Low-Density Lipoprotein Cholesterol and Prostate Cancer: A Retrospective Study.

BACKGROUND: This work aimed to investigate the potential role of abnormal lipid metabolism in the development of prostate cancer (PCa). METHODS: A retrospective study design was used. The clinical data of 520 patients who underwent rectal prostate biopsy in our hospital from January 2020 to June 2023 were analysed. The patients were enrolled and divided into the anterior PCa group including 112 patients and benign prostatic hyperplasia (BPH) group including 408 patients. Univariate and multivariate logistic regression analyses were performed for the two patient groups, and further comparisons were made according to the Gleason score and TNM staging. RESULTS: Low-density lipoprotein cholesterol (LDL-C) level may be an independent risk factor for PCa, and it was significantly associated with the risk of PCa (odds ratio (OR) = 1.363, p = 0.030). Patients with PCa were further divided into the low risk group and the high risk group according to the Gleason score. Univariate analysis (p = 0.047) and logistic regression analysis (OR = 2.249, p = 0.036) revealed that LDL-C was a significant factor influencing the Gleason score. Patients with PCa were categorised into four groups based on TNM staging. One-way analysis of variance (ANOVA) analysis (p = 0.015) and ordinal logistic regression analysis (OR = 2.414, p = 0.007) demonstrated that LDL-C was a significant factor influencing TNM staging. CONCLUSIONS: This study revealed the important role of LDL-C in the development of PCa, highlighting its influence as an independent risk factor. Thus, LDL-C may promote the proliferation and invasion of PCa cells.

Predicting clinically significant prostate cancer following suspicious mpMRI: analyses from a high-volume center.

PURPOSE: mpMRI is routinely used to stratify the risk of clinically significant prostate cancer (csPCa) in men with elevated PSA values before biopsy. This study aimed to calculate a multivariable risk model incorporating standard risk factors and mpMRI findings for predicting csPCa on subsequent prostate biopsy. METHODS: Data from 677 patients undergoing mpMRI ultrasound fusion biopsy of the prostate at the TUM University Hospital tertiary urological center between 2019 and 2023 were analyzed. Patient age at biopsy (67 (median); 33-88 (range) (years)), PSA (7.2; 0.3-439 (ng/ml)), prostate volume (45; 10-300 (ml)), PSA density (0.15; 0.01-8.4), PI-RADS (V.2.0 protocol) score of index lesion (92.2% ≥3), prior negative biopsy (12.9%), suspicious digital rectal examination (31.2%), biopsy cores taken (12; 2-22), and pathological biopsy outcome were analyzed with multivariable logistic regression for independent associations with the detection of csPCa defined as ISUP ≥ 3 (n = 212 (35.2%)) and ISUP ≥ 2 (n = 459 (67.8%) performed on 603 patients with complete information. RESULTS: Older age (OR: 1.64 for a 10-year increase; p < 0.001), higher PSA density (OR: 1.60 for a doubling; p < 0.001), higher PI-RADS score of the index lesion (OR: 2.35 for an increase of 1; p < 0.001), and a prior negative biopsy (OR: 0.43; p = 0.01) were associated with csPCa. CONCLUSION: mpMRI findings are the dominant predictor for csPCa on follow-up prostate biopsy. However, PSA density, age, and prior negative biopsy history are independent predictors. They must be considered when discussing the individual risk for csPCa following suspicious mpMRI and may help facilitate the further diagnostical approach.

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

BACKGROUND: Accumulating 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. METHODS: From 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. RESULTS: The 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. CONCLUSIONS: Our 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.

Development of a multigenomic liquid biopsy (PROSTest) for prostate cancer in whole blood.

INTRODUCTION: We describe the development of a molecular assay from publicly available tumor tissue mRNA databases using machine learning and present preliminary evidence of functionality as a diagnostic and monitoring tool for prostate cancer (PCa) in whole blood. MATERIALS AND METHODS: We assessed 1055 PCas (public microarray data sets) to identify putative mRNA biomarkers. Specificity was confirmed against 32 different solid and hematological cancers from The Cancer Genome Atlas (n = 10,990). This defined a 27-gene panel which was validated by qPCR in 50 histologically confirmed PCa surgical specimens and matched blood. An ensemble classifier (Random Forest, Support Vector Machines, XGBoost) was trained in age-matched PCas (n = 294), and in 72 controls and 64 BPH. Classifier performance was validated in two independent sets (n = 263 PCas; n = 99 controls). We assessed the panel as a postoperative disease monitor in a radical prostatectomy cohort (RPC: n = 47). RESULTS: A PCa-specific 27-gene panel was identified. Matched blood and tumor gene expression levels were concordant (r = 0.72, p < 0.0001). The ensemble classifier ("PROSTest") was scaled 0%-100% and the industry-standard operating point of ≥50% used to define a PCa. Using this, the PROSTest exhibited an 85% sensitivity and 95% specificity for PCa versus controls. In two independent sets, the metrics were 92%-95% sensitivity and 100% specificity. In the RPCs (n = 47), PROSTest scores decreased from 72% ± 7% to 33% ± 16% (p < 0.0001, Mann-Whitney test). PROSTest was 26% ± 8% in 37 with normal postoperative PSA levels (<0.1 ng/mL). In 10 with elevated postoperative PSA, PROSTest was 60% ± 4%. CONCLUSION: A 27-gene whole blood signature for PCa is concordant with tissue mRNA levels. Measuring blood expression provides a minimally invasive genomic tool that may facilitate prostate cancer management.

Development and validation of an imageless machine-learning algorithm for the initial screening of prostate cancer.

PURPOSE: Prostate specific antigen (PSA) testing is a low-cost screening method for prostate cancer (PCa). However, its accuracy is limited. While progress is being made using medical imaging for PCa screening, PSA testing can still be improved as an easily accessible first step in the screening process. We aimed to develop and validate a new model by further personalizing the analysis of PSA with demographic, medical history, lifestyle parameters, and digital rectal examination (DRE) results. METHODS: Using data from 34,224 patients in the screening arm of the PLCO trial (22,188 for the training set and 12,036 for the validation set), we applied a gradient-boosting model whose features (Model 1) were one PSA value and the personal variables available in the PLCO trial except those that signaled an ex-ante assumption of PCa. A second algorithm (Model 2) included a DRE result. The primary outcome was the occurrence of PCa, while the aggressiveness of PCa was a secondary outcome. ROC analyses were used to compare both models to other initial screening tests. RESULTS: The areas under the curve (AUC) for Model 2 was 0.894 overall and 0.908 for patients with a suspicious DRE, compared to 0.808 for PSA for patients with a suspicious DRE. The AUC for Model 1 was 0.814 compared to 0.821 for PSA. Model 2 predicted 58% more high-risk PCa than PSA ≥4 combined with an abnormal DRE and had a positive predictive value of 74.7% (vs. 50.6%). CONCLUSION: Personalizing the interpretation of PSA values and DRE results with a gradient-boosting model showed promising results as a potential novel, low-cost method for the initial screening of PCa. The importance of DRE, when included in such a model, was also highlighted.

Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial.

Importance: Prostate-specific antigen (PSA) screening has potential to reduce prostate cancer mortality but frequently detects prostate cancer that is not clinically important. Objective: To describe rates of low-grade (grade group 1) and high-grade (grade groups 2-5) prostate cancer identified among men invited to participate in a prostate cancer screening protocol consisting of a PSA test, a 4-kallikrein panel, and a magnetic resonance imaging (MRI) scan. Design, Setting, and Participants: The ProScreen trial is a clinical trial conducted in Helsinki and Tampere, Finland, that randomized 61 193 men aged 50 through 63 years who were free of prostate cancer in a 1:3 ratio to either be invited or not be invited to undergo screening for prostate cancer between February 2018 and July 2020. Interventions: Participating men randomized to the intervention underwent PSA testing. Those with a PSA level of 3.0 ng/mL or higher underwent additional testing for high-grade prostate cancer with a 4-kallikrein panel risk score. Those with a kallikrein panel score of 7.5% or higher underwent an MRI of the prostate gland, followed by targeted biopsies for those with abnormal prostate gland MRI findings. Final data collection occurred through June 31, 2023. Main Outcomes and Measures: In descriptive exploratory analyses, the cumulative incidence of low-grade and high-grade prostate cancer after the first screening round were compared between the group invited to undergo prostate cancer screening and the control group. Results: Of 60 745 eligible men (mean [SD] age, 57.2 [4.0] years), 15 201 were randomized to be invited and 45 544 were randomized not to be invited to undergo prostate cancer screening. Of 15 201 eligible males invited to undergo screening, 7744 (51%) participated. Among them, 32 low-grade prostate cancers (cumulative incidence, 0.41%) and 128 high-grade prostate cancers (cumulative incidence, 1.65%) were detected, with 1 cancer grade group result missing. Among the 7457 invited men (49%) who refused participation, 7 low-grade prostate cancers (cumulative incidence, 0.1%) and 44 high-grade prostate cancers (cumulative incidence, 0.6%) were detected, with 7 cancer grade groups missing. For the entire invited screening group, 39 low-grade prostate cancers (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected. During a median follow-up of 3.2 years, in the group not invited to undergo screening, 65 low-grade prostate cancers (cumulative incidence, 0.14%) and 282 high-grade prostate cancers (cumulative incidence, 0.62%) were detected. The risk difference for the entire group randomized to the screening invitation vs the control group was 0.11% (95% CI, 0.03%-0.20%) for low-grade and 0.51% (95% CI, 0.33%-0.70%) for high-grade cancer. Conclusions and Relevance: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT03423303.

Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial.

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Intervention: 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). Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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. Trial Registration: isrctn.org Identifier: ISRCTN92187251.

Relationship between circulating FSH levels and body composition and bone health in patients with prostate cancer who undergo androgen deprivation therapy: The BLADE study.

Background: Among its extragonadal effects, follicle-stimulating hormone (FSH) has an impact on body composition and bone metabolism. Since androgen deprivation therapy (ADT) has a profound impact on circulating FSH concentrations, this hormone could potentially be implicated in the changes of fat body mass (FBM), lean body mass (LBM), and bone fragility induced by ADT. The objective of this study is to correlate FSH serum levels with body composition parameters, bone mineral density (BMD), and bone turnover markers at baseline conditions and after 12 months of ADT. Methods: Twenty-nine consecutive non-metastatic prostate cancer (PC) patients were enrolled from 2017 to 2019 in a phase IV study. All patients underwent administration of the luteinizing hormone-releasing hormone antagonist degarelix. FBM, LBM, and BMD were evaluated by dual-energy x-ray absorptiometry at baseline and after 12 months of ADT. FSH, alkaline phosphatase, and C-terminal telopeptide of type I collagen were assessed at baseline and after 6 and 12 months. For outcome measurements and statistical analysis, t-test or sign test and Pearson or Spearman tests for continuous variables were used when indicated. Results: At baseline conditions, a weak, non-significant, direct relationship was found between FSH serum levels and FBM at arms (r = 0.36) and legs (r = 0.33). Conversely, a stronger correlation was observed between FSH and total FBM (r = 0.52, p = 0.006), fat mass at arms (r = 0.54, p = 0.004), and fat mass at trunk (r = 0.45, p = 0.018) assessed after 12 months. On the other hand, an inverse relationship between serum FSH and appendicular lean mass index/FBM ratio was observed (r = -0.64, p = 0.001). This is an ancillary study of a prospective trial and this is the main limitation. Conclusions: FSH serum levels after ADT could have an impact on body composition, in particular on FBM. Therefore, FSH could be a promising marker to monitor the risk of sarcopenic obesity and to guide the clinicians in the tailored evaluation of body composition in PC patients undergoing ADT. Funding: This research was partially funded by Ferring Pharmaceuticals. The funder had no role in design and conduct of the study, collection, management, analysis, and interpretation of the data and in preparation, review, or approval of the manuscript. Clinical trial number: clinicalTrials.gov NCT03202381, EudraCT Number 2016-004210-10.

Treatments given to cancer patients can cause negative side effects. For example, a treatment known as androgen deprivation therapy ­ which is used to reduce male sex hormone levels in prostate cancer patients ­ can lead to increased body fat percentage and decreased bone density. These adverse effects can have further negative impacts on patient health, such as increasing the risk of cardiovascular disease and fractures from falls from standing height or less, respectively. Understanding how androgen deprivation therapy contributes to these negative side effects may help clinicians better manage care and outcomes for patients with prostate cancer. Follicle stimulating hormone (or FSH for short) has roles in male and female reproduction but has also been linked to changes in body composition. For example, elevated FSH levels are associated with higher total fat body mass in post-menopausal women. While androgen deprivation therapy is known to alter FSH blood levels, the impact of this change in prostate cancer patients was not well understood. To investigate the effect of androgen deprivation therapy on FSH levels and body composition, Bergamini et al. used X-ray technology to measure total fat body mass in prostate cancer patients before and after undergoing 12 months of androgen deprivation therapy. The findings showed that patient FSH blood levels significantly decreased after 12 months of treatment. Higher FSH blood levels strongly correlated with increased total fat body mass after 12 months of treatment. The findings of this clinical trial suggest that FSH blood levels impact the body composition of patients undergoing androgen deprivation therapy. As a result, FSH blood levels may be a suitable biomarker for identifying patients that are more likely to develop obesity and are therefore at greater risk of complications such as cardiovascular disease.

Salvage Radiotherapy PSMA PET/CT-guided in Men With PSA Recurrence.

BACKGROUND/AIM: To evaluate the clinical outcome in men with recurrent prostate cancer (PCa) treated by salvage radiotherapy (sRT) prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT)-guided. PATIENTS AND METHODS: From January 2021 to January 2023, 33 patients who previously underwent definitive/systemic therapy were submitted to sRT PSMA PET/CT-guided for PCa recurrence: 16 (48.5%) on the prostate bed (PB), 12 (36.4%) on the lymph node (LN) and five (15.1%) on the bone. The median PSA value was 3.3 ng/ml (range=0.3-15.5 ng/ml): 0.2-0.5 ng/ml (18.2% cases), 0.51-1 ng/ml (39.4% cases) and >1 ng/ml (42.4% cases). Median 18F PSMA PET/CT standardized uptake value (SUVmax) was evaluated on PB, vs. LN vs. bones PCa recurrences and was equal to 12.5 vs. 19.0 vs. 30.1, respectively. RESULTS: Overall, at a median follow up of 12 months, 23/33 patients (69.7%) had local control without distant progression (PSA and SUVmax evaluation): 14/16 (87.5%) vs. 7/12 (58.3%) vs. 2/5 (40%) underwent sRT on the PB vs. LN vs. bone metastases, respectively. CONCLUSION: PSMA PET/CT allows to perform sRT early in men with PCa recurrence and low PSA values obtaining a complete clinical response in approximately 70% of the cases one year from treatment.

[Exploration and validation of optimal cut-off values for tPSA and fPSA/tPSA screening of prostate cancer at different ages].

Objective: To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China. Methods: Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (＜60, 60-＜70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values. Results: A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening. Conclusion: To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.

[Prostate cancer - diagnostics and screening]. / Prostatacancer ­ utredning, klinisk diagnostik och screening.

Prostate-specific antigen (PSA) based screening is controversial, even though randomised trials show that screening can reduce prostate cancer mortality. The main reason is that screening leads to overdiagnosis of indolent cancers that would never have surfaced clinically in the absence of screening. Recently, several large studies have shown that magnetic resonance imaging (MRI) improves prostate cancer diagnostics. With MRI, up to half of all men with elevated PSA values can be spared a biopsy. When a biopsy is needed, the needles can be directed towards the suspicious area in the prostate, which increases the detection of clinically significant tumors. In Sweden, regional programmes with organised prostate cancer testing were introduced in 2020. These programmes aim to make prostate cancer testing more standardized, efficient, and equitable. In the future, biomarkers and AI-based systems will likely be important to further improve prostate cancer diagnostics.

Biomarker vs MRI-Enhanced Strategies for Prostate Cancer Screening: The STHLM3-MRI Randomized Clinical Trial.

Importance: Prostate cancer guidelines often recommend obtaining magnetic resonance imaging (MRI) before a biopsy, yet MRI access is limited. To date, no randomized clinical trial has compared the use of novel biomarkers for risk estimation vs MRI-based diagnostic approaches for prostate cancer screening. Objective: To evaluate biomarker-based risk estimation (Stockholm3 risk scores or prostate-specific antigen [PSA] levels) with systematic biopsies vs an MRI-enhanced strategy (PSA levels and MRI with systematic and targeted biopsy) for the detection of clinically significant prostate cancer in a screening setting. Design, Setting, and Participants: This open-label randomized clinical trial conducted in Stockholm, Sweden, between April 4, 2018, and December 10, 2020, recruited men aged 50 to 74 years with no history of prostate cancer. Participants underwent blood sampling for PSA and Stockholm3 tests to estimate their risk of clinically significant prostate cancer (Gleason score ≥3 + 4). After the blood tests were performed, participants were randomly assigned in a 2:3 ratio to receive a Stockholm3 test with systematic biopsy (biomarker group) or a PSA test followed by MRI with systematic and targeted biopsy (MRI-enhanced group). Data were analyzed from September 1 to November 5, 2023. Interventions: In the biomarker group, men with a Stockholm3 risk score of 0.15 or higher underwent systematic biopsies. In the MRI-enhanced group, men with a PSA level of 3 ng/mL or higher had an MRI and those with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3 or higher (range: 1-5, with higher scores indicating a higher likelihood of clinically significant prostate cancer) underwent targeted and systematic biopsies. Main Outcomes and Measures: Primary outcome was detection of clinically significant prostate cancer (Gleason score ≥3 + 4). Secondary outcomes included detection of clinically insignificant cancer (Gleason score ≤6) and the number of biopsy procedures performed. Results: Of 12 743 male participants (median [IQR] age, 61 [55-67] years), 5134 were assigned to the biomarker group and 7609 to the MRI-enhanced group. In the biomarker group, 8.0% of men (413) had Stockholm3 risk scores of 0.15 or higher and were referred for systematic biopsies. In the MRI-enhanced group, 12.2% of men (929) had a PSA level of 3 ng/mL or higher and were referred for MRI with biopsies if they had a PI-RADS score of 3 or higher. Detection rates of clinically significant prostate cancer were comparable between the 2 groups: 2.3% in the biomarker group and 2.5% in the MRI-enhanced group (relative proportion, 0.92; 95% CI, 0.73-1.15). More biopsies were performed in the biomarker group than in the MRI-enhanced group (326 of 5134 [6.3%] vs 338 of 7609 [4.4%]; relative proportion, 1.43 [95% CI, 1.23-1.66]), and more indolent prostate cancers were detected (61 [1.2%] vs 41 [0.5%]; relative proportion, 2.21 [95% CI, 1.49-3.27]). Conclusions and Relevance: Findings of this randomized clinical trial indicate that combining a Stockholm3 test with systematic biopsies is comparable with MRI-based screening with PSA levels and systematic and targeted biopsies for detection of clinically significant prostate cancer, but this approach resulted in more biopsies as well as detection of a greater number of indolent cancers. In regions where access to MRI is lacking, the Stockholm3 test can aid in selecting patients for systematic prostate biopsy. Trial Registration: ClinicalTrials.gov Identifier: NCT03377881.

Limited prognostic role of routine serum markers (AP, CEA, LDH and NSE) in oligorecurrent prostate cancer patients undergoing PSMA-radioguided surgery.

INTRODUCTION: We evaluated the prognostic role of pre-salvage prostate-specific membrane antigen-radioguided surgery (PSMA-RGS) serum levels of alkaline phosphatase (AP), carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH), and neuron-specific enolase (NSE). MATERIALS AND METHODS: Patients who consecutively underwent PSMA-RGS for prostate cancer (PCa) oligorecurrence between January 2019 and January 2022 were selected. Biomarkers were assessed one day before surgery. Cox regression and logistic regression models tested the relationship between biochemical recurrence-free survival (BFS), 6- and 12-month biochemical recurrence (BCR), and several independent variables, including biomarkers. RESULTS: 153 consecutive patients were analyzed. In the univariable Cox regression analysis, none of the biomarkers achieved predictor status (AP: hazard ratio [HR] = 1.03, 95% CI 0.99, 1.01; p = 0.19; CEA: HR = 1.73, 95% CI 0.94, 1.21; p = 0.34; LDH: HR = 1.01, 95% CI 1.00, 1.01; p = 0.05; NSE: HR = 1.02, 95% CI 0.98, 1.06; p = 0.39). The only independent predictor of BFS was the number of positive lesions on PSMA PET (HR = 1.17, 95% CI 1.02, 1.30; p = 0.03). The number of positive lesions was confirmed as independent predictor for BCR within 6 and 12 months (BCR < 6 months: odds ratio [OR] = 1.1, 95% CI 1.0, 1.3; p = 0.04; BCR < 12 months: OR = 1.1, 95% CI 1.0, 1.3; p = 0.04). CONCLUSION: The assessment of AP, CEA, LDH, and NSE before salvage PSMA-RGS showed no prognostic impact. Further studies are needed to identify possible predictors that will optimize patient selection for salvage PSMA-RGS.

Precise prostate cancer diagnosis using fluorescent nanoprobes for detecting PSA and PSMA in serum.

Novel Au-Se bond-based nanoprobes were designed for concurrent detection of PSA and PSMA in serum samples, aiming to enhance the early diagnosis of prostate cancer. These probes demonstrate robust stability, specificity and accuracy, underscoring their potential as non-invasive tools for diagnosis.

Prostate Health Index (PHI) as a triage tool for reducing unnecessary magnetic resonance imaging (MRI) in patients at risk of prostate cancer.

INTRODUCTION: The aim of this study is to assess the usefulness of the Prostate Health Index (PHI) as a triage tool for selecting patients at risk of prostate cancer (PCa) who should undergo multiparametric Magnetic Resonance Imaging (mpMRI). MATERIAL AND METHODS: We enrolled 204 patients with suspected PCa. For each patient, a blood sample was collected before mpMRI to measure PHI. Findings on mpMRI were assessed according to the Prostate Imaging Reporting & Data System version 2.0 (PI-RADSv2) category scale. RESULTS: According to PI-RADSv2, patients were classified into two groups: PI-RADS < 3 (48 %) and ≥ 3 (52 %). PHI showed the best performance for predicting PI-RADS ≥ 3 [AUC: 0,747 (0,679-0,815), 0,680(0,607-0,754), and 0,613 (0,535-0,690) for PHI, PSA ratio, and total PSA, respectively]. The best PHI cut-off was 30, with a sensitivity of 90%. At the univariate logistic regression, total PSA (p = 0.007), PSA ratio (p = 0.001), [-2]proPSA (p = 0.019) and PHI (p < 0.001) were associated with PI-RADS ≥ 3; however, at the multivariate analysis, only PHI (p < 0.001) was found to be an independent predictor of PI-RADS ≥ 3. CONCLUSION: PHI could represent a reliable noninvasive tool for selecting patients to undergo mpMRI.

Acoustic Enrichment of Heterogeneous Circulating Tumor Cells and Clusters from Metastatic Prostate Cancer Patients.

BACKGROUND: There are important unmet clinical needs to develop cell enrichment technologies to enable unbiased label-free isolation of both single cell and clusters of circulating tumor cells (CTCs) manifesting heterogeneous lineage specificity. Here, we report a pilot study based on the microfluidic acoustophoresis enrichment of CTCs using the CellSearch CTC assay as a reference modality. METHODS: Acoustophoresis uses an ultrasonic standing wave field to separate cells based on biomechanical properties (size, density, and compressibility), resulting in inherently label-free and epitope-independent cell enrichment. Following red blood cell lysis and paraformaldehyde fixation, 6 mL of whole blood from 12 patients with metastatic prostate cancer and 20 healthy controls were processed with acoustophoresis and subsequent image cytometry. RESULTS: Acoustophoresis enabled enrichment and characterization of phenotypic CTCs (EpCAM+, Cytokeratin+, DAPI+, CD45-/CD66b-) in all patients with metastatic prostate cancer and detected CTC-clusters composed of only CTCs or heterogeneous aggregates of CTCs clustered with various types of white blood cells in 9 out of 12 patients. By contrast, CellSearch did not detect any CTC clusters, but detected comparable numbers of phenotypic CTCs as acoustophoresis, with trends of finding a higher number of CTCs using acoustophoresis. CONCLUSION: Our preliminary data indicate that acoustophoresis provides excellent possibilities to detect and characterize CTC clusters as a putative marker of metastatic disease and outcomes. Moreover, acoustophoresis enables the sensitive label-free enrichment of cells with epithelial phenotypes in blood and offers opportunities to detect and characterize CTCs undergoing epithelial-to-mesenchymal transitioning and lineage plasticity.

Impact of Circulating Tumor Cell-Expressed Prostate-Specific Membrane Antigen and Prostate-Specific Antigen Transcripts in Different Stages of Prostate Cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA)-based images, which visually quantify PSMA expression, are used to determine prostate cancer micrometastases. This study evaluated whether a circulating tumor cell (CTC)-based transcript platform, including PSMA mRNA, could help identify potential prognostic markers in prostate cancer. EXPERIMENTAL DESIGN: We prospectively enrolled 21 healthy individuals and 247 patients with prostate cancer [localized prostate cancer (LPCa), n = 94; metastatic hormone-sensitive prostate cancer (mHSPC), n = 44; and metastatic castration-resistant prostate cancer (mCRPC), n = 109]. The mRNA expression of six transcripts [PSMA, prostate-specific antigen (PSA), AR, AR-V7, EpCAM, and KRT 19] from CTCs was measured, and their relationship with biochemical recurrence (BCR) in LPCa and mCRPC progression-free survival (PFS) rate in mHSPC was assessed. PSA-PFS and radiological-PFS were also calculated to identify potential biomarkers for predicting androgen receptor signaling inhibitor (ARSI) and taxane-based chemotherapy resistance in mCRPC. RESULTS: CTC detection rates were 75.5%, 95.3%, and 98.0% for LPCa, mHSPC, and mCRPC, respectively. In LPCa, PSMA [hazard ratio (HR), 3.35; P = 0.028) and PSA mRNA (HR, 1.42; P = 0.047] expressions were associated with BCR. Patients with mHSPC with high PSMA (HR, 4.26; P = 0.020) and PSA mRNA (HR, 3.52; P = 0.042) expressions showed significantly worse mCRPC-PFS rates than those with low expression. Increased PSA and PSMA mRNA expressions were significantly associated with shorter PSA-PFS and radiological PFS in mCPRC, indicating an association with drug resistance. CONCLUSIONS: PSMA and PSA mRNA expressions are associated with BCR in LPCa. In advanced prostate cancer, PSMA and PSA mRNA can also predict rapid progression from mHSPC to mCRPC and ARSI or taxane-based chemotherapy resistance.

Contemporary risk of biochemical recurrence after radical prostatectomy in the active surveillance era.

OBJECTIVES: To assess whether contemporary risks of biochemical recurrence (BCR) after radical prostatectomy (RP) in the AS era differ from historical estimates due to changes in tumor risk case mix and improvements in risk stratification. MATERIALS AND METHODS: We sampled 6,682 men who underwent RP for clinically localized disease between 2000 and 2017 from the VA SEARCH database. Kaplan Meier analysis was used to calculate incidence of BCR before and after 2010 overall and within tumor risk subgroups. Multivariable Cox proportional hazard regression analysis including an interaction term between era and tumor risk was used to compare risk of BCR before and after 2010 overall and across tumor risk subgroups. RESULTS: About 3,492 (52%) and 3,190 (48%) men underwent RP before and after 2010, respectively. In a limited multivariable model excluding tumor risk, overall BCR risk was higher post-2010 vs. pre-2010 (HR: 1.15, 95%CI: 1.05-1.25; 40% vs 36% at 8 years post-RP). However, this effect was eliminated after correcting for tumor risk (HR: 0.95, 95%CI: 0.87-1.04), suggesting that differences in tumor risk between eras mediated the change. Yet, within tumor-risk subgroups, BCR risk was significantly lower for favorable intermediate-risk (HR: 0.76, 95%CI:0.60-0.96) and unfavorable intermediate-risk PC (HR: 0.78, 95%CI: 0.67-0.90), but significantly higher for high-risk PC (HR: 1.22, 95%CI: 1.07-1.38) in the post-2010 era. 8-year risks of BCR in the post-2010 era were 21% (95%CI: 16%-25%), 25% (95%CI: 20%-30%), 41% (95%CI: 37%-46%), and 60% (95%CI: 56%-64%) for low-, FIR-, UIR-, and high-risk disease, respectively. Limitations include limited long-term follow-up in the post-2010 subgroup. CONCLUSIONS: Overall BCR risk has increased in the AS era, driven by a higher risk case mix and increased BCR risk among high-risk patients. Physicians should quote contemporary estimates of BCR when counseling patients.