Prostate最新文献

Background: The efficacy of abiraterone acetate varies among patients with high-risk metastatic castration-sensitive prostate cancer (mCSPC). Both androgen receptor (AR) and cytokeratin 18 (CK18) are markers of the luminal lineage of prostate cancer, and their expression levels have been suggested to affect the response to androgen deprivation therapy (ADT). This study aimed to predict the efficacy of abiraterone acetate in high-risk mCSPC via immunohistochemical staining of biopsy specimens obtained at the time of prostate cancer diagnosis.

Methods: We retrospectively analyzed 44 patients treated with abiraterone acetate in combination with ADT. AR and CK18 expression in prostate biopsy specimens were assessed using immunohistochemical staining.

Results: AR and CK18 staining was not significantly associated with overall survival (OS). However, low AR staining was significantly associated with a shorter time to castration-resistant prostate cancer (TTCRPC) compared with high AR staining (log-rank test, p = 0.018). Similarly, low CK18 staining was significantly associated with a shorter TTCRPC compared with high CK18 staining (log-rank test, p = 0.037).

Conclusions: Immunohistochemical analysis of AR or CK18 expression in biopsy specimens may serve as a predictive biomarker of high-risk mCSPC treated with abiraterone acetate.

Trial registration: None.

Background: Prior studies have concentrated exclusively on how different prostate-specific antigen (PSA) levels affect the prognosis of high-grade prostate cancer (PCa), often overlooking the prognosis of low-grade PCa.

Methods: The present cohort study included individuals diagnosed with PCa from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2021. The all-cause mortality (ACM) and prostate cancer-specific mortality (PCSM) for each treatment group was calculated stratified by the four PSA levels (≤ 4.0, 4.1-10.0, 10.1-20.0, and > 20.0 ng/mL). Fine and Gray competing-risks analyses were conducted to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Cox proportional hazards regression analyses using PSA as a continuous variable with restricted cubic splines (RCS) were conducted to allow for potential nonlinear relationships.

Results: This study encompassed 416,825 male patients diagnosed with PCa. Compared to individuals with PSA value between 4.1 and 10.0 ng/mL, a significant association between low levels of PSA (≤ 4.0 ng/mL) and an increased risk of ACM (AHR = 1.15, 95% CI: 1.12-1.19; p < 0.001) and PCSM (AHR = 1.49, 95% CI: 1.38-1.61; p < 0.001) was observed. Additionally, the increased risk of ACM (AHR = 1.35, 95% CI: 1.29-1.40; p < 0.001) and PCSM (AHR = 1.84, 95% CI: 1.67-2.02; p < 0.001) are more pronounced within the first 5 years post-diagnosis. In most subgroups, similar results were observed. The RCS curves further corroborated the correlation between PSA value and the risk of mortality.

Conclusion: Low PSA levels are notably linked to a heightened risk for both ACM and PCSM, irrespective of the grade of PCa being high or low. There is a need to initiate new studies that tackle novel diagnostics and therapeutics.

Objective: A number of susceptibility genes in prostate tissue have been identified to be associated with prostate cancer (PCa) risk. However, the reported genes based on assessing prostate tissue could not fully explain PCa genetic susceptibility. It is believed that genes functioning in the immune system may fill in the gap of some missing heritability.

Methods: To study potential susceptibility genes acting in such pathways, we performed a transcriptome-wide association study (TWAS) of 79,194 PCa cases and 61,112 control of European ancestry by using three sets of gene expression prediction models of blood tissue.

Results: A total of 470 genes were associated at false discovery rates-corrected p-value < 0.05, of which 51 were implicated as likely causal genes based on fine-mapping analysis. Compared with previous literature, 133 novel genes were reported for the first time. Of the identified genes, five (CREB3L4, GSTP1, MAPK3, NKX3-1, and PIK3C2B) were enriched in a PCa signaling pathway, and 128 genes were enriched in five PCa categories. Importantly, 13 genes (SCP2, LMNA, ZNF148, H2AFV, TACC1, FLII, SUPT4H1, CD300LF, MYO9B, COX6B1, CTSA, EP300, and TSPO) showed consistent effect directions for the measured levels in circulating immune cells between PCa cases and controls, and 14 genes (SLC39A1, ZBTB7B, TRIM59, NCEH1, N4BP2, TAGAP, TACC1, TRAF1, AIP, SECTM1, C18orf54, ZNF793, YIF1B, and TSPO) showed consistency for levels in blood exosomes between PCa patients and controls.

Conclusion: The identified blood-based candidate susceptibility genes provide further insights into the genetic basis of PCa risk.

Introduction: We aim to critically assess Microultrasound (mUS) clinical performance in an outpatient setting, focusing on its ability to reduce unnecessary diagnostic procedures, potentially reshape prostate cancer (PCa) diagnostic protocols, and increase the ability to rule out clinically significant (Gleason Score ≥ 3 + 4) PCa (csPCa).

Materials and methods: Between November 2018 and April 2022, we conducted a prospective study involving men who underwent mUS examination due to clinical symptoms, PSA elevation, or opportunistic early detection of PCa. Experienced urologists performed mUS assessments in an outpatient setting using the prostate risk identification using micro-ultrasound (PRI-MUS) protocol to identify lesions suspicious of csPCa (PRI-MUS score ≥ 3). Men with negative mUS results were followed through consistent phone follow-up calls and visits until October 2023 to assess their diagnostic and therapeutic pathways. Using Cox regression models adjusted for PSA levels, DRE results, age, and previous biopsy history, we calculated the hazard ratio (HR) for biopsy-free (BFS), defined as the time from mUS to biopsy or last follow-up, cancer-free survival (CFS), and clinically significant cancer-free survival (csCFS) within the cohort based on mUS results.

Results: Overall, 425 men were enrolled. The median (IQR) age was 66 (59-72) years, PSA levels were 5.7 (4.0-7.9) ng/mL, prostate volume was 44 (31.5-62.1) mL, and the median follow-up was 39 months (27-53). mUS identified lesions suggesting csPCa in 201/425 (47.3%) men. Overall, mUS resulted negative in 224/425 (52.7%) men, of whom 207/224 (92.4%) did not undergo subsequent mpMRI, while 22/224 (9.8%) proceeded with mpMRI according to the referring physician's decision. The latter detected suspicious lesions in 12/22 cases (54.5%), but only 2/12 (16.7%) were confirmed by biopsy as csPCa. Among those with negative mUS results, 192/224 (85.7%) men avoided additional biopsies during follow-up. Men with negative mUS results exhibited superior BFS (aHR: 0.17; p < 0.001), CFS (aHR:0.12; p < 0.001), and csCFS (aHR:0.09; p < 0.001) survival rates compared to their mUS-positive counterparts.

Conclusions: Our findings suggest that mUS can potentially refine patient stratification and transform PCa screening and diagnostic protocols. Pending validation by other studies, a wider implementation of mUS could optimize resource allocation, minimize wastage, and reserve additional costly tests.

Introduction: PSA screening remains a pivotal tool for early prostate cancer (PCa) detection. International guidelines rely on evidence from three major randomized clinical trials: ERSPC, PLCO, and CAP. We aim to examine the percentage of patients in real-world practice who get PSA screening as defined by each of the aforementioned trials. Moreover, we seek to evaluate if the different PSA screening patterns have a different impact on PCa incidence and its features at diagnosis.

Materials and methods: Our institutional database was queried to identify men aged 55-69 who received at least one PSA test, did not develop PCa or die within 6 years of the initial test, had follow-up within our system at least 6 years after the initial test, and did not have a previous PCa diagnosis. A total of 28,612 patients met our selection criteria. We categorized patients into three distinct PSA screening patterns based on testing frequency (PLCO: 1 PSA test per year for 6 years; ERSPC: 2 or 3 PSA tests over 6 years; CAP: 1 PSA test over 6 years). Our primary outcomes were any PCa incidence and clinically significant PCa (csPCa, defined as ISUP ≥ 3) incidence. Secondary outcome was the rate of cM1 disease. Competing risks cumulative incidence curves were used to depict any PCa and csPCa diagnosis with death before a diagnosis considered a competing risk. Multivariable competing risks regression (CRR) was used to assess the impact of the different screening patterns on any PCa and csPCa incidence, after adjusting for confounding factors.

Results: The most prevalent PSA screening pattern was ERSPC, including 15,530 patients (54.3%), followed by the CAP with 9003 patients (31.5%), and the PLCO with only 4079 patients (14.2%). The median (IQR) follow-up time was 4.8 (1.7-10.8) years. At 10 years, any PCa incidence was 7.4% versus 5.6% versus 2.5% for PLCO versus ERSPC versus CAP, respectively, while for csPCa, the rates were 2.5% versus 2.5% versus 1.2% (both p < 0.001). On multivariable analyses, PLCO and ERSPC patterns were associated with 2.92-fold and 2.31-fold higher risks from 1 year to the next of any PCa diagnosis, respectively, compared to CAP pattern (both p < 0.001). Similarly, patients with PLCO and ERSPC patterns had 2.07-fold and 2.31-fold higher risks, respectively, of csPCa diagnosis compared to CAP pattern (both p < 0.001). In men with PCa diagnosis, the rates of cM1 disease were respectively 1.7% vs 5.6% vs 10.8% for PLCO versus ERSPC versus CAP, respectively (p = 0.0009).

Conclusion: We observed that the most common screening pattern in "real-world" clinical practice is close to what ERSPC recommend, and this pattern seems to achieve a reasonable reduction in the risk of advanced PCa, while limiting overdiagnosis.

Background: Metastatic castration resistance prostate cancer (mCRPC) is a challenging disease with a significant burden of mortality and morbidity. Most of the patients attain resistance to the available treatments, necessitating further novel therapies in this clinical setting. Actinium 225 (²²⁵Ac) prostate-specific membrane antigen (PSMA) radioligand therapy has emerged as a promising option and has been utilized for the last decade. Although a few meta-analyses were performed on the efficacy and safety of ²²⁵Ac-PSMA RLT in mCRPC patients, several current studies have been added to the literature since the latest meta-analysis. We aimed to gather all individual studies to perform up-to-date meta-analyses.

Methods: We searched the literature using Pubmed-Medline, Web of Science, Elsevier-Sceince Direct, and Cochrane-Central databases. The data for any PSA decline, over 50% PSA decline, overall survival (OS), progression-free survival (PFS), and toxicity profile were captured from the studies eligible for meta-analysis. We utilized the random effect model to generate pooled estimates.

Results: The sixteen eligible studies contained 1102 patients. Sixty-three percent of patients achieved more than 50% PSA decline, while 82% had any PSA decline after the completion of therapy. The pooled mean OS and PFS were 12.72 months (9.52-15.91) and 11.02 months (6.88-15.15), respectively. The most common adverse event was xerostomia, with a pooled proportion of 84%. Grade ≥ 3 anemia, thrombocytopenia, leucopenia, and nephrotoxicity were encountered in 9%, 5%, 4%, and 4% of the patients.

Conclusions: ²²⁵Ac-PSMA RLT is an efficacious and safe treatment for mCRPC. Future well-designed randomized controlled studies comparing ²²⁵Ac-PSMA RLT with other approved therapeutic options would better comprehend the exact role of this therapy in the treatment sequence of mCRPC.

Introduction: Prostate cancer (PCa) is the most commonly diagnosed cancer in men in the United States, following skin cancer, with an incidence rate of 112.7 per 100,000 men per year. The need for a reliable, non-invasive diagnostic tool for early PCa detection (screening, biochemical residual disease) remains unmet due to the limitations of PSA testing, which often leads to overdiagnosis and overtreatment. The PROSTest is a novel, blood-based qPCR assay that assesses gene expression to diagnose PCa and predict patient outcomes to different treatments. This study aimed to validate the sensitivity and specificity of the PROSTest in a diverse cohort of US-based PCa patients compared to healthy controls.

Materials and methods: This prospective study included 143 PCa patients and 92 healthy controls. Blood samples were collected, and the PROSTest was conducted following RNA isolation and cDNA production, using a predefined 27-gene algorithm to provide a binary output. The assay's sensitivity and specificity were evaluated using receiver operating characteristic (ROC) analysis, with a 50% score cut-off distinguishing PCa from non-PCa patients. Analytical reproducibility was assessed with intra- and inter-assay comparisons of Ct values and PROSTest scores.

Results: The PROSTest demonstrated a sensitivity of 94% (95% CI 89-98%) and a specificity of 88% (95% CI 80-94%) in distinguishing PCa patients from controls, with an area under the ROC curve (AUROC) of 0.97. The false positive rate among controls was 12%. Intra- and inter-assay reproducibility was confirmed with no significant differences in Ct values or PROSTest scores between operators or assays. PROSTest scores were significantly higher in PCa patients compared to controls and in those undergoing treatment versus untreated patients.

Conclusion: This validation study confirms the high sensitivity and specificity of the PROSTest in detecting PCa in a diverse USA cohort. The assay's robustness and reproducibility support its potential as a reliable diagnostic tool for PCa detection and monitoring. Further studies are warranted to evaluate its utility across broader populations and treatment settings.

Background: Differences in the effectiveness of second-generation androgen receptor axis-targeted agents (ARATs) in high-risk metastatic hormone-sensitive prostate cancer (mHSPC) remain unclear. This study aimed to identify the factors influencing the efficacy of ARATs in patients with high-risk mHSPC and compare their long-term effectiveness.

Methods: Four hundred and sixty-six patients with mHSPC treated with ARATs were retrospectively recruited from our hospital and affiliated hospitals of the Kindai Oncology Study Group and Kyoto Prefectural University of Medicine Oncology Study Group between December 2013 and March 2024. Cox proportional hazards analysis was performed to identify prognostic factors for overall survival in patients with mHSPC. Propensity score matching was used to adjust for the differences in clinical backgrounds of the patients.

Results: Univariate and multivariable analyses revealed that Gleason pattern 5 and pretreatment ALP levels were notable prognostic factors for overall survival in patients with mHSPC treated with ARATs. In the subgroup of patients with high-risk mHSPC with Gleason pattern 5, apalutamide and enzalutamide showed significantly better outcomes in terms of PSA-PFS, PFS2, and overall survival compared to abiraterone acetate though selection bias and the small number of patients may be associated with the results in this study. Univariate and multivariable analyses suggested that ARATs selection (ABI vs. APA or ENZ) may serve as an independent predictor of overall survival in patients with high-risk mHSPC with Gleason pattern 5 treated with ARATs.

Conclusion: Gleason pattern 5 may be a predictive factor for ARAT efficacy in patients with high-risk mHSPCs.

Introduction: Prostate cancer (PCa) is the second most common cancer in men worldwide, with significant incidence and mortality, particularly in Mexico, where diagnosis at advanced stages is common. Early detection through screening methods such as digital rectal examination and prostate-specific antigen testing is essential to improve outcomes. Despite current efforts, compliance with prostate screening (PS) remains low due to several barriers. This study aims to develop and validate a predictive model for PCa screening compliance in Mexican men.

Materials and methods: Retrospective observational design with data from the Mexican Health and Aging Study (MHAS). Participants were men aged 50-69 from three cohorts: development/internal validation, temporal validation, and external validation. Key predictors were identified using relaxed Least Absolute Shrinkage and Selection Operator (LASSO) regression, and model performance was assessed using the area under the curve (AUC) from receiver operating characteristic (ROC) analyses, along with calibration and decision curve analysis (DCA). A web nomogram was also developed.

Results: The final model included seven key predictors. AUC values indicated good predictive performance: 0.783 for the training subgroup, 0.722 for the test subgroup, 0.748 for the time cohort, and 0.756 for the external cohort, with sensitivities of 73.5%. The DCA demonstrated the superior clinical utility of the model compared to the reference strategies.

Conclusions: The predictive model developed for performance to PCa screening is robust across different cohorts and highlights critical factors influencing performance. The accompanying web-based nomogram enhances clinical applicability and supports interventions aimed at improving PCa screening rates among Mexican men.

Background: The medication used to treat benign prostate hyperplasia (BPH), a common condition in men over 50 years of age, can alter the levels of biomarkers used in prostate cancer detection. Commonly used medications for BPH include alpha-blockers, 5-alpha reductase inhibitors (5-ARIs), and muscarinic antagonists. We studied the impact of these drugs on total prostate-specific antigen (tPSA), free PSA (fPSA), [-2]proPSA, fPSA/tPSA ratio, and the Prostate Health Index (PHI), as well as novel potential biomarkers in the form of glycan composition of fPSA.

Patients and methods: Serum samples were collected from 564 males with BPH, with a mean age of 68.5 years. The samples were used to measure levels of tPSA, fPSA, and [-2]proPSA. The fPSA/tPSA and PHI were then calculated. The glycan composition of fPSA was analyzed using lectin-based glycoprofiling. Pharmacotherapy data was collected from the patients' medical records.

Results: Alpha-blocker monotherapy was associated with higher fPSA and fPSA/tPSA ratio, and decreased PHI. Levels of tPSA were not impacted. Alpha-blocker and 5-ARI dual therapy was associated with reduced levels of fPSA, [-2]proPSA, and PHI. Therapy combining alpha-blockers and antimuscarinic agents did not significantly influence biomarker levels apart from an increase in a Maackia amurensis lectin-recognized glycan originating in fPSA.

Conclusion: BPH pharmacotherapy notably affects prostate cancer biomarkers. Recognizing the impact of pharmacotherapy is crucial for achieving an accurate diagnosis of prostate cancer and for planning treatment.