Time on treatment with abiraterone in men with de novo metastatic castration sensitive prostate cancer: a drug utilization study

: Prostate cancer is second most common cancer affecting male population all over the world. The existence of a correlation between lipid metabolism disorders and cancer of the prostate gland has been widely known for a long time. According to hypotheses, cholesterol may contribute to prostate cancer progression as a result of its participation as a signalling molecule in prostate growth and differentiation via numerous biologic mechanisms including Akt signalling and de novo steroidogenesis. The results of some studies suggest that increased cholesterol levels may be associated with higher risk of more aggressive course of disease. The aforementioned alterations in the synthesis of fatty acids are a unique feature of cancer and, therefore, it constitutes an attractive target for therapeutic intervention in the treatment of prostate cancer. Pharmacological or gene therapy aimed to reduce the activity of enzymes involved in de novo synthesis of fatty acids, FASN, ACLY (ATP citrate lyase) or SCD-1 (stearoyl-CoA desaturase) in particular, may result in cells growth arrest. Nevertheless, not all cancers are unequivocally associated with hypocholesterolaemia. It cannot be ruled out that the relationship between prostate cancer and lipid disorders is not a direct quantitative correlation between carcinogenesis and the amount of the circulating cholesterol. Perhaps the correspondence is more sophisticated and connected to the distribution of cholesterol fractions, or even sub-fractions of e.g. HDL cholesterol.

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Clinical Translation of Positive Metastases Identified on Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Imaging in the Management of De Novo Synchronous Oligometastatic Prostate Cancer

European Urology Focus ◽

10.1016/j.euf.2020.12.002 ◽

2020 ◽

Author(s):

Martin J. Connor ◽

Suriaya Dubash ◽

Edward J. Bass ◽

Henry Tam ◽

Tara Barwick ◽

...

Keyword(s):

Prostate Cancer ◽

Computed Tomography ◽

De Novo ◽

Emission Tomography ◽

Prostate Specific Membrane Antigen ◽

Computed Tomography Imaging ◽

Tomography Imaging ◽

Positron Emission ◽

Oligometastatic Prostate Cancer ◽

Specific Membrane

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Prognostic Association between Common Laboratory Tests and Overall Survival in Elderly Men with De Novo Metastatic Castration Sensitive Prostate Cancer: A Population-Based Study in Canada

Cancers ◽

10.3390/cancers13112844 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2844

Author(s):

Christopher J. D. Wallis ◽

Bobby Shayegan ◽

Scott C. Morgan ◽

Robert J. Hamilton ◽

Ilias Cagiannos ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Clinical Decision Making ◽

Cox Regression ◽

De Novo ◽

Population Based ◽

Population Based Study ◽

Cox Regression Analysis ◽

Lymphocyte Ratio ◽

Laboratory Markers

De novo cases of metastatic prostate cancer (mCSPC) are associated with poorer prognosis. To assist in clinical decision-making, we aimed to determine the prognostic utility of commonly available laboratory-based markers with overall survival (OS). In a retrospective population-based study, a cohort of 3556 men aged ≥66 years diagnosed with de novo mCSPC between 2014 and 2019 was identified in Ontario (Canada) administrative database. OS was assessed by using the Kaplan–Meier method. Multivariate Cox regression analysis was performed to evaluate the association between laboratory markers and OS adjusting for patient and disease characteristics. Laboratory markers that were assessed include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, hemoglobin, serum testosterone and PSA kinetics. Among the 3556 older men with de novo mCSPC, their median age was 77 years (IQR: 71–83). The median survival was 18 months (IQR: 10–31). In multivariate analysis, a statistically significant association with OS was observed with all the markers (NLR, PLR, albumin, hemoglobin, PSA decrease, reaching PSA nadir and a 50% PSA decline), except for testosterone levels. Our findings support the use of markers of systemic inflammation (NLR, PLR and albumin), hemoglobin and PSA metrics as prognostic indicators for OS in de novo mCSPC.

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Reply to Salma Kaochar, Nicholas Mitsiades’ Letter to the Editor re: Umang Swami, Pedro Isaacsson Velho, Roberto Nussenzveig, et al. Association of SPOP Mutations with Outcomes in Men with De Novo Metastatic Castration-sensitive Prostate Cancer. Eur Urol 2020, 78:652–6. Can Mutant SPOP Become an Actionable Biomarker for Precision Oncology Management of Prostate Cancer?

European Urology ◽

10.1016/j.eururo.2020.12.009 ◽

2021 ◽

Author(s):

Umang Swami ◽

Emmanuel S. Antonarakis ◽

Neeraj Agarwal

Keyword(s):

Prostate Cancer ◽

De Novo ◽

Precision Oncology ◽

Letter To The Editor

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Use of non‐insulin antidiabetic drugs in children and young adults – A Scandinavian drug utilization study from 2010–2019

British Journal of Clinical Pharmacology ◽

10.1111/bcp.14867 ◽

2021 ◽

Author(s):

Helene K. Jensen ◽

Lotte Rasmussen ◽

Kari Furu ◽

Øystein Karlstad ◽

Marie Linder ◽

...

Keyword(s):

Young Adults ◽

Drug Utilization ◽

Antidiabetic Drugs ◽

Drug Utilization Study ◽

Children And Young Adults

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Circulating tumor cell heterogeneity in neuroendocrine prostate cancer by single cell copy number analysis

npj Precision Oncology ◽

10.1038/s41698-021-00211-1 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Vincenza Conteduca ◽

Sheng-Yu Ku ◽

Luisa Fernandez ◽

Angel Dago-Rodriquez ◽

Jerry Lee ◽

...

Keyword(s):

Prostate Cancer ◽

Single Cell ◽

De Novo ◽

Genomic Analysis ◽

Treatment Resistance ◽

Circulating Tumor Cell ◽

Prostate Adenocarcinoma ◽

Neuroendocrine Prostate Cancer ◽

Patient Heterogeneity ◽

Tumor Cell Heterogeneity

AbstractNeuroendocrine prostate cancer is an aggressive variant of prostate cancer that may arise de novo or develop from pre-existing prostate adenocarcinoma as a mechanism of treatment resistance. The combined loss of tumor suppressors RB1, TP53, and PTEN are frequent in NEPC but also present in a subset of prostate adenocarcinomas. Most clinical and preclinical studies support a trans-differentiation process, whereby NEPC arises clonally from a prostate adenocarcinoma precursor during the course of treatment resistance. Here we highlight a case of NEPC with significant intra-patient heterogeneity observed across metastases. We further demonstrate how single-cell genomic analysis of circulating tumor cells combined with a phenotypic evaluation of cellular diversity can be considered as a window into tumor heterogeneity in patients with advanced prostate cancer.

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Health-Related Quality of Life following Cytoreductive Radical Prostatectomy in Patients with de-novo Oligometastatic Prostate Cancer

Cancers ◽

10.3390/cancers13225636 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5636

Author(s):

Michael Chaloupka ◽

Lina Stoermer ◽

Maria Apfelbeck ◽

Alexander Buchner ◽

Vera Wenter ◽

...

Keyword(s):

Quality Of Life ◽

Prostate Cancer ◽

Radical Prostatectomy ◽

De Novo ◽

Health Related Quality ◽

Significant Difference ◽

Related Quality ◽

Health Related

(1) Background: local treatment of the primary tumor has become a valid therapeutic option in de-novo oligo-metastatic prostate cancer (PC). However, evidence regarding radical prostatectomy (RP) in this setting is still subpar, and the effect of cytoreductive RP on postoperative health-related quality of life (HRQOL) is still unclear. (2) Methods: for the current study, patients with de-novo oligo-metastatic PC (cM1-oligo), defined as ≤5 bone lesions in the preoperative staging, were included, and matched cohorts using the variables age, body-mass index (BMI), and pT-stage were generated. Patient-reported outcome measures (PROMS) were assessed pre- and postoperatively using the validated EORTC-QLQ-C30, IIEF-5, and ICIQ-SF questionnaires. The primary endpoint for univariate and multivariable analysis was good general HRQOL defined by previously validated cut-off values. (3) Results: in total, 1268 patients (n = 84 (7%) cM1-oligo) underwent RP between 2012 and 2020 at one tertiary care center. A matched cohort of 411 patients (n = 79 with oligo-metastatic bone disease (cM1-oligo) and n = 332 patients without clinical indication of metastatic disease (cM0)) was created. The median follow-up was 25mo. There was no significant difference in good general HRQOL rates between cM1-oligo-patients and cM0-patients before RP (45.6% vs. 55.2%, p = 0.186), and at time of follow-up (44% vs. 56%, p = 0.811). Global health status (GHS) worsened significantly in cM0-patients compared to baseline (−5, p = 0.001), whereas GHS did not change significantly in cM1-oligo-patients (+3.2, p = 0.381). In multivariate analysis stratified for good erectile function (IIEF5 > 18; OR 5.722, 95% CI 1.89–17.36, p = 0.002) and continence recovery (OR 1.671, 95% CI 1.03–2.70, p = 0.036), cM1-oligo was not an independent predictive feature for general HRQOL (OR 0.821, 95% CI 0.44–1.53, p = 0.536). (4) Conclusions: in this large contemporary retrospective analysis, we observed no significant difference in HRQOL in patients with the oligometastatic bone disease after cytoreductive radical prostatectomy, when compared to patients with localized disease at time of surgery.

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