Prostate-specific Antigen Research Articles

Preclinical and clinical evaluation of [64Cu]Cu-PSMA-Q PET/CT for prostate cancer detection and its comparison with [18F]FDG imaging

This study aimed to develop and evaluate [64Cu]Cu-PSMA-Q as a novel positron emission tomography (PET) imaging agent for prostate cancer detection, assessing its diagnostic accuracy and clinical applicability in comparison to [18F]FDG PET imaging. [64Cu]Cu-PSMA-Q was synthesized, purified, and subjected to comprehensive quality control. Its binding affinity, cellular uptake, and internalization were assessed in vitro using prostate-specific membrane antigen (PSMA)-positive LNCaP C4-2B cells. In vivo toxicity studies were conducted in 12 mouse models (6 per group). Small-animal PET/CT (positron emission tomography/computed tomography) imaging and biodistribution studies were performed on tumor-bearing mice. Clinical evaluation involved PET/CT imaging with [64Cu]Cu-PSMA-Q in 29 prostate cancer patients, with comparative analysis against [18F]FDG PET/CT imaging. Radiation dosimetry was calculated using OLINDA/EXM software, and diagnostic performance metrics, including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and tumor-to-background ratio, were analyzed using SPSS v24.0, with P < 0.05 considered statistically significant. Comparative analyses utilized t-tests or Mann–Whitney U tests as appropriate. [64Cu]Cu-PSMA-Q achieved over 99% radiochemical purity and a specific activity of 20.5 ± 1 GBq/μmol. In vitro studies demonstrated a dissociation constant (Kd) of 4.083 nM, along with high cellular uptake and internalization in LNCaP C4-2B cells. No significant toxicity was observed in mouse models. Small -animal PET/CT imaging revealed peak tumor uptake at 4 h post-injection in LNCaP C4-2B tumor xenografts. In clinical evaluations, [64Cu]Cu-PSMA-Q PET/CT detected more lesions than [18F]FDG, with significantly higher SUVmax, SUVmean, and tumor-to-background ratios. The mean effective radiation dose was calculated as 4.48 ± 0.99 mSv. [64Cu]Cu-PSMA-Q PET/CT demonstrated superior lesion detection and higher tumor-to-background ratios compared to [18F]FDG PET/CT for prostate cancer visualization. Its advantageous properties, including a favorable half-life, excellent safety profile, and enhanced diagnostic accuracy, support its potential for broad clinical adoption. This study establishes a foundation for further validation of [64Cu]Cu-PSMA-Q in prostate cancer management.

Neutrophil-and-monocyte-to-lymphocyte ratio is positively associated with elevated prostate-specific antigen levels and high-risk prostate cancer: evidence from the NHANES (2003–2008)

Neutrophil-and-monocyte-to-lymphocyte ratio is positively associated with elevated prostate-specific antigen levels and high-risk prostate cancer: evidence from the NHANES (2003–2008)

Percentage of free to total PSA as a biomarker of survival in metastatic castration-resistant prostate cancer.

To analyse whether the percentage of free to total prostate-specific antigen (%fPSA) is a prognostic biomarker in metastatic castration-resistant prostate cancer (mCRPC), as novel studies suggest an elevated %fPSA is associated with adverse oncological outcomes for men with biochemical recurrence of prostate cancer. A biobank prospectively collated at mCRPC diagnosis was analysed for %fPSA. Clinicopathological characteristics, systemic therapies and survival outcomes were recorded. Patients were stratified by a %fPSA cut-off of 15%. Cox proportional hazard models evaluated whether %fPSA was associated with overall survival (OS) and cancer-specific survival (CSS) across the cohort and by treatment. A total of 254 patients analysed with newly diagnosed mCRPC: 161 (63%) men having a %fPSA ≥15%. The median follow-up was 25.6 months. The median cohort OS and CSS was 39.6 and 43.8 months, respectively. Patients with a %fPSA ≥15% had lower median PSA level (31.30 vs 50.80 ng/mL; P = 0.007) and otherwise comparable clinicopathological and treatment profiles to men with a %fPSA <15%. Adjusting for PSA and on multivariable analysis, a %fPSA ≥15% was associated with shorter OS (multivariable hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.02-2.40; P = 0.039). Among men treated with docetaxel, a %fPSA ≥15% was associated with worse OS (HR 1.84, 95% CI 1.03-3.26; P = 0.038) and CSS. Conversely, %fPSA was not associated with outcomes for men receiving androgen receptor pathway inhibitors (abiraterone acetate or enzalutamide). An elevated %fPSA appears to be an adverse prognostic biomarker. Findings are consistent with biochemical recurrence studies, suggesting a biological basis. Validation and mechanistic studies are warranted.

Amorphous RuO2 Nanozymes with an Excellent Catalytic Efficiency Superior to Natural Peroxidases.

Developing efficient peroxidase-like nanozymes to surpass natural enzymes remains a significant challenge. Herein, an amorphous RuO2 nanozyme with peroxidase-like activity is synthesized for activating H2O2 with a specific activity of 1492.52Umg-1, outperforming the crystalline RuO2 nanozymes by a factor of 22 and far superior to natural peroxidases. Amorphous RuO2 nanozymes with long-range disordered atomic arrangements can effectively elongate the O─O bonds in H2O2. Abundant oxygen vacancies in amorphous RuO2 nanozymes lead to an upshift of the d-band center, enhancing the exceptional adsorption strength of H2O2, which improve the electron transfer efficiency and ensure superior peroxidase-like activity. Accordingly, a nanozyme-linked immunosorbent assay is developed for the precise and sensitive detection of prostate-specific antigens with a detection limit as low as 0.52pgmL-1. This study introduces a simple approach for developing high-performance peroxidase-like nanozymes to improve the analytical performances of prostate-specific antigens in clinical diagnostics.

Incidence, surveillance and natural history of high-grade prostatic epithelial neoplasia in the era of multiparametric MRI and targeted biopsy.

To determine the incidence of isolated high grade prostatic epithelial neoplasia (iHGPIN) following magnetic resonance imaging (MRI)-ultrasonography co-registration fusion targeted biopsy (MRFTB) coupled with systematic biopsy (SB) and to assess the detection rates of clinically significant prostate cancer (csPCa). Beginning in June 2012, most patients at our institution underwent multiparametric MRI (mpMRI) before prostate biopsy. Biopsies were performed between June 2012 and October 2021. The surveillance protocol for iHGPIN included prostate-specific antigen assessment every 6 months, digital rectal examinations annually, and multiparametric MRI (mpMRI) at 3 years. Repeat biopsies were recommended primarily for suspicious mpMRI, defined as a new Prostate Imaging-Reporting and Data System (PI-RADS) score >2 region of interest (ROI) or an increase in size of the pre-existing ROI. Of the 628 biopsies, 230 (33.7%), 48 (7.0%), 404 (59.2%) were interpreted as benign, iHGPIN, or prostate cancer (PCa), respectively. Of these cancers 140 (34.7%) and 264 (65.3%) were low-risk PCa and csPCa, respectively. iHGPIN was detected in MRRFTB only, SB only, and both MRFRB + SB in six (12.5%) 36 (75%), and six patients (12.5%), respectively. Of the 32 MRI scans performed at 3 years, a new PI-RADS score >2 ROI or an increase in the size or PI-RADS score of a pre-existing ROI was observed in four and eight patients, respectively. Nine of these underwent biopsy. Three additional biopsies were performed on non-suspicious mpMRI. csPCa was detected in two patients, both with an enlarging ROI. To our knowledge, this is the first study examining the incidence, natural history, and subsequent csPCa detection rates for iHGPIN in the era of mpMRI and MRI targeted biopsy. The lower prevalence of iHGPIN is attributed to the selection of biopsy candidates based on mpMRI and an increased likelihood of detecting pre-existing csPCa. Our findings provide compelling evidence that biopsy strategies limited to MRI targets will almost eliminate iHGPIN detection while decreasing detection of csPCa. A 3-year biopsy should be performed only in men with suspicious mpMRI.

Evidence-Based Clinical Protocols to Monitor Efficacy of [177Lu]Lu-PSMA Radiopharmaceutical Therapy in Metastatic Castration-Resistant Prostate Cancer Using Real-World Data.

Our objectives were to assess the prognostic value of posttherapy [177Lu]Lu-PSMA (LuPSMA) SPECT/CT by visual evaluation using RECIP 1.0 during LuPSMA therapy and develop an evidence-based clinical protocol to monitor the efficacy of LuPSMA. Methods: Patients with metastatic castration-resistant prostate cancer who received at least 2 LuPSMA cycles between April 2019 and November 2023 were retrospectively included in this study. Pairs of baseline and interim LuPSMA SPECT/CT (SPECT) and PSMA PET/CT (PET) images after 2 therapy cycles were analyzed per visual RECIP 1.0. Changes in prostate-specific antigen (PSA) levels at 12 wk were categorized by Prostate Cancer Working Group Criteria 3 guidelines and combined with RECIP 1.0 reads to determine disease progression using a composite classification method (PSA + RECIP). The primary outcome was the prognostic value of posttherapeutic SPECT by RECIP 1.0 for overall survival (OS). The clinical protocol was developed on the basis of the prognostic accuracy (Harrell concordance index, or C-index) of SPECT versus PET and the combination of SPECT plus PSA (SPECT + PSA) versus the combination of PET plus PSA (PET + PSA). Results: Data from 105 patients were evaluated. Progressive disease determined by SPECT was associated with shorter OS compared with stable disease (hazard ratio, 2.5; 95% CI, 1.2-5.3; P = 0.015) and with partial response (hazard ratio, 6.5; 95% CI, 2.7-15.7; P < 0.001). Of the 73 patients who underwent PET after 2 cycles, 7 (10%), 30 (41%), 22 (30%), and 30 (41%) had tumor progression shown by SPECT, PET, SPECT + PSA, and PET + PSA, respectively. The C-index for SPECT was inferior compared with that for PET (0.54 vs. 0.66; P < 0.001), whereas the C-indices for SPECT + PSA and PET + PSA did not differ significantly (0.62 vs. 0.66, respectively; P = 0.07). Conclusion: Posttherapeutic LuPSMA SPECT/CT per RECIP 1.0 after 2 therapy cycles was prognostic for OS. LuPSMA SPECT/CT identified significantly fewer patients with RECIP-classified progressive disease; however, SPECT + PSA achieved similar prognostic accuracy to PET + PSA for LuPSMA response evaluation.

Assessment of prostate cancer awareness and screening knowledge among men in Najran, Saudi Arabia: a cross-sectional study

Assessment of prostate cancer awareness and screening knowledge among men in Najran, Saudi Arabia: a cross-sectional study

Positive surgical margin and oncological outcomes after robot-assisted radical prostatectomy in different Cancer of the Prostate Risk Assessment risk groups.

To evaluate the impact of a positive surgical margin (PSM) in relation to the risk of biochemical recurrence (BCR) and additional treatment in different preoperative Cancer of the Prostate Risk Assessment (CAPRA) risk groups after robot-assisted radical prostatectomy (RARP). Retrospective cohort study of 1039 patients subjected to RARP for prostate cancer at a single European institution. PSM was stratified by extent (focal extensive). The CAPRA score was used for risk group stratification. BCR was defined as a prostate-specific antigen level >0.2 ng/mL. Additional treatment was defined as salvage radiotherapy (sRT) and/or androgen-deprivation therapy (ADT). In total 227 patients had a PSM (21.8%). When compared to a negative surgical margin, an extensive PSM was associated with an increased risk of BCR (hazard ratio [HR] 2.16, 95% confidence interval [CI] 2.09-8.29; HR 3.76, 95% CI 2.33-6.06; HR 2.35, 95% CI 1.03-5.38) and sRT (HR 3.75, 95% CI 1.45-9.7; HR 4.57, 95% CI 2.47-8.43; HR 9.32, 95% CI 1.06-14.82) in the low-, intermediate- and high-risk groups, respectively. In high-risk patients a focal PSM was associated with an increased risk of BCR (HR 5.79, 95% CI 1.62-20.65), sRT (HR 9.32, 95% CI 1.7-50.95) and ADT (HR 4.11, 95% CI 1.08-15.57) whereas in low- and intermediate-risk patients a modest effect on BCR but no significant effect on sRT or ADT was found. We found no significant interaction between CAPRA risk group and PSM (P = 0.25). While an extensive PSM was associated with an increased risk of recurrence in all risk groups, a focal PSM was associated with additional treatment only among men with high-risk tumours.

Prognostic [68Ga]Ga-PSMA-11 PET Biomarkers for [177Lu]Lu-PSMA Radioligand Therapy in Metastatic Castrate-Resistant Prostate Cancer (Asian Population Study).

Gallium-68 (68Ga) prostate-specific membrane antigen (PSMA) ([68Ga]Ga-PSMA-11) directed PET/CT reflects PSMA expression at metastatic sites and can hence be a surrogate of lutetium-177 (177Lu) PSMA ([177Lu]Lu-PSMA) radiation delivery. This retrospective analysis aims to explore the association between quantitative baseline [68Ga]Ga-PSMA-11 PET imaging biomarkers and treatment outcomes in our Asian cohort. We included patients with progressive metastatic castrate-resistant prostate cancer (mCRPC) who received [177Lu]Lu-PSMA radioligand therapy at our institution. The association between baseline [68Ga]Ga-PSMA-11 PET parameters (SUVmax, SUVmean, total tumor volume [PSMA-TV], total lesion uptake [PSMA-TLU = PSMA-TV × SUVmean], and total lesion quotient [PSMA-TLQ = PSMA-TV / SUVmean]) and overall survival (OS), prostate specific antigen (PSA) progression free survival (PFS), PSA response, and toxicity were analyzed using univariate analysis. Optimal cut-points were also explored. Between May 9, 2018 and October 7, 2024, 71 of 84 screened patients were eligible. The median whole-body SUVmean in our cohort was 8.04. Higher PSMA-TLQ and PSMA-TV (per 10-unit increment) were associated with shorter OS (HR 1.005; HR 1.005) and shorter PSA PFS (HR 1.005; HR 1.004). A higher PSMA-TLQ was also associated with poorer odds of PSA response (OR 0.994). Conversely, higher SUVmean was associated with longer PSA PFS (HR 0.911) and improved odds of PSA response (OR 1.34). Higher PSMA-TV (per 10-unit increment) and PSMA-TLU (per 100-unit increment) were associated with increased hematological toxicity (OR 1.008; OR 1.012). PSMA-TLQ and PSMA-TV were negative prognostic markers and SUVmean was a positive prognostic marker among Asian patients with mCRPC who received [177Lu]Lu-PSMA radioligand therapy.

Prostate-specific membrane antigen positron-emission tomography for novel risk-stratification of biochemical recurrence.

The variety of prostate cancer aggressiveness in patients with biochemical recurrence (BCR) leads to the unmet need of accurate risk stratification. This review examined the recently published risk stratification tool using prostate-specific membrane antigen positron-emission tomography (PSMA-PET) compared to the risk categories by European Association of Urology (EAU). The risk stratification by EAU was proposed for patients with BCR, including the doubling time of the prostate-specific-antigen and Gleason score as predictors for survival. Although stratification into low- vs. high-risk groups reached significant differences in the external validation, C-indices determined moderate discriminative ability and the need to improve the EAU risk categories. PSMA-PET was recently validated as prognostic biomarker and PSMA-PET standardized by Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) metrics were combined to create a visual and a quantitative nomogram to predict overall survival. The unmet need to improve risk stratification for prostate cancer patients experiencing BCR was addressed with PSMA-PET PROMISE (PPP) nomograms. Although PPP nomograms are not applied for individual patient counselling yet, they can be used additionally to EAU risk categories.

Integrative analysis of blood biomarkers and clinical variables improves early detection of aggressive prostate cancer

Aggressive prostate cancer (PC) represents a significant health concern. Conventional screening methods, primarily based on prostate-specific antigen (PSA) levels, lack specificity, leading to an urgent need for more accurate diagnostic tools. This study investigates whether integrating clinical and routine blood laboratory parameters can improve the early non-invasive prediction of aggressive PC. In a pilot study of 578 patients with suspicion of PC, 28 laboratory values alongside data on family history, diet, and lifestyle were analyzed. A logistic regression classifier was developed, with model performance evaluated using repeated k-fold cross-validation on the complete dataset (n = 282). Participants were categorized into healthy, moderate PC (ISUP 1–2), and aggressive PC (ISUP 3–5). Significant associations were found between PC aggressiveness and lower levels of androstenedione, dehydroepiandrosterone-sulfate (DHEA-S) and free PSA%, as well as higher levels of sex hormone binding globulin (SHBG). The integration of these serum markers with clinical parameters into a new multi-stage risk classifier significantly improved the predictive accuracy for aggressive PC, outperforming PSA-only methods. The integration of DHEA-S, androstenedione, and SHBG as widely available and cost-effective novel blood biomarkers offers a more targeted, non-invasive prediction of aggressive PC. This approach could reduce reliance on invasive prostate biopsies and expensive magnetic resonance imaging.

The evolving role of positron emission tomography in precision prostate cancer biopsy.

Prostate cancer is one of the most common cancers among men, and accurate detection and diagnosis are crucial for effective treatment planning. Diagnostic prostate biopsy plays a pivotal role in the detection and characterization of prostate cancer. Recent advancements in molecular imaging, particularly with Positron Emission Tomography (PET) using radiolabelled Prostate-Specific Membrane Antigen (PSMA) tracers, have shown significant improvements in enhancing prostate cancer detection. PSMA PET, when combined with magnetic resonance imaging (MRI) in hybrid PET/MRI systems, provides improved sensitivity and specificity, enabling more precise localization of clinically significant prostate cancer (csPCa) lesions. This narrative review explores the evolving role of PET/CT and PET/MRI-guided prostate biopsy. We examine the integration of PET with MRI for the detection of prostate cancer, highlighting key studies that have demonstrated improved diagnostic outcomes. Additionally, we discuss the current limitations, including the high costs and longer scan times associated with PET/MRI, as well as the challenges in data interpretation. The review also considers emerging technologies, such as promising molecular probes for prostate PET imaging, such as gastrin-releasing peptide receptor (GRPR) and fibroblast activation protein inhibitor (FAPI). Finally, the present work provides the clinician with a comprehensive yet concise up-to-date review of the literature to easily evaluate the possibilities currently offered by hybrid imaging technologies of personalized imaging-guided biopsy for prostate cancer patients.

Integrating multi-cohort machine learning and clinical sample validation to explore peripheral blood mRNA diagnostic biomarkers for prostate cancer

BackgroundThe global incidence of prostate cancer (PCa) has been rising annually, and early diagnosis and treatment remain pivotal for improving therapeutic outcomes and patient prognosis. Concurrently, advancements in liquid biopsy technology have facilitated disease diagnosis and monitoring, with its minimally invasive nature and low heterogeneity positioning it as a promising approach for predicting disease progression. However, current liquid biopsy strategies for PCa predominantly rely on prostate-specific antigen (PSA), which lacks specificity and compromises diagnostic accuracy. Thus, there is an urgent need to identify novel liquid biopsy biomarkers to enable early and precise PCa diagnosis.MethodsWe integrated 12 machine learning algorithms to construct 113 combinatorial models, screening and validating an optimal PCa diagnostic panel across five datasets from TCGA and GEO databases. Subsequently, the biological feasibility of the selected predictive model was verified in one prostate epithelial cell line and five PCa cell lines. Robust RNA diagnostic targets were further validated for their expression in plasma samples to establish an RNA-based liquid biopsy strategy for PCa. Finally, plasma samples from PCa and benign prostatic hyperplasia (BPH) patients at Wuhan Tongji Hospital were collected to evaluate the strategy’s clinical significance.ResultsDifferential analysis identified 1,071 candidate mRNAs, which were input into the integrated machine learning framework. Among the 113 combinatorial models, the 9-gene diagnostic panel selected by the Stepglm[both] and Enet[alpha = 0.4] algorithms demonstrated the highest diagnostic efficacy (mean AUC = 0.91), including JPH4, RASL12, AOX1, SLC18A2, PDZRN4, P2RY2, B3GNT8, KCNQ5, and APOBEC3C. Cell line experiments further validated AOX1 and B3GNT8 as robust RNA biomarkers, both exhibiting consistent PCa-specific expression in human plasma samples. In liquid biopsy analyses, AOX1 and B3GNT8 outperformed PSA in diagnostic accuracy, achieving a combined AUC of 0.91. Notably, these biomarkers also demonstrated diagnostic utility in patients with ISUP ≤ 2.ConclusionsThrough an integrated machine learning approach and clinical validation, we developed an RNA-based diagnostic panel for PCa. Specifically, we identified AOX1 and B3GNT8 as novel liquid biopsy biomarkers with promising clinical diagnostic value. These findings provide new targets and insights for early and precise PCa diagnosis.

Genomic instability is associated with response to [¹⁷⁷Lu]Lu-PSMA-I&T radioligand therapy: an exploratory, preliminary liquid biopsy analysis.

PSMA-targeted radioligand therapies (PSMA RLT) are an effective and safe option for metastatic castration-resistant prostate cancer, but responsive subtypes and their biomarkers are not fully defined. Plasma samples for cell-free DNA (cfDNA) analysis were collected from 17 patients undergoing [¹⁷⁷Lu]Lu-PSMA-I&T. CfDNA underwent whole-genome sequencing to establish copy number variation (CNV) profiles and circulating-tumor DNA (ctDNA) levels and compared between prostate-specific antigen (PSA) response- and 1-year overall survival (1YOS) groups. Non-responders exhibited higher degrees of cfDNA CNV burden (P = 0.048) and higher ctDNA levels (P = 0.036) than responders. Both markers allowed for the differentiation of responses (AUC: 0.792, 0.806) and 1YOS (AUC: 0.778, 0.847). Unresponsive patients exhibited higher levels of cfDNA genomic instability and ctDNA levels, warranting genome-wide CNV profiling studies next to targeted approaches for mechanistic radiobiological insights and their value as response biomarkers for PSMA RLTs.

Impact of PSMA PET on Radiation Oncology Planning.

Impact of PSMA PET on Radiation Oncology Planning.

Preservation of Neurovascular Bundles in High-risk Prostate Cancer Patients: Long-term Oncological Outcomes from Two High-volume Tertiary Centers.

Preservation of Neurovascular Bundles in High-risk Prostate Cancer Patients: Long-term Oncological Outcomes from Two High-volume Tertiary Centers.

Abstract 4954: Age- and race/ethnicity-specific values of prostate-specific antigen levels: Implications for prostate cancer screening

Background: A significant limitation in prostate cancer screening is the limited diversity and scope of data that have defined prostate-specific antigen (PSA) values. The use of PSA in prostate cancer screening could be enhanced with knowledge of the distribution of PSA in diverse groups of men. These data may inform triggers for clinical actionability, including biopsy. Objective: This study aims to evaluate the distribution of PSA values among healthy men of different ethnicities and age groups to derive age- and ethnicity-specific low, middle, and upper PSA distribution values. Methods: We meta-analyzed studies that reported PSA reference values in healthy men by age and self-identified race or ethnicity. The analysis was restricted to full text articles published in English. Participants were healthy men, aged 40-79 years with no history of prostate cancer, prostate disease, or prostate surgery. PSA values were not age-adjusted. We included data for either observed or estimated PSA values. Studies were excluded if they reported PSA in men with prostate cancer diagnosis, prostate disease, history of prostate surgery, suspicious DRE/TRUS values, age-adjusted results, or a small sample size (N&amp;lt;50). The primary outcomes of interest were to estimate PSA values to construct age- and race-stratified PSA values. Estimates were calculated for the upper limits of the following percentiles: 5th, 10th, 25th, 50th, 75th, 90th, and 95th for 16 race/ethnicity groups. Results were stratified by the original exclusion criteria used by the individual studies, including 1) PSA&amp;gt;4.0 ng/ml, Suspicious DRE/TRUS; or 2) history of prostate disease, surgery, or cancer. Forty-two studies met our criteria and were included in this report. Results: Men of African descent had higher PSA values followed by men of Asian and European descent. Within the 95th percentile, African descent men had PSA estimates of 4.78 ng/ml, 5.47 ng/ml, 8.93 ng/ml. White men had PSA values of 1.90 ng/ml, 2.06 ng/ml, and 3.31 ng/ml respectively for 40-49 years, 50-59 years, and 60-69 years. When stratified, the distribution of PSA was overall higher among those studies which excluded based on PSA levels greater than 4.0 ng/ml compared to studies which excluded based on history or prostate disease, surgery, or cancer; for both race and age. However, Japanese men had higher a higher distribution compared to African descent men for all ages in the 95thpercentile among those with no history of prostate disease, surgery, or cancer. Conclusion: We report an association of PSA levels with race and age. PSA was elevated among men of African descent and increase with age. Our data may inform the use of PSA in screening for prostate cancer in diverse populations Citation Format: Pranoti Pradhan, Timothy R. Rebbeck, William K. Oh, Sigrid Carlsson, Kevin H. Kensler. Age- and race/ethnicity-specific values of prostate-specific antigen levels: Implications for prostate cancer screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4954.

68Ga-labeled prostate specific membrane antigen HBED-CC PET/MRI for staging and evaluating the clinicopathological characteristics in newly diagnosed prostate cancer

ObjectiveThe purpose of this study was to investigate the role of 68Ga-labeled prostate specific membrane antigen HBED-CC (68Ga-PSMA-11) PET/MRI in primary staging and to evaluate the relationship between PSMA-derived parameters and clinicopathological characteristics in newly diagnosed prostate cancer (PCa).Materials and methodsThis study reports the findings from 72 patients newly diagnosed with primary PCa, all of whom underwent 68Ga-PSMA-11 PET/MRI scans. Calculated the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 68Ga-PSMA-11 PET/MRI for T, N, M staging, respectively. The maximum standardized uptake value (SUVmax), PSMA-tumor volume (PSMA-TVp), and total lesion-PSMA (TL-PSMAp) of primary lesion, PSMA-TV of total lesions (PSMA-TVt), and TL-PSMA of total lesions (TL-PSMAt) were measured, and Spearman correlation analysis was performed to assess their correlation with baseline prostate-specific antigen (PSA). Non-parametric Mann–Whitney U test was conducted to assess the difference of PSMA-derived parameters among clinicopathological characteristics of PCa. Receiver operating characteristic (ROC) curve was used to evaluate the performance of PSMA-derived parameters in diagnosing the clinicopathological characteristics of PCa.ResultsThe overall accuracy of 68Ga-PSMA-11 PET/MRI in detecting T staging of PCa was 80.7%. Diagnostic accuracy for T2a, T2b, T2c, T3a, and T3b were 94.2%, 92.3%, 90.4%, 90.4%, and 94.2%, respectively. Diagnostic accuracy for N and M staging were 96.1% and 97.2% based on patients-level, respectively. There were significant correlation between the SUVmax, PSMA-TVp, TL-PSMAp, PSMA-TVt, TL-PSMAt and baseline PSA values. Significant differences were observed in SUVmax, PSMA-TVp, TL-PSMAp, PSMA-TVt, and TL-PSMAt between T3 and T2 staging. Statistical differences were observed in SUVmax, TL-PSMAp, PSMA-TVt, and TL-PSMAt between Gleason Score (GS) > 7 and GS ≤ 7, as well as positive and negative regional lymph node metastasis. TL-PSMAt show the highest value in assessing clinicopathological characteristics.Conclusions68Ga-PSMA-11 PET/MRI can provide accurate TNM staging for PCa, particularly in local staging. TL-PSMAt accurately evaluate overall tumor burden and aids in diagnosing clinicopathological characteristics in mid-to-late-stage patients, outperforming SUVmax.

Abstract 1058: The prediction of positive prostate biopsies in men is significantly enhanced when PVT1 Exon 4A is combined with serum Prostate Specific Antigen (PSA)

Abstract Prostate cancer (PCa) remains a significant public health challenge, ranking as the second leading cause of cancer-related deaths among men in the United States. Current diagnostic approaches, predominantly centered on prostate-specific antigen (PSA) testing, often lead to overdiagnosis and unnecessary biopsies. The long nonprotein coding gene, PVT1 (plasmacytoma variant translocation 1), has shown promise as a biomarker, being upregulated in PCa and associated with disease progression and metastasis. This study investigates the potential of incorporating PVT1 biomarkers to improve diagnostic accuracy for PCa detection, focusing on both the general population and men of African ancestry, who are disproportionately impacted by PCa incidence and mortality.A total of 144 serum samples were analyzed, with 72 samples from men diagnosed with PCa and 72 from men without cancer. Serum levels of PVT1 Exons 4A, 4B, and 9 were quantified using digital PCR. Multiple logistic regression models were developed to predict cancer status based on PSA alone, PVT1 biomarkers alone, and combinations of PSA with PVT1 biomarkers. Model performance was assessed using stratified k-fold cross-validation, with comparisons made using likelihood ratio tests, and z-tests for statistical significance.The results show that combining PSA with PVT1 Exon 4A improves specificity in predicting cancer status in the general population from 0.45 to 0.54 while maintaining sensitivity at 0.81. Within the subpopulation of men of African Ancestry, PVT1 Exon 4A alone achieves an accuracy of 0.75 with a sensitivity of 1.0 and specificity of 0.5 compared to PSA alone which had an accuracy of 0.38, sensitivity of 0.5 and specificity of 0.25.This study underscores the potential clinical utility of integrating PVT1 biomarkers into prostate cancer screening programs. The inclusion of Exon 4A enhanced PSA-based prediction by addressing its limitations in overdiagnosis and unnecessary biopsies, providing a balanced improvement in diagnostic performance. By improving the accuracy of PCa detection while reducing the burden of overdiagnosis, this approach provides significant value for healthcare providers, diagnostic laboratories, and insurers aiming to enhance early detection and equitable screening outcomes. Citation Format: Tinovimba L. Hove, Rachel E. Sexton, Michael Liss, Robin Leach, Emmanuel Asante-Asamani, Olorunseun O. Ogunwobi. The prediction of positive prostate biopsies in men is significantly enhanced when PVT1 Exon 4A is combined with serum Prostate Specific Antigen (PSA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1058.

Abstract 7469: Molecular insights and biology of low-PSA high-risk prostate cancer

Abstract Background: Aggressive prostate cancer (PCa) often progresses to castration-resistant disease (CRPC), which becomes incurable and lethal. Although most PCa tumors are initially responsive to androgen deprivation therapy (ADT), duration of this response varies, and relapse typically occurs as disease transitions to CRPC in most patients. Although there have been advancements in molecular genetics and genome sequencing, early identification of lethal versus non-lethal forms of PCa remains difficult. A substantial number of PCa patients are present with high-risk tumors that produce low levels of prostate-specific antigen (PSA) at diagnosis. Research suggests that therapeutic outcomes for these patients may be unfavorable, as they may not respond as effectively to ADT or androgen receptor pathway inhibitors (ARPI). As a result, this high-risk PCa with low PSA secretion may represent an understudied subtype of the disease. Methods: Between 2013 and 2023, a total of 3619 PCa patients underwent robotic-assisted radical prostatectomy (RARP). Patients were divided into four groups based on PSA levels: very low (&amp;lt;2.5 ng/ml), low (2.6-5.0 ng/ml), medium (5.1-8.0 ng/ml), and high (&amp;gt;8.0 ng/ml). ANOVA and Pearson’s chi-squared tests were performed to compare clinical characteristics among these groups. In addition, gene expression profiles from TCGA PCa cohort were analyzed to assess differential PSA/KLK3 mRNA expression within cancer cells. To further investigate, single-cell clones from LNCaP parental population were selected to study molecular characteristics of tumor cells with low PSA expression. Results: We observed that patients with high-risk PCa and very low PSA levels (&amp;lt;2.5 ng/ml) experienced higher rates of biochemical recurrence than those with high-grade cancer who had PSA levels above 2.5 ng/ml. Furthermore, we observed a significantly higher occurrence of seminal vesicle invasion (p=1.058e-05) and neurovascular invasion (p=0.0047) in both very low and high PSA groups compared to other two groups. Notably, very low PSA group showed a higher rate of lymph node invasion (p=0.00095) than other three groups. Transcriptomic analysis of TCGA cohort showed genes upregulated in very low PSA group compared to high PSA group, were significantly enriched (p&amp;lt;0.001) in metastatic castration-resistant prostate cancer (mCRPC). Furthermore, our study of LNCaP-derived naturally occurring low-PSA clones demonstrated enhanced migratory potential and higher expression of EMT markers compared to parental LNCaP cells, which express high levels of PSA. Conclusions: Our study reveals a distinct subtype of localized PCa characterized by low PSA levels while still displaying high-risk features. This subtype is particularly invasive and linked to potentially poor outcomes, highlighting the necessity for further investigation to gain deeper understanding of its aggressive biology and characteristics that remain largely unexplored. Citation Format: Nabila Zaman, Adriana M. Pedraza, Sarah Ann King, Prathiksha Prabhakaraalva, Natasha Kyprianou, Ashutosh K. Tewari, Goutam Chakraborty. Molecular insights and biology of low-PSA high-risk prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7469.