Prostate Cancer

Adiposity and Muscle Strength in Men With Prostate Cancer and Cardiovascular Outcomes

Background: There are limited data on the physical effects of androgen deprivation therapy (ADT) for prostate cancer (PC), and on the relationships of such measures of adiposity and strength to cardiovascular outcomes.

Objectives: The primary objective of this study was to evaluate the relationships of measures of adiposity and strength to cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, heart failure, arterial revascularization, peripheral arterial disease, and venous thromboembolism) in patients with PC. A secondary objectives was to characterize the relationships between ADT use and 12-month changes in these physical measures.

Methods: This international, prospective cohort study included 3,967 patients with PC diagnosed in the prior 12 months or being treated with ADT for the first time. Median follow-up duration was 2.3 years.

Results: Participants’ mean age was 68.5 years, and 1,731 (43.6%) were exposed to ADT. ADT was associated with a 1.6% increase in weight, a 2.2% increase in waist circumference, a 1.6% increase in hip circumference, a 0.1% increase in waist-to-hip ratio, a 27.4% reduction in handgrip strength, and a 0.1% decrease in gait speed. High waist circumference and low handgrip strength were associated with adverse cardiovascular outcomes. Adjusting for age, education, race, tobacco and alcohol use, physical activity, cardiovascular disease, glomerular filtration rate, and ADT use, waist circumference above the highest quartile (110 cm) and handgrip strength below the lowest quartile (29.5 kg) were associated with higher likelihoods of a future cardiovascular event, with respective HRs of 1.40 (95% CI: 1.03-1.90; P = 0.029) and 1.59 (95% CI: 1.14-2.22; P = 0.006).

Conclusions: ADT was associated with increased adiposity and reduced strength over 12-month follow-up. High waist circumference and low baseline strength were associated with future adverse cardiovascular outcomes.

Darryl P. Leong MBBS, MPH, MBiostat, PhD a b, Vincent Fradet MD, PhD c, Tamim Niazi MD d, Joseph B. Selvanayagam MBBS, DPhil e, Robert Sabbagh MD, MSc f, Celestia S. Higano MD g, Steven Agapay BSc a, Sumathy Rangarajan MSc a, Rajibul Mian PhD a, Carlos A.K. Nakashima MD, PhD h, Negareh Mousavi MD i, Ian Brown MD j, Felipe H. Valle MD, PhD k, Luke T. Lavallée MDCM, MSc l, Bobby Shayegan MD m, Kelvin K.H. Ng MBBS b, Darin D. Gopaul MD n, Germano D. Cavalli MD b, Sonia Saavedra MD o, Jose P. Lopez-Lopez MD p, Cristiano Freitas de Souza MD, PhD q, Emmanuelle Duceppe MD, PhD r, Lívia F. Avezum Oliveira MD s, Avirup Guha MBBS, MPH t, Juan Esteban Gomez-Mesa MD u, Luis Eduardo Silva Móz MD, PhD v, Philippe D. Violette MDCM, MSc w, Álvaro Avezum MD, PhD x, Gustavo B.F. Oliveira MD, PhD x, Ariel G. Kann MD x, Edilson Walter MD y, Cesar O.L. Dusilek MD z, Nicolas Villareal Trujillo MD aa, Patricia Beato MD bb, Ludhmila A. Hajjar MD, PhD cc, Patrick P.W. Luke MD dd, Eduardo Schlabendorff MD ee, David Sarid MD ff, Jehonathan Pinthus MD, PhD gg

a Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
b Department of Medicine, McMaster University, Hamilton, Ontario, Canada
c Centre de Recherche du CHU de Québec, Université Laval, Quebec City, Quebec, Canada
d Jewish General Hospital, Montreal, Quebec, Canada
e Southern Area Local Health Network and Flinders University of South Australia, Adelaide, Australia
f Faculty of Medicine, University of Sherbrooke, Montreal, Quebec, Canada
g University of British Columbia and Madrona Oncology, Seattle, Washington, USA
h Faculdades Pequeno Príncipe, Sociedade Hospitalar Angelina Caron, Araçatuba, Brazil
i McGill University Health Centre, Montreal, Quebec, Canada
j Division of Urology, Niagara Health System, St. Catharines, Ontario, Canada
k Division of Cardiology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
l Division of Urology, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
m Division of Urology, Department of Surgery, St. Joseph’s Healthcare Hamilton and McMaster University, Hamilton, Ontario, Canada
n Grand River Regional Cancer Centre, Kitchener, Ontario, Canada
o Faculty of Medicine, University of La Frontera, Temuco, Chile
p Masira Research Institute, Universidad de Santander, Bucaramanga, Colombia
q Núcleo de Pesquisa Clínica – Rede São Camilo and Instituto Brasileiro de Controle do Cancer, São Paolo, Brazil
r Department of Medicine, Centre Hospitalier de l’Université de Montreal, Montreal, Quebec, Canada
s Centro de Pesquisa Clínica do HC-UFTM, Uberaba, Brazil
t Augusta University, Augusta, Georgia, USA
u Department of Health Sciences and Fundacíon Valle del Lili, Universidad Icesi, Cali, Colombia
v Clinical Oncology Department, Santa Casa de São Paolo Hospital, São Paolo, Brazil
w Woodstock Hospital, McMaster University, Woodstock, Ontario, Canada
x International Research Center, Hospital Alemão Oswaldo Cruz, São Paolo, Brazil
y Centro de Oncologia do Hospital de Clínicas Ijuí, Ijuí, Brazil
z Hospital Rocio, Curitiba, Brazil
aa FOSCAL Internacional Clinic, Floridablanca, Colombia
bb Centro de Pesquisas Clínicas da Fundação Doutor Amaral Carvalho, São Paolo, Brazil
cc Faculdade de Medicina da Universidade de São Paolo, São Paolo, Brazil
dd Department of Surgery, London Health Science Centre, London, Ontario, Canada
ee Mãe de Deus Hospital, Porto Alegre, Brazil
ff Tel Aviv Sourasky Medical Centre, Tel Aviv, Israel
gg Department of Surgery, McMaster University, Hamilton, Ontario, Canada

Source: Leong DP., Fradet V., Niazi T. et al. Adiposity and Muscle Strength in Men With Prostate Cancer and Cardiovascular Outcomes. JACC: CardioOncology. 2024. ISSN 2666-0873, https://doi.org/10.1016/j.jaccao.2024.07.011.

Germline Pathogenic Variants Identified in Patients With Genitourinary Malignancies Undergoing Universal Testing: A Multisite Single-Institution Prospective Study

Purpose: This study aimed to investigate the prevalence of pathogenic germline variants (PGVs) in hereditary cancer genes utilizing a universal testing approach and to determine the rate of PGVs that would have been missed based on National Comprehensive Cancer Network (NCCN) guidelines in genitourinary (GU) malignancies.

Materials and methods: A multisite, single-institution prospective germline genetic test (GGT) was universally offered to patients with new or active diagnoses of GU malignancies (prostate, bladder, and renal) from April 2018 to March 2020 at Mayo Clinic sites. Participants were offered GGT using a next-generation sequencing panel of > 80 genes. Demographic, tumor characteristics, and genetic results were evaluated. NCCN GU cancer guidelines were used to identify whether patients had incremental findings, defined as PGV-positive patients who would not have received testing based on NCCN guidelines.

Results: Of 3095 individuals enrolled in the study, 601 patients had GU cancer (prostate = 358, bladder = 106, and renal = 137). The mean enrollment age was 67 years (SD 9.1), 89% were male, and 86% of patients were non-Hispanic White. PGVs were identified in 82 (14%) of all GU patients. PGV prevalence breakdown by cancer type was: 14% prostate, 14% bladder, and 13% renal cancer. Nearly one-third of identified PGVs were high penetrance, and the majority of these (67%) were clinically actionable. Incremental PGVs were identified in 28 (57%) prostate, 15 (100%) bladder, and 14 (78%) renal cancer patients. Of the 82 patients with PGV findings, 29 (35%) had at least 1 relative undergo cascade testing for the familial variant(s) identified.

Conclusions: More than 1 in 8 patients with GU malignancies were found to carry a PGV, with 67% of patients with high-penetrance PGVs undergoing clinically actionable changes. The majority of these PGVs would not have been identified based on current testing criteria. These findings support universal GGT for GU malignancies and underscore its potential to enhance risk assessment and guide precision interventions in urologic oncology.

Mouneeb M Choudry,¹ Adri M Durant,¹ Victoria S Edmonds,¹ Christopher J Warren,¹ Katie L Kunze,² Michael A Golafshar,² Sarah M Nielsen,³ Edward D Esplin,³ Jack R Andrews,¹ N Jewel Samadder,^4,5,6 Mark D Tyson¹

Department of Urology, Mayo Clinic, Phoenix, Arizona.
Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, Arizona.
Invitae Corporation, San Francisco, California.
Department of Clinical Genomics, Mayo Clinic, Phoenix, Arizona.
Center for Individualized Medicine, Mayo Clinic, Phoenix, Arizona.
Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Phoenix, Arizona.

Source: Choudry MM., Durant AM., Edmonds VS. et al. Germline Pathogenic Variants Identified in Patients With Genitourinary Malignancies Undergoing Universal Testing: A Multisite Single-Institution Prospective Study. J Urol. 2024 Oct;212(4):590-599. doi: 10.1097/JU.0000000000004089.

Integrative identification of non-coding regulatory regions driving metastatic prostate cancer.

Large-scale sequencing efforts have been undertaken to understand the mutational landscape of the coding genome. However, the vast majority of variants occur within non-coding genomic regions. We designed an integrative computational and experimental framework to identify recurrently mutated non-coding regulatory regions that drive tumor progression.

Risk of Anxiety Disorders in Men With Prostate Cancer: A National Cohort Study.

Men with prostate cancer (PC) may experience significant psychosocial distress from physical symptoms, treatment side effects, or fear of recurrence. However, little is known about the long-term risk of anxiety disorders in men with PC.

Current uses and resistance mechanisms of enzalutamide in prostate cancer treatment.

Prostate cancer continues to be a major cause of morbidity and mortality for men worldwide. Enzalutamide, a second-generation non-steroidal antiandrogen that blocks androgen receptor (AR) transcriptional activity, is a treatment for biochemically-recurrent, metastatic, castration sensitive, and castration resistant tumors.

Ejaculatory function after radiotherapy for prostate cancer: a systematic review and meta-analysis.

Scant data exists on the impacts of prostate radiation on ejaculatory function. We performed a systematic review and meta-analysis to assess ejaculatory outcomes in men after prostate radiation.

We queried PubMed, Embase, and Web of Science to identify 17 articles assessing ejaculatory function post-radiation.

Prognostic factors in post-prostatectomy salvage radiotherapy setting with and without hormonotherapy: An individual patient data analysis of randomized trials from ICECaP database.

Early salvage radiotherapy (SRT) is the standard of care for biochemical recurrence post-prostatectomy but outcomes are heterogeneous.

To develop a risk scoring system based on relevant standard-of-care clinico-pathological prognostic factors for patients treated with SRT with and without hormonal therapy (HT).

Intra-prostatic recurrences after radiotherapy with focal boost: Location and dose mapping in the FLAME trial.

The FLAME trial demonstrated that the dose to the gross tumor volume (GTV) is associated with tumour control in prostate cancer patients. This raises the question if dose de-escalation to the remaining prostate gland can be considered.

Prostate cancer incidence and mortality in Europe and implications for screening activities: population based study.

To provide a baseline comparative assessment of the main epidemiological features of prostate cancer in European populations as background for the proposed EU screening initiatives.

Population based study.

Extracellular Vesicles heterogeneity through the lens of multiomics.

Extracellular vesicles (EVs) are heterogenous in size, biogenesis, cargo and function. Beside small EVs, aggressive tumor cells release a population of particularly large EVs, namely large oncosomes (LO).

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Prostate Cancer

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