Bladder cancer has been successfully treated with immunotherapy, whereas prostate cancer is a cold tumor with inadequate immune-related treatment response. A greater understanding of the tumor ...microenvironment and methods for harnessing the immune system to address tumor growth will be needed to improve immunotherapies for both prostate and bladder cancer. Here, we provide an overview of prostate and bladder cancer, including fundamental aspects of the disease and treatment, the elaborate cellular makeup of the tumor microenvironment, and methods for exploiting relevant pathways to develop more effective treatments.
We sought to 1) assess the association of radiomics features based on multiparametric magnetic resonance imaging with histopathological Gleason score, gene signatures and gene expression levels in ...prostate cancer and 2) build machine learning models based on radiomics features to predict adverse histopathological scores and the Decipher® genomics metastasis risk score.
We retrospectively analyzed the records of 64 patients with prostate cancer with a mean age of 64 years (range 41 to 76) who underwent magnetic resonance imaging between January 2016 and January 2017 before radical prostatectomy. A total of 226 magnetic resonance imaging radiomics features, including histogram and texture features in addition to lesion size and the PI-RADS™ (Prostate Imaging Reporting and Data System) score, were extracted from T2-weighted, apparent diffusion coefficient and diffusion kurtosis imaging maps. Radiomics features were correlated with the pathological Gleason score, 40 gene expression signatures, including Decipher, and 698 prostate cancer related gene expression levels. Cross-validated, lasso regularized, logistic regression machine learning models based on radiomics features were built and evaluated for the prediction of Gleason score 8 or greater and Decipher score 0.6 or greater.
A total of 14 radiomics features significantly correlated with the Gleason score (highest correlation r = 0.39, p = 0.001). A total of 31 texture and histogram features significantly correlated with 19 gene signatures, particularly with the PORTOS (Post-Operative Radiation Therapy Outcomes Score) signature (strongest correlation r = -0.481, p = 0.002). A total of 40 diffusion-weighted imaging features correlated significantly with 132 gene expression levels. Machine learning prediction models showed fair performance to predict a Gleason score of 8 or greater (AUC 0.72) and excellent performance to predict a Decipher score of 0.6 or greater (AUC 0.84).
Magnetic resonance imaging radiomics features are promising markers of prostate cancer aggressiveness on the histopathological and genomics levels.
Objectives
To develop a nomogram for predicting side‐specific extracapsular extension (ECE) for planning nerve‐sparing radical prostatectomy.
Materials and Methods
We retrospectively analysed data ...from 561 patients who underwent robot‐assisted radical prostatectomy between February 2014 and October 2015. To develop a side‐specific predictive model, we considered the prostatic lobes separately. Four variables were included: prostate‐specific antigen; highest ipsilateral biopsy Gleason grade; highest ipsilateral percentage core involvement; and ECE on multiparametric magnetic resonance imaging (mpMRI). A multivariable logistic regression analysis was fitted to predict side‐specific ECE. A nomogram was built based on the coefficients of the logit function. Internal validation was performed using ‘leave‐one‐out’ cross‐validation. Calibration was graphically investigated. The decision curve analysis was used to evaluate the net clinical benefit.
Results
The study population consisted of 829 side‐specific cases, after excluding negative biopsy observations (n = 293). ECE was reported on mpMRI and final pathology in 115 (14%) and 142 (17.1%) cases, respectively. Among these, mpMRI was able to predict ECE correctly in 57 (40.1%) cases. All variables in the model except highest percentage core involvement were predictors of ECE (all P ≤ 0.006). All variables were considered for inclusion in the nomogram. After internal validation, the area under the curve was 82.11%. The model demonstrated excellent calibration and improved clinical risk prediction, especially when compared with relying on mpMRI prediction of ECE alone. When retrospectively applying the nomogram‐derived probability, using a 20% threshold for performing nerve‐sparing, nine out of 14 positive surgical margins (PSMs) at the site of ECE resulted above the threshold.
Conclusion
We developed an easy‐to‐use model for the prediction of side‐specific ECE, and hope it serves as a tool for planning nerve‐sparing radical prostatectomy and in the reduction of PSM in future series.
Benign prostatic hyperplasia (BPH) is the most common urologic disease in aging males, affecting 50% of men over 50 and up to 80% of men over 80 years old. Its negative impact on health-related ...quality of life implores further investigation into its risk factors and strategies for effective management. Although the exact molecular mechanisms underlying pathophysiological onset of BPH are poorly defined, the current hypothesized contributors to BPH and lower urinary tract symptoms (LUTS) include aging, inflammation, metabolic syndrome, and hormonal changes. These processes are indirectly influenced by circadian rhythm disruption. In this article, we review the recent evidence on the potential association of light changes/circadian rhythm disruption and the onset of BPH and impact on treatment.
A narrative literature review was conducted using PubMed and Google Scholar to identify supporting evidence. The articles referenced ranged from 1975 to 2023.
A clear relationship between BPH/LUTS and circadian rhythm disruption is yet to be established. However, common mediators influence both diseases, including proinflammatory states, metabolic syndrome, and hormonal regulation that can be asserted to circadian disruption. Some studies have identified a possible relationship between general LUTS and sleep disturbance, but little research has been done on the medical management of these diseases and how circadian rhythm disruption further affects treatment outcomes.
There is evidence to implicate a relationship between BPH/LUTS and circadian rhythm disruptions. However, there is scarce literature on potential specific link in medical management of the disease and treatment outcomes with circadian rhythm disruption. Further study is warranted to provide BPH patients with insights into circadian rhythm directed appropriate interventions.
The recent outbreak of infections and the pandemic caused by SARS-CoV-2 represent one of the most severe threats to human health in more than a century. Emerging data from the United States and ...elsewhere suggest that the disease is more severe in men. Knowledge gained, and lessons learned, from studies of the biological interactions and molecular links that may explain the reasons for the greater severity of disease in men, and specifically in the age group at risk for prostate cancer, will lead to better management of COVID-19 in prostate cancer patients. Such information will be indispensable in the current and post-pandemic scenarios.
Inflammation is involved in regulation of cellular events in prostate carcinogenesis through control of the tumour micro‐environment. A variety of bone marrow‐derived cells, including CD4+ ...lymphocytes, macrophages and myeloid‐derived suppressor cells, are integral components of the tumour micro‐environment.
On activation by inflammatory cytokines, NF‐κB complexes are capable of promoting tumour cell survival through anti‐apoptotic signalling in prostate cancer (PCa). Positive feedback loops are able to maintain NF‐κB activation.
NF‐κB activation is also associated with the metastatic phenotype and PCa progression to castration‐resistant prostate cancer (CRPC).
A novel role for inhibitor of NF‐κB kinase (IKK)‐α in NF‐κB‐independent PCa progression to metastasis and CRPC has recently been uncovered, providing a new mechanistic link between inflammation and PCa. Expansion of PCa progenitors by IKK‐α may be involved in this process.
In this review, we offer the latest evidence regarding the role of the NF‐κB pathway in PCa and discuss therapeutic attempts to target the NF‐κB pathways. We point out the need to further dissect inflammatory pathways in PCa in order to develop appropriate preventive measures and design novel therapeutic strategies.
TMPRSS2-ERG gene fusions occur in 50% of prostate cancers and result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG product. Previous attempts to detect truncated ...ERG products have been hindered by a lack of specific antibodies. Here, we characterize a rabbit anti-ERG monoclonal antibody (clone EPR 3864; Epitomics, Burlingame, CA) using immunoblot analysis on prostate cancer cell lines, synthetic TMPRSS2-ERG constructs, chromatin immunoprecipitation, and immunofluorescence. We correlated ERG protein expression with the presence of ERG gene rearrangements in prostate cancertissues using a combined immunohistochemistry(IHC) and fluorescence in situ hybridization (FISH) analysis. We independently evaluated two patient cohorts and observed ERG expression confined to prostate cancer cells and high-grade prostatic intraepithelial reoplasia associated with ERG-positive cancer, as well as vessels and lymphocytes (where ERG has a known biologic role). Image analysis of 131 cases demonstrated nearly 100% sensitivity for detecting ERG rearrangement prostate cancer, with only 2 (1.5%) of 131 cases demonstrating strong ERG protein expression without any known ERG gene fusion. The combired pathology evaluation of 207 patient tumors for ERG protein expression had 95.7% sensitivity and 96.5% specificity for determining ERG rearrangement prostate cancer. Ir conclusion, this study qualifies a specific anti-ERG antibody and demonstrates exquisite association between ERG gene rearrangement and truncated ERG protein product expression. Giver the ease of performing IHC versus FISH, ERG protein expression may be useful for molecularly subtypirg prostate cancer based or ERG rearrangement status and suggests clinical utility it prostate needle biopsy evaluation.
Androgen receptor signaling plays a critical role in prostate cancer pathogenesis. Yet, the regulation of androgen receptor signaling remains elusive. Even with stringent androgen deprivation ...therapy, androgen receptor signaling persists. Here, our data suggest that there is a complex interaction between the expression of the tumor suppressor miRNA, miR-31, and androgen receptor signaling. We examined primary and metastatic prostate cancer and found that miR-31 expression was reduced as a result of promoter hypermethylation, and importantly, the levels of miR-31 expression were inversely correlated with the aggressiveness of the disease. As the expression of androgen receptor and miR-31 was inversely correlated in the cell lines, our study further suggested that miR-31 and androgen receptor could mutually repress each other. Upregulation of miR-31 effectively suppressed androgen receptor expression through multiple mechanisms and inhibited prostate cancer growth in vivo. Notably, we found that miR-31 targeted androgen receptor directly at a site located in the coding region, which was commonly mutated in prostate cancer. In addition, miR-31 suppressed cell-cycle regulators including E2F1, E2F2, EXO1, FOXM1, and MCM2. Together, our findings suggest a novel androgen receptor regulatory mechanism mediated through miR-31 expression. The downregulation of miR-31 may disrupt cellular homeostasis and contribute to the evolution and progression of prostate cancer. We provide implications for epigenetic treatment and support clinical development of detecting miR-31 promoter methylation as a novel biomarker.
Prostate cancer is diagnosed mostly in men over the age of 50 years, and has favorable 5-year survival rates due to early cancer detection and availability of curative surgical management. However, ...progression to metastasis and emergence of therapeutic resistance are responsible for the majority of prostate cancer mortalities. Recent advancement in sequencing technologies and computational capabilities have improved the ability to organize and analyze large data, thus enabling the identification of novel biomarkers for survival, metastatic progression and patient prognosis. Large-scale sequencing studies have also uncovered genetic and epigenetic signatures associated with prostate cancer molecular subtypes, supporting the development of personalized targeted-therapies. However, the current state of mainstream prostate cancer management does not take full advantage of the personalized diagnostic and treatment modalities available. This review focuses on interrogating biomarkers of prostate cancer progression, including gene signatures that correspond to the acquisition of tumor lethality and those of predictive and prognostic value in progression to advanced disease, and suggest how we can use our knowledge of biomarkers and molecular subtypes to improve patient treatment and survival outcomes.
Abstract Background Positive surgical margins (PSMs) are a known risk factor for biochemical recurrence in patients with prostate cancer (PCa) and are potentially affected by surgical technique and ...volume. Objective To investigate whether radical prostatectomy (RP) modality and volume affect PSM rates. Design, setting, and participants Fourteen institutions in Europe, the United States, and Australia were invited to participate in this study, all of which retrospectively provided margins data on 9778 open RP, 4918 laparoscopic RP, and 7697 robotic RP patients operated on between January 2000 and October 2011. Outcome measurements and statistical analyses The outcome measure was PSM rate. Multivariable logistic regression analyses and propensity score methods identified odds ratios for risk of a PSM for one modality compared with another, after adjustment for age, preoperative prostate-specific antigen, postoperative Gleason score, pathologic stage, and year of surgery. Classic adjustment using standard covariates was also implemented to compare PSM rates based on center volume for each minimally invasive surgical cohort. Results and limitations Open RP patients had higher-risk PCa at time of surgery on average and were operated on earlier in the study time period on average, compared with minimally invasive cohorts. Crude margin rates were lowest for robotic RP (13.8%), intermediate for laparoscopic RP (16.3%), and highest for open RP (22.8%); significant differences persisted, although were ameliorated, after statistical adjustments. Lower-volume centers had increased risks of PSM compared with the highest-volume center for both laparoscopic RP and robotic RP. The study is limited by its nonrandomized nature; missing data across covariates, especially year of surgery in many of the open cohort cases; lack of standardized histologic processing and central pathology review; and lack of information regarding potential confounders such as patient comorbidity, nerve-sparing status, lymph node status, tumor volume, and individual surgeon caseload. Conclusions This multinational, multi-institutional study of 22 393 patients after RP suggests that PSM rates might be lower after minimally invasive techniques than after open RP and that PSM rates are affected by center volume in laparoscopic and robotic cases. Patient summary In this study, we compared the effectiveness of different types of surgery for prostate cancer by looking at the rates of cancer cells left at the margins of what was removed in the operations. We compared open, keyhole, and robotic surgery from many centers across the globe and found that robotic and keyhole operations appeared to have lower margin rates than open surgeries. How many cases a center and surgeon do seems to affect this rate for both robotic and keyhole procedures.
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