Prostate最新文献

Introduction: The 12th Annual 2025 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Deciphering Resistance: Beyond the Androgen Paradigm," was held at the University of California, Los Angeles (UCLA), Luskin Conference Center, in Los Angeles, CA, from June 19 to 22, 2025.

Methods: The CHPCA Meeting is a discussion-focused conference held annually by the Prostate Cancer Foundation (PCF), for in-depth academic analysis of emerging research with the greatest potential to drive new understandings and treatments for prostate cancer. The 2025 CHPCA Meeting included attendance by 79 academic investigators and 39 talks over 8 sessions.

Results: The session topics included: drug discovery in academia, non-apoptotic cell death mechanisms, understanding and overcoming treatment resistance, chromosomal instability (CIN) as a driver of metastasis and treatment resistance, targeting metastatic sites, immunotherapy sensitizers, and optimizing therapy delivery and biomedical engineering.

Discussion: This meeting report summarizes the presentations from the 2025 CHPCA Meeting. We hope that disseminating this information will directly contribute to novel research efforts and improved treatment strategies for patients with prostate cancer.

Background: To evaluate the diagnostic accuracy, procedural feasibility, and clinical outcomes of a novel cystoscopic-guided indocyanine green (ICG) injection technique followed by fluorescence-guided sentinel lymph node dissection (SLND) during robotic-assisted radical prostatectomy (RaRP), hereafter referred to as CysICG-SLND.

Methods: We prospectively enrolled patients with clinically localized prostate cancer (cT1-cT3, cN0) scheduled for RaRP between November 2019 and May 2020. Each patient received cystoscopic-guided intraprostatic injections of ICG, with injection volumes tailored according to prostate size. SLND was performed using the da Vinci Xi Surgical System equipped with near-infrared imaging and followed by a routine extended pelvic lymph node dissection (ePLND). Diagnostic accuracy, procedural complications, and medium-term oncological outcomes were analyzed.

Results: A total of 34 patients were included (risk category: low = 2, intermediate = 11, high = 21). Cystoscopic ICG injection was technically successful in all cases. The overall fluorescence detection rate was 97.1%, with excellent per-patient sensitivity (100%) and negative predictive value (NPV) (100%) across all patients. However, per-node diagnostic performance was moderate (sensitivity 66.7%, specificity 47.8%). Notably, in the high-risk group, per-node performance was modest, with sensitivity, specificity, positive predictive value (PPV), and NPV of 66.7%, 55.2%, 20.5%, and 90.7%, respectively. No metastatic nodes were identified in low-risk and intermediate-risk groups, demonstrating a reliable 100% NPV in these subpopulations. High-risk patients had significantly higher biochemical recurrence (BCR) rates compared to lower-risk groups (p = 0.017). There were no allergic reactions or postoperative complications attributable to ICG.

Conclusions: CysICG-SLND is a feasible, accurate approach for nodal staging in prostate cancer, particularly beneficial in low- to intermediate-risk groups, achieving excellent sensitivity and NPV. Although diagnostic performance is limited in high-risk patients, high per-patient accuracy still supports clinical utility. Larger prospective studies are warranted to validate these results and further elucidate the technique's clinical role.

Background: Plasticity of cancer, including epithelial-mesenchymal transition (EMT), cancer stem cell (CSC) self-renewal, and microenvironmental adaptation, drives metastasis, therapy resistance, and poor outcomes in prostate cancer (PCa). Ion channels and extrachromosomal DNA (ecDNA) have emerged as key drivers of such adaptive processes by influencing signaling, metabolism, and immune interactions.

Methods: We evaluated available evidence on ion channel biology, ecDNA dynamics, and their roles in tumor plasticity and drug resistance in PCa. Further, we analyzed two publicly accessible single-cell RNA-sequencing (scRNA-seq) datasets (primary PCa and castration-resistant PCa) to determine ion channel and transporter expression profiles in tumor and stromal cell populations.

Results: Our analysis showed cell type-specific expression of many ion channels, including KCNJ10, CACNA1H, and CLIC1, and identification of six transporters (SLC25A1, SLC25A10, SLC25A33, SLC25A42, SLC29A2, SLC7A11) strongly enriched in luminal tumor cells. The discovered genes regulate mitochondrial metabolism, redox homeostasis, nucleotide biosynthesis, immune modulation, and resistance to ferroptosis, all contributing to tumor growth. ecDNA facilitates oncogene amplification (e.g., MYC, EGFR), induction of EMT, and immune evasion, driving intratumoral heterogeneity and therapy-resistant clones.

Conclusions: Ion channels and ecDNA are central to the disease progression and treatment resistance of PCa through regulation of EMT, CSC phenotype, and tumor microenvironment (TME) interactions. Targeting the drivers-through ion channel modulators, ferroptosis induction, and ecDNA-targeting interventions (BET/HDAC inhibitors, CRISPR-based methods) offers a promising way to overcome resistance. Integration of multi-omics, and combination treatments will be key to construct precision medicine strategies and improve clinical outcomes in advanced PCa.

Background: To implement "MeinLUKS," an automated e-health follow-up system within the EPIC MyChart portal after radical prostatectomy (RP), and to examine factors influencing portal adoption, as well as functional and oncological outcome differences between users and non-users.

Methods: We retrospectively analyzed men undergoing RP at a tertiary center (January/2022-October/2023). Patients were classified as "users" if they submitted follow-up data via MeinLUKS or "non-users" if monitored through referring physicians. Sociodemographic, clinical, functional, and oncological outcomes were retrieved from institutional registries and included standardized patient-reported outcome measures. Both groups were invited to structured telephone interviews addressing barriers and facilitators of adoption.

Results: Of 274 patients, 128 (47%) used MeinLUKS and 146 (53%) relied on traditional follow-up. Users were younger, more educated, and often urban residents, while oncological characteristics were comparable. Median time to no pad use was not different (11 vs. 28 days, p = 0.3) with similar long-term continence (79% vs. 73% pad-free, p = 0.3). Patient reported sexual function recovery was better among users (56% vs. 36%, p = 0.01). MeinLUKS automatically flagged two biochemical recurrences and unreported complications not identified in routine care. Among 91 interviewees, users emphasized organizational benefits and digital competence, while non-users cited poor onboarding, limited physician advocacy, and interface complexity. Limitations include single-center, retrospective design and non-randomized comparisons.

Conclusions: Automated e-health follow-up improved data completeness, reduced workforce demands, and detected clinically relevant events missed in routine care. Optimizing onboarding, clinician engagement, and usability may increase adoption and enhance quality and efficiency in prostate cancer survivorship care.

Background: The management of mCSPC has improved with the addition of docetaxel and androgen receptor pathway inhibitors (ARPi) to androgen deprivation therapy. However, patient outcomes remain heterogeneous, highlighting the need for practical prognostic models. The Bellmunt risk score, based on ECOG status, hemoglobin, and liver metastases, was developed for urothelial carcinoma, but its role in mCSPC is unclear.

Methods: This retrospective study analyzed 182 mCSPC patients treated with first-line docetaxel or ARPi from 2010 to 2024. Patients were stratified into low- and high-risk groups by the Bellmunt score. Overall survival (OS) was assessed with Kaplan-Meier and Cox models. Subgroup and interaction analyses were performed to evaluate the consistency of the Bellmunt risk score's prognostic value across treatment modalities. The Bellmunt, CHAARTED, and LATITUDE criteria were compared using the concordance index (C-index).

Results: Patients with a low Bellmunt risk score had significantly longer OS than high-risk patients (median OS: 44.4 vs. 14.1 months; p < 0.001). This prognostic effect was consistent in both ARPi and docetaxel subgroups, with no significant interaction between treatment type and Bellmunt score (p-interaction = 0.185). In multivariate analysis, the Bellmunt score remained an independent predictor of OS (HR: 3.13; 95% CI: 1.16-8.43; p = 0.024). The Bellmunt score showed better discriminative ability for OS (C-index: 0.67) than CHAARTED (0.62) and LATITUDE (0.64) criteria. However, the absolute differences in C-index values were modest, and the analysis was restricted to patients with complete data, potentially introducing selection bias.

Conclusion: The Bellmunt risk score appears to offer a practical approach to risk stratification in mCSPC, with promising prognostic value across treatment types. However, its incremental clinical utility over existing criteria is limited, and its role in guiding therapy remains unestablished. These exploratory findings warrant prospective validation.

Background: Survival differs markedly between men with metastatic prostate cancer (mPC) confined to lymph nodes (LNM) versus bone (BM). We examined whether site-specific genomic alterations-and their combinations-explain this disparity and could inform intensity-modulated follow-up or therapy.

Methods: Clinical and targeted-sequencing data for 1011 men with mPC in the cBioPortal for Cancer Genomics registry were analyzed (LNM-only = 622; BM-only = 389). Genes altered in > 5% of tumors (two-sided p < 0.05) were assessed individually and in every possible multigene cluster for associations with overall survival (OS). Survival was evaluated with Kaplan-Meier curves and the difference in restricted mean survival time (dRMST) to pinpoint the first significant curve divergence. Synthetic-lethal (SL) interactions were explored via the SLOAD database.

Results: In total, 18 of 184 profiled genes (9.8%) exceeded the 5% alteration threshold. FOXA1 was enriched in BM, whereas TMPRSS2, ERG, PTEN, ZFHX3, CDK12, and KMT2C were enriched in LNM (p < 0.05). Among 9143 tested gene clusters, 65 were associated with inferior OS; 48 occurred in the LNM subgroup, 17 in the combined cohort, and none in the BM alone. High-risk clusters showed first OS divergence 10-60 months after diagnosis of metastasis. SLOAD identified 615 putative SL pairs involving these genes.

Conclusions: We identified 65 site-specific multigene clusters-chiefly in lymph node-only mPC-that underlie the survival gap between nodal and bone metastases. These signatures suggest a 10-60-month interval that may lend itself for intensity-modulated follow-up. We also discovered hundreds of synthetic-lethal gene-alteration pairs, opening future research opportunities in combinatorial therapeutic targeting.

Background: Chronic inflammation is commonly observed in benign prostatic hyperplasia (BPH) tissue and may contribute to lower urinary tract symptoms (LUTS) as well as disease progression. This study evaluated the efficacy of combining a standardized extract of Serenoa repens (Sr) with alfuzosin versus alfuzosin monotherapy in men with LUTS due to BPH.

Methods: In this prospective Phase III, randomized, multicenter, real-world study, 300 treatment-naïve men with moderate-to-severe LUTS (IPSS > 7) and prostate volume > 30 cc were enrolled. Patients received either alfuzosin 10 mg/day or alfuzosin 10 mg plus HESr 320 mg/day for 12 months. Primary endpoints included changes in IPSS and uroflowmetry (Q_max). Secondary endpoints included quality of life (IPSS-Q8), storage symptoms (IPSS-Q2 and Q4), nocturia (IPSS-Q7), erectile function (IIEF-5), and ejaculatory function (MSHQ-Ej). Outcomes were analyzed using mixed-model ANOVA with post hoc Tukey's tests. Statistical analysis was performed using JMP Pro 14 (SAS Institute Inc.). The protocol was approved by our Ethical Committee Lazio Area 1, Protocol 0949/2023, Rif 7385 on December 12, 2023.

Results: Both treatments significantly improved total IPSS over time (p < 0.0001). Across all time points, combination therapy was associated with consistently lower IPSS scores, demonstrating a significant time-by-treatment interaction (p = 0.007). Nocturia improved significantly over time (p < 0.0001); the combination group showed greater benefit from Month 3 onward (p = 0.006), though the main treatment effect was not statistically significant (p = 0.076). Q_max improved in both groups (p < 0.0001), with a significant time-treatment interaction (p = 0.006), but no significant main effect of treatment type (p = 0.113). A mild but significant decline in IIEF-5 was observed in both groups over time. Treatment adherence exceeded 86% in both arms.

Conclusions: The combination of HESr and alfuzosin was significantly more effective than alfuzosin monotherapy in relieving LUTS, with greater benefits from Month 3 onward. Q_max and nocturia also showed greater, although mild, improvements with combination therapy. Sexual function outcomes were comparable between groups. High adherence and real-world applicability support the clinical value of this combination in managing BPH-related LUTS.

Background: The prognostic value of the PSA ELIMination rate constant K (PRO-KELIM) score was investigated in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with novel androgen receptor inhibitors.

Methods: This multicenter retrospective study included 160 patients diagnosed with prostate adenocarcinoma between 2011 and 2024 who received enzalutamide or abiraterone during the mCSPC and had at least three PSA measurements within the first 100 days of treatment. The patients were categorized into favorable (PRO-KELIM ≥ 1.0) and unfavorable (PRO-KELIM < 1.0) groups. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier survival analysis and Cox regression.

Results: Median PFS was significantly higher in the favorable group than in the unfavorable group (not reached vs. 40.0 months, p < 0.001). The estimated 2-year PFS rates in the favorable and unfavorable groups were 78% and 52%, respectively. In multivariate analyses, a high PRO-KELIM score (HR 2.99; 95% CI 1.35-6.66, p = 0.007) and good initial response to treatment (p = 0.001) were independent favorable prognostic factors for PFS. The median OS did not differ significantly between the groups (p = 0.27). PRO-KELIM score was not an independent prognostic factor for OS (p = 0.76).

Conclusion: These findings suggest that the PRO-KELIM score can be a valuable prognostic tool in the mCSPC to assess early treatment response and predict disease progression.

Purpose: The limited resolution of standard transrectal ultrasound (TRUS) has made it difficult to perform biopsies of the prostate bed in cases of suspected local recurrence following radical prostatectomy. The aim of this study was to benchmark the performance of using high resolution micro-ultrasound (microUS) in place of standard TRUS for performing post-prostatectomy biopsies.

Materials and methods: We conducted a retrospective review of pathology reports from January 2013 to October 2024, identifying patients who underwent biopsies of the prostate bed for suspected local recurrence after radical prostate. Sensitivity and specificity were compared for biopsies performed using standard TRUS. A biopsy was deemed diagnostic if it revealed prostate tissue (cancerous or benign) or non-prostatic tissue when a previously suspicious lesion was no longer detectable on subsequent imaging. The ground truth for local recurrence was defined by biochemical recurrence (prostate-specific antigen [PSA] ≥ 0.2 ng/mL in two consecutive measurements) accompanied by reproducible findings in the prostate bed on MRI and/or PET.

Results: Of the 24 patients included, 10 (42%) underwent microUS-guided biopsy and 14 (58%) underwent TRUS-guided biopsy. The median PSA levels at biopsy for the microUS and TRUS cohorts were 0.39 ng/mL (range 0.39-6.40) and 0.45 ng/mL (range 0.20-30.82), respectively. The median lesion sizes on MRI were 0.9 cm (IQR 0.7-1.8) for microUS and 2.5 cm (IQR 1.2-6) for TRUS. MicroUS demonstrated a sensitivity of 89% (95% CI: 52-100), compared with 43% (95% CI: 18-71) for TRUS. Specificity could not be reliably assessed, as only one recurrence-negative patient was available in the microUS group and none in the TRUS group.

Conclusion: MicroUS-guided transrectal biopsies appear to offer superior diagnostic performance in detecting local recurrences following radical prostatectomy compared to standard TRUS-guided biopsy. Further study is needed to confirm our findings and to evaluate the performance of microUS-guided biopsies independently of pre-biopsy imaging results.

Background: Prostate cancer (PCa) is the most common solid organ cancer in men and the fifth leading cause of cancer-related deaths globally. PSA helps identify men at risk but has low specificity and has resulted in unnecessary biopsies. The PROSTest, a novel machine learning-based 27-gene mRNA liquid biopsy assay, was developed to detect PCa. We evaluated its utility as a stratification tool in symptomatic men undergoing biopsy or surgery for PSA > 2 ng/mL.

Methods: Of 123 men assessed, 105 (85%) met eligibility criteria (age > 55 years, PSA > 2 ng/mL, symptomatic) and underwent image-guided biopsy or surgery. Blood samples for PROSTest were collected prebiopsy, and RNA-stabilized samples underwent RNA isolation and cDNA production. PCR results were analyzed using a machine learning algorithm, generating a 0-100 score with a cutoff of 50 for a binary (positive/negative) readout. The performance of PROSTest was against PSA using AUROC and evaluated for Gleason Grade (GG) 1 versus GG2-5 patients.

Results: Median age was 68 years (55-86 years); median PSA was 8.2 ng/mL (IQR: 7.2-92 ng/mL). PCa was diagnosed in 65 men (62%) (27 GG1; 38 GG2-5). PROSTest was positive in 63/65 (97%) of those with PCa and in 2/40 (5%) without PCa. Sensitivity was 97%, specificity 96%. PROSTest outperformed PSA (AUROC: 0.99 vs. 0.61, p < 0.0001). GG2-5 had significantly higher (p < 0.0001) PROSTest scores (92 ± 3).

Conclusions: PROSTest demonstrated superior sensitivity and specificity compared to PSA for detecting prostate cancer across all Gleason grades. Additionally, it showed potential for distinguishing GG2-5 from GG1 + BPH, which could help guide clinical decision-making and reduce unnecessary biopsies. By leveraging a machine learning-based approach, PROSTest may offer a more accurate and less invasive diagnostic tool for prostate cancer stratification. However, larger prospective studies are needed to validate these findings and further define its clinical utility.