Prostate最新文献

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.

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: 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.