Prostate-specific Antigen Level Research Articles

Can weight-adjusted waist circumference index become a single anthropometric predictor of prostate-specific antigen concentration? A National Health and Nutrition Examination Survey analysis (2003-2010).

Recent studies have introduced the weight-adjusted waist circumference index (WWI) as a viable obesity indicator that may better reflect centripetal obesity and its associated risks. In examining the connection between WWI and prostate-specific antigen (PSA), this study leveraged data from the National Health and Nutrition Examination Survey 2003-2010, including 5732 participants. Our initial analysis indicated a significant positive association between WWI and PSA levels. However, subsequent models that adjusted for covariates such as age, race, and a range of metabolic and cardiovascular health-related factors revealed that the strength and significance of this relationship were attenuated. Model 1 showed a highly significant correlation (p < 0.0001). Yet, in Model 2, which accounted for age and race, the association softened (p = 0.0520). Moreover, when a full spectrum of health covariates was included in Model 3, the association was no longer significant (p = 0.9775). These findings suggest that while an unadjusted correlation exists, its potential use as a diagnostic predictor is limited without considering the broader health context. Therefore, it is crucial to review such data with multiple considerations in mind, and extensive attention should be paid to the evaluation of covariates.

Association between vitamin B2 intake and prostate-specific antigen in American men: 2003–2010 National Health and Nutrition Examination Survey

BackgroundAccumulating evidence suggests a pivotal role of vitamin B2 in the pathogenesis and progression of prostate cancer (PCa). Vitamin B2 intake has been postulated to modulate the screening rate for PCa by altering the concentration of prostate-specific antigen(PSA). However, the relationship between vitamin B2 and PSA remains indeterminate. Hence, we conducted a comprehensive evaluation of the association between vitamin B2 intake and PSA levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database.MethodsFrom a pool of 20,371 participants in the NHANES survey conducted between 2003 and 2010, a cohort of 2,323 participants was selected for the present study. The male participants were classified into four distinct groups based on their levels of vitamin B2 intake. We employed a multiple linear regression model and a non-parametric regression method to investigate the relationship between vitamin B2 and PSA levels.ResultsThe study cohort comprised of 2,323 participants with a mean age of 54.95 years (± 11.73). Our findings revealed a statistically significant inverse correlation between vitamin B2 intake (mg) and PSA levels, with a reduction of 0.13 ng/ml PSA concentration for every unit increase in vitamin B2 intake. Furthermore, we employed a fully adjusted model to construct a smooth curve to explore the possible linear relationship between vitamin B2 intake and PSA concentration.ConclusionsOur study in American men has unveiled a notable inverse association between vitamin B2 intake and PSA levels, potentially posing a challenge for the identification of asymptomatic prostate cancer. Specifically, our findings suggest that individuals with higher vitamin B2 intake may be at a greater risk of being diagnosed with advanced prostate cancer in the future, possibly indicating a detection bias. These results may offer a novel explanation for the observed positive correlation between vitamin B2 intake and prostate cancer.

The Prevalence of Prostate Cancer in Organ Donors With Increased Prostate-Specific Antigen

Elevated PSA levels were found in 139 kidney donors out of a total of 472 donors from our Transplant Centre tested between 2009 and 2022, representing 29,4%. We analyzed these kidney donors with elevated prostate specific antigen (PSA) levels, at mean age 47,3 years. PSA values ranged from 2.8 to 160.4 ng/ml, mean 13,9ng/ml), proper range <2.5 ng/ml. Prostate hist-pat examination was performed in 38/139 - 27% donors. 14 cases of prostate cancer (Pca) were found, Gleason 3+3 in 8 cases, 3+4 in four cases (one donor disqualification), one case Gleason 4+3 (donor disqualification), one case Gleason 4+5 (donor disqualification). There were 33 patients who met the criteria, age ≥50 years and PSA level > 10 mg/mL; of these, prostate hist-pat was performed in 24 cases, Pca was found in 10/42% cases. There were no difference between donors ≥ 50 years old, PSA>10 ng/ml with and without pathomorphological diagnosis of Pca in respect of age (mean 60,4 vs. 60,6 years), creatinine clearance according to the Cockroft-Gaulta formula (mean 101,6 vs. 94,8 ml/min) and PSA levels (mean 34,1 vs. 29,3 ng/ml). Among other donors with Pca three were <50 years with PSA >10 ng/ml and one was ≥ 50 years and PSA< 8 ng/ml. Kidneys from donors with prostate cancer were transplanted into 19 recipients, 10 men, nine women, follow-up time 1-10 years. There was no case of prostate cancer transmission. One of the recipients died of neoplasm – breast cancer. ConclusionsDonors ≥ 50 years old, PSA>10 ng/ml have higher risk of Pca. Accepting donors with Pca (Gleason 3+3, and 3+4) possesses minimal risk of transmission. All donors ≥ 50 years and also younger with increased PSA require further diagnostic procedure (e.g. DRE, USG, eventually histological examination).

Combination of Abiraterone Acetate, Prostate Bed Radiotherapy, and Luteinizing Hormone-releasing Hormone Agonists in Biochemically Relapsing Patients After Prostatectomy (CARLHA): A Phase 2 Clinical Trial

BackgroundThe relevance of next-generation hormone therapies and circulating tumor cells (CTCs) are not elucidated in biochemical recurrence after prostatectomy. ObjectiveTo evaluate the combination of abiraterone acetate plus prednisone (AAP), prostate bed radiotherapy (PBRT), and goserelin in biochemically relapsing men after prostatectomy, and to investigate the utility of CTCs. Design, setting, and participantsIn this single-arm multicenter phase 2 trial, 46 biochemically relapsing men were enrolled between December 2012 and January 2019. The median follow-up was 47 mo. InterventionAll patients received AAP 1000 mg daily (but 750 mg during PBRT), salvage PBRT, and goserelin. Outcome measurements and statistical analysisThe primary outcome was 3-yr biochemical recurrence-free survival (bRFS) when prostate-specific antigen (PSA) levels were ≥0.2 ng/ml. The secondary outcomes included alternative bRFS (alt-bRFS) when PSA levels were ≥0.5 ng/ml and safety assessment. CTC count was assessed. Results and limitationsThe 3-yr bRFS and alt-bRFS were 81.5% (95% confidence interval or CI [66.4–90.3%]) and 95.6% (95% CI [83.5-98.9%]), respectively. The most common acute radiotherapy-related adverse effect (AE; all grades was pollakiuria (41.3%). The most common late AE (all grades) was urinary incontinence (15.2%). Grade 3-4 acute or late radiotherapy-related AEs were scarce. Most frequent AEs nonrelated to radiotherapy were hot flashes (76%), hypertension (63%), and hepatic cytolysis (50%, of which 20% were of grades 3-4). Of the patients, 11% had a CTC count of ≥5, which was correlated with poorer bRFS (p = 0.042) and alt-bRFS (p = 0.008). The association between CTC count and higher rates of relapse was independent of the baseline PSA level and PSA doubling time (p = 0.42 and p = 0.09, respectively). This study was nonrandomized with a limited number of patients, and few clinical events were reported. ConclusionsAdding AAP to salvage radiation therapy and goserelin resulted in high bRFS and alt-bRFS. AEs remained manageable, although a close liver surveillance is advised. CTC count appears as a promising biomarker for prognosis and predicting response to treatment. Patient summaryOur study was a phase 2 clinical trial that exhibited the efficacy and tolerance of a novel androgen-receptor targeting agent (abiraterone acetate plus prednisone) in patients with prostate cancer who experienced rising prostate-specific antigen after radical prostatectomy, in combination with prostate bed radiotherapy. The results also indicated the feasibility and potential value of circulating tumor cell detection, which constitutes a possible advance in managing prostate cancers.

Predictive value of magnetic resonance imaging diffusion parameters using artificial intelligence in low-and intermediate-risk prostate cancer patients treated with stereotactic ablative radiotherapy: A pilot study

IntroductionTo investigate the predictive value of the pre-treatment diffusion parameters of diffusion-weighted magnetic resonance imaging (DW-MRI) using artificial intelligence (AI) for prostate-specific antigen (PSA) response in patients with low- and intermediate-risk prostate cancer (PCa) treated with stereotactic ablative radiotherapy (SABR). MethodsRetrospective evaluation was performed for 30 patients using pre-treatment multi-parametric MR image datasets between 2017 and 2021. MR-based mean- and minimum apparent diffusion coefficients (ADCmean, ADCmin) were calculated for the intraprostatic dominant lesion. Therapeutic response was assessed using PSA levels. Predictive performance was assessed by the receiver operating characteristic (ROC) analysis. Statistics performed with a significance level of p ≤ 0.05. ResultsNo biochemical relapse was detected after a median follow-up of twenty-three months (range: 3–50), with a median PSA of 0.01 ng/ml (range: 0.006–2.8) at the last examination. Significant differences were observed between the pre-treatment ADCmean, ADCmin parameters, and the group averages of patients with low and high 1-year-PSA measurements (p < 0.0001, p < 0.0001). In prediction, the random forest (RF) model outperformed the decision tree (DT) and support vector machine (SVM) models by yielding area under the curves (AUC), with 0.722, 0.685, and 0.5, respectively. ConclusionOur findings suggest that pre-treatment MR diffusion data may predict therapeutic response using the novel approach of machine learning in PCa patients treated with SABR. Implications for practiceClinicians shall measure and implement the evaluation of the suggested parameters (ADCmin, ADCmean) to provide the most accurate therapy for the patient.

Biochemical Response of

BackgroundIn a subset of patients with oligorecurrent prostate cancer (PCa), salvage surgery with prostate-specific membrane antigen (PSMA) radioguided surgery (PSMA-RGS) seems to be of value. ObjectiveTo evaluate whether a lower level of postoperative prostate-specific antigen (PSA; <0.1 ng/ml) is predictive of therapy-free survival (TFS) following salvage PSMA-RGS. Design, setting, and participantsThis cohort study evaluated patients with biochemical recurrence after radical prostatectomy and oligorecurrent PCa on PSMA positron emission tomography treated with PSMA-RGS in three tertiary care centers (2014–2022). InterventionPSMA-RGS. Outcome measurements and statistical analysisPostsalvage surgery PSA response was categorized as <0.1, 0.1–<0.2, or >0.2 ng/ml. Kaplan-Meier and multivariable Cox regression models evaluated TFS according to PSA response. Results and limitationsAmong 553 patients assessed, 522 (94%) had metastatic soft tissue lesions removed during PSMA-RGS. At 2–16 wk after PSMA-RGS, 192, 62, and 190 patients achieved PSA levels of <0.1, 0.1–<0.2, and >0.2 ng/ml, respectively. At 2 yr of follow-up, TFS rate was 81.1% versus 56.1% versus 43.1% (p < 0.001) for patients with PSA <0.1 versus 0.1–<0.2 versus >0.2 ng/ml. In multivariable analyses, PSA levels of 0.1–0.2 ng/ml (hazard ratio [HR]: 1.9, confidence interval [CI]: 1.1–3.1) and ≥0.2 ng/ml (HR: 3.2, CI: 2.2–4.6, p < 0.001) independently predicted the need for additional therapy after PSMA-RGS. The main limitation is the lack of a control group. ConclusionsFor patients after salvage PSMA-RGS, a lower biochemical response (PSA <0.1 ng/ml) seems to predict longer TFS. This insight may help in counseling patients postoperatively as well as guiding the timely selection of additional therapy. Patient summaryWe studied what happened to prostate cancer patients in three European centers who had salvage surgery using a special method called prostate-specific membrane antigen–targeted radioguidance. We found that patients who had low prostate-specific antigen levels soon after surgery were less likely to need further treatment for a longer time.

Effect of methanol extract of Plectranthus esculentus N.E.Br tuber and its fractions on indices of benign prostatic hyperplasia in Wistar rats

Ethnopharmacological relevanceMany ethnopharmacological properties (anti-tumor, etc.) have been credited to Plectranthus esculentus tuber but the scientific basis has not been established.Aim of the study: To evaluate the effect of methanol extract of P. esculentus tuber (MEPET) (phase 1) and its fractions (phase 2) on benign prostatic hyperplasia (BPH) in rats Materials and methodsThe study was conducted in two phases. Phase 1, thirty-five male albino rats (6 weeks old) were divided into seven groups of five rats each: normal control (NC) received olive oil (subcutaneously) and water (orally); disease control (DC) received testosterone propionate (TP) (3 mg/kg) and water; test groups (1,2,3 and 4) received TP + MEPET at 100, 200, 400, 600 mg/kg respectively; positive control, received TP + finasteride (5 mg/70 kg). After 28 days, their relative prostate weights (RPW) and prostate specific antigen (PSA) were determined. Phase 2, thirty rats were divided into 6 groups of 5 rats each: NC received olive oil (subcutaneously daily) and dimethyl sulfoxide (DMSO) (orally); DC received TP (3 mg/kg), and DMSO; test group 1 received TP and aqueous fraction of MEPET (400 mg/kg); test group 2 received TP and methanol fraction of MEPET (400 mg/kg); test group 3 received TP, and ethyl acetate fraction of MEPET (400 mg/kg); positive control received TP and finasteride (5 mg/70 kg). After 28 days, their erythrocyte sedimentation rates, RPW, prostate levels of PSA, DHT, inflammatory, apoptotic markers and prostate histology were determined. ResultsEthyl acetate fraction of MEPET modulated most of the parameters of BPH in the rats in a manner akin to finasteride as corroborated by prostate histology. ConclusionsEFPET could be useful in the treatment of BPH.

Non-infectious adverse events of transperineal prostate biopsies performed under local anaesthesia.

To report non-infectious adverse events associated with transperineal prostate biopsy (TPBx) performed under local anaesthesia (LA) in an outpatient setting. This study reports secondary outcomes from the Norwegian arm of the prospective NORAPP study (ClinicalTrials.gov identifier NCT04146142) and included all patients referred for prostate biopsy from November 2019 to February 2021. Transperineal magnetic resonance imaging-transrectal ultrasonography fusion TPBx were taken using 40 mL 1% lidocaine with 4 mL of 8.4% sodium bicarbonate placed in the perineal skin, under the prostatic apex, in the m. levator ani bilaterally, and along the path of the needle. Follow-up using patient-reported questionnaires was done immediately after TPBx, and after 2 weeks and 2 months. Pain was reported using a visual analogue scale (VAS) during placement of the LA, and during and after TPBx. Haematuria and acute urinary retention (AUR) rates were recorded. We included 402 patients, and the response rate was 99.8% (401/402). The median (interquartile range [IQR]) age was 69 (63-74) years, the prostate volume was 40 (27-58) mL, the prostate-specific antigen level was 7.0 (4.5-11) ng/mL, and the number of biopsy cores taken was 8 (6-10). The median (IQR) VAS pain score was 1 (1-2) during placement of LA, 1 (0-2) during TPBx, and 0 (0-0) after TPBx. Haematuria and AUR rates were 64% (95% confidence interval [CI] 60-69%) and 0.5% (95% CI 0.1-1.8%), respectively. No patients were hospitalised or required after the TPBx surgical intervention. Transperineal prostate biopsies can be performed under LA with limited discomfort to the patient and few post-TPBx adverse events.

Evaluation of the relationship between prostate volume and prostate specific antigen in patients diagnosed with benign prostatic hyperplasia

Aims: The aim of this study was to investigate the relationship between prostate volume and prostate specific antigen (PSA) levels in patients diagnosed with benign prostatic hyperplasia (BPH). In addition, it is aimed to show that BPH may be one of the causes of PSA elevation in patients without prostate cancer. Methods: Prostate volume was calculated in 60 BPH patients who underwent prostate magnetic resonance imaging (MRI) imaging in radiology department between December 1, 2023 and March 1, 2024 due to elevated PSA. The relationship between prostate volume and the tpsa and fpsa values of the patients in the last month was evaluated. Results: There was a positive correlation between age and total prostate specific antigen (tpsa) and free prostate specific antigen (fpsa) in patients with benign prostatic hyperplasia. However, the correlation between age and fpsa was stronger. Similarly, a positive correlation was found between prostate volume and tpsa and fpsa. The correlation between increased prostate volume and increased fpsa was also stronger. Conclusion: In our study, a positive correlation was found between prostate volume and tpsa and fpsa in patients diagnosed with BPH. It was determined that one of the reasons for the increase in PSA values may be the increase in prostate volume.

Parathyroid hormone related-protein (PTHrP) in tissues with poor prognosis in prostate cancer patients.

Parathyroid hormone-related peptide (PTHrP) is known to have a pivotal role in the progression of various solid tumors, among which prostate cancer stands out. However, the extent of PTHrP expression and its clinical implications in prostate cancer patients remain shrouded in obscurity. The primary objective of this research endeavor was to shed light on the relevance of PTHrP in the context of prostate cancer patients and to uncover the potential underlying mechanisms. The expression of PTHrP, E-cadherin, and vimentin in tumor tissues of 88 prostate cancer patients was evaluated by immunohistochemical technique. Subsequently, the associations between PTHrP and clinicopathological parameters and prognosis of patients with prostate cancer were analyzed. Immunohistochemical analysis showed that the expression rates of PTHrP, E-cadherin, and vimentin in prostate cancer tissues were 95.5%, 88.6%, and 84.1%, respectively. Patients with a high level of PTHrP had a decreased expression of E-cadherin (P = .013) and an increased expression of vimentin (P = .010) compared with patients with a low level of PTHrP. Besides, the high expression of PTHrP was significantly correlated with a higher level of initial prostate-specific antigen (P = .026), positive lymph node metastasis (P = .010), osseous metastasis (P = .004), and Gleason score (P = .026). Moreover, patients with a high level of PTHrP had shorter progression-free survival (P = .002) than patients with a low level of PTHrP. The present study indicates that PTHrP is associated with risk factors of poor outcomes in prostate cancer, while epithelial-mesenchymal transition may be involved in this process.

Prospective Comparison of 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI in Patients with Biochemically Recurrent Prostate Cancer.

Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptors are both overexpressed in prostate cancer (PC) but may provide complementary information.68Ga-PSMA-R2 and 68Ga-NeoB (DOTA-p-aminomethylaniline-diglycolic acid-DPhe-Gln-Trp-Ala-Val-Gly-His-NH-CH[CH2-CH(CH3)2]2) are novel PET radiopharmaceuticals that were developed for theranostic use. In this phase II imaging study, we assessed the feasibility, safety, and diagnostic performance of 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI for detection of biochemically recurrent PC. Methods: We prospectively enrolled 27 men with suspected biochemically recurrent PC after initial treatment but noncontributory conventional imaging results (negative or equivocal findings on MRI, CT, and/or bone scan). Participants underwent 68Ga-NeoB and 68Ga-PSMA-R2 PET/MRI within 2 wk in noncontrolled order. The SUVmax of putative PC lesions was measured and compared with a composite reference standard (histopathology, follow-up imaging, prostate-specific antigen change). The SUVmax and SUVmean of background organs were measured. Vital signs were recorded before injection of the radiopharmaceuticals and after the scans. Adverse events were recorded up to 72 h after each scan. Results: The prostate-specific antigen level at enrollment was 3.5 ± 3.9 ng/mL (range, 0.3-13.5 ng/mL). 68Ga-NeoB PET/MRI detected 31 lesions in 18 patients (66.7%), whereas 68Ga-PSMA-R2 identified 20 lesions in 15 participants (55.6%). 68Ga-NeoB PET/MRI showed higher sensitivity (85.7% vs. 71.4%), accuracy (88.9% vs. 77.8%), and negative predictive value (66.7% vs. 50.0%) than 68Ga-PSMA-R2, whereas specificity and positive predictive value were equally high (100.0% for both). In 6 patients, 68Ga-NeoB PET/MRI identified 14 lesions that were false-negative on 68Ga-PSMA-R2 PET/MRI. The mean lesion SUVmax was 6.6 ± 3.2 (range, 2.9-13.2) for 68Ga-NeoB and 4.4 ± 1.5 (range, 2.6-8.8) for 68Ga-PSMA-R2 (P = 0.019). Overall lower uptake was noted in tumors and background organs for 68Ga-PSMA-R2. There were no significant changes in vital signs before and after the scans. No adverse events were reported in the 72-h period after scans. Conclusion: 68Ga-NeoB and 68Ga-PSMA-R2 are safe for diagnostic imaging. 68Ga-NeoB PET/MRI showed better diagnostic performance than 68Ga-PSMA-R2. 68Ga-PSMA-R2 showed overall lower uptake, equally in background organs and tumors, and might therefore not be an ideal theranostic compound. Further evaluation in larger cohorts is needed to confirm our preliminary data.

Exposure to environmental pollutants and genetic variants related to oxidative stress and xenobiotic metabolism—Association with prostate cancer

This study assessed whether genetic variants coding for certain enzymes involved in xenobiotic detoxification, antioxidant defences and DNA repair, along with exposure to environmental chemicals, were associated with an increased prostate cancer (PCa) risk. The study population consisted of 300 men (150 PCa cases and 150 controls) which underwent prostate biopsy as their serum prostate specific antigen (PSA) levels were greater than 4 ng/ml. Genetic variants in GSTM1, GSTP1, SOD2, CAT, GPX1, XRCC1 were determined and data for chemical exposures was obtained through a structured questionnaire and by biomonitoring in a subsample of cases and controls. High serum PSA levels were associated with a greater risk of PCa, while physical exercise appears to exert a protective effect against its development. In addition, elevated urinary levels of certain organic pollutants, such as benzo(a)pyrene (BaP), bisphenol A (BPA), and ethyl-paraben (EPB), were associated with an increased risk of PCa.

The role of multiparametric magnetic resonance ımaging in the diagnosis of granulomatous prostatitis mimicking prostate cancer.

Aimed to investigate the role of multiparametric magnetic resonance imaging (mp-MRI) in the diagnosis of granulomatous prostatitis caused by intravesical Bacillus Calmette-Guérin (BCG). In this prospective, single-center study, 10 male patients who were given intravesical BCG due to intermediate- and high-risk bladder cancer were included. Before transurethral resection of bladder tumors (TURB), all patients were evaluated by mp-MRI, serum prostate-specific antigen (PSA), and digital rectal examination (DRE). Serum PSA levels and DRE findings were evaluated before and after intravesical BCG treatment. Prostate mp-MRI was performed for patients with elevated levels of serum PSA and/or with abnormal DRE findings. Then, MRI fusion + systematic prostate biopsy was performed. Demographic data of the patients before and after intravesical BCG were compared. The average age of the patients was 66.9years (55-87years). While PSA was 1.7ng/ml before intravesical BCG treatment, it was 4.3ng/ml after intravesical BCG treatment (p = 0.005). PSA density (PSAD) was 0.04 and 0.10 before and after the treatment, respectively (p = 0.012). DRE findings of all patients were normal before the treatment. However, abnormal findings were detected in 80% of them after the treatment (p = 0.008). PI-RADS ≥ 3 lesions were found to be significantly higher in all patients after intravesical BCG (p = 0.004). Granulomatous prostatitis is a rare complication of intravesical BCG. High PSA, abnormal DRE, and PI-RADS ≥ 3 lesions detected after intravesical BCG should suggest granulomatous prostatitis and unnecessary biopsies may be avoided.

Atypical Pulmonary Metastasis of Prostate Adenocarcinoma: A Rare Phenomenon.

Lymphangitic metastasis of prostate cancer to the lung with diffuse reticulonodular infiltrate is a rare presentation.In chemical castration-sensitive prostate cancer, prostate-specific antigen (PSA) levels can be improving but the patient can still develop new distant metastases.

Prostate-specific antigen (PSA) levels in men with Prader-Willi syndrome

Prader-Willi syndrome (PWS) is a rare genetic disorder typically characterized by body composition abnormalities, hyperphagia, behavioral challenges, cognitive dysfunction, and hormone deficiencies. Hypogonadism is common but knowledge on potential side effects of testosterone replacement is limited, in particular, the long-term effects on behavior and PSA. Patients and methodsRetrospective case studies of seven men, median age 46 years, with genetically verified PWS, testosterone treated hypogonadism and available PSA values were included. Long-term follow-up of PSA was accessible in four patients. Medical records were reviewed for adverse effects. ResultsFive men were treated with intramuscular testosterone undecanoate, two had no hypogonadism. Median PSA was 0.68 μg/L (0.23–1.3), median testosterone 15 nmol/L. After a median time of 17 years of testosterone replacement median PSA was 0.75 μg/L (range 0.46–1.4). Testosterone replacement was well tolerated, and no major behavioral changes were reported. Five were treated with growth hormone for >20 years. ConclusionLevels of PSA were low. Long-term treatment with testosterone was working well and did not result in any clinically meaningful increase in PSA. Our results indicate that testosterone replacement is neither associated with serious adverse events regarding changes in behavior or effect on PSA. However, larger studies are needed to confirm our results.

Development and Validation of an 18-Gene Urine Test for High-Grade Prostate Cancer

Benefits of prostate cancer (PCa) screening with prostate-specific antigen (PSA) alone are largely offset by excess negative biopsies and overdetection of indolent cancers resulting from the poor specificity of PSA for high-grade PCa (ie, grade group [GG] 2 or greater). To develop a multiplex urinary panel for high-grade PCa and validate its external performance relative to current guideline-endorsed biomarkers. RNA sequencing analysis of 58 724 genes identified 54 markers of PCa, including 17 markers uniquely overexpressed by high-grade cancers. Gene expression and clinical factors were modeled in a new urinary test for high-grade PCa (MyProstateScore 2.0 [MPS2]). Optimal models were developed in parallel without prostate volume (MPS2) and with prostate volume (MPS2+). The locked models underwent blinded external validation in a prospective National Cancer Institute trial cohort. Data were collected from January 2008 to December 2020, and data were analyzed from November 2022 to November 2023. Protocolized blood and urine collection and transrectal ultrasound-guided systematic prostate biopsy. Multiple biomarker tests were assessed in the validation cohort, including serum PSA alone, the Prostate Cancer Prevention Trial risk calculator, and the Prostate Health Index (PHI) as well as derived multiplex 2-gene and 3-gene models, the original 2-gene MPS test, and the 18-gene MPS2 models. Under a testing approach with 95% sensitivity for PCa of GG 2 or greater, measures of diagnostic accuracy and clinical consequences of testing were calculated. Cancers of GG 3 or greater were assessed secondarily. Of 761 men included in the development cohort, the median (IQR) age was 63 (58-68) years, and the median (IQR) PSA level was 5.6 (4.6-7.2) ng/mL; of 743 men included in the validation cohort, the median (IQR) age was 62 (57-68) years, and the median (IQR) PSA level was 5.6 (4.1-8.0) ng/mL. In the validation cohort, 151 (20.3%) had high-grade PCa on biopsy. Area under the receiver operating characteristic curve values were 0.60 using PSA alone, 0.66 using the risk calculator, 0.77 using PHI, 0.76 using the derived multiplex 2-gene model, 0.72 using the derived multiplex 3-gene model, and 0.74 using the original MPS model compared with 0.81 using the MPS2 model and 0.82 using the MPS2+ model. At 95% sensitivity, the MPS2 model would have reduced unnecessary biopsies performed in the initial biopsy population (range for other tests, 15% to 30%; range for MPS2, 35% to 42%) and repeat biopsy population (range for other tests, 9% to 21%; range for MPS2, 46% to 51%). Across pertinent subgroups, the MPS2 models had negative predictive values of 95% to 99% for cancers of GG 2 or greater and of 99% for cancers of GG 3 or greater. In this study, a new 18-gene PCa test had higher diagnostic accuracy for high-grade PCa relative to existing biomarker tests. Clinically, use of this test would have meaningfully reduced unnecessary biopsies performed while maintaining highly sensitive detection of high-grade cancers. These data support use of this new PCa biomarker test in patients with elevated PSA levels to reduce the potential harms of PCa screening while preserving its long-term benefits.

Transrectal versus transperineal prostate biopsy for cancer detection in patients with gray-zone prostate-specific antigen: a multicenter, real-world study.

Knowledge about the effect of different prostate biopsy approaches on the prostate cancer detection rate (CDR) in patients with gray-zone prostate-specific antigen (PSA) is limited. We performed this study to compare the CDR among patients who underwent different biopsy approaches and had rising PSA levels in the gray zone. Two hundred and twenty-two patients who underwent transrectal prostate biopsy (TRB) and 216 patients who underwent transperineal prostate biopsy (TPB) between June 2016 and September 2022 were reviewed in this study. In addition, 110 patients who received additional targeted biopsies following the systematic TPB were identified. Clinical parameters, including age, PSA derivative, prostate volume (PV), and needle core count, were recorded. The data were fitted via propensity score matching (PSM), adjusting for potential confounders. TPB outperformed TRB in terms of the CDR (49.6% vs 28.3%, P = 0.001). The clinically significant prostate cancer (csPCa) detection rate was not significantly different between TPB and TRB (78.6% vs 68.8%, P = 0.306). In stratified analysis, TPB outperformed TRB in CDR when the age of patients was 65-75 years (59.0% vs 22.0%, P < 0.001), when PV was 25.00-50.00 ml (63.2% vs 28.3%, P < 0.001), and when needle core count was no more than 12 (58.5% vs 31.5%, P = 0.005). The CDR (P = 0.712) and detection rate of csPCa (P = 0.993) did not significantly differ among the systematic, targeted, and combined biopsies. TPB outperformed TRB in CDR for patients with gray-zone PSA. Moreover, performing target biopsy after systematic TPB provided no additional benefits in CDR.

A meta-analysis comparing treatment of benign prostatic hyperplasia with holmium laser enucleation and photoselective greenlight vaporization

Abstract Background We compared the safety and efficacy of treating benign prostatic hyperplasia with photoselective greenlight vaporization (PVP) versus holmium laser enucleation of the prostate (HoLEP). Methods Databases (PubMed, Embase, Cochrane Library, Chinese CBM, and CNKI) were searched for eligible studies evaluating HoLEP or PVP outcomes, published until May 2022. We analyzed the incidence of relative complications and postoperative outcomes, including the international prostate symptom score, maximum flow rate (Qmax), postvoid residual urine volume, quality of life index, and prostate-specific antigen levels. Results Eleven studies involving 4763 patients were included in this meta-analysis. The significant differences in postoperative Qmax at 1 month (mean difference [MD], 3.31, 95% confidence interval [CI], 0.45–6.16, p = 0.02, I 2 = 92%), 3 months (MD, 2.78, 95% CI, 0.53 to 5.02, p = 0.02, I 2 = 89%), 6 months (MD, 2.13, 95% CI, 1.11 to 3.15, p &lt; 0.0001, I 2 = 87%), and 12 months (MD, 3.98, 95% CI, 2.06 to 5.89, p &lt; 0.0001, I 2 = 58%) further confirmed unique advantage of HoLEP over PVP. We used forest plots to determine significant differences in the severe complication rates among patients in the PVP and HoLEP groups (odds ratio, 0.05, 95% CI, 0.01 to 0.28, p = 0.0005). Conclusions Holmium laser enucleation of the prostate and PVP showed comparable international prostate symptom scores, quality of life index, postvoid residual urine volumes, prostate-specific antigen levels, perioperative factors, and total complication rates. Compared with PVP, HoLEP had a greater Qmax 1 year postoperatively, decreased energy expenditure, and fewer high-grade complications. These results need to be verified in long-term follow-up studies with well-structured randomized controlled trials.

Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality

The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear. To evaluate the effect of a single invitation for PSA screening on prostate cancer-specific mortality at a median 15-year follow-up compared with no invitation for screening. This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021. Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation). The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis. Of 415 357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P = .03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] ≤6: 2.2% vs 1.6%; P < .001) and localized (T1/T2: 3.6% vs 3.1%; P < .001) disease but not intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45 084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50 336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P = .11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment. In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small. isrctn.org Identifier: ISRCTN92187251.

Effects of natural extract interventions in prostate cancer: A systematic review and network meta-analysis

BackgroundOver years, there has been a widespread quest for effective dietary patterns and natural extracts to mitigate prostate cancer risk. However, despite numerous experimental studies conducted on various natural extracts, the evidence substantiating their efficacy remains largely insufficient. This dearth of compelling evidence presents a significant challenge in advocating for their widespread use as preventive measures against prostate cancer. ObjectiveOur study endeavors to undertake a network meta-analysis to evaluate the influence of natural extracts on prostate cancer. MethodsResearchers systematically searched through Embase, PubMed, Cochrane Library, and Web of Science databases until December 2023. The main focus was on assessing primary outcomes comprising prostate-specific antigen (PSA), insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1). We conducted data analysis utilizing StataMP 15.0 software. Therapeutic effects were ranked based on the probability values derived from Surface Under the Cumulative Ranking curve (SUCRA). Additionally, cluster analysis was employed to assess the impacts of natural extracts on three distinct outcomes. ResultsFollowing screening procedures, the 28 eligible studies were incorporated, the selected studies encompassed 1,566 prostate cancer patients and evaluated 16 different natural extract treatments. Specifically, 24 trials included PSA indicators, 10 included IGF-1 indicators, and 8 included IGFBP-3 indicators. The findings revealed that, based on the SUCRA values, the combined therapy of silybin with selenium (74%) appears to be the most effective approach for reducing serum PSA levels. Simultaneously, silybin alone (84.6%) stands out as the most promising option for decreasing serum IGF-1 levels. Lastly, concerning IGFBP-3, silybin alone (67.7%) emerges as the optimal choice. Twelve studies provided comprehensive information on adverse drug reactions/events (ADR/ADE), whereas five articles did not report any significant ADR/ADE. ConclusionThe NMA suggests that, compared to placebo, utilizing silybin either alone or in combination with selenium has been shown to enhance therapeutic effects, offering potential benefits to patients with prostate cancer. This study can offer valuable insights for prostate patients considering natural extract treatments. Further evidence is required to confirm the safety profile of these treatments.