Prostate最新文献

Background: The aim of this study is to investigate the relationship between the gut microbial profiles, occurrence of side effects, total testosterone (TS) levels, and pretreatment dietary habits among patients with high-risk localized prostate cancer who were subjected to androgen-deprivation therapy (ADT).

Methods: This prospective study included patients diagnosed with high-risk localized prostate cancer who underwent ADT between March 2021 and August 2022. The correlation between the pre- and post (after 3 months)-ADT gut microbial profiles, laboratory tests, body consumption data, and pretreatment dietary habits was analyzed.

Results: No significant differences were observed in the alpha- and beta-diversities of the gut microbiota during pre- and post-ADT. The relative abundance of genus Ruminococcus 2 (p = 0.013) and genus [Eubacterium] ruminantium group (p = 0.043) were significantly higher during post-ADT compared with those during pre-ADT. Twenty percent of the patients with a post-ADT TS level of < 20 ng/dL had a significantly high proportion of genus Ruminococccus 2, whereas no significant proportion was observed in patients with a TS level of ≥ 20 ng/dL. In terms of the impact of the pretreatment dietary habits on the changes of the gut microbiota, genus Romboutsia and genus Fusicatenibacter showed a positive correlation with n-6 polyunsaturated fatty acid intake, whereas the amounts of genus Ruminococcus 2 and genus Veillonella showed a negative correlation with n-3 polyunsaturated fatty acids.

Conclusions: Short-term ADT was found to increase the proportion of gut genus Ruminococcus 2 in patients with advanced prostate cancer, which was associated with low TS levels and showed a negative correlation with n-3 polyunsaturated fatty acid intake. Further validation is important to identify specific changes in the gut microbiota during ADT in patients with prostate cancer.

Background: Inactivating missense mutations in the tumor suppressor gene speckle-type pox virus and zinc finger protein (SPOP) occur in 5%-15% of men with prostate cancer (PC). SPOP mutations increase androgen receptor-mediated transcription and enhance sensitivity to hormonal therapies. Here we describe the clinical characteristics, outcomes, and mutational patterns in Veterans with SPOP-mutated PC.

Methods: This retrospective cohort was defined as men diagnosed with PC between January 1, 2000 and September, 30 2024 in the Veterans Affairs health care system with an SPOP mutation identified on genomic testing. The primary and secondary outcomes were overall survival (OS) from date of metastasis and metastatic castration-resistant PC (mCRPC) to death or censoring on December 31, 2024, and adjusted for left truncation.

Results: Of 984 Veterans with SPOP-mutated PC, most Veterans (78.4%) received at least one androgen receptor pathway inhibitor (ARPI) and 20.2% received docetaxel. Median OS from date of metastasis (n = 898) was 42.0 mo (95% CI: 38.1-48.2). Median OS from mCRPC diagnosis (n = 425) was 23.5 mo (95% CI: 19.4-29.5). We also identified a subgroup of 114 patients with de novo metastatic hormone-sensitive PC (mHSPC), 96 who received androgen deprivation therapy (ADT) + ARPI (doublet) and 18 who received ADT + ARPI + docetaxel (triplet) as initial therapy. Median OS from diagnosis to death was 48.3 mo (CI not estimable) in the doublet subgroup and not estimable in the triplet subgroup. The most common co-occurring genetic alterations with SPOP in de novo mHSPC were APC (21.9%; 25/114), TP53 (18.4%; 21/114), and PTEN (8.3%; 8/114).

Conclusions: This is the largest cohort of men with SPOP mutations, including those with de novo mHSPC treated with an ARPI, reported to date. Further prospective study of SPOP-mutated PC may help guide which patients with de novo mHSPC may either benefit from or can forego the addition of chemotherapy.

Background: To compare the effectiveness of triplet versus doublet therapy for time to castration-resistant prostate cancer (CRPC) in Japanese patients with high-volume metastatic hormone-sensitive prostate cancer and examine Bayesian integration of external phase III trials.

Methods: We analyzed patients in the YUSHIMA registry with CHAARTED high-volume metastatic hormone-sensitive prostate cancer who started first-line therapy between 2021 and 2024 and received triplet (androgen-deprivation therapy + docetaxel + androgen receptor pathway inhibitor [ARPI]; n = 36) or ARPI-based doublet (androgen-deprivation therapy + ARPI; n = 104). The primary endpoint was time to CRPC. Confounding was addressed using overlap weighting. Weighted Cox models and restricted mean survival time (RMST) were estimated at 12 and 24 months. An exploratory Bayesian power-prior synthesis combined the YUSHIMA likelihood with reconstructed individual patient data from seven trials.

Results: Median follow-up was 23 months; 34 patients progressed to CRPC. Overlap-weighted Cox analysis showed a statistically nonsignificant difference between triplet and doublet therapy (hazard ratio: 0.81, 95% confidence interval: 0.31-2.12). RMST differences (triplet minus doublet) were 0.21 months (95% confidence interval from -0.64 to 1.15) at 12 months and 0.95 months (95% confidence interval from -1.95 to 3.96) at 24 months. Bayesian synthesis analysis with borrowing strength α = 0.5 revealed posterior mean RMST differences of 1.42 and 3.19 months at 12 and 24 months, respectively.

Conclusions: In this propensity-weighted registry analysis, triplet therapy was not demonstrably superior to ARPI-based doublet therapy for time to CRPC. Exploratory Bayesian synthesis suggests a modest CRPC-free RMST advantage with triplet therapy, but inferences depend on external evidence and remain hypothesis-generating.

Background: Benign prostatic hyperplasia (BPH) is a common urologic condition in aging men, often linked to systemic inflammation and metabolic dysfunction. Emerging evidence suggests that the gut microbiome may contribute to prostate health and disease. Here we aim to explore potential associations between gut microbiota composition and clinical parameters, such as prostate volume (PV) and residual bladder volume (RBV).

Methods: This cross-sectional study analyzed stool samples from 28 patients undergoing transurethral surgery. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Patients were stratified into groups based on PV ( ≤ 40 mL vs. > 40 mL) and RBV ( ≤ 100 mL vs. > 100 mL). α-diversity (Chao1 and Shannon indices) and β-diversity (Jaccard distance) were calculated. Linear discriminant analysis effect size (LEfSe) was used to identify differentially abundant taxa between groups.

Results: No significant differences in gut microbial α- or β-diversity were observed between groups stratified by PV or RBV. Nevertheless, several specific bacterial taxa showed significant variation between groups. Methanobrevibacter smithii was markedly less abundant in patients with PV > 40 mL (p < 0.01). Similarly, patients with high RBV ( ≥ 100 mL) exhibited distinct gut microbial profiles compared to those with lower RBV, characterized by a reduced abundance of Collinsella and an increased abundance of Gastranaerophilales (both p < 0.01).

Conclusion: Our findings suggest that while overall gut microbial diversity may remain stable, specific taxa are associated with prostate and bladder phenotypes, supporting the concept of a gut-prostate axis. Future research should focus on longitudinal studies to investigate how gut (and urinary) microbiota evolve alongside BPH and/or LUTS over time, with the goal of determining whether microbial signatures could serve as early indicators for symptomatic BPH.

Background: Further work is needed to improve treatment outcomes for prostate cancer (PCa), with the repurposing of the α₁-adrenoreceptor antagonists presenting a potential solution. This feasibility clinical trial presents the first prospective data of the use of an α₁-adrenoreceptor antagonist in men undergoing radiotherapy for PCa.

Methods: The study enrolled men planned to receive radiotherapy for PCa. Participants received escalating doses of prazosin administered during radiotherapy. Blood pressure was recorded at each radiotherapy fraction. The primary outcome was treatment protocol feasibility and secondary outcomes were maximum tolerated dose (MTD) of prazosin, safety, and progression-free survival (PFS).

Results: Ten participants were enrolled into the study and all achieved > 90% treatment compliance and > 80% assessment compliance. One participant and four participants achieved an MTD of 1 mg and 0.5 mg, respectively, and the remaining five participants had an MTD of 0 mg, with the overall protocol defined MTD being 0 mg. There were no Grades 3/4 adverse events. All treatment-related adverse events (TRAE) were either hypotension or orthostatic hypotension, of the 17 reported TRAEs 16 were asymptomatic. No participants had evidence of disease progression at the 36-week follow-up.

Conclusions: Our study demonstrated that coadministration of prazosin during radiotherapy is feasible. However, the incidence of hypotension resulted in a protocol-defined MTD (under conservative blood pressure based DLT definition) of 0 mg, although 16 of the 17 reports were asymptomatic. Combined with monitoring used in other studies utilizing prazosin, this suggests that our safety monitoring and dose-limiting toxicity (DLT) definition may have been too strict and did not accurately reflect a clinically relevant MTD. As this study achieved its primary aim and demonstrated the feasibility of the administration of prazosin during radiotherapy, further prospective studies are justified, with greater consideration given to the definition of DLTs.

Trial registration: Australian New Zealand Clinical Trials Registry (381954).

Introduction: PSMA-PET offers an opportunity to reduce the mischaracterization of disease in active surveillance (AS) and focal therapy (FT) candidates. We describe the results of a pilot clinical trial evaluating ¹⁸F-radiohybrid(rh)PSMA-7.3-PET/MRI to detect occult adverse pathology among potential AS and FT candidates (NCT05852041).

Methods: We enrolled 20 men with low risk or favorable intermediate risk prostate cancer and Decipher score ≥ 0.45 diagnosed after an MRI-informed prostate biopsy. All patients underwent PSMA-PET/MRI followed by either PET/MRI-guided biopsy or radical prostatectomy within 90 days. The outcome of interest was detection of grade group (GG) 3-5 disease, seminal vesicle invasion (pT3b), or lymph node involvement (pN1). A detection rate of 15% for this outcome was considered clinically significant. Management decisions and confidence in those decisions were recorded before and after the scan using a 3-point scale. A paired t-test was performed to compare the change in confidence decisions.

Results: At enrollment, 17 patients (85%) had favorable intermediate risk and 3 (15%) had low risk prostate cancer. The median Decipher score was 0.58 (IQR 0.49-0.65). Five patients (25%) demonstrated the outcome of interest based on upgrading alone. None had upstaging to pT3b or pN1. Major changes in management plan occurred in 7 patients (35%). Average confidence in decisions improved from moderate (2.05) to high (2.80) after the scan (p < 0.001).

Conclusions: ¹⁸F-rhPSMA-7.3-PET/MRI can detect occult higher risk disease in men who are otherwise candidates for AS or FT. The scan prompted major changes in management and increased confidence in the final treatment strategy.

Background: Radiographic progression (RP) without prostate-specific antigen (PSA) elevation has emerged as a clinically important pattern in the androgen receptor pathway inhibitors (ARPI) era, but its prevalence and prognostic significance in real-world metastatic hormone-sensitive prostate cancer (mHSPC) cohorts remain unclear.

Objective: To assess the prevalence and prognostic implications of RP alone progression in mHSPC patients treated with first-line ARPIs.

Methods: We retrospectively analyzed 518 mHSPC patients treated with abiraterone acetate plus prednisolone, enzalutamide, or apalutamide. PSA progression was defined using PCWG3 criteria. Patients were categorized into PSA progression or RP alone progression groups, and clinical outcomes were compared.

Results: Among 169 patients who developed castration-resistant prostate cancer (CRPC), 34 (20.1%) experienced RP alone. RP alone patients had significantly worse overall survival compared to those with PSA progression (median 21 vs. 39 months, p = 0.007), despite exhibiting deeper biochemical responses-PSA nadir (0.055 vs. 0.86 ng/mL, p < 0.001) and a higher rate of PSA nadir < 0.2 ng/mL (61.8% vs. 27.4%, p < 0.001). The baseline characteristic differing between groups was CHAARTED volume classification; high volume disease was markedly more common in RP alone patients (94.1% vs. 77.8%). In univariate and multivariate analyses of the overall cohort, CHAARTED high volume disease was identified as an independent risk factor for RP alone (HR 10.3, 95% CI 1.20-89.3; p = 0.034).

Conclusion: RP alone progression occurred in approximately one-fifth of patients and was associated with significantly poorer survival despite excellent PSA responses, underscoring the limitation of PSA-based monitoring and supporting routine imaging for early detection of PSA-incongruent disease progression in mHSPC.

Background: Calcitonin (CT) and its receptor promote prostate cancer (PC) progression and metastasis. Identifying downstream CT-regulated genes may provide clinically useful biomarkers.

Methods: Subtraction hybridization was used to identify CT-inducible genes. Expression of zinc finger protein-like 1 (ZFPL1) was examined in malignant versus benign prostate tissues and evaluated for regulation by CT and androgens. Exosomal secretion of ZFPL1 protein was assessed, and plasma levels were measured in PC patients compared with cancer-free individuals. Immunohistochemistry was performed to assess ZFPL1 localization with neuroendocrine (NE) and stem cell markers.

Results: ZFPL1 was strongly expressed in malignant prostates but nearly absent in benign tissues. Its expression was upregulated by both CT and androgens. ZFPL1 protein was secreted through exosomes, and plasma concentrations in PC patients were at least fourfold higher than in cancer-free controls. Immunohistochemistry confirmed ZFPL1 co-localization with NE and stem cell markers, suggesting an association with aggressive, androgen-resistant PC.

Conclusions: ZFPL1 is a CT- and androgen-regulated protein selectively expressed in malignant prostate cells and secreted via exosomes. Its elevated plasma levels and association with aggressive disease highlight its promise as a non-invasive biomarker for PC detection and monitoring.

Background: We previously found that higher insulin resistance (IR) was associated with larger prostate size and greater risk of benign prostatic hyperplasia (BPH). Since BPH is the most common cause of lower urinary tract symptoms (LUTS), we investigated whether IR is also linked to incidence and progression of LUTS in the REDUCE study, a 4-year randomized trial of dutasteride vs. placebo for prostate cancer prevention.

Methods: Participants were required to complete the International Prostate Symptom Score (IPSS) questionnaire at recruitment and every subsequent 6 months. Fasting insulin and glucose levels were measured at study baseline, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated based on these values. Multivariable Cox regression was used to assess associations between HOMA-IR and (1) LUTS incidence among asymptomatic patients (baseline IPSS < 8); or (2) LUTS progression among symptomatic patients (baseline IPSS ≥ 8) respectively.

Results: As previously reported within this cohort, at baseline, higher HOMA-IR quartiles were correlated with larger prostate volumes among both asymptomatic (N = 2745; p < 0.001) and symptomatic patients (N = 1942; p = 0.007). However, among asymptomatic patients, HOMA-IR whether analyzed as a continuous (p = 0.74) or categorized variable (all p ≥ 0.60) was not associated with LUTS incidence in multivariable analysis. Similarly, in symptomatic participants, no associations were found between HOMA-IR and LUTS progression in multivariable analyses, whether HOMA-IR was assessed as a categorical (all p ≥ 0.46) or continuous variable (p = 0.83).

Conclusions: Although IR was linked to larger prostate volumes, it was not an independent risk factor of LUTS development or progression despite the known associations between BPH and LUTS.

Background: Urinary incontinence (UI) remains a common complication after radical prostatectomy, even with advancements such as robotic-assisted radical prostatectomy (RARP). Preoperative membranous urethral length (MUL) has been suggested as a predictor of early continence recovery, but its role in Retzius Sparing RARP (RSRARP) remains unclear. This study evaluated the association between preoperative MUL and early postoperative UI in patients undergoing RSRARP.

Methods: We retrospectively analyzed 157 patients who underwent RSRARP between March 2024 and February 2025 at a high-volume center. All had preoperative multiparametric MRI (mpMRI) with MUL measurements and documented continence outcomes at 6 weeks and 3 months. Continence was defined by pad use: pad-free, mild incontinence (1 pad/day), or moderate-to-severe ( ≥ 2 pads/day). Correlation testing and ordinal logistic regression assessed MUL's predictive value. Secondary analysis included age, BMI, prostate volume, and bladder neck preservation.

Results: At 3 months, 97% of patients were pad-free and 3% used one pad. Mean MUL was 12.6 mm (SD 2.7). No significant correlation existed between MUL and continence (Spearman's ρ = -0.046, p = 0.570). Regression confirmed MUL was not predictive (p = 0.745). Bladder neck preservation strongly correlated with pad-free continence, while larger prostate size trended toward higher UI but without significance.

Conclusions: Preoperative MUL was not identified as a statistically significant predictor of early continence after RSRARP. Bladder neck preservation was associated with favorable continence outcomes; however, given the small number of incontinence events, these findings should be interpreted cautiously. Overall, the high continence rates observed highlight the potential benefit of the Retzius-sparing approach.