Prostate Cancer and Prostatic Diseases最新文献

Background: Black individuals in the U.S. experience significantly higher prostate cancer mortality and are more likely to be diagnosed at younger ages with aggressive disease. This disparity may be influenced by negative healthcare perceptions and racial discordance between patients and providers, impacting lower rates of prostate-specific antigen (PSA) screening. We hypothesized that these factors would be associated with reduced PSA screening uptake, particularly among Black men.

Objectives: This study aimed to examine the association between negative healthcare perceptions and PSA screening, assess whether this relationship differs by race, and evaluate the role of racial discordance in influencing screening behavior.

Methods: We analyzed data from the 2018-2022 Medical Expenditure Panel Survey. The sample included 2373 men aged 45-70 who self-identified as non-Hispanic White or Black and had complete data on PSA screening, healthcare perceptions, and demographics. Negative healthcare perceptions were measured using a Health Perceptions Index (HePI), constructed from MEPS items (higher scores reflect more negative perceptions).

Results: Higher HePI scores were significantly associated with lower PSA screening rates (p < 0.01). Interaction models indicated that Black men with higher HePI scores were disproportionately less likely to undergo screening. Racial discordance with providers was independently associated with reduced screening likelihood (~10.2 percentage points; p < 0.01). Models including interaction terms (age, race, and discordance) showed that older Black men with high HePI scores and discordant providers were least likely to be screened.

Conclusions: PSA screening disparities are shaped by negative healthcare perceptions and racial discordance, particularly among older Black men. Addressing these barriers through culturally tailored education, improved workforce diversity, and strengthened provider-patient relationships may help close screening gaps. These findings highlight the relevance of healthcare system perceptions in understanding screening disparities and may inform future strategies to identify at-risk individuals.

Background: Benign prostatic hyperplasia (BPH) frequently leads to bladder outlet obstruction (BOO) and lower urinary tract symptoms (LUTS) in aging men. Detrusor overactivity (DO) is a common functional consequence of BOO, often persisting even after surgical intervention. Prostatic inflammation (PI) has been implicated in BPH pathogenesis, but its relationship with DO remains unclear. This study aimed to evaluate the association between histologically confirmed PI and DO in men undergoing transurethral resection of the prostate (TURP) for BPH-related BOO.

Methods: We conducted a prospective, observational study involving 125 men aged ≥50 years with BPH, BOO confirmed by pressure-flow studies, and moderate-to-severe LUTS (IPSS ≥ 7). All patients had received standard medical therapy and were candidates for TURP. Urodynamic testing was performed before and three months after surgery. Based on baseline urodynamic findings, patients were categorized into two groups: those with DO (Group A) and those without (Group B). Resected prostate tissue was examined histologically, and PI was graded using the Irani score. Statistical analysis was performed using SPSS v26, with odds ratios (OR) and 95% confidence intervals (CI) reported.

Results: Prostatic inflammation was identified in 78.4% of patients overall and was significantly more prevalent in those with DO (84.9% vs. 69.2%; OR = 2.47, 95% CI: 1.11-5.49, p = 0.02). Inflammation was also more severe in Group A. DO resolved postoperatively in 75.3% of patients, while persistent DO was associated exclusively with moderate-to-severe PI. The odds of persistent DO following TURP were significantly higher in this subgroup (OR = 4.00, 95% CI: 1.33-12.05).

Conclusions: Prostatic inflammation is more frequent and severe in men with DO and is associated with its persistence after TURP. These findings suggest that PI contributes to both the pathogenesis and postoperative course of DO, supporting its role as a therapeutic target in BPH-related LUTS management.

Background: Abiraterone acetate/prednisone (AAP) plus a luteinizing hormone releasing hormone agonist or antagonist (LHRH-A) is commonly used for treating high risk M0 or oligometastatic prostate cancer, but prolonged LHRH-A can be associated with delayed and incomplete testosterone (T) recovery after discontinuation.

Methods: We assessed impact of earlier LHRH-A discontinuation prior to stopping AAP on testosterone recovery (TR) to ≥150 ng/dl in an institutional cohort of patients who received 500-800 days of treatment.

Results: 100% (89/89) had testosterone <20 ng/dl at AAP end of treatment, and discontinuing LHRH-A ≥ 12 months prior to stopping AAP demonstrated improvement in 6-month TR (76.9%, 95% CI 39.7-92.8) compared to <3 months prior to stopping AAP (13.0%, 95% CI 4.7-25.8; HR 0.27[0.11-0.66], p < 0.01).

Conclusions: Early LHRH-A discontinuation 12 months or more prior to stopping AAP is associated with faster and more frequent T recovery compared to LHRH-A discontinuation within 3 months of AAP cessation, with T levels remaining appropriately suppressed during abiraterone monotherapy.

Background: Human leukocyte antigen (HLA) class I encompasses peptide-binding proteins that regulate T-cell interactions. We examined HLA class I expression in prostate cancers (PC), exploring associations with clinical outcomes, molecular features, and tumor immune microenvironment.

Methods: We analyzed 8040 PC samples from the Caris Life Sciences database, stratifying them into HLA-high (upper quartile) and -low (lower quartile) groups. Genomic and transcriptomic alterations were compared. Immune cell fractions were inferred using quanTIseq, and overall survival (OS) data was obtained from insurance claims. Differences were computed with Cox proportional hazards.

Results: Among 66 cancer types, PC ranked 3^rd-, 11^th-, and 19^th-lowest for HLA-A, -B, and -C expression, respectively. In PC, genes tied to androgen receptor (AR) signaling, immune checkpoint molecules (CTLA4, PD-L1), and the epithelial-mesenchymal transition were significantly higher in HLA-high tumors. HLA-high status was linked to greater tumor immune activity, marked by higher T cell fractions and enhanced immune hallmarks. HLA-high tumors were less likely to possess alterations in AR, FOXA1, and CDK12, but harbored increased alterations in tumor suppressor gene (RB1, PTEN) alterations. Tumors with high HLA-A and HLA-B had elevated TMB-H/MSI-H/dMMR status. Finally, shorter OS was observed in patients with high HLA-A or HLA-B expression, while longer OS was associated with high HLA-C expression.

Conclusions: In PC, elevated HLA class I levels correlate with immune activity, molecular characteristics, and clinical outcomes. We suggest considering HLA expression as a supplementary marker of immune activity in PC, alongside genetic mutations and transcriptomic markers.

Background/objectives: Six transmembrane epithelial antigen of prostate 1 (STEAP1), a cell surface protein, is highly expressed in prostate cancer and is known to be associated with disease progression and poor prognosis. Based on its specificity for prostate cancer, significant progress has been made over the past decade to capitalize on STEAP1 as a diagnostic and treatment target, and its potential future role in prostate cancer care is of considerable interest.

Subjects/methods: This review evaluates the current and emerging strategies targeting STEAP1, integrating findings from preclinical studies and clinical trials.

Results: This review discusses STEAP1-based diagnostics, including molecular imaging (89Zr-DFO-MSTP2109A) and liquid biopsy methods, as well as therapeutics, such as STEAP1 antibodies, antibody-drug conjugates (DSPT3086S, ADRX-0405, ABBV-969, and DXC008), chimeric antigen receptor T-cell therapy (STEAP1 CAR-T), bispecific T-cell engagers (Xaluritamig/AMG 509, BC261), and cancer vaccines.

Conclusions: STEAP1 represents a promising diagnostic and therapeutic target in prostate cancer, and its potential role in shaping future management of the disease warrants continued investigation.

Background: The 4K Score is a blood-based test that estimates the risk of clinically significant prostate cancer (Grade Group ≥2, GG2 + ) by combining four kallikrein markers with clinical variables. However, benign prostatic hyperplasia (BPH) can elevate PSA levels, potentially leading to risk overestimation in men with large prostates. We developed a novel metric, 4K Density (4K Score divided by prostate volume), to adjust for prostate size and improve risk stratification.

Methods: We retrospectively reviewed 3150 men who underwent 4K Score testing at the University of Miami Desai Sethi Urology Institute from 2014 to 2024. After excluding those without a prostate biopsy or MRI within six months of the 4K Score, 1983 men remained. Statistical analysis using SAS v9.4 included logistic regression, receiver operating characteristic (ROC) analysis, and Youden's Index to determine optimal cutoffs for GG2+ detection. The performance of 4K Density was compared to the 4Kscore and PSA Density in predicting GG2+ cancer.

Results: Among the 1983 men, 661 (33%) had GG2+ cancer. 4K Density was significantly higher in men with GG2+ cancer compared to those without (median 0.93 vs. 0.25, p < .0001). In multivariable analysis, 4K Density was the strongest independent predictor (OR 3.51, 95% CI 3.64-4.66), outperforming 4Kscore and PSA density. 4K Density also had the highest AUC (0.81, (95%CI)), compared to 4Kscore (0.76, 95 %CI, <0.0001) and PSA density (0.76, 95% CI, <0.0001). At an optimized cutoff of 0.56, 4K Density achieved 89.9% NPV and 48.5% PPV for detecting GG2+ cancer.

Conclusions: 4K Density is a novel, volume-adjusted biomarker that improves detection of clinically significant prostate cancer and outperforms PSA density and the 4Kscore test. It may be helpful in larger prostates, where confounding from BPH is present. Prospective validation is warranted to confirm its clinical utility.

Background: Emerging evidence in cancer neuroscience indicates that the nervous system interacts directly or indirectly with cancer cells, promoting tumor progression. The prostate gland contains an extensive neural network essential for regulating key physiological functions of prostate cells, and the significant neural distribution observed in prostate cancer highlights its critical role in driving cancer pathogenesis. Unfortunately, Comprehensive reviews systematically summarizing progress in cancer neuroscience for prostate cancer are currently lacking.

Method: We synthesize existing research on interactions between the nervous system and prostate cancer cells, explore the neural distribution within the prostate, and evaluate the impact of neural innervation on prostate cancer development and progression. Additionally, we also assess the potential neural regulation mechanisms in neuroendocrine prostate cancer (NEPC).

Result: We found that neural interactions significantly influence prostate cancer development. Neural circuitry within the tumor microenvironment drives progression and contributes to the aggressiveness of lethal subtypes like NEPC. Targeting neuromodulation emerges as a promising therapeutic approach, potentially allowing the repurposing of established medications for treating advanced tumors.

Conclusion: Neuromodulation offers a promising therapeutic option for advanced prostate cancer, particularly NEPC, which faces limited treatment options. However, further research is necessary to fully understand the neural regulatory mechanisms involved in prostate cancer development and to identify new therapeutic targets and strategies for advanced stages.

Background: Oligometastatic hormone-sensitive prostate cancer (omHSPC) represents a favorable and potentially curable disease state in which metastasis-directed therapy (MDT) improves outcomes. The combination of MDT and systemic treatment is the next frontier of omHSPC.

Objective: To review and synthesize current evidence from prospective trials evaluating MDT alone or combined with systemic therapy in synchronous and metachronous omHSPC, and to highlight the evolving role of advanced imaging, genomics, and ongoing efforts in refining treatment strategies.

Methods: This review synthesizes data from prospective trials, meta-analyses, and ongoing studies assessing MDT in omHSPC. Key trials include STOMP, ORIOLE, EXTEND, RADIOSA, and the X-MET meta-analysis, with emphasis on clinical outcomes and biomarkers RESULTS: In metachronous omHSPC, STOMP and ORIOLE phase II trials demonstrated that MDT significantly improves progression-free survival (PFS) and delays androgen deprivation therapy (ADT) compared to observation. The EXTEND and RADIOSA trials suggest combining MDT with short-term ADT further improves outcomes. The X-MET meta-analysis confirmed benefits in PFS, radiographic PFS, and castration-resistance-free survival with MDT. No randomized trial has yet evaluated MDT with current standard of care ADT + androgen receptor pathway inhibitor (ARPI) therapy, though EXTEND did include a limited subset of patients receiving ARPI. Advanced imaging, especially PSMA-PET, is transforming MDT planning by enabling more accurate lesion detection than conventional imaging. In synchronous omHSPC, the role of MDT remains under investigation in ongoing trials such as TERPS, STAMPEDE2 and START-MET.

Conclusions: MDT offers clinical benefit in metachronous omHSPC, particularly when combined with systemic therapy. Advanced imaging and genomic profiling are critical tools for refining patient selection. Most data stem from phase II studies without ADT + ARPI control groups; larger randomized trials are needed to define the role of MDT in standard practice and optimize personalized care strategies.