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Dysregulated lipid metabolism is associated with more aggressive pathology and poorer prognosis in prostate cancer (PC). selleckchem The primary aim of the study is to assess the relationship between the plasma lipidome and clinical outcomes in localised and metastatic PC. The secondary aim is to validate a prognostic circulating 3-lipid signature specific to metastatic castration-resistant PC (mCRPC).

Comprehensive lipidomic analysis was performed on pre-treatment plasma samples from men with localised PC (N = 389), metastatic hormone-sensitive PC (mHSPC)(N = 44), or mCRPC (validation cohort, N = 137). Clinical outcomes from our previously published mCRPC cohort (N = 159) that was used to derive the prognostic circulating 3-lipid signature, were updated. Associations between circulating lipids and clinical outcomes were examined by Cox regression and latent class analysis.

Circulating lipid profiles featuring elevated levels of ceramide species were associated with metastatic relapse in localised PC (HR 5.80, 95% CI 3.04-11.1, P = 1 × 10

), earlier testosterone suppression failure in mHSPC (HR 3.70, 95% CI 1.37-10.0, P = 0.01), and shorter overall survival in mCRPC (HR 2.54, 95% CI 1.73-3.72, P = 1 × 10

). The prognostic significance of circulating lipid profiles in localised PC was independent of standard clinicopathological and metabolic factors (P < 0.0002). The 3-lipid signature was verified in the mCRPC validation cohort (HR 2.39, 95% CI 1.63-3.51, P = 1 × 10

).

Elevated circulating ceramide species are associated with poorer clinical outcomes across the natural history of PC. These clinically actionable lipid profiles could be therapeutically targeted in prospective clinical trials to potentially improve PC outcomes.

Elevated circulating ceramide species are associated with poorer clinical outcomes across the natural history of PC. These clinically actionable lipid profiles could be therapeutically targeted in prospective clinical trials to potentially improve PC outcomes.

Targeted radionuclide therapy with Actinium-225-labeled prostate-specific membrane antigen ligands (

Ac-PSMA) has emerged as a promising treatment modality in the management of metastatic castration-resistant prostate cancer (mCRPC). With its high linear energy transfer and short path length,

Ac induces double-stranded DNA breaks and is expected to have excellent efficacy and safety profile. This systematic review was conducted to precisely evaluate the role of

Ac-PSMA radioligand therapy (RLT) in mCRPC.

This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Searches were made using relevant keywords in the PubMed, Embase, and Scopus databases, and articles up to December 2020 were included. Data on efficacy and toxicity were extracted from the individual articles. Random-effects model was used for generating pooled estimates through meta-analysis.

Ten articles comprising 256 patients were included. Overall, 62.8% (95% confidence als are required to establish its therapeutic efficacy and survival benefit vis-à-vis other approved treatment modalities.

225Ac-PSMA RLT is an efficacious and safe treatment option for patients with mCRPC. Future randomized controlled trials are required to establish its therapeutic efficacy and survival benefit vis-à-vis other approved treatment modalities.

In 2004 docetaxel was the first life-prolonging drug (LPD) registered for metastatic castration-resistant prostate cancer (mCRPC) patients. Between 2011 and 2014 new LPDs for mCRPC (cabazitaxel, abiraterone, enzalutamide, and radium-223) were introduced in the Netherlands. The objective of this study is to assess the impact of the introduction of new LPDs on treatment patterns and overall survival (OS) over time.

CRPC patients diagnosed in the years 2010-2016 in the observational, retrospective CAPRI registry (20 hospitals) were included and followed up to 2018. Two subgroups were analyzed treatment-naïve patients (subgroup 1, n = 3600) and post-docetaxel patients (subgroup 2, n = 1355).

In both subgroups, the use of any LPD increased from 57% (2010-2011) to 69% (2014-2015) in subgroup 1 and from 65% (2011-2012) to 79% (2015-2016) in subgroup 2. Chemotherapy as first mCRPC-treatment (i.e., docetaxel) and first post-docetaxel treatment (i.e., cabazitaxel or docetaxel rechallenge) decreased (46-29% and 20-9% in subgroup 1 and 2, respectively), while the use of androgen-receptor targeting treatments (ART) increased from 11% to 39% and 46% to 64% in subgroup 1 and 2, respectively. In subgroup 1, median OS (mOS) from diagnosis CRPC increased from 28.5 months to 31.0 months (p = 0.196). In subgroup 2, mOS from progression on docetaxel increased from 7.9 months to 12.5 months (p < 0.001). After multiple imputations of missing values, in multivariable cox-regression analysis with known prognostic parameters, the treatment period was independent significant for OS in subgroup 1 (2014-2015 vs. 2010-2011 with HR 0.749, p < 0.001) and subgroup 2 (2015-2016 vs. 2011-2012 with HR 0.811, p = 0.037).

Since 2010, a larger proportion of mCRPC patients was treated with LPDs, which was related to an increased mOS.

Since 2010, a larger proportion of mCRPC patients was treated with LPDs, which was related to an increased mOS.Androgen deprivation therapy (ADT) has a deleterious effect on sexual functions and general well-being in men. Despite this evidence, however, patient and couple knowledge about ADT side effects as well as their management is poor. Similar considerations can be made for physician endorsement of management strategies. In this paper, we summarize and critically discuss available evidence regarding the possible associations between ADT and sexual dysfunction as well as the best therapeutical options. Preclinical data show that ADT is associated with penile contractility impairment as well as lower response to phosphodiesterase type 5 inhibitors (PDE5i). Available data indicate that ADT resulted in a five to sixfold increased risk of reduced libido and in a threefold increased risk of ED confirming the main role of testosterone in regulating sexual desire. Despite this evidence, sexuality remains an important aspect of health and well-being for men and their partner. The best therapeutical options depend on patient and couple desires and needs.