Prostate最新文献

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.

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.

Background: Prostatic tissue is richly vascularized by large venous sinuses that may rupture during transurethral resection of the prostate (TURP), which may lead to unwanted functional outcomes and intraoperative bleeding. However, tranexamic acid (TXA) may be a valid strategy to reduce bleeding complications. Thus, we aimed to analyze the efficacy and safety of TXA administration in patients undergoing TURP.

Methods: We systematically reviewed the Medline, Embase, CENTRAL, and clinical trials registry platforms from their inceptions through April 2025 for randomized and quasi-randomized controlled trials with patients undergoing TURP that compared TXA versus placebo or no treatment. A pairwise meta-analysis with random-effects was performed to estimate risk ratios (RR), mean differences (MD) and their 95% confidence intervals (CI).

Results: A total of 13 studies (N = 1140) were included in our synthesis. We found that patients using TXA (mean: 1.20 g/dL) compared to control (mean: 1.79 g/dL) had less reduction in postoperative hemoglobin concentration (MD: -0.58 g/dL, CI -0.95-[-0.22]). Additionally, patients using TXA (mean: 162.3 mL) compared to control (mean: 231.1 mL) had fewer intraoperative blood loss (MD: -68.7 mL, CI -128.73-[-8.67]). We did not find differences between TXA and control when analyzing risk of blood transfusion (RR: 0.71, CI 0.46-1.10), length of stay (MD: -1.50, CI -6.91-3.92), operative time (MD: -9.34, CI -19.40-0.72), or risk of thromboembolic events (RR: 1.15, CI 0.89-1.49). There were, however, differences in intervention protocols and the number of participants in each study, in addition to high heterogeneity in some endpoints.

Conclusion: TXA is associated with lower intraoperative blood loss and higher postoperative hemoglobin concentrations without increasing the risk of thromboembolic events, indicating a valid prophylaxis before TURP. However, further studies should better address the blood transfusion risk and be adequately powered for that purpose.

Background: Cabazitaxel is a taxane agent associated with fewer symptomatic adverse events than docetaxel in treating castration-resistant prostate cancer (CRPC), yet it is typically reserved for post-docetaxel failure. This study assessed whether early switching from docetaxel to cabazitaxel could improve clinical outcomes.

Methods: Beginning in 2019, a treatment approach was adopted wherein patients with CRPC were switched to cabazitaxel after three cycles of docetaxel, regardless of response. Patients who initiated docetaxel between February 2019 and March 2022 were classified as the switch group, while those who started between September 2014 and February 2019 were designated as the historical non-switch group. Chemotherapy duration, number of chemotherapy cycles, and adverse events were compared. Progression-free survival (PFS), time to failure of both taxanes, and overall survival (OS) were analyzed using propensity score matching.

Results: The switch and non-switch groups included 36 and 37 patients, respectively. The switch group received significantly more chemotherapy cycles (p = 0.043) and had a longer cumulative chemotherapy duration (p = 0.035), even when including chemotherapy administered in subsequent lines. The cumulative incidence of peripheral neuropathy was significantly lower in the switch group (p = 0.037). Within the switch group, symptomatic adverse events, including fatigue, anorexia, and alopecia, were significantly reduced after switching to cabazitaxel. PFS was significantly prolonged in the switch group (p = 0.002), although time to failure of both taxanes and OS did not differ significantly between groups.

Conclusions: Early switching to cabazitaxel after three cycles of docetaxel may reduce symptomatic adverse events, including peripheral neuropathy, while enabling longer chemotherapy exposure and improved PFS in patients with CRPC.

Background: To investigate the role of HSD3B1 germline variant (1245C) in hormone therapy outcomes in Chinese prostate cancer (PCa) patients.

Methods: A multi-center observational study was conducted enrolling 785 PCa patients who received primary androgen deprivation therapy (ADT) in China. Genotyping of germline variant and survival data were obtained, and clinical outcomes were analysed using Cox regression models.

Results: The median follow-up time was 31 months. In the entire study cohort, the HSD3B1 variant (1245C) was significantly associated with a shorter time to castration resistance after adjusting for Gleason grade group (dominant model: hazard ratio, HR = 1.62, 95% confidence interval, 95% CI: 1.10-2.40, p = 0.015; additive model: HR = 1.55, 95% CI: 1.12-2.13, p = 0.008). Subgroup analysis (n = 438) with patients receiving only ADT for HSPC revealed a more significant association between the C allele and ADT failure (dominant model: HR = 2.37, 95% CI: 1.49-3.77, p < 0.001; additive model: HR = 1.93, 95% CI: 1.34-2.79, p < 0.001). Among patients who received next-generation hormone therapy after ADT failure, the C allele was associated with poorer abiraterone response (HR = 3.02, 95% CI: 1.07-8.50, p = 0.037); however, no significant change of response from enzalutamide was observed (HR = 0.98, 95% CI: 0.27-3.51, p = 0.972).

Conclusions: The HSD3B1 germline variant (1245C) is linked to earlier ADT failure and diminished efficacy of abiraterone but does not affect enzalutamide in the treatment of PCa patients. These findings underscore its potential as a biomarker to guide personalized treatment in PCa.

Background: Intraductal carcinoma of the prostate (IDC-P) is most often considered a retrograde spread of invasive prostate cancer (PCa) into prostatic ducts, and its presence is associated with a poor prognosis. The aim of our study was to evaluate the differential expression between IDC-P and the associated invasive component and the heterogeneity of expression within IDC-P foci.

Methods: We studied 79 cases of PCa with an intraductal component treated by prostatectomy. TMA blocks were constructed with the intraductal and invasive components and used for immunohistochemical analysis of markers involved in the cell cycle, androgen signaling, hypoxia, DNA repair, and immune checkpoints.

Results: We found a good concordance of expression between both components for ERG, PTEN, p53, and MMR genes, which nevertheless show in some cases a loss restricted to the intraductal component. The expression of Ki67, PD-L1, and GLUT1 was increased in IDP-C compared to the invasive component. Furthermore, spatial heterogeneity was observed in the intraductal component: Ki67, ERG, androgen receptor and p53 were more expressed in the periphery of the lesion, while the expression of PD-L1 and GLUT1 was restricted to the center.

Conclusions: Our results support a relatedness between invasive PCa and IDC-P, and show increased expression of markers related to PCa aggressiveness in the intraductal component. The spatial heterogeneity within IDC-P suggests a higher degree of hypoxia in the center of the lesion. Increased PD-L1 expression and loss of expression of some MMR genes in IDC-P could lead to increased sensitivity to immunomodulatory treatments.

Background: Rezūm therapy is a minimally invasive treatment for male lower urinary tract symptoms (LUTS) related to benign prostatic obstruction (BPO), validated in selected patients through randomized trials. However, its effectiveness in broader real-world populations remains underreported.

Methods: This single-center retrospective study included 110 patients treated with Rezūm between 2020 and 2022. Patients were stratified according to their conformity to the original trial criteria ("pilot" vs. "nonpilot" groups). Functional outcomes, retreatment rates, sexual function and adverse events were analyzed at 24 months.

Results: At 24 months, both groups experienced a significant and sustained reduction in IPSS from baseline, with a median decrease of 18 points (IQR: 15-20) in the pilot group and 19 points (IQR: 16-22) in the non-pilot group (p = 0.2). Improvements in IPSS-QoL, Q_max, and PVR were also significant and comparable between groups. Overall, 23% of patients required retreatment: 24% in the pilot group and 24% in the non-pilot group (p = 0.9), including medical retreatment in 15% and 5%, and surgical retreatment in 8% and 16%, respectively (p = 0.2). No independent predictor of retreatment was identified. Ejaculatory function was preserved in over 90% of patients at 24 months in both groups, and erectile function remained stable throughout follow-up.

Conclusions: Rezūm therapy provides effective, durable symptom relief and preserves sexual function at 2 years, even in patients with larger prostates, prior surgery, or indwelling catheters.

Background and objective: Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive, lethal state of prostate cancer, for which early progression is an indicator of poor prognosis. The ability to predict this progression is of paramount clinical importance for guiding personalized treatment strategies. We aimed to develop and validate a novel machine learning (ML) model to predict early progression (≤ 12 months) to mCRPC and compare its performance against standard ML algorithms.

Methods: This was a retrospective analysis of 172 patients with mHSPC from the publicly available MSK-IMPACT cohort. Inclusion criteria specified patients with mHSPC who had undergone genomic profiling and progressed to mCRPC during follow-up. Patients with incomplete data were excluded. We collected 11 clinical, pathological, and genomic variables. The primary outcome was early progression (≤ 12 months) to mCRPC. Model performance was evaluated using a stratified fivefold cross-validation, with AUC as the primary metric.

Key findings and limitations: A novel Rivality Index (RINH)-based model, adapted from chemoinformatics, demonstrated significantly superior predictive performance (AUC: 0.86) compared to a panel of standard ML algorithms, none of which exceeded an AUC of 0.67. The model achieved an accuracy of 0.74, a sensitivity of 0.70, and a specificity of 0.77. Key limitations include the retrospective design and use of a single-institution data set.

Conclusions and clinical implications: This novel RINH model offers a robust tool for risk stratification in mHSPC patients, capable of personalizing therapeutic strategies. However, external validation in multi-center, prospective cohorts is an essential next step before its consideration as a clinical decision support tool.

Objective: To evaluate the value of circulating free DNA (cfDNA) in prostate cancer (PCa) by cfDNA assay and analysis of plasma and urinary cfDNA fragmentation to determine the usefulness of this parameter for risk staging and tumor progression monitoring.

Materials and methods: A prospective, longitudinal study was conducted with 143 individuals, including a control group and a cohort of patients with PCa at different stages: localized, metastatic hormone-sensitive (mHSPC), and metastatic castration-resistant (mCRPC). Plasma and urine samples were collected to measure the concentration, fluorescence units (FU), and cfDNA fragmentation, correlating them with clinical and pathological variables.

Results: Plasma cfDNA levels were higher in patients with PCa than in control subjects (14.3 ng/mL vs. 4.2 ng/mL, p = 0.04) and even higher in metastatic disease than in localized (20.8 ng/mL vs. 3.6 ng/mL, p < 0.001). The fragmentation size of plasma cfDNA was smaller in metastatic PCa (168.7 base pairs) than in localized PCa (172.8 base pairs, p < 0.001), suggesting that shorter fragments are associated with more aggressive disease. Following systemic treatment, the patients decreased cfDNA levels (8.3 ng/mL vs. 4.9 ng/mL, p = 0.027) and plasma FU (35.2 vs. 12.9, p < 0.001). In urine, differences were only observed in patients who progressed to CRPC than in those who remained HSPC (261.8 ng/mL vs. 43.5 ng/mL, p = 0.046).

Conclusions: The assay and analysis of plasma and urinary cfDNA fragmentation may provide useful biomarkers for PCa diagnosis and follow-up, particularly when differentiating between localized and metastatic disease. These findings are promising, but further research is required to determine their potential utility in clinical risk stratification and treatment monitoring.