Prostate最新文献

Purpose: As the incidence of prostate cancer rises in Asian countries, notable disparities in life expectancy, economic status, and education levels are observed. This study aimed to use the Human Development Index (HDI), which reflects these factors, to explore differences in prostate cancer diagnosis, staging, and initial treatment across various Asian nations and areas, and uncover the impact of socioeconomic factors on patient outcomes.

Methods: We analyzed patients diagnosed with prostate cancer between January 2016 and December 2018 who were enrolled in the Asian Prostate Cancer Study Group (A-CaP). Patients were grouped into three HDI categories (medium, high, very high). A statistical comparison was conducted to evaluate differences in diagnostic methods and initial treatments across 12 Asian countries and areas based on HDI classification.

Results: In total, 35,776 prostate cancer patients were included. Patients in the very high HDI group had lower PSA levels, fewer ISUP Grade 5 cases, and reduced metastatic disease (M1) compared to the other groups. Advanced diagnostic modalities (e.g., CT, MRI, and bone scintigraphy) were more commonly used in the very high HDI group. Imaging modalities were less frequently used in medium HDI countries with low PSA, and in high HDI countries with high PSA. Regarding treatment, patients in very high HDI countries and areas were more likely to receive radiation therapy or active surveillance. Surgical treatment was more common for metastatic patients in high and medium HDI countries and areas.

Conclusion: This study highlights significant differences in prostate cancer management across 12 Asian countries and areas, emphasizing the influence of HDI on diagnostic and treatment outcomes.

Objective: Androgen deprivation therapy (ADT) was the frontline treatment for patients with prostate cancer ineligible for radical prostatectomy. However, the development of resistance to ADT significantly limits its clinical efficacy.

Methods: Using a genome-wide CRISPR/Cas9 knockout (GeCKO) library screen combined with single-cell RNA sequencing (scRNA-seq) analysis, we identified key genes involved in ADT resistance.

Results: Macrophage migration inhibitory factor (MIF) was identified as a critical mediator of ADT resistance. Inhibition of MIF significantly overcomes ADT resistance. Moreover, we found that the androgen receptor (AR), but not its splice variant AR-V7, negatively regulates MIF expression. Consequently, inhibition of the AR signaling pathway via ADT results in the upregulation of MIF expression. Elevated expression of MIF promotes prostate cancer cell proliferation by upregulating AMPD2 expression.

Conclusions: Our findings demonstrate that ADT induces MIF upregulation, which in turn drives prostate cancer cell proliferation via upregulating AMPD2 expression, eventually contributing to the development of resistance to ADT.

Background: Prostate-specific antigen (PSA) remains the standard biomarker for prostate cancer (PCa) detection, but its limited specificity-particularly in the 3-10 ng/mL range-leads to overdiagnosis and unnecessary biopsies. Including multiparameteric MRI (mpMRI) helps to reduce the number of PSA-false-positive biopsies, but there is still a need for noninvasive diagnostics that improve risk stratification and reduce unnecessary interventions.

Methods: PROSTest is a peripheral blood-based assay that quantifies a 27-gene signature in the androgen receptor (AR) signaling pathway in addition to 3 housekeeping genes (HKGs). PCR results are fed into a proprietary machine learning (ML) algorithm to produce a numerical score on a scale of 0-100 with a clinically validated cutoff of 50 for a final binary readout; positive or negative for likelihood of cancer on biopsy. In this report, the diagnostic performance of PROSTest was evaluated in 1,894 male subjects including 970 individuals with actionable results (PSA ≥ 3.0 ng/mL). We focused on two PSA-graded intended-use populations: subjects aged ≥ 45 years with PSA 3-10 ng/mL (n = 467), and those with PSA > 10 ng/mL (n = 503). PSA and PROSTest were conducted on all subjects.

Results: In the 970 cohort, adding the PROSTest achieved an AUC of 0.96 and was significantly more accurate than PSA alone for differentiating PCa from benign prostatic disease (Chi² = 134.1, p < 0.0001). In the 467 subjects with PSA 3-10 ng/mL, the PROSTest achieved an AUC of 0.94, with 94% sensitivity and 91% specificity. The PPV for PROSTest was 91.6% (95%CI: 88.3-94.1%) and NPV was 95.6% (95%CI: 91.6-97.7%). The blood-based gene expression profiling correctly identified 435 of 467 subjects (93.1%) and was significantly more accurate than PSA alone where only 271 of 467 (58.0%) with high PSA had PCa (Chi² = 155.9, p < 0.0001). The sensitivity of the assay for detecting PCa was 97.0% (263/271). In the 503 subjects with PSA > 10 ng/mL, PROSTest yielded an AUC of 0.93 versus 0.76 for PSA (z = 5.3, p < 0.0001). Despite the very high levels of PSA ( > 10 g/mL), 63 (20 BPH and 43 non-BPH controls) out of the 503 (12.5%) subjects were negative for PCa. PROSTest sensitivity was 93.6% (412/440) and the accuracy was 92.8% (467/503). The PPV for PROSTest was 98.1% (95%CI: 96.4-99.0%) and NPV was 66.3% (95%CI: 57.6-74.0%). If PROSTest was used, it would have precluded 55 of the 63 (87.5%) PSA-falsely driven biopsies.

Conclusions: PROSTest demonstrates improved stratification value relative to PSA and could significantly reduce PSA-driven false positive biopsies. Out of 259 non-PCa subjects biopsied based on high PSA levels, applying PROSTest could potentially eliminate 227 biopsies (87.6%). PROSTest superior NPV was not confounded as a tradeoff for the PPV as PROSTest exhibited a sensitivity of ~95% (675/711 PCa detected).

Background: EAU guidelines recommend salvage radical prostatectomy (sRP) only in highly selected patients with recurrent prostate cancer in experienced centers.

Methods: The Junior ERUS/Young Academic Urologist Working Group on Robot-Assisted Surgery conducted a multicentric project to investigate biochemical recurrence-free (BCR), metastases-free (MFS), and overall survival (OS) outcomes in robotic sRP patients stratified according to EAU criteria.

Results: Of 180 patients, 49% fulfilled EAU criteria. Patients not fulfilling EAU criteria more frequently underwent focal therapy as primary treatment (53% vs. 33%) and exhibited significantly higher rates of pT3-4 (70% vs. 48%), positive surgical margins (48% vs. 24%), and pathological Gleason score 8-10 (72% vs. 48%, all p < 0.01), with no differences in postoperative complications. Rates of PSA persistence were significantly higher in patients not fulfilling EAU criteria (16% vs. 0%, p < 0.001). Regarding BCR, patients not fulfilling EAU criteria harbored significantly worse BCR-free survival (hazard ratio (HR): 1.96, p = 0.046) with 24- and 48-month BCR-free survival rates of 81.7% and 73.9% vs. 65.0% and 58.5% for patients fulfilling EAU criteria. After multivariable adjustment, patients not fulfilling EAU criteria harbored higher risk of BCR (HR: 2.94, p = 0.045). Regarding MFS and OS outcomes, no significant differences were observed in the comparison between both groups. Incorporating presalvage surgery features into a new classification yielded better discrimination for BCR analysis, but were comparable to EAU criteria for MFS and OS outcomes.

Conclusions: The majority of patients do not fulfill EAU criteria, and even more so after focal therapy. These patients harbor worse BCR rates after robotic sRP. However, within our short-term follow-up, no differences in MFS and OS were observed.

Background: The response of prostate cancer (PCa) to immunotherapy remains suboptimal. Although MEIS homeobox 2 (MEIS2) has been shown to delay the malignant progression of PCa by inhibiting cancer cell proliferation, promoting DNA damage, and affecting CD8⁺ T cell immune surveillance, its role in immune regulation and the underlying mechanisms remain elusive.

Methods: MEIS2 expression in PCa and its correlation with CD8⁺ T cells were characterized using bioinformatics analysis and cell experiments. Using qPCR, flow cytometry, and ELISA, the impact of MEIS2 on CD8⁺ T cell antitumor immunity was assessed. To delineate the role of MEIS2 in oxidative phosphorylation and ROS generation, OCR, ATP, and ROS measurements were collected. Finally, the oxidative phosphorylation inhibitor MCH32 was introduced and rescue experiments were conducted to elucidate the mechanism by which MEIS2 regulated CD8⁺ T cell cytotoxicity.

Results: MEIS2 expression in PCa was found to be downregulated, positively correlating with CD8⁺ T cell infiltration. Functionally, MEIS2 overexpression enhanced the cytotoxicity of CD8⁺ T cells. Mechanistically, MEIS2 was notably enriched in oxidative phosphorylation and ROS pathways. Knockdown of MEIS2 in cancer cells stimulated oxidative phosphorylation and ROS production, which impaired CD8⁺ T cell antitumor immunity. Treatment with the oxidative phosphorylation inhibitor MCH32 reversed these effects induced by MEIS2 knockdown.

Conclusion: Targeting MEIS2 could represent a clinically relevant approach to enhancing CD8⁺ T cell antitumor efficacy in PCa, our findings indicate.

Background: The diagnostic reliability of magnetic resonance imaging (MRI)/transrectal ultrasound (TRUS) fusion-targeted re-biopsy for prostate cancer (PCa) remains limited. Therefore, additional predictive markers are needed to improve patient selection. This study aimed to identify factors predictive of clinically significant PCa (csPCa) to develop a risk stratification model. The role of systematic biopsies was also investigated.

Methods: We retrospectively analyzed 194 patients who underwent MRI/TRUS fusion-targeted re-biopsies between 2017 and 2024. Lesions were scored according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2.0 or 2.1. Univariate and multivariate logistic regression analyses were conducted to identify predictors of csPCa, defined as Gleason score ≥ 3 + 4. Detection rates for csPCa were compared between groups. The diagnostic contribution of systematic biopsies was assessed separately.

Results: Of the 194 patients, 82 (42.3%) were diagnosed with csPCa. Multivariate analysis identified prostate-specific antigen density (PSAD) ≥ 0.20 (odds ratio (OR): 6.56) and PI-RADS ≥ 4 (OR: 12.38) as independent predictors of csPCa. Based on the PI-RADS category and PSAD, patients were stratified into high-, intermediate-, and low-risk groups. These risk stratification factors led to the classification of 83 (42.8%) patients as high-risk, 77 (39.7%) as intermediate-risk, and 34 (17.5%) as low-risk, with csPCa detection rates of 74.7% (62/83), 24.7% (19/77), and 2.9% (1/34), respectively. Of the 82 patients with csPCa, 21 were diagnosed exclusively via systematic biopsies.

Conclusions: Combining PSAD with PI-RADS improved risk stratification for csPCa in men who underwent MRI/TRUS fusion re-biopsies, while systematic biopsies added diagnostic value. These findings support individualized evidence-based re-biopsy strategies.

Background: Benign prostatic hyperplasia (BPH) is the most common urological disorder of the prostate in aged men. Oxidative stress and environmental factors have been associated with BPH. However, information on infectious agents association with BPH remains scarce. This study aims to determine Escherichia coli (E. coli) infection and virulence gene association with BPH in patients.

Methods: A case-control study was conducted with 61 BPH patients and 52 controls. Prostate volume (PV) was estimated for diagnosis of BPH using abdominal ultrasound. Serum malondialdehyde (MDA) levels were measured, and data on alcohol intake and physical exercise were obtained with questionnaire. E. coli DNA was extracted from urine samples, and targeted 16S rRNA and fimH gene primers were used for PCR amplifications.

Results: Mean difference of PV between patients (55.10 ± 27.37) and controls (26.33 ± 6.37) was statistically significant (p < 0.01). Serum MDA was significantly and positively correlated with PV (p < 0.001). Exercise correlate inversely with prostate volume. Intriguingly, alcohol intake significantly and inversely correlated with PV (p < 0.05). E. coli infection, but not virulence, was associated with an almost 12-fold increased risk of PV (p < 0.01). No fimH gene sequence variation was observed in isolates from patients and controls. However, Ghanaian isolates displayed sequence diversity when compared with isolates from other countries.

Conclusion: Escherichia coli infection, particularly variant carrying the fimH virulence gene, was more frequent among the BPH patients. These findings suggest that E. coli infection should be considered as a key factor in the management of BPH.

Objective: To investigate the application value of Rapid On-Site Evaluation (ROSE) in prostate biopsy.

Methods: All consecutive subjects who attended our clinic to underwent magnetic resonance imaging (MRI)-ultrasound fusion biopsy due to highly suspicious findings on MRI for prostate cancer (PCa) and met the inclusion criteria were enrolled into our prospective study between October 2020 and January 2025. ROSE was performed concurrently in the same operating room with MRI-ultrasound fusion biopsy. For each lesion with Prostate Imaging-Reporting and Data System (PI-RADS) 4-5, one to two additional needle passes were taken for ROSE, in addition to the standard biopsy. The results of ROSE during the biopsy were recorded. The sensitivity, specificity, positive predictive value, and negative predictive value of ROSE were assessed using paraffin-embedded histopathology of the biopsy specimens as the gold standard.

Results: A total of 313 lesions with PI-RADS 4-5 from 147 patients were ultimately included in this study. All biopsies were performed smoothly, with no severe complications occurring postoperatively. 192 lesions were pathologically diagnosed with PCa, yielding a positive detection rate of 61.3% (192/313). With paraffin-embedded histopathology of the biopsy specimens serving as the gold standard, the sensitivity of ROSE for detecting PCa was 71.9% (138/192), specificity was 100% (121/121), accuracy was 82.7% (259/313), positive predictive value was 100% (138/138), and negative predictive value was 69.1% (121/175).

Conclusions: The application of ROSE technology in the diagnosis during prostate biopsy is accurate and reliable, with specificity and positive predictive value both reaching 100%.