Prostate Cancer最新文献

Background: Prostate cancer is the second leading cause of cancer death among men, with a disproportionate burden on Black men. Racial disparities in care delivery for early-stage disease are well documented but less is known about racial gaps in advanced prostate cancer care, a stage where effective therapies can prolong life for years. We sought to evaluate potential treatment disparities among Black and White men with metastatic prostate cancer.

Methods: We performed a retrospective cohort study of patients with metastatic prostate cancer receiving treatment at a large public tertiary care health system between 2015 and 2020 using electronic health record data. We estimated the prevalence ratio (PR) of being prescribed each of the recommended treatment options for metastatic prostate cancer as per National Comprehensive Care Network guidelines, including androgen receptor pathway inhibitors (ARPIs) and other antiandrogens, chemotherapy, and bone protection, comparing Black men to White men.

Results: We identified 1166 patients with metastatic prostate cancer treated with androgen deprivation therapy (ADT); 370 (32%) were Black. Prescribing of systemic treatments did not differ by race, notably including ARPI (PR: 0.98 95% CI: 0.98-1.1, p=0.8). About 30% of both Black and White patients interacted with our patient navigation team, a group of oncology nurses focused on ensuring patients receive recommended care.

Conclusions: In a large public tertiary care health system, we did not observe racial disparities in the prescribing of guideline-recommended therapies for metastatic prostate cancer. High rates of insurance, a robust patient navigation program, and a well-developed pharmacy assistance program may have helped mitigate racial disparities in care. Future studies should prospectively evaluate the delivery of prostate cancer therapies across health systems and the influence of navigation and pharmacy assistance programs.

Objectives: To assess the validity of magnetic resonance imaging-determined tumor contact area (MRI-TCA) as a predictive factor for pathological extraprostatic extension (EPE) in cT2N0M0 prostate cancer patients.

Methods: We retrospectively analyzed 72 cT2N0M0 prostate cancer patients who underwent multiparametric MRI (mpMRI) followed by robot-assisted laparoscopic prostatectomy (RARP) between February 2014 and April 2021. Patients whose MRI-based index lesion did not match the pathological specimens were excluded. MRI-TCA was approximated using an elliptical shape and calculated by two different methods: MRI-TCA1: Calculated using the tumor contact length (TCL) in the axial plane and the longer TCL in either the sagittal or coronal plane, capturing tumor dimensions across two planes. MRI-TCA2: Calculated using the TCL in the axial plane and tumor thickness derived from MRI slice data, reflecting the tumor's contact area within the MRI volume. We compared postoperative prostate-specific antigen (PSA) recurrence-free survival by stratifying patients based on the optimal thresholds of MRI-TCL, MRI-TCA1, MRI-TCA2, pathological-TCL, and pathological-TCA.

Results: Sixteen patients (22.2%) were pathologically positive for EPE. MRI-TCL, MRI-TCA1, and MRI-TCA2 were significantly greater in patients with EPE-positive (EPE+) tumors than in those with EPE-negative (EPE-) tumors (p < 0.0001, p < 0.0001, and p = 0.0026, respectively). No statistically significant differences were found between MRI-TCL and MRI-TCA1 (p = 0.914) or between MRI-TCL and MRI-TCA2 (p = 0.112) in predicting pathological EPE. A significant difference in postoperative PSA recurrence rate was observed in the stratified analysis based on pathological-TCA (p = 0.022).

Conclusion: Both MRI-TCA1 and MRI-TCA2 are clinically accessible and effective parameters for predicting pathological EPE in cT2N0M0 prostate cancer patients. However, neither method demonstrated clear superiority over MRI-TCL. Pathological-TCA was shown to be a significant predictor of both pathological EPE and postoperative PSA recurrence.

Prostate cancer is the most frequently diagnosed tumor of male reproductive system. Clinically, there is a lack of effective treatment drugs for prostate cancer. Previous studies have shown that AMPK inhibitor dorsomorphin was demonstrated to have potent antitumor effects. However, the effect of dorsomorphin on prostate cancer and its molecular mechanism are still unclear. In this study, the effects of dorsomorphin on the invasion and infiltration, epithelial-mesenchymal transition (EMT), and angiogenesis were investigated in two types of prostate cancer cells (DU145 and PC-3). In addition, nude mouse tumorigenic experiments were performed to confirm the antitumor effect of dorsomorphin. We found that dorsomorphin treatment concentration- and time-dependently inhibited the invasion and infiltration of DU145 and PC-3 cells. In addition, dorsomorphin reduced the expression levels of extracellular matrix components and angiogenesis-related proteins (HIF-1α and VEGF). Further study showed that dorsomorphin inhibited matrix deposition by antagonizing the EMT. Our results from nude mouse tumorigenic experiments further demonstrated dorsomorphin's tumor-growth inhibitory effect, whereas its antimetastatic potential is supported by in vitro invasion and EMT assays. Mechanistically, dorsomorphin treatment suppressed TGF-β1 expression and thereby inhibited the phosphorylation and nucleation of Smad2/3 signaling, which plays a key role in the regulation of EMT. Further study showed that dorsomorphin-triggered inactivation of JAK2/STAT3 and sonic hedgehog (Shh) signaling was involved in the inhibition of TGF-β1-mediated EMT. Interestingly, dorsomorphin inhibited the expression and nucleation of Gli1 and Gli3 but not affected the expression of Gli2. Thus, these findings reveal that the new mechanism of AMPK inhibitor dorsomorphin against prostate cancer metastasis is through synergistically antagonizing JAK2/STAT3 and Gli2-independent Shh activation.

Background: Fibroblast growth factor receptor 1 (FGFR1) signaling is activated by fibroblast growth factors (FGFs) during prostate cancer (PCa) progression. However, the mechanisms by which FGFR1 signaling regulates PCa progression are not fully understood. The objective of this study was to investigate the cross talk between autocrine FGF/FGFR1 loop and aerobic glycolysis in progression of advanced PCa. Method: DU145 cells were used as an advanced PCa model. FGFR1 expression was knockdowned by stable expression of anti-FGFR1 shRNA, and lactate dehydrogenase A (LDHA) levels were rescued by ectopic expression of LDHA cDNA. Protein expression was determined using Western blotting and immunohistochemistry. Tumorigenicity of DU145 cells was defined by cell growth, invasion, and survival in both cultures and xenografts in mice. Results: Here, we showed that DU145 cells in cultures expressed both FGF2 and FGFR1, and knockdown of FGFR1 expression or inactivation of FGFR1 signaling reduced LDHA expression or aerobic glycolysis, which was correlated with suppression of both cell proliferation and invasion, and with promotion of apoptosis. Ectopic expression of LDHA cDNA rescued LDHA levels in FGFR1-deficient cells, restoring their aerobic glycolysis, cell growth, and survival. Similarly, the growth rates of xenografted DU145 cells in mice were decreased by the loss of FGFR1 expression but were rescued by the ectopic expression of LDHA. Conclusion: Our data indicate autocrine FGF/FGFR1 signaling regulates aerobic glycolysis in PCa DU145 cells via LDHA, suggesting the potential of targeting FGFs/FGFRs-LDHA for the management of advanced PCa. The regulation of aerobic glycolysis by other growth factors in PCa remains further investigation.

High-intensity focused ultrasound (HIFU) is a noninvasive modality that is gaining prominence for the localized treatment of malignant tumors. Most current HIFU research utilizes mouse tumor models, where selection of appropriate mouse breed is important for conducting thermal ablation experiments on tumors with consistency. In this study, three breeds (NOD/SCID GammaC -/- (NSG), NSG-SGM3 (NSGS), and Homozygote J:NU (Nude); n = 2 per group) originating from Jackson Laboratory were tested for identifying the breed that has sufficient size for conducting HIFU experiments. Tumors were developed using a human PC3 (CRL-1435) prostate cancer cell line and monitored over 5 to 7 weeks. The surface area and volume of the implanted tumors were determined by assuming the tumor having an ellipsoidal shape. At the end of the growth period, NSG mice exhibited 29% larger tumor surface area than NSGS and 58% larger than Nude mice. Similarly, NSG mice had a 55% larger tumor volume than NSGS mice and 100% larger than Nude mice. Therefore, this research established NSG mice as the superior mouse breed for the PC3 cell-induced tumor growth having established size within a reasonable timeline (5-7 weeks). Subsequently, the NSG model with a larger sample size (n = 48) was selected for HIFU ablation, and histopathological analysis revealed a significantly higher number of apoptotic cells in the HIFU-treated tumors compared to controls. This further confirmed the model's suitability for HIFU research. Tumor surface area and volume compared between the tested (n = 2) and selected (n = 48) groups were statistically insignificant (p = 0.78 for surface area and p = 0.60 for volume).

Background: Prostate cancer (PCa) is a prevalent malignancy in men, with increasing incidence and longer wait times for curative surgery, particularly in public health systems. While the impact of surgical wait time (SWT) on oncological outcomes in PCa remains controversial, its influence on patient-reported outcomes has not been thoroughly evaluated. Objective: To assess the impact of SWT on both oncological and psychological outcomes in patients undergoing robot-assisted radical prostatectomy (RARP) for preoperative ISUP grade 2 and 3 PCa. Methods: This retrospective single-center study included patients who underwent RARP for intermediate risk localized PCa between April 2016 and August 2024. Patients were stratified into two groups based on SWT: < 6 months vs. ≥ 6 months. The primary outcome was recurrence-free survival (RFS) for all patients. Secondary outcomes included RFS in a high-risk subgroup defined by pathological features (pT3 stage, seminal vesicle invasion, extracapsular extension, and positive surgical margins), as well as a comparison of functional outcomes between the two groups. Patient-reported outcomes were evaluated using SF-36 (mental and physical components) and the Decision Regret Scale (DRS) at 6 weeks, 3 months, 6 months, and 1 year. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazard models, and comparative tests with p < 0.05 considered significant. Results: 218 patients have been included. RFS did not significantly differ between groups (p=0.98), including among high-risk patients (p=1.00). No significant differences were found in extraprostatic extension, seminal vesicle invasion, positive surgical margins, or ISUP upgrading between groups. Similarly, changes in both SF-36 physical and mental and DRS scores showed no statistically significant differences at all time points. Conclusion: In this cohort of patients with intermediate-risk PCa, SWT beyond 6 months did not adversely affect oncological or health-related quality of life outcomes.

Background: Prostate cancer is the most common malignancy in men. Sestrin2 (SESN2) has antitumor activity against several types of cancers. However, the effect of SESN2 on prostate cancer is not well known. In this study, we showed that SESN2 inhibits human prostate cancer. Materials and Methods: To investigate the contribution of Sestrin2 to prostate cancer, we performed a bioinformatic analysis of the Cancer Genome Atlas database and Gene Expression Profiling Interactive Analysis. Using the Sestrin2 overexpression vector, we identified proliferation, migration, and invasion in prostate cancer cells. Furthermore, the effect of Sestrin2 on autophagy was confirmed by Western blot analysis and immunofluorescence staining. Results: We showed that expression of SESN2 was reduced in prostate cancer tissues and cell lines, and low expression of SESN2 correlated with decreased survival in prostate cancer patients. We have shown that SESN2 inhibits cell viability and cell proliferation-related protein levels in PC3 and DU145 prostate cancer cells. SESN2 inhibited EMT-related protein and migration and invasion levels. SESN2 promoted autophagy by increasing autophagy-related protein levels and LC3-positive cells. SESN2 increased pAMPK and decreased pmTOR protein levels. Furthermore, we used rapamycin, an mTOR inhibitor, to determine whether the AMPK/mTOR signaling pathway regulates autophagy in prostate cancer cells. Conclusion: Our study suggests that SESN2 inhibits prostate cancer cells by inducing autophagy through the AMPK/mTOR signaling pathway. These results indicate that SESN2 might be a novel target for prostate cancer.

Background: Abiraterone acetate is an androgen-receptor pathway inhibitor commonly used for treatment of metastatic prostate cancer. The levels of androgens during treatment with abiraterone acetate with prednisone (AAP) are lower than those achieved by androgen-deprivation therapy only, potentially resulting in a high risk of skeletal muscle loss. Methods: The cohort included 43 patients treated with AAP for metastatic hormone-sensitive prostate cancer or metastatic castration-resistant prostate cancer. To detect and quantify sarcopenia, we utilized standard computer tomography (CT) imaging. Skeletal muscle mass index (SMI) was evaluated by assessing two adjacent axial sections at the level of the L3 vertebra. Results: Sarcopenia at the time of AAP initiation was present in 72.1% of patients. Body mass index (BMI) was inversely associated with the presence of sarcopenia at the time of AAP initiation. There was a statistically significant decrease in SMI over AAP treatment. Age > 75 years and the absence of previous radiotherapy were associated with a higher rate of SMI decrease during AAP therapy. Overall and progression-free survival was not significantly associated with SMI decrease during AAP therapy. Conclusions: SMI decline occurs during AAP treatment for mHSPC and mCRPC, and is more pronounced in patients over 75 years old and those without previous local treatment. There was no statistically significant association between survival outcomes and SMI decline during AAP therapy.

Introduction: Prostate cancer is the second most common cancer among men worldwide. This cancer has become extremely noticeable due to the increase of prostate cancer in Iranian men in recent years due to the lack of marriage and sexual intercourse, as well as the abuse of hormones in sports without any standards. Methods: The histopathology images from a treatment center to diagnose prostate cancer are used with the help of deep learning methods, considering the two characteristics of Tile and Grad-CAM. The approach of this research is to present a prostate cancer diagnosis model to achieve proper performance from histopathology images with the help of a developed deep learning method based on the manifold model. Results: Similarly, in addition to the diagnosis of prostate cancer, a study on the methods of preventing this disease was investigated in literature reviews, and finally, after simulation, prostate cancer presentation factors were determined. Conclusions: The simulation results indicated that the proposed method has a performance advantage over the other state-of-the-art methods, and the accuracy of this method is up to 97.41%.

Background: Prostate cancer (PC) ranks as the third cause of cancer-related deaths among Iranian men. The age-period-cohort (APC) model helps identify critical ages, periods, and high-risk birth cohorts to prevent and control PC. Thus, this research aimed to evaluate the effect of APC on PC mortality in Iran from 1990 to 2021. Method: Our data include the number of PC deaths and population, collected by the Global Burden of Disease (GBD) and categorized by 5-year age groups. We computed average annual percentage changes (AAPCs) and relative risks by using joinpoint regression analysis and APC models, respectively. Results: Crude and age-standardized mortality rates for PC were increasing, with AAPC of 2.254% (95% CI: 2.099% and 2.410%; p < 0.001) and 0.257% (95% CI: 0.088% and 0.428%; p < 0.001), respectively. Furthermore, an increase occurred in both age effect from ages 20-24 years (RR = 0.033; 95% CI: 0.023 and 0.046) to over 95 years (RR = 16.183; 95% CI: 14.702 and 17.814) and the period from 1992 (RR = 0.542; 95% CI: 0.516 and 0.570) to 2021 (RR = 1.892; 95% CI: 1.809 and 1.979). While, the cohort effect demonstrated a lower mortality rate in later born than earlier born (Coef = 2.302 for the < 1901 cohort compared to Coef = -2.249 for the 2002-2006 cohort). Conclusion: Our study indicated that the trend of PC deaths in Iran increased during 1990-2021, and the period effect confirms this. Considering fewer deaths in high-income countries due to the widespread implementation of PSA testing, the occurrence of the aging phenomenon in our country, and the upward trend in deaths related to the age effect, sensitizing people and policymakers to conduct PSA screening seems necessary.