were estimated from a healthcare perspective and discounted at 3% per year; incremental cost-effectiveness ratio (ICER) was the primary outcome. The P-score led to cost savings and generated an additional 0.19 QALYs compared with D'Amico. The added costs of the genetic test and higher costs of active surveillance and radiotherapy were counterbalanced by savings from reduced costs of surgery, treatment-related side-effects, and metastatic disease. The gain in QALYs was primarily due to the avoidance of metastatic disease and a reduction in treatment-related side-effects. The results of this study suggest that the P-score is likely to be a cost-effective alternative to D'Amico for prognostic evaluation of newly diagnosed prostate cancer in Sweden and compared with NPCR when health-related quality of life was included.

Using XBGoost, an interpretable machine learning model, for diagnosing prostate cancer in patients with PSA < 20 ng/ml based on the PSAMR indicator

To create a diagnostic tool before biopsy for patients with prostate-specific antigen (PSA) levels < 20 ng/ml to minimize prostate biopsy-related discomfort and risks. Data from 655 patients who underwent transperineal prostate biopsy at the First Affiliated Hospital of Wannan Medical College from July 2021 to January 2023 were collected and analyzed. After applying the Synthetic Minority Over-sampling TEchnique class balancing on the training set, multiple machine learning models were constructed by using the Least Absolute Shrinkage and Selection Operator (LASSO) feature selection to identify the significant variables. The best-performing model was selected and evaluated through tenfold cross-validation to ensure interpretability. Finally, the performance was assessed using the test set data for validation. The age, prostate-specific antigen mass ratio (PSAMR), Prostate Imaging–Reporting and Data System, and prostate volume were selected as the variables for model construction based on the LASSO regression. The receiver operating characteristic (ROC) results for multiple models in the validation set were as follows: XGBoost: 0.93 (0.88–0.97); logistic: 0.89 (0.83–0.95); LightGBM: 0.87 (0.80–0.93); AdaBoost: 0.90 (0.85–0.96); GNB: 0.88 (0.82–0.95); CNB: 0.79 (0.71–0.87); MLP: 0.78 (0.69–0.86); and Support Vector Machine: 0.81 (0.73–0.89). XGBoost was selected as the best model and reconstructed with tenfold cross-validation on the training data, resulting in the following ROC scores: training set 0.995 (0.991–0.999), validation set 0.945 (0.885–0.997 ), and test set 0.920 (0.868–0.972). The Kolmogorov–Smirnov curve, calibration curve and learning curve yielded positive results; The decision curve demonstrates that patients with threshold probabilities ranging from 10 to 95% can benefit from this model. We developed an XGBoost machine learning model based on the PSAMR indicator and interpreted it using the SHapley Additive exPlanations method. The model offered a high-performance non-invasive technique to diagnose prostate cancer in patients with PSA levels < 20 ng/ml.

Diagnostic Efficacy of grey-zone Serum Prostate Specific Antigen level in patients with Benign Prostatic Hyperplasia and Prostate Carcinoma

Objective: Evaluation of diagnostic role of grey zone serum prostate specific antigen level(4-10ng/ml) in patients with benign prostatic hyperplasia (BPH) and prostate carcinoma keeping histopathology as gold standard. Study design and setting: Cross-sectional study conducted in department of urology and chemical pathology, sheikh Zayed hospital Rahim yar khan. Methodology: Patients with grey zone serum prostate specific antigen level (4-10ng/ml), lower urinary tract symptoms or abnormal DRE (digital rectal examination) were included and diagnosis was confirmed on the basis of histopathology. Chi square test used to see the statistically significant difference between subgroups. P value &lt;0.05 was deemed as significant. Diagnostic role evaluated by ROC curve analysis. Results: Mean age of study subjects was 60.21±10.046 years and 155 (81.2%) subjects were having serum prostate specific antigen level in grey zone (4-10ng/ml). Of the total 191 study subjects, 59(30.9%) were histopathologically confirmed cases of benign prostatic hyperplasia and 34(17.8%) were confirmed cases of prostate carcinoma. 41 (26.45%) cases of benign prostatic hyperplasia were having serum PSA level in grey zone (4-10ng/ml) and 16(10.32%) cases with prostate carcinoma were having PSA level in grey zone (4-10ng /ml). ROC curve analysis shows AUC=0.584 in case of BPH and AUC=0.707 in case of CA prostate. Conclusion: On the basis of our study, it is concluded that grey zone serum PSA level in symptomatic individuals should be used in conjunction with other non-invasive diagnostic and clinical parameters to improve diagnosis and to avoid unnecessary biopsy in every symptomatic individual

Early experience of prostate artery embolization: a retrospective single-centre study.

The aim of this study was to evaluate the early experiences of prostate artery embolization (PAE) in patients with benign prostatic hyperplasia (BPH). This retrospective study included all patients treated for BPH who were referred to the radiology department for PAE in Västmanland between 2018 and 2021. Data were collected on patient demographics, International Prostate Symptom Score (IPSS), prostate-specific antigen level, and peri- and post-procedure outcomes. Clinical success was defined as a decrease in the IPSS by ≤3 points or catheter freedom. A total of 96 patients (median age 74 years) underwent PAE. Before PAE, 65% of the patients were treated with α-blockers and 83% with 5α-reductase inhibitors. Clinical success was achieved in 60 patients (63%). Among catheterized patients, 33 (53%) achieved catheter freedom. In the non-catheterized group, 27 (79%) experienced clinical success. No significant differences in outcomes were observed based on the presence of a median lobe. PAE appears to be a viable treatment option for BPH and may provide substantial symptom relief and catheter freedom for most patients. These findings suggest that PAE may be an effective alternative to more invasive procedures. Further research is needed to refine the patient selection criteria.

Prostate cancer screening: Is it time for a new approach? A review article.

Prostate cancer screening has presented a challenge to clinicians. Although the implementation of screening tests such as prostate-specific antigen (PSA) and digital rectal exam (DRE) has had a significant impact on prostate-cancer-specific mortality, these traditional screening tests have a relatively poor positive predictive value of clinically significant prostate cancer (CSPC), leading to unnecessary biopsies and treatment with a host of potential complications. Fortunately, much research has been done to optimize prostate cancer screening. This includes the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which underwent a secondary analysis to identify an association between PSA level and CSPC, and the IP1-PROSTAGRAM Tri.

Robot-Assisted PSMA-Radioguided Salvage Surgery for Oligorecurrent Prostate Cancer Using the Novel SENSEI® Drop-in Gamma Probe: Correlation of Intraoperative Measurements to Preoperative Imaging and Final Histology.

To examine the feasibility and safety of the SENSEI® drop-in gamma probe for robot-assisted, prostate-specific membrane antigen (PSMA)-radioguided salvage surgery (RGS) in lymph node or local oligorecurrent prostate cancer (PCa), detected via PSMA positron emission tomography/computed tomography (PET/CT). The first thirteen patients with pelvic oligorecurrent PCa who underwent [99mTc]Tc-PSMA-I&S RGS using the SENSEI® drop-in gamma probe at the Martini-Klinik (February-June 2024) were retrospectively analyzed. Radioactivity measurements in counts per second (CPS) as absolute values or ratios (CPS of tumor specimens/mean CPS from the patients' benign tissues) were correlated with preoperative imaging and pathological findings (benign/malignant, lesion size). Postoperative complete biochemical response (cBR) was defined as prostate-specific antigen (PSA) levels of <0.2 ng/mL. Fifty-four specimens were removed from 13 patients, with nineteen (35%) containing PCa. All patients had one PSMA PET/CT-positive lesion, which were all detected intraoperatively. These lesions showed higher ex vivo CPS, CPS ratios, and larger cancer diameters than PSMA PET/CT-negative lesions (all p < 0.05). Cancer-containing specimens exhibited higher CPS and CPS ratios than benign tissues (median values of 45 vs. 3, and 9.9 vs. 1.0, both p < 0.001). In total, 12/13 (92%) patients achieved cBR. This device yielded excellent detection rates with good correlation to preoperative imaging and histological results without adverse events.

Contemporary prostate cancer radiation therapy trials may underestimate the risk of biochemical recurrence.

Radiotherapy is often given with androgen deprivation therapy for prostate cancer which causes a reduction in testosterone levels, which when below castrate levels, can cause the prostate specific antigen (PSA) levels to be artificially low. To determine if high-level radiotherapy clinical trials are underestimating biochemical recurrence (BCR) rates due to inadequate measurement of testosterone levels. The study plans for clinical trials performed by the Radiation Therapy Oncology Group (RTOG [now NRG]) on clinicaltrials.gov were reviewed for details on testosterone measurement in trials from 1994 to 2023, namely if the testosterone levels were indexed to PSA levels. PSA being indexed to testosterone levels and other metrics of testosterone measurement, including time of day of measurement, assay used, and mean testosterone measurement. Five of 21 (24%) trials stipulated that testosterone levels should be indexed to PSA levels. Eleven of 21 (52%) trials made no mention of testosterone. No trial reported testosterone assay or time of day of measurement. Thirteen of 21 (62%) trials did not require regular follow-up testosterone measurements. The number of clinical trials indexing or regularly measuring testosterone was surprisingly low, which could cause an underestimation of BCR rates. Strengths include being the first study, to our knowledge, to analyze the details of testosterone measurement in high-level radiotherapy trials. Limitations include only analyzing RTOG/NRG trials, analyzing unpublished data, and using clinicaltrials.gov rather than official trial protocols to determine details of testosterone measurement. Indexing of testosterone levels to PSA levels in high-level radiotherapy trials using androgen deprivation therapy was uncommon, possibly rendering data on BCR unreliable, potentially underestimating BCR rates.

Exploring the Link Between Obligate Anaerobe-Related Dysbiosis and Prostate Cancer Development: A Pilot Study.

Several independent studies have associated prostate cancer (PCa) with specific groups of bacteria, most of them reporting the presence of anaerobic or microaerophilic species such as Cutibacterium acnes (C. acnes). Such findings suggest a prostate cancer-related bacterial dysbiosis, in a manner similar to the association between Helicobacter pylori infection and gastric cancer. In an earlier exploratory study looking for such dysbiosis events, using a culturomics approach, we discovered that the presence of obligate anaerobes (OAs) along with C. acnes was associated with increased prostate-specific antigen (PSA) levels in 39 participants. Building on this, in this study, we analyzed 89 post-rectal examination urine samples, from men with prostate cancer attending the PROVENT trial, using 16S rDNA sequencing. Our investigation focused on the impact of six previously identified OA genera (Finegoldia, Fusobacterium, Prevotella, Peptoniphilus_A, Peptostreptococcus, and Veillonella_A) on PSA levels. However, an additional data-driven approach was followed to uncover more taxa linked to increased PSA. Our analysis revealed a statistically significant association between Peptostreptococcus and elevated PSA levels. Additionally, there were potential interactions between Prevotella and Fusobacterium. Interestingly, we also found that an aerobe, Ochrobactrum_A,was significantly linked to higher PSA levels. These findings suggest that OA-related dysbiosis may contribute to elevated PSA levels through prostate cell damage even before prostate cancer develops, possibly playing a role in chronic inflammation and the hypervascular changes seen in precancerous lesions. Future clinical trials with larger cohorts are needed to further evaluate the role of OA in prostate cancer development and progression.

PI-RADS in Predicting csPCa: A Comparison Between Academic and Nonacademic Centers.

The introduction of multiparametric prostate magnetic resonance imaging (mpMRI) has revolutionized prostate cancer (PCa) diagnosis, enhancing the localization of clinically significant prostate cancer (csPCa) and guiding targeted biopsies. However, significant disparities in the execution, interpretation, and reporting of prostate MRI examinations across centers necessitate greater standardization and accuracy. This study compares the diagnostic efficacy of mpMRI from academic and nonacademic centers in detecting csPCa and identifies factors associated with csPCa detection. Between July 2018 and October 2023, we prospectively followed 810 men at SS. Annunziata Hospital of Chieti who underwent MRI/US fusion biopsies due to elevated prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE). Patients with mpMRI-documented suspicious lesions classified as PI-RADS ≥ 3 were included. Patients were divided into two groups based on the source of their mpMRI (academic or nonacademic centers). All biopsies were conducted using the MRI/US fusion technique. Clinical, mpMRI, and pathological data were collected and analyzed. Statistical analyses were performed using R software. The cohort included 354 patients from academic centers and 456 from nonacademic centers. There were no significant differences in patient demographics, such as age and PSA levels, between the groups. Patients at academic centers were more likely to receive a higher number of elevated PI-RADS scores compared to those at nonacademic centers (PI-RADS > 3: 72.6% vs. 62.3%, p = 0.003). Histopathological analysis revealed no significant differences in the ISUP grade distribution between groups. Increased age, PSA levels, and positive DRE were significantly associated with higher odds of detecting csPCa. Median PSA density was significantly higher in patients with csPCa compared to those without csPCa (0.14 vs. 0.11 ng/mL/cm³, p < 0.001). Academic centers exhibited a higher odds ratio for csPCa detection in patients with PI-RADS scores > 3 compared to nonacademic centers. Our study highlights significant variability in PI-RADS score assignments between academic and nonacademic centers, affecting csPCa detection rates. This variability underscores the need for greater standardization in PI-RADS scoring to reduce disparities and improve diagnostic uniformity across centers.

Isolation of Plasma Extracellular Vesicles for High-Depth Analysis of Proteomic Biomarkers in Metastatic Castration-Resistant Prostate Cancer Patients.

Introduction: Prostate cancer treatment has been revolutionized by targeted therapies, including PARP inhibitors, checkpoint immunotherapies, and PSMA-targeted radiotherapies. Despite such advancements, accurate patient stratification remains a challenge, with current methods relying on genomic markers, tissue staining, and imaging. Extracellular vesicle (EV)-derived proteins offer a novel non-invasive alternative for biomarker discovery, holding promise for improving treatment precision. However, the characterization of plasma-derived EVs in prostate cancer patients remains largely unexplored. Methods: We conducted proteomic analyses on EVs isolated from plasma in 27 metastatic castration-resistant prostate cancer (mCRPC) patients. EVs were purified using ultracentrifugation and analyzed via mass spectrometry. Proteomic data were correlated with clinical markers such as serum prostate-specific antigen (PSA) and bone lesion counts. Statistical significance was assessed using Mann-Whitney t-tests and Spearman correlation. Results: The median age of patients was 74 (range: 44-94) years. At the time of blood collection, the median PSA level was 70 (range: 0.5-1000) ng/mL. All patients had bone metastasis. A total of 5213 proteins were detected, including EV-related proteins (CD9, CD81, CD63, FLOT1, TSG101) and cancer-related proteins (PSMA, B7-H3, PD-L1). Proteomic profiling of plasma EVs revealed a significant correlation between specific EV-derived proteins and clinical prognostic markers. B7-H3, LAT1, and SLC29A1 showed a strong association with serum PSA levels and number of bone lesions, indicating potential for these proteins to serve as biomarkers of disease burden and therapy response. Conclusions: Our findings demonstrate the potential of EV-based proteomics for identifying biomarkers in mCRPC patients. Proteins such as B7-H3 and LAT1 could guide precision oncology approaches, improving patient stratification. Future research incorporating outcomes data and EV subpopulation analysis is needed to establish clinical relevance.

AMPK down-regulating Beclin-1 in prostate cancer patients with bone metastasis: An observational study.

Bone metastasis is frequently seen in patients, particularly those with prostate cancer, showing a higher hazard that deteriorates the quality of life of patients, leading to poor prognosis, which eventually causes significant mortality in prostate cancer patients. The present study investigated the mechanism of prostate cancer with bone metastasis by utilizing prostate specimens from patients. A total of 418 patients were initially enrolled for clinical analysis, including age, prostate-specific antigen (PSA) levels, body mass index (BMI), prostate magnetic resonance imaging (MRI), and bone MRI, while pathological analysis included grade group and carcinoma of the prostate. Patients were divided into a prostate cancer with bone metastasis group (group 1, prostate cancer patients) and benign prostate patient group (group 2, control group) and underwent subsequent immunohistochemical (IHC) detection. Expression of AMPK/Beclin-1 signaling pathways was analyzed through immunohistochemistry. Finally, 46 patients with prostate cancer bone metastasis (prostate cancer patients) and 61 patients with benign prostate (control group) met the inclusion criteria. We examined the expression levels of Beclin-1 and AMPK in human prostate tissues by IHC and found that Beclin-1 levels were negatively correlated with AMPK in prostate cancer with bone metastasis (P < .05). The results of this study suggest that AMPK-Beclin-1 significantly reduces prostate cancer metastasis to the bone in human tissues.

PSA bounce: understanding temporal fluctuations in prostate cancer after external radiotherapy.

Prostate-specific antigen (PSA) bounce is a transient elevation in PSA levels commonly observed after radiotherapy. This study aims to investigate the characteristics, timing, and clinical implications of PSA bounce (PSA-B) in prostate cancer patients treated with external beam radiotherapy (EBRT), exploring potential causes and its relevance in patient management. Between 2013 and 2019, 629 patients with localized prostate cancer were treated with EBRT. After excluding patients with fewer than four PSA measurements or follow-up under 3years (n = 184), 445 patients were analyzed. The median follow-up duration was 5.9years (36-105months). PSA-B was defined as a rise of ≥ 0.2ng/mL above the nadir, followed by a subsequent decline to or below the nadir. PSA relapse was defined according to Phoenix definition. A total of 64 patients (14.4%) experienced PSA-B at a median of 31months (6-68months). Univariable analysis identified age (p < 0.001), risk group (p < 0.001), perineural invasion (p < 0.007), radiotherapy duration (p < 0.001), and the absence of concurrent hormonal therapy (p < 0.001) as independent predictors of PSA-B. Multivariable analysis confirmed age and high-risk group as significant factors. PSA relapse occurred in 10.3% of cases, with only one patient who experienced both PSA-B and relapse. PSA-B is a common phenomenon in localized prostate cancer patients post-EBRT. Factors such as age, risk group, perineural invasion, radiotherapy duration, and hormonal treatment use are associated with PSA-B occurrence. Understanding its mechanisms is crucial for optimizing prostate cancer management.

The accuracy of fluorine 18-labelled prostate-specific membrane antigen PET/CT and MRI for diagnosis of prostate cancer in PSA grey zone.

The diagnostic utility of prostate biopsy is limited for prostate cancer (PCa) in the prostate-specific antigen (PSA) grey zone. This study aims to evaluate the diagnostic performance of multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) for PSA grey zone PCa and clinically significant PCa (csPCa). A total of 82 patients with PSA levels ranging from 4 to 10 ng/mL who underwent 18F-PSMA-1007 PET/CT, mpMRI, and prostate biopsy were prospectively enrolled. For 18F-PSMA-1007 PET/CT and mpMRI in detecting PCa and csPCa, sensitivity, specificity, and area under the curve (AUC) were assessed using biopsy histology as the standard. 18F-PSMA-1007 PET/CT demonstrated better diagnostic performance for PCa than mpMRI (AUC 0.81 vs. 0.63, P = 0.02). 11.0% of patients with PI-RADS 3-5 had no PCa on biopsy, of whom 77.8% were correctly differentiated by 18F-PSMA-1007 PET/CT. Combined 18F-PSMA-1007 PET/CT + mpMRI improved sensitivity (92.5% vs. 73.6%) and negative predictive value(NPV,78.9% vs. 53.3%) compared with mpMRI alone. 18F-PSMA-1007 PET/CT outperformed mpMRI for detecting PCa in the grey zone level of PSA. 18F-PSMA-1007 PET/CT in combination with mpMRI has additional improvement in sensitivity and NPV for csPCa detection. NCT05958004, 2024-07.

Effectiveness of cognitive fusion transrectal ultrasound prostate biopsy when compared with final prostatectomy histology.

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men. Cognitive fusion transrectal ultrasound prostate biopsy is one of several modalities for diagnosing this disease. However, no existing studies have shown the clear superiority of one image-guided technique over another. This investigation aimed to evaluate the efficacy of targeted biopsy through cognitive guidance, as well as to assess the accuracy of multiparametric magnetic resonance imaging (mpMRI) in the detection of PCa compared to the specimen obtained by radical prostatectomy (RP). We conducted a retrospective observational single-center study approved by the ethical committee, including men with prostate-specific antigen (PSA) levels between 2-10 mg/ml who underwent RP and cognitive fusion biopsy (CFB) between 2017 January and 2022 January. A total of 639 patients were analyzed, 83 of whom met the inclusion criteria and were enrolled in this study. The overall rate of PCa detection with CFB was 79.5% (median of specific PCa detection was 100%), and the rate of detecting clinically significant prostate cancer (csPCa) was 74.7%. In addition, there was 42.2% agreement between the International Society of Urological Pathology (ISUP) score of the CFB and the RP specimen, which increased to 56.6% when the systematic biopsy was added. Regarding the accuracy of mpMRI, several parameters were evaluated with respect to RP sample histology. Of these, tumor location had a total match rate of 39.8% and a partial match rate of 55.4%. Moreover, regarding extraprostatic extension (EPE), the present study found a significant association between the RP specimen and mpMRI (p = 0.002), with an agreement rate of 60% if it was present in the histology and 79.5% if it was not. Additionally, larger prostates and tumors located in the transition zone were significantly associated with a lower CFB accuracy (p = 0.001 and p = 0.030, respectively). After adjusting for all variables evaluated, only prostate volume remains statistically significant (p = 0.029). In this study, we conclude that mpMRI is highly accurate, allowing good characterization of suspicious tumors and reasonably guiding cognitive biopsy. However, the use of both targeted biopsy through cognitive guidance and systematic biopsy increases the diagnostic accuracy for PCa. Although there is no recommendation in the current literature for one guiding technique over another, we believe that cognitive-guided biopsy should only be reserved for centers with no access to ultrasound or magnetic resonance fusion software.

68Ga-PSMA PET CT/MRI in the initial diagnosis and staging of prostate cancer: A review

Prostate-specific membrane antigen-positron emission tomography (PSMA-PET) imaging has demonstrated potential in addressing prostate cancer (PCa) diagnostic difficulties. According to current guidelines, gallium-68 (68Ga)-PSMA-PET is used as an adjunct to traditional imaging modalities in patients with primary PCa. The purpose of this review, conducted using Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, is to give an overview of studies that have examined the role of 68Ga-PSMA in the initial diagnosis of PCa, its performance in TNM staging, its correlation with prostate-specific antigen (PSA) levels, targeted biopsies, and the International Society of Urological Pathology (ISUP) scores using computed tomography (CT) or magnetic resonance imaging (MRI). The findings demonstrate that, in addition to MRI alone, combining 68Ga-PSMA-PET with MRI-targeted biopsy improves the initial identification of clinically significant prostate cancer (csPCa), particularly for ambiguous prostate imaging-reporting and data system (PI-RADS) three lesions. 68Ga-PSMA-PET/CT is useful when MRI results for csPCa are uncertain, but consistent techniques are required. Regarding risk assessment and therapy planning, 68Ga-PSMA-PET has a strong correlation with both PSA levels and ISUP scores. It accurately detects primary PCa lesions, making it suitable for high-risk patients. In 68Ga-PSMA-PET, higher maximum standardized uptake value (SUVmax) readings are linked to more aggressive illness. For N and M staging, 68Ga-PSMA-PET/CT is more sensitive and specific than conventional imaging; however, for T-staging, multiparametric MRI (mpMRI) provides better accuracy. 68Ga-PSMA-PET/MRI shows improved accuracy for primary PCa detection compared to mpMRI alone. Challenges include the lack of standardized SUVmax cutoff values. 68Ga-PSMA-PET is useful for the initial diagnosis and staging of PCa, complementing MRI, although further research is needed to standardize imaging techniques and interpretations.

Prostate cancer screening among apparently healthy adult males

Objectives: This study is set to describe the outcome of tripod-based prostate cancer screening among apparently healthy adult males in tertiary academic and health institutions in Uyo, Akwa Ibom State, Nigeria. Material and Methods: All consenting adult males aged 40 years and above who are staff of the University of Uyo and her teaching hospital were recruited and subjected to questionnaire-based survey, digital rectal examination (DRE), prostate-specific antigens analysis, and transrectal ultrasonography of prostate gland. Results: A total of 201 participants with a mean age of 53.0 + 2.4 years were screened. The majority of the participants were in the 50–59 years of age group (47.8%). Twenty-eight (13.9%) had abnormal, suspicious DRE findings. The mean serum PSA levels were 2.4 ng/mL and 33.7 ng/mL in those with benign and suspicious DRE findings, respectively. Suspicious nodules for prostate cancer were diagnosed in 20 (9.6%) patients who had transrectal ultrasonography (TRUS) of the prostate gland. There was a positive correlation between age and other diagnostic variables, including findings of DRE, PSA, and TRUS. Conclusion: A tripod of DRE, prostate-specific antigen (PSA) analysis, and transrectal ultrasonography of the prostate gland is still relevant as a step-wise prostate cancer screening strategy, prior to deployment of confirmatory prostate biopsy.