Prostate最新文献

Background: Genomic prostate score (GPS) may aid clinical decision-making for active surveillance. We assessed whether GPS adds predictive value beyond established clinical variables for adverse pathology at radical prostatectomy (RP) in active surveillance-eligible patients.

Methods: We retrospectively analyzed 387 men with National Comprehensive Cancer Network very-low- to favorable intermediate-risk prostate cancer who underwent Oncotype DX testing followed by RP without active surveillance. Multivariable logistic regression models were constructed to develop prediction models for adverse pathology at RP (Grade Group ≥ 3 and/or ≥ pT3a), including clinical variables (age, PSA, PSA density, biopsy Grade Group 2 [vs. 1], and PI-RADS 4/5) with and without GPS. Model performance was assessed using the AUC with 10-fold cross-validation and compared using DeLong's test, continuous net reclassification improvement (NRI), and decision curve analysis. The incremental predictive value of GPS was also separately evaluated in very low/low-risk and favorable intermediate-risk subgroups.

Results: GPS independently predicted adverse pathology (p < 0.001). The addition of GPS increased the AUC from 0.69 to 0.73 (ΔAUC = 0.036; 95% CI: 0.006-0.065; p = 0.018) and improved reclassification (NRI 0.41, 95% CI: 0.20-0.61). Decision curve analysis demonstrated added net benefit at intermediate threshold probabilities (0.40-0.70), with limited benefit at low thresholds (0.0-0.40). Improvement was significant in the favorable intermediate-risk subgroup (ΔAUC = 0.039; 95% CI: 0.011-0.124; p = 0.026) but not in the very low/low-risk subgroup (ΔAUC = 0.018; 95% CI: -0.043-0.049; p = 0.20). Surgical selection bias was the main limitation.

Conclusions: In this RP cohort, GPS modestly improved prediction of adverse pathology beyond PSA density and MRI, with clinical utility primarily in favorable intermediate-risk patients, where treatment decisions between active surveillance and definitive therapy are uncertain. These findings suggest selective, risk-adapted application of GPS to guide treatment decision-making. Validation in prospective, diverse cohorts is warranted.

Background: As no randomized study has compared abiraterone acetate (ABI) doublet and triplet therapy, the optimal target for the add-on of docetaxel (DTX) to ABI doublet therapy remains unclear. The present study explored patients who may benefit from add-on DTX using initial prostate-specific antigen (PSA) reduction after ABI doublet therapy.

Methods: We retrospectively reviewed 233 patients with CHAATED high-volume metastatic castration-sensitive prostate cancer (mCSPC) treated with ABI doublet therapy. Using the initial PSA half-life calculated by PSA reduction within 6 weeks of treatment (initial PSA^T1/2), a subgroup of patients with a poor overall survival (OS) was explored. The optimal cutoff value of PSA^T1/2 predicting a PSA decline < 90% after 12 weeks of ABI treatment was investigated using a receiver operating characteristic (ROC) analysis.

Results: A PSA^T1/2 of 0.33 months was an ideal cutoff value for predicting a PSA decline < 90% after 12 weeks of ABI treatment. In addition to Grade Group 5 (hazard ratio [HR]: 3.06, p = 0.002) and an LDH ≥ 250 U/L (HR: 2.30, p = 0.017), an initial PSA^T1/2 ≥ 0.33 months (HR: 3.39, p < 0.001) were identified as significant predictors of a poor OS in mCSPC treated with ABI doublet therapy. Only liver metastasis was significantly associated with an initial PSA^T1/2 of ≥ 0.33 months.

Conclusion: We showed that the initial PSA^T1/2 of treatment was significantly prognostic in high-volume mCSPC patients treated with ABI doublet therapy. Our findings suggest that initial PSA reduction may help identify patients who will benefit from the addition of DTX. A prospective study is required to verify our hypotheses.

Introduction: In real-world practice in Japan, standard treatment for metastatic hormone-naïve prostate cancer (mHNPC) is androgen deprivation therapy (ADT), administered as monotherapy, combined androgen blockade (CAB), ADT plus androgen receptor pathway inhibitors (ARPIs), or ADT plus docetaxel. In a previous interim analysis of the large-scale, longitudinal, multicentre, J-ROCK registry study of real-world clinical and patient-reported outcomes, ADT plus ARPI or ADT plus docetaxel was used more frequently than ADT/CAB in patients (aged ≥ 20 years) with newly diagnosed LATITUDE-criteria high-risk mHNPC.

Methods: This post hoc analysis of the J-ROCK study evaluated prostate-specific antigen (PSA) response, progression-free survival (PFS), time to castration-resistant prostate cancer (CRPC), overall survival (OS) and safety in patients with high-risk mHNPC who received ADT/CAB (cohort 1) or ADT plus ARPI (cohort 2B) in subgroups were defined according to the following known prognostic factors at baseline: age, Gleason Grade Group (GGG), alkaline phosphatase (ALP), hemoglobin (Hb) and lactate dehydrogenase (LDH).

Results: This analysis included 947 evaluable patients (371 in cohort 1 and 576 in cohort 2B). PSA response rates remained similar among age and GGG subgroups in both cohorts, but were reduced in cohort 2B patients with elevated ALP, low Hb, and elevated LDH. Time to CRPC and OS were longer in cohort 2B than in cohort 1, regardless of prognostic factors. Among patients with poor prognosis (older, high GGG, low Hb, elevated LDH), OS decline occurred earlier in cohort 1 versus cohort 2B. A trend towards a plateau in the time to CRPC curve was observed in both cohorts, even in patients with poor prognosis. Safety data were not affected by prognostic factors or treatment.

Conclusions: These findings suggest that novel ADT plus ARPI regimens for LATITUDE-criteria high-risk mHNPC may improve real-world outcomes compared with ADT monotherapy or CAB, particularly among patients with poor prognosis.

Background: To question the necessity of simultaneous benign prostatic obstruction (BPO) intervention with cystolitholapaxy in patients with bladder stone (BS) due to BPO and to investigate the factors predicting secondary intervention.

Methods: A total of 235 male patients over 40 years of age who underwent cystolitholapaxy, had a follow-up period longer than 12 months, and were thought to have BS secondary to BPO were included in the study.

Results: A total of 190 patients who did not require additional intervention were defined as Group 1, and 45 patients who required secondary intervention were defined as Group 2. Secondary surgical intervention was required at a rate of 19.5% with an average follow-up of 49 months. Mean peak urine flow rate (Q_max) was 11 m/s in Group 1 and 8.6 m/s in Group 2 (p < 0.001), postvoid residual urine volume (PVR) was 85.5 mL in Group 1 and 115.3 mL in Group 2 (p < 0.001), International Prostate Symptoms Score (IPSS) was 16.7 in Group 1 and 21.7 in Group 2 (p < 0.001). Total prostate volume (TPV) (p = 0.015) and serum prostate-specific antigen (PSA) (p = 0.005) were also significantly higher in Group 2. In the multivariable Cox proportional hazards regression analysis of factors predicting secondary intervention in patients undergoing cystolitholapaxy, low Q_max (hazard ratio (HR) = 0.905, 95% confidence interval (CI): 0.821-0.997, p = 0.043), high PVR (HR = 1.014, 95% CI: 1.007-1.022, p < 0.001), high IPSS (HR = 1.178, 95% CI: 1.106-1.255, p < 0.001) and high PSA (HR = 1.086, 95% CI: 1.000-1.178, p = 0.05) were found to be predictors.

Conclusions: In patients with BS secondary to BPO, performing cystolitholapaxy offers a high likelihood of avoiding secondary intervention. Low Q_max, high PVR, high IPSS, and high PSA are indicators of a higher risk of secondary intervention in the preoperative period. Therefore, in a patient-centered approach, these predictors should be taken into account when deciding whether BPO surgery is necessary in addition to cystolitholapaxy.

Background: Amyloid bodies (corpora amylacea) are found in the prostate and other organs, and their abnormal accumulation can lead to amyloidosis. However, it remains unclear how the constituents and pathological significance of amyloid bodies differ between tissues.

Methods: We performed pathological, proteomic, and biochemical analyzes of prostatic amyloid bodies isolated from 53 consecutive patients who underwent pathological autopsy at Kumamoto University from 2006 to 2017. Amyloid bodies were isolated using laser microdissection, and their constituents were analyzed by liquid chromatography-tandem mass spectrometry, immunohistochemistry, and immunoblotting.

Results: Prostatic amyloid bodies were found in samples from 47 of the 53 patients (89%). The most frequently detected proteins were lactoferrin (100%), S100-A9 (90.9%), prostate-specific antigen (90.9%), and cytoskeleton-associated protein 2-like (90.9%). Amyloid-associated proteins, such as apolipoprotein E (72.7%), vitronectin (54.5%), and serum amyloid P component (36.4%), were also present but were less prevalent. Prostatic amyloid bodies were more common in patients with benign prostatic hyperplasia (N = 25) than in other patients (N = 28).

Conclusions: These results suggest that amyloid bodies from different tissues may share some constituents. Our findings support further investigation to determine the relationship between the constituents of prostatic amyloid bodies and the pathophysiology of prostatic diseases.

Background: Dogs spontaneously develop prostate carcinoma (PC) and share prostate gland anatomy, physiology, and size to men. Over the last 15 years, we have developed and refined a canine model of focal PC to evaluate therapeutic-diagnostic (theranostic) interventions. A comprehensive description of the pathology and synthesis of the various studies has not been performed. The goal of this manuscript was to describe the canine model tumor pathology within the framework of its methodological development to help guide future translational PC research.

Methods: In published and unpublished studies, we previously inoculated prostate glands of immunosuppressed, intact beagle dogs (n = 56) with a canine PC cell line (Ace-1) transduced with human or canine genes for targeted theranostics. Gross tumor assessment and histology were performed in all cases. Molecular tumor and microenvironmental pathology was investigated using digital image analysis, immunohistochemistry, laser-capture microdissection, and quantitative real-time PCR.

Results: The model reliably (85.7% engraftment rate) formed prostatic tumors resembling intermediate and high-grade localized PC, with poorly differentiated morphology, stromal invasion, and peripheral growth. Soft tissue metastasis occurred in 13/48 (27.1%) dogs. Most dogs formed multifocal prostatic tumors with occasional tumors outside the prostate gland. Tumor location influenced growth behavior and the microenvironment. Allografts were histologically classified as intraglandular intraprostatic, invasive intraprostatic, capsular, or extraprostatic. Compared to intraprostatic tumors, capsular/extraprostatic tumors had increased proliferation (Ki-67 index), epithelial-to-mesenchymal transition, and microenvironmental alterations that included increased collagenous stroma, fibroplasia, and reduced immune cell infiltration.

Conclusions: The canine model of PC captured important pathologic features of men undergoing curative-intent therapy alongside model- and species-specific characteristics of interest to researchers. Beyond defining pathology, the results highlighted applications of the canine model in studying the tumor microenvironment and advancing preclinical, anti-cancer strategies in a large animal species.

Background: There is a complex relationship between body weight and survival in prostate cancer. While increased BMI is associated with increased prostate cancer incidence and death, obesity is associated with improved survival in metastatic castrate-resistant prostate cancer (mCRPC). However, little is known about the effect of weight change before the treatment of mCRPC on survival. We assessed the association between BMI, weight loss before treatment, PSA levels, and overall survival in mCRPC.

Methods: Veterans treated with abiraterone or enzalutamide for de novo mCRPC from May 2011 to June 2017 were identified within the VHA. BMI and weight loss in the year before treatment were determined. Kruskal-Wallis, χ² tests, ANOVA, Kaplan-Meier, and Cox proportional hazard modeling tests were used to assess the association between BMI, weight loss, PSA at the start of treatment, and overall survival, with covariates including age, race, and Charlson Comorbidity Index.

Results: We identified 8857 veterans treated for mCRPC with weight loss values available and 8438 patients with BMI values available. There was shorter survival in veterans with weight loss > 10% of body weight (median = 9.8 months, n = 1332) compared with 5%-10% loss (median = 16.1 months, n = 1619) and stable weight (median = 25.1 months, n = 5906). Mean PSA levels increased (106.3, 160.0, 267.8) as BMI decreased (BMI > 30, BMI 25-30, BMI < 25), respectively. As weight loss increased (stable weight vs. weight loss 5%-10% vs. weight loss > 10%), mean PSA levels increased (112.2, 205.8, 405.9), respectively. Compared with a stable weight, both losing 5%-10% of weight (HR: 1.30, 95% CI: 1.22-1.38) and losing > 10% of weight (HR: 1.98, 95% CI: 1.85-2.12) are independently associated with increased mortality. Analyses in subgroups revealed BMI > 30 with stable weight to be the most favorable group in terms of survival, while BMI < 25 with > 10% weight loss had the highest mortality risk (HR: 2.63, 95% CI: 2.39-2.89).

Conclusion: Weight loss the year before treatment is associated with increased mortality and higher PSA levels in patients with mCRPC. The effect of weight loss is independent of BMI, where we found that lower BMI is associated with increased mortality and higher PSA levels in patients with mCRPC. This risk increases with the magnitude of weight loss, with lower BMI categories compounding the risk. Both weight loss and BMI should be incorporated into survival models to improve prognostication in mCRPC.

Background: Prostate cancer (PCa) diagnosis is often hindered by the need to detect clinically significant disease (csPCa) while minimizing unnecessary biopsies. The Prostate Health Index (PHI) and multiparametric magnetic resonance imaging (mpMRI) are promising tools to address these challenges.

Objective: To develop and internally validate a predictive model for PCa and csPCa by combining PHI and mpMRI in a high-risk population.

Methods: This retrospective study included 179 patients who underwent prostate biopsy between 2019 and 2023. Inclusion criteria comprised elevated PSA (> 3 ng/mL), suspicious digital rectal examination and/or family history, PHI values, and pre-biopsy mpMRI. Logistic regression models were developed, and model performance was assessed using C-statistics, calibration plots, and decision curve analysis (DCA).

Results: PCa was diagnosed in 40.2% of patients, and csPCa in 34.7% of them. A multivariate model including PHI, prostate volume, and mpMRI achieved an AUC of 0.81 for PCa. For csPCa, the best model combined PHI and prostate volume (AUC 0.76). In the PI-RADS 3 subgroup, PHI showed high discriminatory performance (AUC 0.81), surpassing PSA density (PSA-D). The DCA showed a superior net benefit of the multivariable models compared to single-parameter strategies.

Conclusion: Integrating PHI and mpMRI improves PCa diagnostic accuracy and clinical decision-making, especially in ambiguous cases such as PI-RADS 3 lesions, and reduces unnecessary biopsies in clinical practice.

Background: Salvage radiotherapy (RT) is a standard treatment for non-metastatic prostate cancer recurrence after radical prostatectomy (RP), yet the efficacy of concurrent hormone therapy remains debated. This systematic review and meta-analysis evaluates the impact of adding hormone therapy to adjuvant or salvage RT on key survival outcomes.

Methods: We searched PubMed, Scopus, Web of Science, and clinical trial registries for randomized phase 2 or 3 trials comparing RT alone versus RT with hormone therapy (anti-androgens or androgen deprivation therapy) in patients undergoing RP. A random-effects meta-analysis with the inverse variance method was performed for overall survival (OS), metastasis-free survival (MFS), and progression-free survival (PFS) after extracting the corresponding hazard ratios (HR) and 95% confidence intervals (CI).

Results: Four trials with generally low risk of bias were identified. Pooled HRs were 0.85 (95% CI: 0.72-0.99) for OS, 0.82 (95% CI: 0.70-0.96) for MFS, and 0.58 (95% CI: 0.51-0.66) for PFS, favoring hormone therapy. Following a sensitivity analysis that excluded the results of one of the four trials, the significance for OS was no longer observed.

Conclusion: Hormone therapy with post-RP RT significantly improves OS, MFS, and PFS in prostate cancer patients. Although the benefit in OS appears less robust, these findings support the significant role of hormone therapy in delaying disease progression. PROSPERO Registration Number: CRD42024597336.